Subjects -> CHEMISTRY (Total: 1001 journals)
    - ANALYTICAL CHEMISTRY (59 journals)
    - CHEMISTRY (726 journals)
    - CRYSTALLOGRAPHY (23 journals)
    - ELECTROCHEMISTRY (28 journals)
    - INORGANIC CHEMISTRY (45 journals)
    - ORGANIC CHEMISTRY (49 journals)
    - PHYSICAL CHEMISTRY (71 journals)

CHEMISTRY (726 journals)                  1 2 3 4 | Last

Showing 1 - 200 of 735 Journals sorted alphabetically
Accounts of Materials Research     Hybrid Journal   (Followers: 1)
Accreditation and Quality Assurance: Journal for Quality, Comparability and Reliability in Chemical Measurement     Hybrid Journal   (Followers: 36)
ACS Applied Polymer Materials     Hybrid Journal   (Followers: 15)
ACS Catalysis     Hybrid Journal   (Followers: 79)
ACS Chemical Neuroscience     Hybrid Journal   (Followers: 25)
ACS Combinatorial Science     Hybrid Journal   (Followers: 25)
ACS Macro Letters     Hybrid Journal   (Followers: 34)
ACS Materials Letters     Open Access   (Followers: 4)
ACS Medicinal Chemistry Letters     Hybrid Journal   (Followers: 50)
ACS Nano     Hybrid Journal   (Followers: 457)
ACS Photonics     Hybrid Journal   (Followers: 19)
ACS Symposium Series     Full-text available via subscription   (Followers: 3)
ACS Synthetic Biology     Hybrid Journal   (Followers: 41)
Acta Chemica Malaysia     Open Access  
Acta Chimica Slovaca     Open Access   (Followers: 4)
Acta Chimica Slovenica     Open Access   (Followers: 2)
Acta Chromatographica     Full-text available via subscription   (Followers: 9)
Acta Facultatis Medicae Naissensis     Open Access   (Followers: 1)
Acta Metallurgica Sinica (English Letters)     Hybrid Journal   (Followers: 10)
Acta Scientifica Naturalis     Open Access   (Followers: 3)
adhäsion KLEBEN & DICHTEN     Hybrid Journal   (Followers: 9)
Adhesion Adhesives & Sealants     Hybrid Journal   (Followers: 10)
Adsorption Science & Technology     Open Access   (Followers: 9)
Advanced Electronic Materials     Hybrid Journal   (Followers: 7)
Advanced Functional Materials     Hybrid Journal   (Followers: 81)
Advanced Journal of Chemistry, Section A     Open Access   (Followers: 15)
Advanced Journal of Chemistry, Section B     Open Access   (Followers: 14)
Advanced Science Focus     Free   (Followers: 7)
Advanced Theory and Simulations     Hybrid Journal   (Followers: 5)
Advanced Therapeutics     Hybrid Journal   (Followers: 1)
Advances in Chemical Engineering and Science     Open Access   (Followers: 111)
Advances in Chemical Science     Open Access   (Followers: 53)
Advances in Chemistry     Open Access   (Followers: 40)
Advances in Chemistry     Full-text available via subscription   (Followers: 6)
Advances in Colloid and Interface Science     Full-text available via subscription   (Followers: 21)
Advances in Drug Research     Full-text available via subscription   (Followers: 27)
Advances in Environmental Chemistry     Open Access   (Followers: 12)
Advances in Enzyme Research     Open Access   (Followers: 13)
Advances in Fuel Cells     Full-text available via subscription   (Followers: 20)
Advances in Heterocyclic Chemistry     Full-text available via subscription   (Followers: 11)
Advances in Materials Physics and Chemistry     Open Access   (Followers: 36)
Advances in Nanoparticles     Open Access   (Followers: 20)
Advances in Organometallic Chemistry     Full-text available via subscription   (Followers: 20)
Advances in Polymer Science     Hybrid Journal   (Followers: 54)
Advances in Protein Chemistry     Full-text available via subscription   (Followers: 19)
Advances in Protein Chemistry and Structural Biology     Full-text available via subscription   (Followers: 22)
Advances in Quantum Chemistry     Full-text available via subscription   (Followers: 7)
Advances in Science and Technology     Full-text available via subscription   (Followers: 17)
Aerosol Science and Engineering     Hybrid Journal  
African Journal of Bacteriology Research     Open Access  
African Journal of Chemical Education     Open Access   (Followers: 6)
African Journal of Pure and Applied Chemistry     Open Access   (Followers: 7)
Aggregate     Open Access   (Followers: 2)
Agrokémia és Talajtan     Full-text available via subscription   (Followers: 3)
Al-Kimia : Jurnal Penelitian Sains Kimia     Open Access  
Alchemy : Journal of Chemistry     Open Access   (Followers: 6)
Alchemy : Jurnal Penelitian Kimia     Open Access   (Followers: 2)
Alkaloids: Chemical and Biological Perspectives     Full-text available via subscription   (Followers: 2)
Alotrop     Open Access  
AMB Express     Open Access   (Followers: 1)
Ambix     Hybrid Journal   (Followers: 3)
American Journal of Biochemistry and Biotechnology     Open Access   (Followers: 71)
American Journal of Biochemistry and Molecular Biology     Open Access   (Followers: 24)
American Journal of Chemistry     Open Access   (Followers: 42)
American Journal of Plant Physiology     Open Access   (Followers: 13)
Analyst     Full-text available via subscription   (Followers: 40)
Analytical Science Advances     Open Access   (Followers: 2)
Angewandte Chemie     Hybrid Journal   (Followers: 245)
Angewandte Chemie International Edition     Hybrid Journal   (Followers: 356)
Annales Universitatis Mariae Curie-Sklodowska, sectio AA – Chemia     Open Access   (Followers: 1)
Annals of Clinical Chemistry and Laboratory Medicine     Open Access   (Followers: 8)
Annual Reports in Computational Chemistry     Full-text available via subscription   (Followers: 4)
Annual Reports Section B (Organic Chemistry)     Full-text available via subscription   (Followers: 9)
Annual Review of Chemical and Biomolecular Engineering     Full-text available via subscription   (Followers: 13)
Annual Review of Food Science and Technology     Full-text available via subscription   (Followers: 16)
Antiviral Chemistry and Chemotherapy     Open Access   (Followers: 2)
Applied Organometallic Chemistry     Hybrid Journal   (Followers: 12)
Applied Spectroscopy     Full-text available via subscription   (Followers: 27)
Applied Surface Science     Hybrid Journal   (Followers: 33)
Arabian Journal of Chemistry     Open Access   (Followers: 6)
ARKIVOC     Open Access   (Followers: 1)
Asian Journal of Applied Chemistry Research     Open Access   (Followers: 2)
Asian Journal of Biochemistry     Open Access   (Followers: 3)
Asian Journal of Chemical Sciences     Open Access   (Followers: 1)
Asian Journal of Chemistry and Pharmaceutical Sciences     Open Access   (Followers: 2)
Asian Journal of Physical and Chemical Sciences     Open Access   (Followers: 3)
Atomization and Sprays     Full-text available via subscription   (Followers: 8)
Australian Journal of Chemistry     Hybrid Journal   (Followers: 7)
Autophagy     Hybrid Journal   (Followers: 7)
Avances en Quimica     Open Access  
Biochemical Pharmacology     Hybrid Journal   (Followers: 11)
Biochemistry     Hybrid Journal   (Followers: 491)
Biochemistry Insights     Open Access   (Followers: 7)
Biochemistry Research International     Open Access   (Followers: 6)
BioChip Journal     Hybrid Journal  
Bioinorganic Chemistry and Applications     Open Access   (Followers: 11)
Biointerface Research in Applied Chemistry     Open Access   (Followers: 3)
Biointerphases     Open Access   (Followers: 1)
Biology, Medicine, & Natural Product Chemistry     Open Access   (Followers: 4)
Biomacromolecules     Hybrid Journal   (Followers: 27)
Biomass Conversion and Biorefinery     Partially Free   (Followers: 11)
Biomedical Chromatography     Hybrid Journal   (Followers: 6)
Biomolecular NMR Assignments     Hybrid Journal   (Followers: 4)
BioNanoScience     Partially Free   (Followers: 6)
Bioorganic & Medicinal Chemistry     Hybrid Journal   (Followers: 220)
Bioorganic & Medicinal Chemistry Letters     Hybrid Journal   (Followers: 88)
Bioorganic Chemistry     Hybrid Journal   (Followers: 10)
Biopolymers     Hybrid Journal   (Followers: 18)
Biosensors     Open Access   (Followers: 4)
Biotechnic and Histochemistry     Hybrid Journal   (Followers: 1)
Bitácora Digital     Open Access  
Boletin de la Sociedad Chilena de Quimica     Open Access  
Bulletin of Institute of Chemistry and Chemical Technology, Mongolian Academy of Sciences     Open Access  
Bulletin of the Chemical Society of Ethiopia     Open Access   (Followers: 1)
Bulletin of the Chemical Society of Japan     Full-text available via subscription   (Followers: 26)
Bulletin of the Korean Chemical Society     Hybrid Journal   (Followers: 1)
C - Journal of Carbon Research     Open Access   (Followers: 5)
Cakra Kimia (Indonesian E-Journal of Applied Chemistry)     Open Access  
Canadian Association of Radiologists Journal     Full-text available via subscription   (Followers: 2)
Canadian Journal of Chemistry     Hybrid Journal   (Followers: 13)
Canadian Mineralogist     Full-text available via subscription   (Followers: 7)
Carbohydrate Polymer Technologies and Applications     Open Access   (Followers: 3)
Carbohydrate Polymers     Hybrid Journal   (Followers: 13)
Carbohydrate Research     Hybrid Journal   (Followers: 26)
Carbon     Hybrid Journal   (Followers: 76)
Carbon Capture Science & Technology     Open Access  
Catalysis for Sustainable Energy     Open Access   (Followers: 13)
Catalysis Reviews: Science and Engineering     Hybrid Journal   (Followers: 9)
Catalysis Science and Technology     Hybrid Journal   (Followers: 13)
Catalysis Surveys from Asia     Hybrid Journal   (Followers: 4)
Catalysts     Open Access   (Followers: 14)
Cell Reports Physical Science     Open Access  
Cellulose     Hybrid Journal   (Followers: 17)
Cereal Chemistry     Full-text available via subscription   (Followers: 6)
Chem     Hybrid Journal  
Chem Catalysis     Hybrid Journal  
ChemBioEng Reviews     Full-text available via subscription   (Followers: 3)
ChemCatChem     Hybrid Journal   (Followers: 11)
Chemical and Engineering News     Free   (Followers: 24)
Chemical Bulletin of Kazakh National University     Open Access  
Chemical Communications     Full-text available via subscription   (Followers: 88)
Chemical Engineering Research and Design     Hybrid Journal   (Followers: 28)
Chemical Physics Impact     Full-text available via subscription  
Chemical Research in Chinese Universities     Hybrid Journal   (Followers: 4)
Chemical Research in Toxicology     Hybrid Journal   (Followers: 26)
Chemical Reviews     Hybrid Journal   (Followers: 271)
Chemical Science     Open Access   (Followers: 44)
Chemical Science International Journal     Open Access   (Followers: 1)
Chemical Technology     Open Access   (Followers: 74)
Chemical Thermodynamics and Thermal Analysis     Open Access  
Chemical Vapor Deposition     Hybrid Journal   (Followers: 5)
Chemie in Unserer Zeit     Hybrid Journal   (Followers: 56)
Chemie-Ingenieur-Technik (Cit)     Hybrid Journal   (Followers: 23)
ChemInform     Hybrid Journal   (Followers: 9)
Chemistry     Open Access  
Chemistry & Biodiversity     Hybrid Journal   (Followers: 7)
Chemistry & Industry     Full-text available via subscription   (Followers: 8)
Chemistry - A European Journal     Hybrid Journal   (Followers: 229)
Chemistry - An Asian Journal     Hybrid Journal   (Followers: 20)
Chemistry Africa : A Journal of the Tunisian Chemical Society     Hybrid Journal  
Chemistry and Materials Research     Open Access   (Followers: 24)
Chemistry Central Journal     Open Access   (Followers: 5)
Chemistry Education Research and Practice     Free   (Followers: 8)
Chemistry Education Review     Open Access   (Followers: 5)
Chemistry in Education     Open Access   (Followers: 9)
Chemistry International     Open Access   (Followers: 3)
Chemistry Letters     Full-text available via subscription   (Followers: 49)
Chemistry of Heterocyclic Compounds     Hybrid Journal   (Followers: 4)
Chemistry of Materials     Hybrid Journal   (Followers: 342)
Chemistry of Natural Compounds     Hybrid Journal   (Followers: 10)
Chemistry World     Full-text available via subscription   (Followers: 20)
Chemistry-Didactics-Ecology-Metrology     Open Access   (Followers: 1)
ChemistryOpen     Open Access   (Followers: 1)
ChemistrySelect     Hybrid Journal  
Chemistry–Methods     Open Access   (Followers: 2)
Chemkon - Chemie Konkret, Forum Fuer Unterricht Und Didaktik     Hybrid Journal  
ChemNanoMat     Hybrid Journal   (Followers: 1)
Chemoecology     Hybrid Journal   (Followers: 3)
Chemometrics and Intelligent Laboratory Systems     Hybrid Journal   (Followers: 14)
Chemosensors     Open Access   (Followers: 1)
ChemPhotoChem     Hybrid Journal  
ChemPhysChem     Hybrid Journal   (Followers: 14)
ChemPhysMater     Full-text available via subscription  
ChemPlusChem     Hybrid Journal   (Followers: 2)
Chempublish Journal     Open Access   (Followers: 1)
ChemSystemsChem     Hybrid Journal   (Followers: 2)
ChemTexts     Hybrid Journal   (Followers: 1)
CHIMIA International Journal for Chemistry     Open Access   (Followers: 2)
Chinese Journal of Chemistry     Hybrid Journal   (Followers: 6)
Chinese Journal of Polymer Science     Hybrid Journal   (Followers: 13)
Chromatographia     Hybrid Journal   (Followers: 22)
Chromatography     Open Access   (Followers: 3)
Chromatography Research International     Open Access   (Followers: 5)
Ciencia     Open Access   (Followers: 1)
Clay Minerals     Hybrid Journal   (Followers: 9)
Cogent Chemistry     Open Access   (Followers: 3)
Colloid and Interface Science Communications     Open Access  
Colloid and Polymer Science     Hybrid Journal   (Followers: 12)
Colloids and Interfaces     Open Access  
Colloids and Surfaces B: Biointerfaces     Hybrid Journal   (Followers: 8)

        1 2 3 4 | Last

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Journal Prestige (SJR): 0.829
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Number of Followers: 4  

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ISSN (Print) 2079-6374
Published by MDPI Homepage  [240 journals]
  • Biosensors, Vol. 11, Pages 471: Real-Time Longitudinal Evaluation of Tumor
           Blood Vessels Using a Compact Preclinical Fluorescence Imaging System

    • Authors: Hoibin Jeong, Song-Rae Kim, Yujung Kang, Huisu Kim, Seo-Young Kim, Su-Hyeon Cho, Kil-Nam Kim
      First page: 471
      Abstract: Tumor angiogenesis is enhanced in all types of tumors to supply oxygen and nutrients for their growth and metastasis. With the development of anti-angiogenic drugs, the importance of technology that closely monitors tumor angiogenesis has also been emerging. However, to date, the technology for observing blood vessels requires specialized skills with expensive equipment, thereby limiting its applicability only to the laboratory setting. Here, we used a preclinical optical imaging system for small animals and, for the first time, observed, in real time, the entire process of blood vessel development in tumor-bearing mice injected with indocyanine green. Time-lapse sequential imaging revealed blood vessel volume and blood flow dynamics on a microscopic scale. Upon analyzing fluorescence dynamics at each stage of tumor progression, vessel volume and blood flow were found to increase as the tumor developed. Conversely, these vascular parameters decreased when the mice were treated with angiogenesis inhibitors, which suggests that the effects of drugs targeting angiogenesis can be rapidly and easily screened. The results of this study may help evaluate the efficacy of angiogenesis-targeting drugs by facilitating the observation of tumor blood vessels easily in a laboratory unit without large and complex equipment.
      Citation: Biosensors
      PubDate: 2021-11-23
      DOI: 10.3390/bios11120471
      Issue No: Vol. 11, No. 12 (2021)
  • Biosensors, Vol. 11, Pages 472: Biocompatible and Biodegradable Polymer
           Optical Fiber for Biomedical Application: A Review

    • Authors: Yue Wang, Yu Huang, Hongyi Bai, Guoqing Wang, Xuehao Hu, Santosh Kumar, Rui Min
      First page: 472
      Abstract: This article discusses recent advances in biocompatible and biodegradable polymer optical fiber (POF) for medical applications. First, the POF material and its optical properties are summarized. Then, several common optical fiber fabrication methods are thoroughly discussed. Following that, clinical applications of biocompatible and biodegradable POFs are discussed, including optogenetics, biosensing, drug delivery, and neural recording. Following that, biomedical applications expanded the specific functionalization of the material or fiber design. Different research or clinical applications necessitate the use of different equipment to achieve the desired results. Finally, the difficulty of implanting flexible fiber varies with its flexibility. We present our article in a clear and logical manner that will be useful to researchers seeking a broad perspective on the proposed topic. Overall, the content provides a comprehensive overview of biocompatible and biodegradable POFs, including previous breakthroughs, as well as recent advancements. Biodegradable optical fibers have numerous applications, opening up new avenues in biomedicine.
      Citation: Biosensors
      PubDate: 2021-11-23
      DOI: 10.3390/bios11120472
      Issue No: Vol. 11, No. 12 (2021)
  • Biosensors, Vol. 11, Pages 473: Selective Detection of an Infection
           Biomarker by an Osteo-Friend Scaffold: Development of a Multifunctional
           Artificial Bone Substitute

    • Authors: Kim, Raja, Choi, Kim, Sung, Choi, Yun, Park
      First page: 473
      Abstract: Developments in three-dimensional (3D) printing technologies have led to many potential applications in various biomedical fields, especially artificial bone substitutes (ABSs). However, due to the characteristics of artificial materials, biocompatibility and infection remain issues. Here, multifunctional ABSs have been designed to overcome these issues by the inclusion of a biochemical modality that allows simultaneous detection of an infection biomarker by osteo-friend 3D scaffolds. The developed multifunctional scaffolds consist of calcium-deficient hydroxyapatite (CDHA), which has a similar geometric structure and chemical composition to human bone, and gold nanoparticles (Au NPs), which assists osteogenesis and modulates the fluorescence of labels in their microenvironment. The Au NPs were subsequently conjugated with fluorescent dye-labeled probe DNA, which allowed selective interaction with a specific target biomarker, and the fluorescent signal of the dye was temporally quenched by the Au NP-derived Förster resonance energy transfer (FRET). When the probe DNA unfolded to bind to the target biomarker, the fluorescence signal was recovered due to the increased distance between the dye and Au NPs. To demonstrate this sensing mechanism, a microbial oligonucleotide was selected as a target biomarker. Consequently, the multifunctional scaffold simultaneously facilitated osteogenic proliferation and the detection of the infection biomarker.
      Citation: Biosensors
      PubDate: 2021-11-24
      DOI: 10.3390/bios11120473
      Issue No: Vol. 11, No. 12 (2021)
  • Biosensors, Vol. 11, Pages 474: A Customized Microfluidic Paper-Based
           Platform for Colorimetric Immunosensing: Demonstrated via hCG Assay for
           Pregnancy Test

    • Authors: Mohammad Rahbar, Siyi Zou, Mahroo Baharfar, Guozhen Liu
      First page: 474
      Abstract: Over the past decades, paper-based lateral flow immunoassays (LFIAs) have been extensively developed for rapid, facile, and low-cost detection of a wide array of target analytes in a point-of-care manner. Conventional home pregnancy tests are the most significant example of LFAs, which detect elevated concentrations of human chorionic gonadotrophin (hCG) in body fluids to identify early pregnancy. In this work, we have upgraded these platforms to a higher version by developing a customized microfluidic paper-based analytical device (μPAD), as the new generation of paper-based point-of-care platforms, for colorimetric immunosensing. This will offer a cost-efficient and environmentally friendly alternative platform for paper-based immunosensing, eliminating the need for nitrocellulose (NC) membrane as the substrate material. The performance of the developed platform is demonstrated by detection of hCG (as a model case) in urine samples and subsequently indicating positive or negative pregnancy. A dual-functional silane-based composite was used to treat filter paper in order to enhance the colorimetric signal intensity in the detection zones of μPADs. In addition, microfluidic pathways were designed in a manner to provide the desired regulated fluid flow, generating sufficient incubation time (delays) at the designated detection zones, and consequently enhancing the obtained signal intensity. The presented approaches allow to overcome the existing limitations of μPADs in immunosensing and will broaden their applicability to a wider range of assays. Although, the application of the developed hCG μPAD assay is mainly in qualitative (i.e., positive or negative) detection of pregnancy, the semi-quantitative measurement of hCG was also investigated, indicating the viability of this assay for sensitive detection of the target hCG analyte within the related physiological range (i.e., 10–500 ng/mL) with a LOD value down to 10 ng/mL.
      Citation: Biosensors
      PubDate: 2021-11-25
      DOI: 10.3390/bios11120474
      Issue No: Vol. 11, No. 12 (2021)
  • Biosensors, Vol. 11, Pages 475: MoS2 QDs/8-Armed Poly(Ethylene Glycol)
           Fluorescence Sensor for Three Nitrotoluenes (TNT) Detection

    • Authors: Xiaoyuan Zhang, Zhiqiang Su
      First page: 475
      Abstract: In this work, ammonia cross-linked 8-armed polyethylene glycol hydrogel material was successfully synthesized and used as a template for synthesizing nanoparticles with fluorescent properties. The 8-armed polyethylene glycol hydrogel template was used to prepare molybdenum disulfide quantum dots (MoS2 QDs). The ammonium tetrathiomolybdate functioned as a molybdenum source and hydrazine hydrate functioned as a reducing agent. The fluorescence properties of the as-prepared MoS2 QDs were investigated. The bursting of fluorescence caused by adding different concentrations of explosive TNT was studied. The study indicated that the synthesized MoS2 QDs can be used for trace TNT detection with a detection limit of 6 nmol/L and a detection range of 16–700 nmol/L. Furthermore, it indicated that the fluorescence-bursting mechanism is static bursting.
      Citation: Biosensors
      PubDate: 2021-11-25
      DOI: 10.3390/bios11120475
      Issue No: Vol. 11, No. 12 (2021)
  • Biosensors, Vol. 11, Pages 476: Exhaled Breath Analysis for Diabetes
           Diagnosis and Monitoring: Relevance, Challenges and Possibilities

    • Authors: Kaushiki Dixit, Somayeh Fardindoost, Adithya Ravishankara, Nishat Tasnim, Mina Hoorfar
      First page: 476
      Abstract: With the global population prevalence of diabetes surpassing 463 million cases in 2019 and diabetes leading to millions of deaths each year, there is a critical need for feasible, rapid, and non-invasive methodologies for continuous blood glucose monitoring in contrast to the current procedures that are either invasive, complicated, or expensive. Breath analysis is a viable methodology for non-invasive diabetes management owing to its potential for multiple disease diagnoses, the nominal requirement of sample processing, and immense sample accessibility; however, the development of functional commercial sensors is challenging due to the low concentration of volatile organic compounds (VOCs) present in exhaled breath and the confounding factors influencing the exhaled breath profile. Given the complexity of the topic and the skyrocketing spread of diabetes, a multifarious review of exhaled breath analysis for diabetes monitoring is essential to track the technological progress in the field and comprehend the obstacles in developing a breath analysis-based diabetes management system. In this review, we consolidate the relevance of exhaled breath analysis through a critical assessment of current technologies and recent advancements in sensing methods to address the shortcomings associated with blood glucose monitoring. We provide a detailed assessment of the intricacies involved in the development of non-invasive diabetes monitoring devices. In addition, we spotlight the need to consider breath biomarker clusters as opposed to standalone biomarkers for the clinical applicability of exhaled breath monitoring. We present potential VOC clusters suitable for diabetes management and highlight the recent buildout of breath sensing methodologies, focusing on novel sensing materials and transduction mechanisms. Finally, we portray a multifaceted comparison of exhaled breath analysis for diabetes monitoring and highlight remaining challenges on the path to realizing breath analysis as a non-invasive healthcare approach.
      Citation: Biosensors
      PubDate: 2021-11-25
      DOI: 10.3390/bios11120476
      Issue No: Vol. 11, No. 12 (2021)
  • Biosensors, Vol. 11, Pages 477: MoS2 Nanodonuts for High-Sensitivity
           Surface-Enhanced Raman Spectroscopy

    • Authors: Ghopry, Sadeghi, Berrie, Wu
      First page: 477
      Abstract: Nanohybrids of graphene and two-dimensional (2D) layered transition metal dichalcogenides (TMD) nanostructures can provide a promising substrate for extraordinary surface-enhanced Raman spectroscopy (SERS) due to the combined electromagnetic enhancement on TMD nanostructures via localized surface plasmonic resonance (LSPR) and chemical enhancement on graphene. In these nanohybrid SERS substrates, the LSPR on TMD nanostructures is affected by the TMD morphology. Herein, we report the first successful growth of MoS2 nanodonuts (N-donuts) on graphene using a vapor transport process on graphene. Using Rhodamine 6G (R6G) as a probe, SERS spectra were compared on MoS2 N-donuts/graphene nanohybrids substrates. A remarkably high R6G SERS sensitivity up to 2 × 10−12 M has been obtained, which can be attributed to the more robust LSPR effect than in other TMD nanostructures such as nanodiscs as suggested by the finite-difference time-domain simulation. This result demonstrates that non-metallic TMD/graphene nanohybrids substrates can have SERS sensitivity up to one order of magnitude higher than that reported on the plasmonic metal nanostructures/2D materials SERS substrates, providing a promising scheme for high-sensitivity, low-cost applications for biosensing.
      Citation: Biosensors
      PubDate: 2021-11-25
      DOI: 10.3390/bios11120477
      Issue No: Vol. 11, No. 12 (2021)
  • Biosensors, Vol. 11, Pages 478: Ten Years Progress of Electrical Detection
           of Heavy Metal Ions (HMIs) Using Various Field-Effect Transistor (FET)
           Nanosensors: A Review

    • Authors: Shaili Falina, Mohd Syamsul, Nuha Abd Rhaffor, Sofiyah Sal Hamid, Khairu Anuar Mohamed Zain, Asrulnizam Abd Manaf, Hiroshi Kawarada
      First page: 478
      Abstract: Heavy metal pollution remains a major concern for the public today, in line with the growing population and global industrialization. Heavy metal ion (HMI) is a threat to human and environmental safety, even at low concentrations, thus rapid and continuous HMI monitoring is essential. Among the sensors available for HMI detection, the field-effect transistor (FET) sensor demonstrates promising potential for fast and real-time detection. The aim of this review is to provide a condensed overview of the contribution of certain semiconductor substrates in the development of chemical and biosensor FETs for HMI detection in the past decade. A brief introduction of the FET sensor along with its construction and configuration is presented in the first part of this review. Subsequently, the FET sensor deployment issue and FET intrinsic limitation screening effect are also discussed, and the solutions to overcome these shortcomings are summarized. Later, we summarize the strategies for HMIs’ electrical detection, mechanisms, and sensing performance on nanomaterial semiconductor FET transducers, including silicon, carbon nanotubes, graphene, AlGaN/GaN, transition metal dichalcogenides (TMD), black phosphorus, organic and inorganic semiconductor. Finally, concerns and suggestions regarding detection in the real samples using FET sensors are highlighted in the conclusion.
      Citation: Biosensors
      PubDate: 2021-11-25
      DOI: 10.3390/bios11120478
      Issue No: Vol. 11, No. 12 (2021)
  • Biosensors, Vol. 11, Pages 479: A Rapid and Easy-to-Perform Method of
           Nucleic-Acid Based Dengue Virus Diagnosis Using Fluorescence-Based
           Molecular Beacons

    • Authors: Soumi Sukla, Prasenjit Mondal, Subhajit Biswas, Surajit Ghosh
      First page: 479
      Abstract: Detecting dengue virus (DENV) infection in patients as early as possible makes the disease management convenient. Conventionally, DENV infection is diagnosed by ELISA-based methods, but sensitivity and specificity are major concerns. Reverse-transcription-PCR (RT-PCR)-based detection confirms the presence of DENV RNA; however, it is expensive, time-consuming, and skilled personnel are required. A fluorescence-based detection system that detects DENV RNA in patient’s serum directly, without any nucleic acid amplification step, has been developed. The method uses target-specific complementary sequence in the molecular beacon, which would specifically bind to the DENV RNA. The molecular beacons are approximately 40 bases long hairpin structures, with a fluorophore-quencher system attached at the terminal ends of the stem. These probes are biotinylated in the stem region, so that they can be immobilized on the streptavidin-tagged magnetic beads. These magnetic beads, coupled with biotinylated molecular beacons, are used for the detection of the target RNA in the serum by incubating the mixture. After incubation, beads are separated and re-suspended in a buffer. The measurement of fluorescence is taken in fluorometer after 15 min incubation at 50 °C. The whole work is carried out in a single tube. This rapid method can precisely detect dengue RNA within two hours, confirming ongoing DENV replication in the patient.
      Citation: Biosensors
      PubDate: 2021-11-26
      DOI: 10.3390/bios11120479
      Issue No: Vol. 11, No. 12 (2021)
  • Biosensors, Vol. 11, Pages 480: RFID-Based Microwave Biosensor for
           Non-Contact Detection of Glucose Solution

    • Authors: Minjia Gao, Tian Qiang, Yangchuan Ma, Junge Liang, Yanfeng Jiang
      First page: 480
      Abstract: Due to the increasing number of diabetic patients, early monitoring of glucose levels is particularly important; therefore, glucose biosensors have attracted enormous attention from researchers. In this paper, we propose a glucose microwave biosensor based on RFID and achieve a non-contact measurement of the concentration of glucose solutions. The Reader is a complementary split-ring resonator (CSRR), and the Tag is comprised of a squared spiral capacitor (SSC). A polydimethylsiloxane microfluidic quantitative cavity with a volume of 1.56 μL is integrated on the Tag to ensure that the glucose solution can be accurately set to the sensitive area and fully contacted with the electromagnetic flux. Because the SSC exhibits different capacitances when it contacts glucose solutions of different concentrations, changing the resonant frequency of the CSRR, we can use the relationship to characterize the biosensing response. Measurement results show that bare CSRR and RFID-based biosensors have achieved sensitivities of 0.31 MHz/mg·dL−1 and 10.27 kHz/mg·dL−1, and detection limits of 13.79 mg/dL and 1.19 mg/dL, respectively, and both realize a response time of less than 1 s. Linear regression analysis of the abovementioned biosensors showed an excellent linear relationship. The proposed design provides a feasible solution for microwave biosensors aiming for the non-contact measurement of glucose concentration.
      Citation: Biosensors
      PubDate: 2021-11-26
      DOI: 10.3390/bios11120480
      Issue No: Vol. 11, No. 12 (2021)
  • Biosensors, Vol. 11, Pages 481: Development of Multiplex PCR Coupled DNA
           Chip Technology for Assessment of Endogenous and Exogenous Allergens in GM

    • Authors: Tamara Kutateladze, Kakha Bitskinashvili, Nelly Sapojnikova, Tamar Kartvelishvili, Nino Asatiani, Boris Vishnepolsky, Nelly Datukishvili
      First page: 481
      Abstract: Allergenicity assessment of transgenic plants and foods is important for food safety, labeling regulations, and health protection. The aim of this study was to develop an effective multi-allergen diagnostic approach for transgenic soybean assessment. For this purpose, multiplex polymerase chain reaction (PCR) coupled with DNA chip technology was employed. The study was focused on the herbicide-resistant Roundup Ready soya (RRS) using a set of certified reference materials consisting of 0, 0.1%, 0.5%, and 10% RRS. Technically, the procedure included design of PCR primers and probes; genomic DNA extraction; development of uniplex and multiplex PCR systems; DNA analysis by agarose gel electrophoresis; microarray development, hybridization, and scanning. The use of the asymmetric multiplex PCR method is shown to be very efficient for DNA hybridization with biochip probes. We demonstrate that newly developed fourplex PCR methods coupled with DNA-biochips enable simultaneous identification of three major endogenous allergens, namely, Gly m Bd 28K, Gly m Bd 30K, and lectin, as well as exogenous 5-enolppyruvyl shikimate-phosphate synthase (epsps) expressed in herbicide-resistant roundup ready GMOs. The approach developed in this study can be used for accurate, cheap, and fast testing of food allergens.
      Citation: Biosensors
      PubDate: 2021-11-26
      DOI: 10.3390/bios11120481
      Issue No: Vol. 11, No. 12 (2021)
  • Biosensors, Vol. 11, Pages 482: Current Challenges and Future Trends of
           Enzymatic Paper-Based Point-of-Care Testing for Diabetes Mellitus Type 2

    • Authors: Margarita Ortiz-Martínez, Raquel Flores-DelaToba, Mirna González-González, Marco Rito-Palomares
      First page: 482
      Abstract: A point-of-care (POC) can be defined as an in vitro diagnostic test that can provide results within minutes. It has gained enormous attention as a promising tool for biomarkers detection and diagnosis, as well as for screening of chronic noncommunicable diseases such as diabetes mellitus. Diabetes mellitus type 2 is one of the metabolic disorders that has grown exponentially in recent years, becoming one of the greatest challenges to health systems. Early detection and accurate diagnosis of this disorder are essential to provide adequate treatments. However, efforts to reduce incidence should remain not only in these stages but in developing continuous monitoring strategies. Diabetes-monitoring tools must be accessible and affordable; thus, POC platforms are attractive, especially paper-based ones. Paper-based POCs are simple and portable, can use different matrixes, do not require highly trained staff, and are less expensive than other platforms. These advantages enhance the viability of its application in low-income countries and hard-to-reach zones. This review aims to present a critical summary of the main components required to create a sensitive and affordable enzymatic paper-based POC, as well as an oriented analysis to highlight the main limitations and challenges of current POC devices for diabetes type 2 monitoring and future research opportunities in the field.
      Citation: Biosensors
      PubDate: 2021-11-27
      DOI: 10.3390/bios11120482
      Issue No: Vol. 11, No. 12 (2021)
  • Biosensors, Vol. 11, Pages 483: Multiplexed, High-Sensitivity Measurements
           of Antibody Affinity Using Interferometric Reflectance Imaging Sensor

    • Authors: Allison Marn, James Needham, Elisa Chiodi, M. Ünlü
      First page: 483
      Abstract: Anthrax lethal factor (LF) is one of the enzymatic components of the anthrax toxin responsible for the pathogenic responses of the anthrax disease. The ability to screen multiplexed ligands against LF and subsequently estimate the effective kinetic rates (kon and koff) and complementary binding behavior provides critical information useful in diagnostic and therapeutic development for anthrax. Tools such as biolayer interferometry (BLI) and surface plasmon resonance imaging (SPRi) have been developed for this purpose; however, these tools suffer from limitations such as signal jumps when the solution in the chamber is switched or low sensitivity. Here, we present multiplexed antibody affinity measurements obtained by the interferometric reflectance imaging sensor (IRIS), a highly sensitive, label-free optical biosensor, whose stability, simplicity, and imaging modality overcomes many of the limitations of other multiplexed methods. We compare the multiplexed binding results obtained with the IRIS system using two ligands targeting the anthrax lethal factor (LF) against previously published results obtained with more traditional surface plasmon resonance (SPR), which showed consistent results, as well as kinetic information previously unattainable with SPR. Additional exemplary data demonstrating multiplexed binding and the corresponding complementary binding to sequentially injected ligands provides an additional layer of information immediately useful to the researcher.
      Citation: Biosensors
      PubDate: 2021-11-27
      DOI: 10.3390/bios11120483
      Issue No: Vol. 11, No. 12 (2021)
  • Biosensors, Vol. 11, Pages 406: High-Throughput, Label-Free Isolation of
           White Blood Cells from Whole Blood Using Parallel Spiral Microchannels
           with U-Shaped Cross-Section

    • Authors: Amirhossein Mehran, Peyman Rostami, Mohammad Said Saidi, Bahar Firoozabadi, Navid Kashaninejad
      First page: 406
      Abstract: Rapid isolation of white blood cells (WBCs) from whole blood is an essential part of any WBC examination platform. However, most conventional cell separation techniques are labor-intensive and low throughput, require large volumes of samples, need extensive cell manipulation, and have low purity. To address these challenges, we report the design and fabrication of a passive, label-free microfluidic device with a unique U-shaped cross-section to separate WBCs from whole blood using hydrodynamic forces that exist in a microchannel with curvilinear geometry. It is shown that the spiral microchannel with a U-shaped cross-section concentrates larger blood cells (e.g., WBCs) in the inner cross-section of the microchannel by moving smaller blood cells (e.g., RBCs and platelets) to the outer microchannel section and preventing them from returning to the inner microchannel section. Therefore, it overcomes the major limitation of a rectangular cross-section where secondary Dean vortices constantly enforce particles throughout the entire cross-section and decrease its isolation efficiency. Under optimal settings, we managed to isolate more than 95% of WBCs from whole blood under high-throughput (6 mL/min), high-purity (88%), and high-capacity (360 mL of sample in 1 h) conditions. High efficiency, fast processing time, and non-invasive WBC isolation from large blood samples without centrifugation, RBC lysis, cell biomarkers, and chemical pre-treatments make this method an ideal choice for downstream cell study platforms.
      Citation: Biosensors
      PubDate: 2021-10-20
      DOI: 10.3390/bios11110406
      Issue No: Vol. 11, No. 11 (2021)
  • Biosensors, Vol. 11, Pages 407: Two-Phase Biocatalysis in Microfluidic

    • Authors: Lanting Xiang, Felix Kaspar, Anett Schallmey, Iordania Constantinou
      First page: 407
      Abstract: This Perspective discusses the literature related to two-phase biocatalysis in microfluidic droplets. Enzymes used as catalysts in biocatalysis are generally less stable in organic media than in their native aqueous environments; however, chemical and pharmaceutical compounds are often insoluble in water. The use of aqueous/organic two-phase media provides a solution to this problem and has therefore become standard practice for multiple biotransformations. In batch, two-phase biocatalysis is limited by mass transport, a limitation that can be overcome with the use of microfluidic systems. Although, two-phase biocatalysis in laminar flow systems has been extensively studied, microfluidic droplets have been primarily used for enzyme screening. In this Perspective, we summarize the limited published work on two-phase biocatalysis in microfluidic droplets and discuss the limitations, challenges, and future perspectives of this technology.
      Citation: Biosensors
      PubDate: 2021-10-21
      DOI: 10.3390/bios11110407
      Issue No: Vol. 11, No. 11 (2021)
  • Biosensors, Vol. 11, Pages 408: Traditional Microscopic Techniques
           Employed in Dental Adhesion Research—Applications and Protocols of
           Specimen Preparation

    • Authors: Agnieszka Nawrocka, Ireneusz Piwonski, Salvatore Sauro, Annalisa Porcelli, Louis Hardan, Monika Lukomska-Szymanska
      First page: 408
      Abstract: Microscopy is a traditional method to perform ex vivo/in vitro dental research. Contemporary microscopic techniques offer the opportunity to observe dental tissues and materials up to nanoscale level. The aim of this paper was to perform a literature review on four microscopic methods, which are widely employed in dental studies concerning the evaluation of resin-dental adhesive interfaces—confocal laser scanning microscopy (CLSM), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and atomic force microscopy (AFM). The literature search was performed using digital databases: PubMed, Web of Science and Scopus. On the basis of key words relevant to the topic and established eligibility criteria, finally 84 papers were included in the review. Presented microscopic techniques differ in their principle of operation and require specific protocols for specimen preparation. With regard to adhesion studies, microscopy assists in the description of several elements involved in adhesive bonding, as well as in the assessment of the condition of enamel surface and the most appropriate etching procedures. There are several factors determining the quality of the interaction between the substrates which could be recognized and a potential for further implementation of microscopic techniques in dental research could be recognized, especially when these techniques are used simultaneously or combined with spectroscopic methods. Through such microscopy techniques it is possible to provide clinically relevant conclusions and recommendations, which can be easily introduced for enamel-safe bonding and bonding protocols, as well as optimal pretreatments in dentine preparation.
      Citation: Biosensors
      PubDate: 2021-10-21
      DOI: 10.3390/bios11110408
      Issue No: Vol. 11, No. 11 (2021)
  • Biosensors, Vol. 11, Pages 409: Non-Enzymatic Detection of Glucose in
           Neutral Solution Using PBS-Treated Electrodeposited Copper-Nickel

    • Authors: Lindsey Goodnight, Derrick Butler, Tunan Xia, Aida Ebrahimi
      First page: 409
      Abstract: Transition metals have been explored extensively for non-enzymatic electrochemical detection of glucose. However, to enable glucose oxidation, the majority of reports require highly alkaline electrolytes which can be damaging to the sensors and hazardous to handle. In this work, we developed a non-enzymatic sensor for detection of glucose in near-neutral solution based on copper-nickel electrodes which are electrochemically modified in phosphate-buffered saline (PBS). Nickel and copper were deposited using chronopotentiometry, followed by a two-step annealing process in air (Step 1: at room temperature and Step 2: at 150 °C) and electrochemical stabilization in PBS. Morphology and chemical composition of the electrodes were characterized using scanning electron microscopy and energy-dispersive X-ray spectroscopy. Cyclic voltammetry was used to measure oxidation reaction of glucose in sodium sulfate (100 mM, pH 6.4). The PBS-Cu-Ni working electrodes enabled detection of glucose with a limit of detection (LOD) of 4.2 nM, a dynamic response from 5 nM to 20 mM, and sensitivity of 5.47 ± 0.45 μA cm−2/log10(mole.L−1) at an applied potential of 0.2 V. In addition to the ultralow LOD, the sensors are selective toward glucose in the presence of physiologically relevant concentrations of ascorbic acid and uric acid spiked in artificial saliva. The optimized PBS-Cu-Ni electrodes demonstrate better stability after seven days storage in ambient compared to the Cu-Ni electrodes without PBS treatment.
      Citation: Biosensors
      PubDate: 2021-10-21
      DOI: 10.3390/bios11110409
      Issue No: Vol. 11, No. 11 (2021)
  • Biosensors, Vol. 11, Pages 410: Enzyme (Single and Multiple) and Nanozyme
           Biosensors: Recent Developments and Their Novel Applications in the
           Water-Food-Health Nexus

    • Authors: Lynette Alvarado-Ramírez, Magdalena Rostro-Alanis, José Rodríguez-Rodríguez, Juan Eduardo Sosa-Hernández, Elda M. Melchor-Martínez, Hafiz M. N. Iqbal, Roberto Parra-Saldívar
      First page: 410
      Abstract: The use of sensors in critical areas for human development such as water, food, and health has increased in recent decades. When the sensor uses biological recognition, it is known as a biosensor. Nowadays, the development of biosensors has been increased due to the need for reliable, fast, and sensitive techniques for the detection of multiple analytes. In recent years, with the advancement in nanotechnology within biocatalysis, enzyme-based biosensors have been emerging as reliable, sensitive, and selectively tools. A wide variety of enzyme biosensors has been developed by detecting multiple analytes. In this way, together with technological advances in areas such as biotechnology and materials sciences, different modalities of biosensors have been developed, such as bi-enzymatic biosensors and nanozyme biosensors. Furthermore, the use of more than one enzyme within the same detection system leads to bi-enzymatic biosensors or multi-enzyme sensors. The development and synthesis of new materials with enzyme-like properties have been growing, giving rise to nanozymes, considered a promising tool in the biosensor field due to their multiple advantages. In this review, general views and a comparison describing the advantages and disadvantages of each enzyme-based biosensor modality, their possible trends and the principal reported applications will be presented.
      Citation: Biosensors
      PubDate: 2021-10-21
      DOI: 10.3390/bios11110410
      Issue No: Vol. 11, No. 11 (2021)
  • Biosensors, Vol. 11, Pages 411: An Ultra-Low Power Surface EMG Sensor for
           Wearable Biometric and Medical Applications

    • Authors: Yi-Da Wu, Shanq-Jang Ruan, Yu-Hao Lee
      First page: 411
      Abstract: In recent years, the surface electromyography (EMG) signal has received a lot of attention. EMG signals are used to analyze muscle activity or to evaluate a patient’s muscle status. However, commercial surface EMG systems are expensive and have high power consumption. Therefore, the purpose of this paper is to implement a surface EMG acquisition system that supports high sampling and ultra-low power consumption measurement. This work analyzes and optimizes each part of the EMG acquisition circuit and combines an MCU with BLE. Regarding the MCU power saving method, the system uses two different frequency MCU clock sources and we proposed a ping-pong buffer as the memory architecture to achieve the best power saving effect. The measured surface EMG signal samples can be forwarded immediately to the host for further processing and additional application. The results show that the average current of the proposed architecture can be reduced by 92.72% compared with commercial devices, and the battery life is 9.057 times longer. In addition, the correlation coefficients were up to 99.5%, which represents a high relative agreement between the commercial and the proposed system.
      Citation: Biosensors
      PubDate: 2021-10-21
      DOI: 10.3390/bios11110411
      Issue No: Vol. 11, No. 11 (2021)
  • Biosensors, Vol. 11, Pages 412: A Review of Advanced Impedance Biosensors
           with Microfluidic Chips for Single-Cell Analysis

    • Authors: Kim, Song, Ahn, Kim, Jung, Cho, Shin, Choi, Hwang, Kim
      First page: 412
      Abstract: Electrical impedance biosensors combined with microfluidic devices can be used to analyze fundamental biological processes for high-throughput analysis at the single-cell scale. These specialized analytical tools can determine the effectiveness and toxicity of drugs with high sensitivity and demonstrate biological functions on a single-cell scale. Because the various parameters of the cells can be measured depending on methods of single-cell trapping, technological development ultimately determine the efficiency and performance of the sensors. Identifying the latest trends in single-cell trapping technologies afford opportunities such as new structural design and combination with other technologies. This will lead to more advanced applications towards improving measurement sensitivity to the desired target. In this review, we examined the basic principles of impedance sensors and their applications in various biological fields. In the next step, we introduced the latest trend of microfluidic chip technology for trapping single cells and summarized the important findings on the characteristics of single cells in impedance biosensor systems that successfully trapped single cells. This is expected to be used as a leading technology in cell biology, pathology, and pharmacological fields, promoting the further understanding of complex functions and mechanisms within individual cells with numerous data sampling and accurate analysis capabilities.
      Citation: Biosensors
      PubDate: 2021-10-22
      DOI: 10.3390/bios11110412
      Issue No: Vol. 11, No. 11 (2021)
  • Biosensors, Vol. 11, Pages 413: Sensing Techniques for Organochlorides
           through Intermolecular Interaction with Bicyclic Amidines

    • Authors: Jong-Won Park, Lee-Woon Jang, Erik C. Jensen, Amanda Stockton, Jungkyu Kim
      First page: 413
      Abstract: Toxic organochloride molecules are widely used in industry for various purposes. With their high volatility, the direct detection of organochlorides in environmental samples is challenging. Here, a new organochloride detection mechanism using 1,5-diazabicyclo[4.3.0]non-5-ene (DBN) is introduced to simplify a sensing method with higher detection sensitivity. Three types of organochloride compounds-trichloroethylene (TCE), dichloromethane (DCM), and dichlorodiphenyltrichloroethane (DDT)—were targeted to understand DCM conjugation chemistry by using nuclear magnetic resonance (NMR) and liquid chromatography with a mass spectrometer (LC-MS). 13C-NMR spectra and LC-MS data indicated that DBN can be labeled on these organochloride compounds by chlorine–nitrogen interaction. Furthermore, to demonstrate the organochloride sensing capability, the labeling yield and limit of detection were determined by a colorimetric assay as well as micellar electrokinetic chromatography (MEKC). The interaction with DBN was most appreciable for TCE, among other organochlorides. TCE was detected at picomolar levels, which is two orders of magnitude lower than the maximum contaminant level set by the United States Environmental Protection Agency. MEKC, in conjunction with this DBN-labeling method, enables us to develop a field-deployable sensing platform for detecting toxic organochlorides with high sensitivity.
      Citation: Biosensors
      PubDate: 2021-10-23
      DOI: 10.3390/bios11110413
      Issue No: Vol. 11, No. 11 (2021)
  • Biosensors, Vol. 11, Pages 414: Functional Ionic Liquids Decorated Carbon
           Hybrid Nanomaterials for the Electrochemical Biosensors

    • Authors: Pushpesh Ranjan, Shalu Yadav, Mohd. Abubakar Sadique, Raju Khan, Jamana Prasad Chaurasia, Avanish Kumar Srivastava
      First page: 414
      Abstract: Ionic liquids are gaining high attention due to their extremely unique physiochemical properties and are being utilized in numerous applications in the field of electrochemistry and bio-nanotechnology. The excellent ionic conductivity and the wide electrochemical window open a new avenue in the construction of electrochemical devices. On the other hand, carbon nanomaterials, such as graphene (GR), graphene oxide (GO), carbon dots (CDs), and carbon nanotubes (CNTs), are highly utilized in electrochemical applications. Since they have a large surface area, high conductivity, stability, and functionality, they are promising in biosensor applications. Nevertheless, the combination of ionic liquids (ILs) and carbon nanomaterials (CNMs) results in the functional ILs-CNMs hybrid nanocomposites with considerably improved surface chemistry and electrochemical properties. Moreover, the high functionality and biocompatibility of ILs favor the high loading of biomolecules on the electrode surface. They extremely enhance the sensitivity of the biosensor that reaches the ability of ultra-low detection limit. This review aims to provide the studies of the synthesis, properties, and bonding of functional ILs-CNMs. Further, their electrochemical sensors and biosensor applications for the detection of numerous analytes are also discussed.
      Citation: Biosensors
      PubDate: 2021-10-23
      DOI: 10.3390/bios11110414
      Issue No: Vol. 11, No. 11 (2021)
  • Biosensors, Vol. 11, Pages 415: CH3NH3PbBr3 Thin Film Served as
           Guided-Wave Layer for Enhancing the Angular Sensitivity of Plasmon

    • Authors: Leiming Wu, Yuanjiang Xiang, Yuwen Qin
      First page: 415
      Abstract: CH3NH3PbBr3 perovskite thin film is used as a guided-wave layer and coated on the surface of an Au film to form the Au-perovskite hybrid structure. Using the hybrid structure, a perovskite-based guided-wave surface plasmon resonance (GWSPR) biosensor is proposed with high angular sensitivity. First, it is found that the electric field at the sensing interface is improved by the CH3NH3PbBr3 perovskite thin film, thereby enhancing the sensitivity. The result demonstrates that the angular sensitivity of the Au-perovskite-based GWSPR biosensor is as high as 278.5°/RIU, which is 110.2% higher than that of a conventional Au-based surface plasmon resonance (SPR) biosensor. Second, the selection of the coupling prism in the configuration of the GWSPR biosensor is also analyzed, and it indicates that a low refractive index (RI) prism can generate greater sensitivity. Therefore, the low-RI BK7 prism is served as the coupling prism for the proposed GWSPR biosensor. Finally, the proposed GWSPR sensing structure can not only be used for liquid sensing, but also for gas sensing, and it has also been demonstrated that the GWSPR gas sensor is 2.8 times more sensitive than the Au-based SPR gas sensor.
      Citation: Biosensors
      PubDate: 2021-10-23
      DOI: 10.3390/bios11110415
      Issue No: Vol. 11, No. 11 (2021)
  • Biosensors, Vol. 11, Pages 416: Probing Individual Particles in Aquatic
           Suspensions by Simultaneously Measuring Polarized Light Scattering and

    • Authors: Zhihang Xiong, Hongjian Wang, Jiajin Li, Ran Liao, Haoji Mai, Caizhong Guan, Zhiming Guo, Shangpan Yang, Yan Chen, Biwang Liu, Tong Liu, Hongyi Li, Wenzheng Ding, Yaguang Zeng, Hui Ma
      First page: 416
      Abstract: Suspended particles play a significant role in aquatic systems. However, existing methods to probe suspended particles have several limitations. In this paper, we present a portable prototype to in situ probe individual particles in aquatic suspensions by simultaneously measuring polarized light scattering and fluorescence, aiming to obtain an effective classification of microplastics and microalgae. Results show that the obtained classification accuracy is significantly higher than that for either of these two methods. The setup also successfully measures submicron particles and discriminates two species of Synechococcus. Our study demonstrates the feasibility of simultaneously measuring polarized light scattering and fluorescence, and the promising capability of our method for further aquatic environmental monitoring.
      Citation: Biosensors
      PubDate: 2021-10-25
      DOI: 10.3390/bios11110416
      Issue No: Vol. 11, No. 11 (2021)
  • Biosensors, Vol. 11, Pages 417: The Effect of Haematocrit on Measurement
           of the Mid-Infrared Refractive Index of Plasma in Whole Blood

    • Authors: David J. Rowe, Daniel R. Owens, Suzanne L. Parker, Saul N. Faust, James S. Wilkinson, Goran Z. Mashanovich
      First page: 417
      Abstract: Recent advances suggest that miniaturised mid-infrared (MIR) devices could replace more time-consuming, laboratory-based techniques for clinical diagnostics. This work uses Fourier transform infrared spectroscopy to show that the MIR complex refractive index of whole blood varies across a range of haematocrit. This indicates that the use of an evanescent measurement is not sufficient to optically exclude the cellular content of blood in the MIR, as previously assumed. Here, spectral refractive index data is presented in two ways. First, it is given as whole blood with varying haematocrit. Second, it is given as the percentage error that haematocrit introduces to plasma. The maximum error in the effective plasma refractive index due to the haematocrit of healthy adults was 0.25% for the real part n and 11% for the imaginary part k. This implies that calibration measurements of haematocrit can be used to account for errors introduced by the cellular content, enabling plasma spectra and analyte concentrations to be indirectly calculated from a whole blood sample. This methodological advance is of clinical importance as plasma concentration of analytes such as drugs can be determined using MIR without the preprocessing of whole blood.
      Citation: Biosensors
      PubDate: 2021-10-25
      DOI: 10.3390/bios11110417
      Issue No: Vol. 11, No. 11 (2021)
  • Biosensors, Vol. 11, Pages 418: Novel Biorecognition Elements against
           Pathogens in the Design of State-of-the-Art Diagnostics

    • Authors: Maria G. Sande, Joana L. Rodrigues, Débora Ferreira, Carla J. Silva, Ligia R. Rodrigues
      First page: 418
      Abstract: Infectious agents, especially bacteria and viruses, account for a vast number of hospitalisations and mortality worldwide. Providing effective and timely diagnostics for the multiplicity of infectious diseases is challenging. Conventional diagnostic solutions, although technologically advanced, are highly complex and often inaccessible in resource-limited settings. An alternative strategy involves convenient rapid diagnostics which can be easily administered at the point-of-care (POC) and at low cost without sacrificing reliability. Biosensors and other rapid POC diagnostic tools which require biorecognition elements to precisely identify the causative pathogen are being developed. The effectiveness of these devices is highly dependent on their biorecognition capabilities. Naturally occurring biorecognition elements include antibodies, bacteriophages and enzymes. Recently, modified molecules such as DNAzymes, peptide nucleic acids and molecules which suffer a selective screening like aptamers and peptides are gaining interest for their biorecognition capabilities and other advantages over purely natural ones, such as robustness and lower production costs. Antimicrobials with a broad-spectrum activity against pathogens, such as antibiotics, are also used in dual diagnostic and therapeutic strategies. Other successful pathogen identification strategies use chemical ligands, molecularly imprinted polymers and Clustered Regularly Interspaced Short Palindromic Repeats-associated nuclease. Herein, the latest developments regarding biorecognition elements and strategies to use them in the design of new biosensors for pathogens detection are reviewed.
      Citation: Biosensors
      PubDate: 2021-10-26
      DOI: 10.3390/bios11110418
      Issue No: Vol. 11, No. 11 (2021)
  • Biosensors, Vol. 11, Pages 419: Breast Mass Classification Using Diverse
           Contextual Information and Convolutional Neural Network

    • Authors: Mariam Busaleh, Muhammad Hussain, Hatim A. Aboalsamh, Fazal-e- Amin
      First page: 419
      Abstract: Masses are one of the early signs of breast cancer, and the survival rate of women suffering from breast cancer can be improved if masses can be correctly identified as benign or malignant. However, their classification is challenging due to the similarity in texture patterns of both types of mass. The existing methods for this problem have low sensitivity and specificity. Based on the hypothesis that diverse contextual information of a mass region forms a strong indicator for discriminating benign and malignant masses and the idea of the ensemble classifier, we introduce a computer-aided system for this problem. The system uses multiple regions of interest (ROIs) encompassing a mass region for modeling diverse contextual information, a single ResNet-50 model (or its density-specific modification) as a backbone for local decisions, and stacking with SVM as a base model to predict the final decision. A data augmentation technique is introduced for fine-tuning the backbone model. The system was thoroughly evaluated on the benchmark CBIS-DDSM dataset using its provided data split protocol, and it achieved a sensitivity of 98.48% and a specificity of 92.31%. Furthermore, it was found that the system gives higher performance if it is trained and tested using the data from a specific breast density BI-RADS class. The system does not need to fine-tune/train multiple CNN models; it introduces diverse contextual information by multiple ROIs. The comparison shows that the method outperforms the state-of-the-art methods for classifying mass regions into benign and malignant. It will help radiologists reduce their burden and enhance their sensitivity in the prediction of malignant masses.
      Citation: Biosensors
      PubDate: 2021-10-26
      DOI: 10.3390/bios11110419
      Issue No: Vol. 11, No. 11 (2021)
  • Biosensors, Vol. 11, Pages 420: Development of a Novel Benzimidazole-Based
           Probe and Portable Fluorimeter for the Detection of Cysteine in Human

    • Authors: Gyu Seong Yeom, In-ho Song, Shrikant Dashrath Warkad, Pramod B. Shinde, Taewoon Kim, Seong-min Park, Satish Balasaheb Nimse
      First page: 420
      Abstract: The measurement of cysteine in human urine and live cells is crucial for evaluating biological metabolism, monitoring and maintaining the immune system, preventing tissue/DNA damage caused by free radicals, preventing autoimmune diseases, and diagnosing disorders such as cystinuria and cancer. A method that uses a fluorescence turn-on probe and a portable fluorescence spectrometer device are crucial for highly sensitive, simple, rapid, and inexpensive cysteine detection. Herein, we present the synthesis and application of a benzimidazole-based fluorescent probe (ABIA) along with the design and development of a portable fluorescence spectrometer device (CysDDev) for detecting cysteine in simulated human urine. ABIA showed excellent selectivity and sensitivity in detecting cysteine over homocysteine, glutathione, and other amino acids with the response time of 1 min and demonstrated a detection limit of 16.3 nM using the developed CysDDev. Further, ABIA also demonstrated its utility in detecting intracellular cysteine, making it an excellent probe for bio-imaging assay.
      Citation: Biosensors
      PubDate: 2021-10-26
      DOI: 10.3390/bios11110420
      Issue No: Vol. 11, No. 11 (2021)
  • Biosensors, Vol. 11, Pages 421: Ultrasensitive Photochemical Immunosensor
           Based on Flowerlike SnO2/BiOI/Ag2S Composites for Detection of

    • Authors: Nuo Zhang, Jinhui Feng, Guanhui Zhao, Xiaoyi Duan, Yaoguang Wang, Daopeng Zhang, Qin Wei
      First page: 421
      Abstract: Based on the necessity and urgency of detecting infectious disease marker procalcitonin (PCT), a novel unlabeled photoelectrochemical (PEC) immunosensor was prepared for the rapid and sensitive detection of PCT. Firstly, SnO2 porous nanoflowers with good photocatalytic performance were prepared by combining hydrothermal synthesis and calcining. BiOI nanoflowers were synthesized by facile ultrasonic mixed reaction. Ag2S quantum dots were deposited on SnO2/BiOI composites by in situ growth method. The SnO2/BiOI/Ag2S composites with excellent photoelectric properties were employed as substrate material, which could provide significantly enhanced and stable signal because of the energy level matching of SnO2, BiOI and Ag2S and the good light absorption performance. Accordingly, a PEC immunosensor based on SnO2/BiOI/Ag2S was constructed by using the layered modification method to achieve high sensitivity analysis of PCT. The linear dynamic range of the detection method was 0.50 pg·mL−1~100 ng·mL−1, and the detection limit was 0.14 pg·mL−1. In addition, the designed PEC immunosensor exhibited satisfactory sensitivity, selectivity, stability and repeatability, which opened up a new avenue for the analyzation of PCT and further provided guidance for antibiotic therapy.
      Citation: Biosensors
      PubDate: 2021-10-28
      DOI: 10.3390/bios11110421
      Issue No: Vol. 11, No. 11 (2021)
  • Biosensors, Vol. 11, Pages 422: DNAzyme-Amplified Label-Free Biosensor for
           the Simple and Sensitive Detection of Pyrophosphatase

    • Authors: Cheng-Yu Lee, Chi-Hsiang Liao, Nei-Mei Fang, You-Zung Hsieh
      First page: 422
      Abstract: The level of pyrophosphatase (PPase) expression has been suggested as a potential biomarker of various cancers, and its prognostic value has been evaluated in patients suffering from lung cancer, colorectal cancer, and hyperthyroidism. However, the detection of PPase usually needs specific materials that require complicated, time-consuming reactions with restricted linear range and sensitivity, limiting their application in early clinical diagnosis. Herein, we developed a DNAzyme-based biosensor for the detection of PPase. In the presence of PPase, pyrophosphate (PPi) and Cu2+ ions released from the PPi–Cu2+–PPi complex induce the cleavage of the DNAzyme and the corresponding substrate. An apurinic/apyrimidinic (AP) site was elaborately designed within substrates that could encase the fluorophore 2-amino-5,6,7-trimethyl-1,8-naphthyridine (ATMND). The fluorescence of ATMND was initially quenched but restored when the DNAzyme/substrate complex was hydrolyzed with the release of ATMND. In this way, the PPase activity can be estimated by detecting the increased fluorescence of the released ATMND. Under optimized conditions, the activity of PPase could be analyzed at concentrations from 0.5 to 1000 mU, with the lowest detectable concentration being 0.5 mU. This work lays a foundation for developing a DNAzyme-amplified fluorescent biosensor with a high sensitivity, a wide linear range, and single-step operation for use as an easy diagnostic for PPase analysis.
      Citation: Biosensors
      PubDate: 2021-10-28
      DOI: 10.3390/bios11110422
      Issue No: Vol. 11, No. 11 (2021)
  • Biosensors, Vol. 11, Pages 423: OralDisk: A Chair-Side Compatible
           Molecular Platform Using Whole Saliva for Monitoring Oral Health at the
           Dental Practice

    • Authors: Desirée Baumgartner, Benita Johannsen, Mara Specht, Jan Lüddecke, Markus Rombach, Sebastian Hin, Nils Paust, Felix von Stetten, Roland Zengerle, Christopher Herz, Johannes R. Peham, Pune N. Paqué, Thomas Attin, Joël S. Jenzer, Philipp Körner, Patrick R. Schmidlin, Thomas Thurnheer, Florian J. Wegehaupt, Wendy E. Kaman, Andrew Stubbs, John P. Hays, Viorel Rusu, Alex Michie, Thomas Binsl, David Stejskal, Michal Karpíšek, Kai Bao, Nagihan Bostanci, Georgios N. Belibasakis, Konstantinos Mitsakakis
      First page: 423
      Abstract: Periodontitis and dental caries are two major bacterially induced, non-communicable diseases that cause the deterioration of oral health, with implications in patients’ general health. Early, precise diagnosis and personalized monitoring are essential for the efficient prevention and management of these diseases. Here, we present a disk-shaped microfluidic platform (OralDisk) compatible with chair-side use that enables analysis of non-invasively collected whole saliva samples and molecular-based detection of ten bacteria: seven periodontitis-associated (Aggregatibacter actinomycetemcomitans, Campylobacter rectus, Fusobacterium nucleatum, Prevotella intermedia, Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola) and three caries-associated (oral Lactobacilli, Streptococcus mutans, Streptococcus sobrinus). Each OralDisk test required 400 µL of homogenized whole saliva. The automated workflow included bacterial DNA extraction, purification and hydrolysis probe real-time PCR detection of the target pathogens. All reagents were pre-stored within the disk and sample-to-answer processing took < 3 h using a compact, customized processing device. A technical feasibility study (25 OralDisks) was conducted using samples from healthy, periodontitis and caries patients. The comparison of the OralDisk with a lab-based reference method revealed a ~90% agreement amongst targets detected as positive and negative. This shows the OralDisk’s potential and suitability for inclusion in larger prospective implementation studies in dental care settings.
      Citation: Biosensors
      PubDate: 2021-10-28
      DOI: 10.3390/bios11110423
      Issue No: Vol. 11, No. 11 (2021)
  • Biosensors, Vol. 11, Pages 424: Synthesis of Copper Nanocluster and Its
           Application in Pollutant Analysis

    • Authors: Yan Xue, Zehua Cheng, Mai Luo, Hao Hu, Chenglai Xia
      First page: 424
      Abstract: Copper nanoclusters (Cu NCs) with their inherent optical and chemical advantages have gained increasing attention as a kind of novel material that possesses great potential, primarily in the use of contaminants sensing and bio-imaging. With a focus on environmental safety, this article comprehensively reviews the recent advances of Cu NCs in the application of various contaminants, including pesticide residues, heavy metal ions, sulfide ions and nitroaromatics. The common preparation methods and sensing mechanisms are summarized. The typical high-quality sensing probes based on Cu NCs towards various target contaminants are presented; additionally, the challenges and future perspectives in the development and application of Cu NCs in monitoring and analyzing environmental pollutants are discussed.
      Citation: Biosensors
      PubDate: 2021-10-28
      DOI: 10.3390/bios11110424
      Issue No: Vol. 11, No. 11 (2021)
  • Biosensors, Vol. 11, Pages 425: Intelligent Bio-Responsive Fluorescent
           Au–shRNA Complexes for Regulated Autophagy and Effective Cancer
           Bioimaging and Therapeutics

    • Authors: Weijuan Cai, Liang Yin, Hui Jiang, Yossi Weizmann, Xuemei Wang
      First page: 425
      Abstract: The long non-coding RNA (lncRNA) MALAT1 acts as an oncogene. RNA interference (RNAi) is an effective method to control the expression of specific genes and can be used for the treatment of tumors, but an effective and safe carrier system is a significant obstacle to gene therapy. Herein, we explored the possibility of constructing an in situ bio-responsive self-assembled fluorescent gold-short hairpin RNA nanocomplex (Au–shRNA NCs) delivery system by co-incubating gold and MALAT1-shRNA for precise hepatocellular carcinoma (HCC) imaging and treatment. Due to the characteristics of the cancer microenvironment, Au–shRNA NCs self-assembled in HCC cells (HepG2) but did not occur in control cells (L02) under the same conditions. The in situ bio-responsive self-assembled Au–shRNA NCs delivery system can realize cancer cell bioimaging and promote cell uptake and endosomal escape mechanism, thereby realizing effective transfection. They effectively silenced target gene MALAT1, and with the downregulation of MALAT1, we found that several molecules involved in autophagic flux were also regulated. In vitro and tumor-bearing mouse model experiments demonstrated that the as-prepared fluorescent Au–shRNA NCs can readily realize tumor bioimaging and effectively silence the target gene MALAT1, and those autophagy-related pathway molecules were significantly downregulated, thereby exerting a tumor suppressor efficiency. This raises the possibility of realizing accurate multi-scale bio-imaging from the molecular-level with targeted gene-recognition to cancer cell imaging as well as in vivo tumor tissue imaging for the simultaneous precise cancer therapy.
      Citation: Biosensors
      PubDate: 2021-10-28
      DOI: 10.3390/bios11110425
      Issue No: Vol. 11, No. 11 (2021)
  • Biosensors, Vol. 11, Pages 426: Voltammetric Immunosensor to Track a Major
           Peanut Allergen (Ara h 1) in Food Products Employing Quantum Dot Labels

    • Authors: Maria Freitas, Henri P. A. Nouws, Cristina Delerue-Matos
      First page: 426
      Abstract: Tracking unreported allergens in commercial foods can avoid acute allergic reactions. A 2-step electrochemical immunosensor was developed for the analysis of the peanut allergen Ara h 1 in a 1-h assay (<15 min hands-on time). Bare screen-printed carbon electrodes (SPCE) were used as transducers and monoclonal capture and detection antibodies were applied in a sandwich-type immunoassay. The short assay time was achieved by previously combining the target analyte and the detection antibody. Core/shell CdSe@ZnS Quantum Dots were used as electroactive label for the detection of the immunological interaction by differential pulse anodic stripping voltammetry. A linear range between 25 and 1000 ng·mL−1 (LOD = 3.5 ng·mL−1), an adequate precision of the method (Vx0 ≈ 6%), and a sensitivity of 23.0 nA·mL·ng−1·cm−2 were achieved. The immunosensor was able to detect Ara h 1 in a spiked allergen-free product down to 0.05% (m/m) of peanut. Commercial organic farming cookies and cereal and protein bars were tested to track and quantify Ara h 1. The results were validated by comparison with an ELISA kit.
      Citation: Biosensors
      PubDate: 2021-10-29
      DOI: 10.3390/bios11110426
      Issue No: Vol. 11, No. 11 (2021)
  • Biosensors, Vol. 11, Pages 427: A 3D-Printed Microfluidic Device for qPCR
           Detection of Macrolide-Resistant Mutations of Mycoplasma pneumoniae

    • Authors: Anyan Wang, Zhenhua Wu, Yuhang Huang, Hongbo Zhou, Lei Wu, Chunping Jia, Qiang Chen, Jianlong Zhao
      First page: 427
      Abstract: Mycoplasma pneumonia (MP) is a common respiratory infection generally treated with macrolides, but resistance mutations against macrolides are often detected in mycoplasma pneumoniae in China. Rapid and accurate identification of mycoplasma pneumoniae and its mutant type is necessary for precise medication. This paper presents a 3D-printed microfluidic device to achieve this. By 3D printing, the stereoscopic structures such as microvalves, reservoirs, drainage tubes, and connectors were fabricated in one step. The device integrated commercial polymerase chain reaction (PCR) tubes as PCR chambers. The detection was a sample-to-answer procedure. First, the sample, a PCR mix, and mineral oil were respectively added to the reservoirs on the device. Next, the device automatically mixed the sample with the PCR mix and evenly dispensed the mixed solution and mineral oil into the PCR chambers, which were preloaded with the specified primers and probes. Subsequently, quantitative real-time PCR (qPCR) was carried out with the homemade instrument. Within 80 min, mycoplasma pneumoniae and its mutation type in the clinical samples were determined, which was verified by DNA sequencing. The easy-to-make and easy-to-use device provides a rapid and integrated detection approach for pathogens and antibiotic resistance mutations, which is urgently needed on the infection scene and in hospital emergency departments.
      Citation: Biosensors
      PubDate: 2021-10-29
      DOI: 10.3390/bios11110427
      Issue No: Vol. 11, No. 11 (2021)
  • Biosensors, Vol. 11, Pages 428: Design and Implementation of a Wearable
           Accelerometer-Based Motion/Tilt Sensing Internet of Things Module and Its
           Application to Bed Fall Prevention

    • Authors: Wen-Yen Lin, Chien-Hung Chen, Ming-Yih Lee
      First page: 428
      Abstract: Accelerometer-based motion sensing has been extensively applied to fall detection. However, such applications can only detect fall accidents; therefore, a system that can prevent fall accidents is desirable. Bed falls account for more than half of patient falls and are preceded by a clear warning indicator: the patient attempting to get out of bed. This study designed and implemented an Internet of Things module, namely, Bluetooth low-energy-enabled Accelerometer-based Sensing In a Chip-packaging (BASIC) module, with a tilt-sensing algorithm based on the patented low-complexity COordinate Rotation DIgital Computer (CORDIC)-based algorithm for tilt angle conversions. It is applied for detecting the postural changes (from lying down to sitting up) and to protect individuals at a high risk of bed falls by prompting caregivers to take preventive actions and assist individuals trying to get up. This module demonstrates how motion and tilt sensing can be applied to bed fall prevention. The module can be further miniaturized or integrated into a wearable device and commercialized in smart health-care applications for bed fall prevention in hospitals and homes.
      Citation: Biosensors
      PubDate: 2021-10-29
      DOI: 10.3390/bios11110428
      Issue No: Vol. 11, No. 11 (2021)
  • Biosensors, Vol. 11, Pages 429: Assessment of Brain Functional Activity
           Using a Miniaturized Head-Mounted Scanning Photoacoustic Imaging System in
           Awake and Freely Moving Rats

    • Authors: Wang, Chu, Lin, Tsao, Tsai, Ger, Chen, Chang, Liao
      First page: 429
      Abstract: Understanding the relationship between brain function and natural behavior remains a significant challenge in neuroscience because there are very few convincing imaging/recording tools available for the evaluation of awake and freely moving animals. Here, we employed a miniaturized head-mounted scanning photoacoustic imaging (hmPAI) system to image real-time cortical dynamics. A compact photoacoustic (PA) probe based on four in-house optical fiber pads and a single custom-made 48-MHz focused ultrasound transducer was designed to enable focused dark-field PA imaging, and miniature linear motors were included to enable two-dimensional (2D) scanning. The total dimensions and weight of the proposed hmPAI system are only approximately 50 × 64 × 48 mm and 58.7 g (excluding cables). Our ex vivo phantom experimental tests revealed that a spatial resolution of approximately 0.225 mm could be achieved at a depth of 9 mm. Our in vivo results further revealed that the diameters of cortical vessels draining into the superior sagittal sinus (SSS) could be clearly imaged and continuously observed in both anesthetized rats and awake, freely moving rats. Statistical analysis showed that the full width at half maximum (FWHM) of the PA A-line signals (relative to the blood vessel diameter) was significantly increased in the selected SSS-drained cortical vessels of awake rats (0.58 ± 0.17 mm) compared with those of anesthetized rats (0.31 ± 0.09 mm) (p < 0.01, paired t-test). In addition, the number of pixels in PA B-scan images (relative to the cerebral blood volume (CBV)) was also significantly increased in the selected SSS-drained blood vessels of awake rats (107.66 ± 23.02 pixels) compared with those of anesthetized rats (81.99 ± 21.52 pixels) (p < 0.01, paired t-test). This outcome may result from a more active brain in awake rats than in anesthetized rats, which caused cerebral blood vessels to transport more blood to meet the increased nutrient demand of the tissue, resulting in an obvious increase in blood vessel volume. This hmPAI system was further validated for utility in the brains of awake and freely moving rats, showing that their natural behavior was unimpaired during vascular imaging, thereby providing novel opportunities for studies of behavior, cognition, and preclinical models of brain diseases.
      Citation: Biosensors
      PubDate: 2021-10-30
      DOI: 10.3390/bios11110429
      Issue No: Vol. 11, No. 11 (2021)
  • Biosensors, Vol. 11, Pages 430: Microfluidic Raman Sensing Using a Single
           Ring Negative Curvature Hollow Core Fiber

    • Authors: Xinyu Wang, Shuguang Li, Shoufei Gao, Yingying Wang, Pu Wang, Heike Ebendorff-Heidepriem, Yinlan Ruan
      First page: 430
      Abstract: A compact microfluidic Raman detection system based on a single-ring negative-curvature hollow-core fiber is presented. The system can be used for in-line qualitative and quantitative analysis of biochemicals. Both efficient light coupling and continuous liquid injection into the hollow-core fiber were achieved by creating a small gap between a solid-core fiber and the hollow-core fiber, which were fixed within a low-cost ceramic ferrule. A coupling efficiency of over 50% from free-space excitation laser to the hollow core fiber was obtained through a 350 μm-long solid-core fiber. For proof-of-concept demonstration of bioprocessing monitoring, a series of ethanol and glucose aqueous solutions at different concentrations were used. The limit of detection achieved for the ethanol solutions with our system was ~0.04 vol.% (0.32 g/L). Such an all-fiber microfluidic device is robust, provides Raman measurements with high repeatability and reusability, and is particularly suitable for the in-line monitoring of bioprocesses.
      Citation: Biosensors
      PubDate: 2021-10-30
      DOI: 10.3390/bios11110430
      Issue No: Vol. 11, No. 11 (2021)
  • Biosensors, Vol. 11, Pages 431: Enhanced Molecular Infrared Spectroscopy
           Employing Bilayer Graphene Acoustic Plasmon Resonator

    • Authors: Chunchao Wen, Jie Luo, Wei Xu, Zhihong Zhu, Shiqiao Qin, Jianfa Zhang
      First page: 431
      Abstract: Graphene plasmon resonators with the ability to support plasmonic resonances in the infrared region make them a promising platform for plasmon-enhanced spectroscopy techniques. Here we propose a resonant graphene plasmonic system for infrared spectroscopy sensing that consists of continuous graphene and graphene ribbons separated by a nanometric gap. Such a bilayer graphene resonator can support acoustic graphene plasmons (AGPs) that provide ultraconfined electromagnetic fields and strong field enhancement inside the nano-gap. This allows us to selectively enhance the infrared absorption of protein molecules and precisely resolve the molecular structural information by sweeping graphene Fermi energy. Compared to the conventional graphene plasmonic sensors, the proposed bilayer AGP sensor provides better sensitivity and improvement of molecular vibrational fingerprints of nanoscale analyte samples. Our work provides a novel avenue for enhanced infrared spectroscopy sensing with ultrasmall volumes of molecules.
      Citation: Biosensors
      PubDate: 2021-10-31
      DOI: 10.3390/bios11110431
      Issue No: Vol. 11, No. 11 (2021)
  • Biosensors, Vol. 11, Pages 432: All-Optical Switching Demonstrated with
           Photoactive Yellow Protein Films

    • Authors: Dániel Petrovszki, Szilvia Krekic, Sándor Valkai, Zsuzsanna Heiner, András Dér
      First page: 432
      Abstract: Integrated optics (IO) is a field of photonics which focuses on manufacturing circuits similar to those in integrated electronics, but that work on an optical basis to establish means of faster data transfer and processing. Currently, the biggest task in IO is finding or manufacturing materials with the proper nonlinear optical characteristics to implement as active components in IO circuits. Using biological materials in IO has recently been proposed, the first material to be investigated for this purpose being the protein bacteriorhodopsin; however, since then, other proteins have also been considered, such as the photoactive yellow protein (PYP). In our current work, we directly demonstrate the all-optical switching capabilities of PYP films combined with an IO Mach–Zehnder interferometer (MZI) for the first time. By exploiting photoreactions in the reaction cycle of PYP, we also show how a combination of exciting light beams can introduce an extra degree of freedom to control the operation of the device. Based on our results, we discuss how the special advantages of PYP can be utilized in future IO applications.
      Citation: Biosensors
      PubDate: 2021-10-31
      DOI: 10.3390/bios11110432
      Issue No: Vol. 11, No. 11 (2021)
  • Biosensors, Vol. 11, Pages 433: Using Graphene-Based Biosensors to Detect
           Dopamine for Efficient Parkinson’s Disease Diagnostics

    • Authors: Małgorzata Kujawska, Sheetal K. Bhardwaj, Yogendra Kumar Mishra, Ajeet Kaushik
      First page: 433
      Abstract: Parkinson’s disease (PD) is a neurodegenerative disease in which the neurotransmitter dopamine (DA) depletes due to the progressive loss of nigrostriatal neurons. Therefore, DA measurement might be a useful diagnostic tool for targeting the early stages of PD, as well as helping to optimize DA replacement therapy. Moreover, DA sensing appears to be a useful analytical tool in complex biological systems in PD studies. To support the feasibility of this concept, this mini-review explores the currently developed graphene-based biosensors dedicated to DA detection. We discuss various graphene modifications designed for high-performance DA sensing electrodes alongside their analytical performances and interference studies, which we listed based on their limit of detection in biological samples. Moreover, graphene-based biosensors for optical DA detection are also presented herein. Regarding clinical relevance, we explored the development trends of graphene-based electrochemical sensing of DA as they relate to point-of-care testing suitable for the site-of-location diagnostics needed for personalized PD management. In this field, the biosensors are developed into smartphone-connected systems for intelligent disease management. However, we highlighted that the focus should be on the clinical utility rather than analytical and technical performance.
      Citation: Biosensors
      PubDate: 2021-10-31
      DOI: 10.3390/bios11110433
      Issue No: Vol. 11, No. 11 (2021)
  • Biosensors, Vol. 11, Pages 434: Emerging Biosensors to Detect Severe Acute
           Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): A Review

    • Authors: Wei Yin Lim, Boon Leong Lan, Narayanan Ramakrishnan
      First page: 434
      Abstract: Coronavirus disease (COVID-19) is a global health crisis caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Real-time reverse transcriptase-polymerase chain reaction (RT-PCR) is the gold standard test for diagnosing COVID-19. Although it is highly accurate, this lab test requires highly-trained personnel and the turn-around time is long. Rapid and inexpensive immuno-diagnostic tests (antigen or antibody test) are available, but these point of care (POC) tests are not as accurate as the RT-PCR test. Biosensors are promising alternatives to these rapid POC tests. Here we review three types of recently developed biosensors for SARS-CoV-2 detection: surface plasmon resonance (SPR)-based, electrochemical and field-effect transistor (FET)-based biosensors. We explain the sensing principles and discuss the advantages and limitations of these sensors. The accuracies of these sensors need to be improved before they could be translated into POC devices for commercial use. We suggest potential biorecognition elements with highly selective target-analyte binding that could be explored to increase the true negative detection rate. To increase the true positive detection rate, we suggest two-dimensional materials and nanomaterials that could be used to modify the sensor surface to increase the sensitivity of the sensor.
      Citation: Biosensors
      PubDate: 2021-11-02
      DOI: 10.3390/bios11110434
      Issue No: Vol. 11, No. 11 (2021)
  • Biosensors, Vol. 11, Pages 435: High Channel Temperature Mapping
           Electronics in a Thin, Soft, Wireless Format for Non-Invasive Body Thermal

    • Authors: Wooyoung Park, Chunki Yiu, Yiming Liu, Tsz Hung Wong, Xingcan Huang, Jingkun Zhou, Jian Li, Kuanming Yao, Ya Huang, Hu Li, Jiyu Li, Yanli Jiao, Rui Shi, Xinge Yu
      First page: 435
      Abstract: Hemodynamic status has been perceived as an important diagnostic value as fundamental physiological health conditions, including decisive signs of fatal diseases like arteriosclerosis, can be diagnosed by monitoring it. Currently, the conventional hemodynamic monitoring methods highly rely on imaging techniques requiring inconveniently large numbers of operation procedures and equipment for mapping and with a high risk of radiation exposure. Herein, an ultra-thin, noninvasive, and flexible electronic skin (e-skin) hemodynamic monitoring system based on the thermal properties of blood vessels underneath the epidermis that can be portably attached to the skin for operation is introduced. Through a series of thermal sensors, the temperatures of each subsection of the arrayed sensors are observed in real-time, and the measurements are transmitted and displayed on the screen of an external device wirelessly through a Bluetooth module using a graphical user interface (GUI). The degrees of the thermal property of subsections are indicated with a spectrum of colors that specify the hemodynamic status of the target vessel. In addition, as the sensors are installed on a soft substrate, they can operate under twisting and bending without any malfunction. These characteristics of e-skin sensors exhibit great potential in wearable and portable diagnostics including point-of-care (POC) devices.
      Citation: Biosensors
      PubDate: 2021-11-02
      DOI: 10.3390/bios11110435
      Issue No: Vol. 11, No. 11 (2021)
  • Biosensors, Vol. 11, Pages 436: Activatable Second Near-Infrared
           Fluorescent Probes: A New Accurate Diagnosis Strategy for Diseases

    • Authors: Dong Li, Jie Pan, Shuyu Xu, Shiying Fu, Chengchao Chu, Gang Liu
      First page: 436
      Abstract: Recently, second near-infrared (NIR-II) fluorescent imaging has been widely applied in biomedical diagnosis, due to its high spatiotemporal resolution and deep tissue penetration. In contrast to the “always on” NIR-II fluorescent probes, the activatable NIR-II fluorescent probes have specific targeting to biological tissues, showing a higher imaging signal-to-background ratio and a lower detection limit. Therefore, it is of great significance to utilize disease-associated endogenous stimuli (such as pH values, enzyme existence, hypoxia condition and so on) to activate the NIR-II probes and achieve switchable fluorescent signals for specific deep bioimaging. This review introduces recent strategies and mechanisms for activatable NIR-II fluorescent probes and their applications in biosensing and bioimaging. Moreover, the potential challenges and perspectives of activatable NIR-II fluorescent probes are also discussed.
      Citation: Biosensors
      PubDate: 2021-11-02
      DOI: 10.3390/bios11110436
      Issue No: Vol. 11, No. 11 (2021)
  • Biosensors, Vol. 11, Pages 437: Urinary Volatiles and Chemical
           Characterisation for the Non-Invasive Detection of Prostate and Bladder

    • Authors: Heena Tyagi, Emma Daulton, Ayman S. Bannaga, Ramesh P. Arasaradnam, James A. Covington
      First page: 437
      Abstract: Bladder cancer (BCa) and prostate cancer (PCa) are some of the most common cancers in the world. In both BCa and PCa, the diagnosis is often confirmed with an invasive technique that carries a risk to the patient. Consequently, a non-invasive diagnostic approach would be medically desirable and beneficial to the patient. The use of volatile organic compounds (VOCs) for disease diagnosis, including cancer, is a promising research area that could support the diagnosis process. In this study, we investigated the urinary VOC profiles in BCa, PCa patients and non-cancerous controls by using gas chromatography-ion mobility spectrometry (GC-IMS) and gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) to analyse patient samples. GC-IMS separated BCa from PCa (area under the curve: AUC: 0.97 (0.93–1.00)), BCa vs. non-cancerous (AUC: 0.95 (0.90–0.99)) and PCa vs. non-cancerous (AUC: 0.89 (0.83–0.94)) whereas GC-TOF-MS differentiated BCa from PCa (AUC: 0.84 (0.73–0.93)), BCa vs. non-cancerous (AUC: 0.81 (0.70–0.90)) and PCa vs. non-cancerous (AUC: 0.94 (0.90–0.97)). According to our study, a total of 34 biomarkers were found using GC-TOF-MS data, of which 13 VOCs were associated with BCa, seven were associated with PCa, and 14 VOCs were found in the comparison of BCa and PCa.
      Citation: Biosensors
      PubDate: 2021-11-03
      DOI: 10.3390/bios11110437
      Issue No: Vol. 11, No. 11 (2021)
  • Biosensors, Vol. 11, Pages 438: Circularly Permuted Far-Red Fluorescent

    • Authors: Tianchen Wu, Yu Pang, Hui-wang Ai
      First page: 438
      Abstract: The color palette of genetically encoded fluorescent protein indicators (GEFPIs) has expanded rapidly in recent years. GEFPIs with excitation and emission within the “optical window” above 600 nm are expected to be superior in many aspects, such as enhanced tissue penetration, reduced autofluorescence and scattering, and lower phototoxicity. Circular permutation of fluorescent proteins (FPs) is often the first step in the process of developing single-FP-based GEFPIs. This study explored the tolerance of two far-red FPs, mMaroon1 and mCarmine, towards circular permutation. Several initial constructs were built according to previously reported circularly permuted topologies for other FP analogs. Mutagenesis was then performed on these constructs and screened for fluorescent variants. As a result, five circularly permuted far-red FPs (cpFrFPs) with excitation and emission maxima longer than 600 nm were identified. Some displayed appreciable brightness and efficient chromophore maturation. These cpFrFPs variants could be intriguing starting points to further engineer far-red GEFPIs for in vivo tissue imaging.
      Citation: Biosensors
      PubDate: 2021-11-03
      DOI: 10.3390/bios11110438
      Issue No: Vol. 11, No. 11 (2021)
  • Biosensors, Vol. 11, Pages 439: Robust Nanozyme-Enzyme Nanosheets-Based
           Lactate Biosensor for Diagnosing Bacterial Infection in Olive Flounder
           (Paralichthys olivaceus)

    • Authors: Thenmozhi Rajarathinam, Seonghye Kim, Dinakaran Thirumalai, Sujin Lee, Minho Kwon, Hyun-jong Paik, Suhkmann Kim, Seung-Cheol Chang
      First page: 439
      Abstract: Bacterial infections in fish farms increase mass mortality and rapid detection of infection can help prevent its widespread. Lactate is an important biomarker for early diagnosis of bacterial infections in farmed olive flounder (Paralichthys olivaceus). To determine the lactate levels, we designed a disposable amperometric biosensor based on Prussian blue nanozyme and lactate oxidase (LOX) entrapped in copolymer-reduced graphene oxide (P-rGO) on screen-printed carbon electrodes. Because LOX is inherently unstable, P-rGO nanosheets were utilized as a base matrix to immobilize it. After optimization in terms of enzyme loading, operating potential, and pH, the biosensor displayed maximum current responses within 5 s at the applied potential of –0.1 V vs. internal Ag/AgCl. The biosensor had Langmuir-type response in the lactate concentration range from 10 µM to 1.6 mM, a dynamic linear response range of 10–100 µM, a sensitivity of 15.9 µA mM−1 cm−2, and a lower detection limit of 3.1 µM (S/N = 3). Additionally, the biosensor featured high reproducibility, good selectivity, and stability till four weeks. Its practical applicability was tested in olive flounder infected by Streptococcus parauberis against the uninfected control. The results were satisfactory compared to those of a standard colorimetric assay kit, validating our method.
      Citation: Biosensors
      PubDate: 2021-11-04
      DOI: 10.3390/bios11110439
      Issue No: Vol. 11, No. 11 (2021)
  • Biosensors, Vol. 11, Pages 440: Room-Temperature Synthesis of Air-Stable
           Near-Infrared Emission in FAPbI3 Nanoparticles Embedded in Silica

    • Authors: Lung-Chien Chen, Li-Wei Chao, Chen-Yu Xu, Chih-Hung Hsu, Yi-Ting Lee, Zi-Min Xu, Chun-Cheng Lin, Zong-Liang Tseng
      First page: 440
      Abstract: Hybrid organic−inorganic and all-inorganic metal halide perovskite nanoparticles (PNPs) have shown their excellent characteristics for optoelectronic applications. We report an atmospheric process to embed formamidinium CH(NH2)2PbI3 (FAPbI3) PNPs in silica protective layer at room temperature (approximately 26 °C) employing (3-aminopropyl) triethoxysilane (APTES). The resulting perovskite nanocomposite (PNCs) achieved a high photoluminescence (PL) quantum yield of 58.0% and good stability under atmospheric moisture conditions. Moreover, the PNCs showed high PL intensity over 1 month of storage (approximately 26 °C) and more than 380 min of PNCs solutions in DI water. The studied near-infrared (NIR) light-emitting diode (LED) combined a NIR-emitting PNCs coating and a blue InGaN-based chip that exhibited a 788 nm electroluminescence spectrum of NIR-LEDs under 2.6 V. This may be a powerful tool to track of muscle and disabled patients in the detection of a blood vessel.
      Citation: Biosensors
      PubDate: 2021-11-04
      DOI: 10.3390/bios11110440
      Issue No: Vol. 11, No. 11 (2021)
  • Biosensors, Vol. 11, Pages 441: Combination of Porous Silk Fibroin
           Substrate and Gold Nanocracks as a Novel SERS Platform for a
           High-Sensitivity Biosensor

    • Authors: Ji Hyeon Choi, Munsik Choi, Taeyoung Kang, Tien Son Ho, Seung Ho Choi, Kyung Min Byun
      First page: 441
      Abstract: Novel concepts for developing a surface-enhanced Raman scattering (SERS) sensor based on biocompatible materials offer great potential in versatile applications, including wearable and in vivo monitoring of target analytes. Here, we report a highly sensitive SERS sensor consisting of a biocompatible silk fibroin substrate with a high porosity and gold nanocracks. Our silk-based SERS detection takes advantage of strong local field enhancement in the nanoscale crack regions induced by gold nanostructures evaporated on a porous silk substrate. The SERS performance of the proposed sensor is evaluated in terms of detection limit, sensitivity, and linearity. Compared to the performance of a counterpart SERS sensor with a thin gold film, SERS results using 4-ABT analytes present that a significant improvement in the detection limit and sensitivity by more than 4 times, and a good linearity and a wide dynamic range is achieved. More interestingly, overlap is integral, and a quantitative measure of the local field enhancement is highly consistent with the experimental SERS enhancement.
      Citation: Biosensors
      PubDate: 2021-11-06
      DOI: 10.3390/bios11110441
      Issue No: Vol. 11, No. 11 (2021)
  • Biosensors, Vol. 11, Pages 442: Silicon Nanowire Field-Effect Transistor
           as Label-Free Detection of Hepatitis B Virus Proteins with Opposite Net

    • Authors: Suh Kuan Yong, Shang-Kai Shen, Chia-Wei Chiang, Ying-Ya Weng, Ming-Pei Lu, Yuh-Shyong Yang
      First page: 442
      Abstract: The prevalence of hepatitis B virus (HBV) is a global healthcare threat, particularly chronic hepatitis B (CHB) that might lead to hepatocellular carcinoma (HCC) should not be neglected. Although many types of HBV diagnosis detection methods are available, some technical challenges, such as the high cost or lack of practical feasibility, need to be overcome. In this study, the polycrystalline silicon nanowire field-effect transistors (pSiNWFETs) were fabricated through commercial process technology and then chemically functionalized for sensing hepatitis B virus surface antigen (HBsAg) and hepatitis B virus X protein (HBx) at the femto-molar level. These two proteins have been suggested to be related to the HCC development, while the former is also the hallmark for HBV diagnosis, and the latter is an RNA-binding protein. Interestingly, these two proteins carried opposite net charges, which could serve as complementary candidates for evaluating the charge-based sensing mechanism in the pSiNWFET. The measurements on the threshold voltage shifts of pSiNWFETs showed a consistent correspondence to the polarity of the charges on the proteins studied. We believe that this report can pave the way towards developing an approachable tool for biomedical applications.
      Citation: Biosensors
      PubDate: 2021-11-10
      DOI: 10.3390/bios11110442
      Issue No: Vol. 11, No. 11 (2021)
  • Biosensors, Vol. 11, Pages 443: Paper-Based Multiplexed Colorimetric
           Device for the Simultaneous Detection of Salivary Biomarkers

    • Authors: Tania Pomili, Paolo Donati, Pier Paolo Pompa
      First page: 443
      Abstract: In this study, we describe a monolithic and fully integrated paper-based device for the simultaneous detection of three prognostic biomarkers in saliva. The pattern of the proposed multiplexed device is designed with a central sample deposition zone and three identical arms, each containing a pre-treatment and test zone. Its one-step fabrication is realized by CO2 laser cutting, providing remarkable parallelization and rapidity (ca. 5 s/device). The colorimetric detection is based on the sensitive and selective target-induced reshaping of plasmonic multibranched gold nanoparticles, which exhibit a clear spectral shift (and blue-to-pink color change) in case of non-physiological concentrations of the three salivary biomarkers. A rapid and multiplexed naked-eye or smartphone-based readout of the colorimetric response is achieved within 10 min. A prototype kit for POCT testing is also reported, providing robustness and easy handling of the device.
      Citation: Biosensors
      PubDate: 2021-11-10
      DOI: 10.3390/bios11110443
      Issue No: Vol. 11, No. 11 (2021)
  • Biosensors, Vol. 11, Pages 444: Mechanism Study of Thermally Induced
           Anti-Tumor Drug Loading to Engineered Human Heavy-Chain Ferritin Nanocages
           Aided by Computational Analysis

    • Authors: Shuang Yin, Yongdong Liu, Sheng Dai, Bingyang Zhang, Yiran Qu, Yao Zhang, Woo-Seok Choe, Jingxiu Bi
      First page: 444
      Abstract: Diverse drug loading approaches for human heavy-chain ferritin (HFn), a promising drug nanocarrier, have been established. However, anti-tumor drug loading ratio and protein carrier recovery yield are bottlenecks for future clinical application. Mechanisms behind drug loading have not been elaborated. In this work, a thermally induced drug loading approach was introduced to load anti-tumor drug doxorubicin hydrochloride (DOX) into HFn, and 2 functionalized HFns, HFn-PAS-RGDK, and HFn-PAS. Optimal conditions were obtained through orthogonal tests. All 3 HFn-based proteins achieved high protein recovery yield and drug loading ratio. Size exclusion chromatography (SEC) and transmission electron microscopy (TEM) results showed the majority of DOX loaded protein (protein/DOX) remained its nanocage conformation. Computational analysis, molecular docking followed by molecular dynamic (MD) simulation, revealed mechanisms of DOX loading and formation of by-product by investigating non-covalent interactions between DOX with HFn subunit and possible binding modes of DOX and HFn after drug loading. In in vitro tests, DOX in protein/DOX entered tumor cell nucleus and inhibited tumor cell growth.
      Citation: Biosensors
      PubDate: 2021-11-11
      DOI: 10.3390/bios11110444
      Issue No: Vol. 11, No. 11 (2021)
  • Biosensors, Vol. 11, Pages 445: Recent Advances in Multicellular Tumor
           Spheroid Generation for Drug Screening

    • Authors: Kwang-Ho Lee, Tae-Hyung Kim
      First page: 445
      Abstract: Multicellular tumor spheroids (MCTs) have been employed in biomedical fields owing to their advantage in designing a three-dimensional (3D) solid tumor model. For controlling multicellular cancer spheroids, mimicking the tumor extracellular matrix (ECM) microenvironment is important to understand cell–cell and cell–matrix interactions. In drug cytotoxicity assessments, MCTs provide better mimicry of conventional solid tumors that can precisely represent anticancer drug candidates’ effects. To generate incubate multicellular spheroids, researchers have developed several 3D multicellular spheroid culture technologies to establish a research background and a platform using tumor modelingvia advanced materials science, and biosensing techniques for drug-screening. In application, drug screening was performed in both invasive and non-invasive manners, according to their impact on the spheroids. Here, we review the trend of 3D spheroid culture technology and culture platforms, and their combination with various biosensing techniques for drug screening in the biomedical field.
      Citation: Biosensors
      PubDate: 2021-11-11
      DOI: 10.3390/bios11110445
      Issue No: Vol. 11, No. 11 (2021)
  • Biosensors, Vol. 11, Pages 446: Fiber Optic Distributed Sensing Network
           for Shape Sensing-Assisted Epidural Needle Guidance

    • Authors: Aida Amantayeva, Nargiz Adilzhanova, Aizhan Issatayeva, Wilfried Blanc, Carlo Molardi, Daniele Tosi
      First page: 446
      Abstract: Epidural anesthesia is a pain management process that requires the insertion of a miniature needle through the epidural space located within lumbar vertebrae. The use of a guidance system for manual insertion can reduce failure rates and provide increased efficiency in the process. In this work, we present and experimentally assess a guidance system based on a network of fiber optic distributed sensors. The fibers are mounted externally to the needle, without blocking its inner channel, and through a strain-to-shape detection method reconstruct the silhouette of the epidural device in real time (1 s). We experimentally assessed the shape sensing methods over 25 experiments performed in a phantom, and we observed that the sensing system correctly identified bending patterns typical in epidural insertions, characterized by the different stiffness of the tissues. By studying metrics related to the curvatures and their temporal changes, we provide identifiers that can potentially serve for the (in)correct identification of the epidural space, and support the operator through the insertion process by recognizing the bending patterns.
      Citation: Biosensors
      PubDate: 2021-11-11
      DOI: 10.3390/bios11110446
      Issue No: Vol. 11, No. 11 (2021)
  • Biosensors, Vol. 11, Pages 447: A Fluorescent Biosensor for Sensitive
           Detection of Salmonella Typhimurium Using Low-Gradient Magnetic Field and
           Deep Learning via Faster Region-Based Convolutional Neural Network

    • Authors: Qiwei Hu, Siyuan Wang, Hong Duan, Yuanjie Liu
      First page: 447
      Abstract: In this study, a fluorescent biosensor was developed for the sensitive detection of Salmonella typhimurium using a low-gradient magnetic field and deep learning via faster region-based convolutional neural networks (R-CNN) to recognize the fluorescent spots on the bacterial cells. First, magnetic nanobeads (MNBs) coated with capture antibodies were used to separate target bacteria from the sample background, resulting in the formation of magnetic bacteria. Then, fluorescein isothiocyanate fluorescent microspheres (FITC-FMs) modified with detection antibodies were used to label the magnetic bacteria, resulting in the formation of fluorescent bacteria. After the fluorescent bacteria were attracted against the bottom of an ELISA well using a low-gradient magnetic field, resulting in the conversion from a three-dimensional (spatial) distribution of the fluorescent bacteria to a two-dimensional (planar) distribution, the images of the fluorescent bacteria were finally collected using a high-resolution fluorescence microscope and processed using the faster R-CNN algorithm to calculate the number of the fluorescent spots for the determination of target bacteria. Under the optimal conditions, this biosensor was able to quantitatively detect Salmonella typhimurium from 6.9 × 101 to 1.1 × 103 CFU/mL within 2.5 h with the lower detection limit of 55 CFU/mL. The fluorescent biosensor has the potential to simultaneously detect multiple types of foodborne bacteria using MNBs coated with their capture antibodies and different fluorescent microspheres modified with their detection antibodies.
      Citation: Biosensors
      PubDate: 2021-11-11
      DOI: 10.3390/bios11110447
      Issue No: Vol. 11, No. 11 (2021)
  • Biosensors, Vol. 11, Pages 448: Stable in Biocompatible Buffers Silver
           Nanoisland Films for SERS

    • Authors: Alexey Skvortsov, Ekaterina Babich, Alexey Redkov, Andrey Lipovskii, Valentina Zhurikhina
      First page: 448
      Abstract: We investigated the stability of silver nanoisland films, which were formed on glass surface by the method of out-diffusion, in biocompatible buffers and the applicability of the films in surface enhanced Raman scattering (SERS). We have shown that silver nanoisland films are stable in one of the most widespread in biological studies buffer—phosphate buffer saline (PBS), and in 1:100 water-diluted PBS, in the PBS-based buffer, in which NaCl is replaced by the same amount of NaClO4, and in acidic phosphate buffer. At the same time, the replacement of NaCl in PBS by N(CH3)4Cl leads to the degradation of the nanoislands. It was shown that after exposure to PBS the nanoisland films provided a good SERS signal from a monolayer of 1,2-di(4-pyridyl)ethylene (BPE), which makes silver nanoisland films promising for biosensor applications. Additionally, in our experiments, we registered for the first time that silver nanoparticles formed in the bulk of the samples dissolved after exposing to PBS, while nanoislands on the glass surface stayed unchanged. We associate this phenomenon with the interaction of ions contained in PBS solution with silver, which results in the shift of corresponding chemical equilibrium.
      Citation: Biosensors
      PubDate: 2021-11-12
      DOI: 10.3390/bios11110448
      Issue No: Vol. 11, No. 11 (2021)
  • Biosensors, Vol. 11, Pages 449: Multiplexed Liquid Biopsy and Tumor
           Imaging Using Surface-Enhanced Raman Scattering

    • Authors: Francesco Dell’Olio
      First page: 449
      Abstract: The recent improvements in diagnosis enabled by advances in liquid biopsy and oncological imaging significantly better cancer care. Both these complementary approaches, which are used for early tumor detection, characterization, and monitoring, can benefit from applying techniques based on surface-enhanced Raman scattering (SERS). With a detection sensitivity at the single-molecule level, SERS spectroscopy is widely used in cell and molecular biology, and its capability for the in vitro detection of several types of cancer biomarkers is well established. In the last few years, several intriguing SERS applications have emerged, including in vivo imaging for tumor targeting and the monitoring of drug release. In this paper, selected recent developments and trends in SERS applications in the field of liquid biopsy and tumor imaging are critically reviewed, with a special emphasis on results that demonstrate the clinical utility of SERS.
      Citation: Biosensors
      PubDate: 2021-11-12
      DOI: 10.3390/bios11110449
      Issue No: Vol. 11, No. 11 (2021)
  • Biosensors, Vol. 11, Pages 450: Real-Time Monitoring of Levetiracetam
           Effect on the Electrophysiology of an Heterogenous Human iPSC-Derived
           Neuronal Cell Culture Using Microelectrode Array Technology

    • Authors: Andrea Di Credico, Giulia Gaggi, Pascal Izzicupo, Laura Ferri, Laura Bonanni, Giovanni Iannetti, Angela Di Baldassarre, Barbara Ghinassi
      First page: 450
      Abstract: Levetiracetam (LEV) is a broad-spectrum and widely used antiepileptic drug that also has neuroprotective effects in different neurological conditions. Given its complex interaction with neuronal physiology, a better comprehension of LEV effects on neurons activity is needed. Microelectrode arrays (MEAs) represent an advanced technology for the non-invasive study of electrophysiological activity of neuronal cell cultures. In this study, we exploited the Maestro Edge MEA system, a platform that allows a deep analysis of the electrical network behavior, to study the electrophysiological effect of LEV on a mixed population of human neurons (glutamatergic, GABAergic and dopaminergic neurons, and astrocytes). We found that LEV significantly affected different variables such as spiking, single-electrode bursting, and network bursting activity, with a pronounced effect after 15 min. Moreover, neuronal cell culture completely rescued its baseline activity after 24 h without LEV. In summary, MEA technology confirmed its high sensitivity in detecting drug-induced electrophysiological modifications. Moreover, our results allow one to extend the knowledge on the electrophysiological effects of LEV on the complex neuronal population that resembles the human cortex.
      Citation: Biosensors
      PubDate: 2021-11-12
      DOI: 10.3390/bios11110450
      Issue No: Vol. 11, No. 11 (2021)
  • Biosensors, Vol. 11, Pages 451: A DNA Electrochemical Sensor via Terminal
           Protection of Small-Molecule-Linked DNA for Highly Sensitive Protein

    • Authors: Ping Ouyang, Chenxin Fang, Jialun Han, Jingjing Zhang, Yuxing Yang, Yang Qing, Yubing Chen, Wenyan Shang, Jie Du
      First page: 451
      Abstract: The qualitative and quantitative determination of marker protein is of great significance in the life sciences and in medicine. Here, we developed an electrochemical DNA biosensor for protein detection based on DNA self-assembly and the terminal protecting effects of small-molecule-linked DNA. This strategy is demonstrated using the small molecule biotin and its receptor protein streptavidin (SA). We immobilized DNA with a designed structure and sequence on the surface of the gold electrode, and we named it M1-Biotin DNA. M1-Biotin DNA selectively combines with SA to generate M1-Biotin-SA DNA and protects M1-Biotin DNA from digestion by EXO III; therefore, M1-Biotin DNA remains intact on the electrode surface. M1-Biotin-SA DNA was modified with methylene blue (MB); the MB reporter molecule is located near the surface of the gold electrode, which generates a substantial electrochemical signal during the detection of SA. Through this strategy, we can exploit the presence or absence of an electrochemical signal to provide qualitative target protein determination as well as the strength of the electrochemical signal to quantitatively analyze the target protein concentration. This strategy has been proven to be used for the quantitative analysis of the interaction between biotin and streptavidin (SA). Under optimal conditions, the detection limit of the proposed biosensor is as low as 18.8 pM, and the linear range is from 0.5 nM to 5 μM, showing high sensitivity. The detection ability of this DNA biosensor in complex serum samples has also been studied. At the same time, we detected the folate receptor (FR) to confirm that this strategy can be used to detect other proteins. Therefore, this electrochemical DNA biosensor provides a sensitive, low-cost, and fast target protein detection platform, which may provide a reliable and powerful tool for early disease diagnosis.
      Citation: Biosensors
      PubDate: 2021-11-13
      DOI: 10.3390/bios11110451
      Issue No: Vol. 11, No. 11 (2021)
  • Biosensors, Vol. 11, Pages 452: Fabrication of Co3O4/NiCo2O4 Nanocomposite
           for Detection of H2O2 and Dopamine

    • Authors: Tianjiao Liu, Xiaoyuan Zhang, Kun Fu, Nan Zhou, Jinping Xiong, Zhiqiang Su
      First page: 452
      Abstract: Herein, the Co3O4/NiCo2O4 nanocomposite has been prepared as a novel electrochemical sensor to accurately detect hydrogen peroxide (H2O2) and glucose. ZIF-67 is a metal-organic framework (MOF) with Co as the center metal ion. Co3O4 can be obtained by calcination of ZIF-67 at 700 °C, which can retain the structure of ZIF-67. The hollow Co3O4 nanocrystal was synthesized based on a calcination process of ZIF-67. This open structure can promote the whole Co3O4/NiCo2O4 nanocomposite larger accessible surface area and reactive sites. Co3O4 has good electrocatalytic performance, which has been applied in many fields. Moreover, H2O2 and dopamine sensing tests indicate that the as-prepared non-enzymatic electrochemical biosensor has good detection properties. The testing results indicate the as-prepared biosensor has a wide detection range, low detection limit, high selectivity, and long-term stability. These testing results suggest the potential application in food security, biomedicine, environmental detection, and pharmaceutical analysis.
      Citation: Biosensors
      PubDate: 2021-11-13
      DOI: 10.3390/bios11110452
      Issue No: Vol. 11, No. 11 (2021)
  • Biosensors, Vol. 11, Pages 453: Automatic Multi-Label ECG Classification
           with Category Imbalance and Cost-Sensitive Thresholding

    • Authors: Yang Liu, Qince Li, Kuanquan Wang, Jun Liu, Runnan He, Yongfeng Yuan, Henggui Zhang
      First page: 453
      Abstract: Automatic electrocardiogram (ECG) classification is a promising technology for the early screening and follow-up management of cardiovascular diseases. It is, by nature, a multi-label classification task owing to the coexistence of different kinds of diseases, and is challenging due to the large number of possible label combinations and the imbalance among categories. Furthermore, the task of multi-label ECG classification is cost-sensitive, a fact that has usually been ignored in previous studies on the development of the model. To address these problems, in this work, we propose a novel deep learning model–based learning framework and a thresholding method, namely category imbalance and cost-sensitive thresholding (CICST), to incorporate prior knowledge about classification costs and the characteristic of category imbalance in designing a multi-label ECG classifier. The learning framework combines a residual convolutional network with a class-wise attention mechanism. We evaluate our method with a cost-sensitive metric on multiple realistic datasets. The results show that CICST achieved a cost-sensitive metric score of 0.641 ± 0.009 in a 5-fold cross-validation, outperforming other commonly used thresholding methods, including rank-based thresholding, proportion-based thresholding, and fixed thresholding. This demonstrates that, by taking into account the category imbalance and predefined cost information, our approach is effective in improving the performance and practicability of multi-label ECG classification models.
      Citation: Biosensors
      PubDate: 2021-11-14
      DOI: 10.3390/bios11110453
      Issue No: Vol. 11, No. 11 (2021)
  • Biosensors, Vol. 11, Pages 454: Non-Interventional and High-Precision
           Temperature Measurement Biochips for Long-Term Monitoring the Temperature
           Fluctuations of Individual Cells

    • Authors: Danhong Han, Jingjing Xu, Han Wang, Zhenhai Wang, Nana Yang, Fan Yang, Qundong Shen, Shengyong Xu
      First page: 454
      Abstract: Monitoring the thermal responses of individual cells to external stimuli is essential for studies of cell metabolism, organelle function, and drug screening. Fluorescent temperature probes are usually employed to measure the temperatures of individual cells; however, they have some unavoidable problems, such as, poor stability caused by their sensitivity to the chemical composition of the solution and the limitation in their measurement time due to the short fluorescence lifetime. Here, we demonstrate a stable, non-interventional, and high-precision temperature-measurement chip that can monitor the temperature fluctuations of individual cells subject to external stimuli and over a normal cell life cycle as long as several days. To improve the temperature resolution, we designed temperature sensors made of Pd–Cr thin-film thermocouples, a freestanding Si3N4 platform, and a dual-temperature control system. Our experimental results confirm the feasibility of using this cellular temperature-measurement chip to detect local temperature fluctuations of individual cells that are 0.3–1.5 K higher than the ambient temperature for HeLa cells in different proliferation cycles. In the future, we plan to integrate this chip with other single-cell technologies and apply it to research related to cellular heat-stress response.
      Citation: Biosensors
      PubDate: 2021-11-15
      DOI: 10.3390/bios11110454
      Issue No: Vol. 11, No. 11 (2021)
  • Biosensors, Vol. 11, Pages 455: Numerical Study of Graphene/Au/SiC
           Waveguide-Based Surface Plasmon Resonance Sensor

    • Authors: Wei Du, Lucas Miller, Feng Zhao
      First page: 455
      Abstract: A new waveguide-based surface plasmon resonance (SPR) sensor was proposed and investigated by numerical simulation. The sensor consists of a graphene cover layer, a gold (Au) thin film, and a silicon carbide (SiC) waveguide layer on a silicon dioxide/silicon (SiO2/Si) substrate. The large bandgap energy of SiC allows the sensor to operate in the visible and near-infrared wavelength ranges, which effectively reduces the light absorption in water to improve the sensitivity. The sensor was characterized by comparing the shift of the resonance wavelength peak with change of the refractive index (RI), which mimics the change of analyte concentration in the sensing medium. The study showed that in the RI range of 1.33~1.36, the sensitivity was improved when the graphene layers were increased. With 10 graphene layers, a sensitivity of 2810 nm/RIU (refractive index unit) was achieved, corresponding to a 39.1% improvement in sensitivity compared to the Au/SiC sensor without graphene. These results demonstrate that the graphene/Au/SiC waveguide SPR sensor has a promising use in portable biosensors for chemical and biological sensing applications, such as detection of water contaminations (RI = 1.33~1.34), hepatitis B virus (HBV), and glucose (RI = 1.34~1.35), and plasma and white blood cells (RI = 1.35~1.36) for human health and disease diagnosis.
      Citation: Biosensors
      PubDate: 2021-11-15
      DOI: 10.3390/bios11110455
      Issue No: Vol. 11, No. 11 (2021)
  • Biosensors, Vol. 11, Pages 456: Microfluidic-Chip-Integrated Biosensors
           for Lung Disease Models

    • Authors: Shuang Ding, Haijun Zhang, Xuemei Wang
      First page: 456
      Abstract: Lung diseases (e.g., infection, asthma, cancer, and pulmonary fibrosis) represent serious threats to human health all over the world. Conventional two-dimensional (2D) cell models and animal models cannot mimic the human-specific properties of the lungs. In the past decade, human organ-on-a-chip (OOC) platforms—including lung-on-a-chip (LOC)—have emerged rapidly, with the ability to reproduce the in vivo features of organs or tissues based on their three-dimensional (3D) structures. Furthermore, the integration of biosensors in the chip allows researchers to monitor various parameters related to disease development and drug efficacy. In this review, we illustrate the biosensor-based LOC modeling, further discussing the future challenges as well as perspectives in integrating biosensors in OOC platforms.
      Citation: Biosensors
      PubDate: 2021-11-15
      DOI: 10.3390/bios11110456
      Issue No: Vol. 11, No. 11 (2021)
  • Biosensors, Vol. 11, Pages 457: Real-World Outcomes of Glucose Sensor Use
           in Type 1 Diabetes—Findings from a Large UK Centre

    • Authors: Kyuhan Lee, Shakthi Gunasinghe, Alyson Chapman, Lynne A. Findlow, Jody Hyland, Sheetal Ohol, Andrea Urwin, Martin K. Rutter, Jonathan Schofield, Hood Thabit, Lalantha Leelarathna
      First page: 457
      Abstract: Flash glucose monitoring (FGM) and real-time continuous glucose monitoring (RT-CGM) are increasingly used in clinical practice, with improvements in HbA1c and time in range (TIR) reported in clinical studies. We aimed to evaluate the impact of FGM and RT-CGM use on glycaemic outcomes in adults with type 1 diabetes (T1DM) under routine clinical care. We performed a retrospective data analysis from electronic outpatient records and proprietary web-based glucose monitoring platforms. We measured HbA1c (pre-sensor vs. on-sensor data) and sensor-based outcomes from the previous three months as per the international consensus on RT-CGM reporting guidelines. Amongst the 789 adults with T1DM, HbA1c level decreased from 61.0 (54.0, 71.0) mmol/mol to 57 (49, 65.8) mmol/mol in 561 people using FGM, and from 60.0 (50.0, 70.0) mmol/mol to 58.8 (50.3, 66.8) mmol/mol in 198 using RT-CGM (p < 0.001 for both). We found that 23% of FGM users and 32% of RT-CGM users achieved a time-in-range (TIR) (3.9 to 10 mmol/L) of >70%. For time-below-range (TBR) < 4 mmol/L, 70% of RT-CGM users and 58% of FGM users met international recommendations of <4%. Our data add to the growing body of evidence supporting the use of FGM and RT-CGM in T1DM.
      Citation: Biosensors
      PubDate: 2021-11-15
      DOI: 10.3390/bios11110457
      Issue No: Vol. 11, No. 11 (2021)
  • Biosensors, Vol. 11, Pages 458: A New Covalent Organic Framework of
           Dicyandiamide-Benzaldehyde Nanocatalytic Amplification SERS/RRS Aptamer
           Assay for Ultratrace Oxytetracycline with the Nanogold Indicator Reaction
           of Polyethylene Glycol 600

    • Authors: Aihui Liang, Shengfu Zhi, Qiwen Liu, Chongning Li, Zhiliang Jiang
      First page: 458
      Abstract: In this paper, dicyandiamide (Dd) and p-benzaldehyde (Bd) were heated at 180 ∘C for 3 h to prepare a new type of stable covalent organic framework (COF) DdBd nanosol with high catalysis. It was characterized by molecular spectroscopy and electron microscopy. The study found that DdBd had a strong catalytic effect on the new indicator reaction of polyethylene glycol 600 (PEG600)-chloroauric acid to form gold nanoparticles (AuNPs). AuNPs have strong resonance Rayleigh scattering (RRS) activity, and in the presence of Victoria Blue B (VBB) molecular probes, they also have a strong surface-enhanced Raman scattering (SERS) effect. Combined with a highly selective oxytetracycline (OTC) aptamer (Apt) reaction, new dual-mode scattering SERS/RRS methods were developed to quantitatively analyze ultratrace OTC. The linear range of RRS is 3.00 × 10−3 –6.00 × 10−2 nmol/L, the detection limit is 1.1 × 10−3 nmol/L, the linear range of SERS is 3.00 × 10−3–7.00 × 10−2 nmol/L, and the detection limit is 9.0 × 10−4 nmol/L. Using the SERS method to analyze OTC in soil samples, the relative standard deviation is 1.35–4.78%, and the recovery rate is 94.3–104.9%.
      Citation: Biosensors
      PubDate: 2021-11-16
      DOI: 10.3390/bios11110458
      Issue No: Vol. 11, No. 11 (2021)
  • Biosensors, Vol. 11, Pages 459: Electrochemical Biosensor for Markers of
           Neurological Esterase Inhibition

    • Authors: Neda Rafat, Paul Satoh, Robert Mark Worden
      First page: 459
      Abstract: A novel, integrated experimental and modeling framework was applied to an inhibition-based bi-enzyme (IBE) electrochemical biosensor to detect acetylcholinesterase (AChE) inhibitors that may trigger neurological diseases. The biosensor was fabricated by co-immobilizing AChE and tyrosinase (Tyr) on the gold working electrode of a screen-printed electrode (SPE) array. The reaction chemistry included a redox-recycle amplification mechanism to improve the biosensor’s current output and sensitivity. A mechanistic mathematical model of the biosensor was used to simulate key diffusion and reaction steps, including diffusion of AChE’s reactant (phenylacetate) and inhibitor, the reaction kinetics of the two enzymes, and electrochemical reaction kinetics at the SPE’s working electrode. The model was validated by showing that it could reproduce a steady-state biosensor current as a function of the inhibitor (PMSF) concentration and unsteady-state dynamics of the biosensor current following the addition of a reactant (phenylacetate) and inhibitor phenylmethylsulfonylfluoride). The model’s utility for characterizing and optimizing biosensor performance was then demonstrated. It was used to calculate the sensitivity of the biosensor’s current output and the redox-recycle amplification factor as a function of experimental variables. It was used to calculate dimensionless Damkohler numbers and current-control coefficients that indicated the degree to which individual diffusion and reaction steps limited the biosensor’s output current. Finally, the model’s utility in designing IBE biosensors and operating conditions that achieve specific performance criteria was discussed.
      Citation: Biosensors
      PubDate: 2021-11-16
      DOI: 10.3390/bios11110459
      Issue No: Vol. 11, No. 11 (2021)
  • Biosensors, Vol. 11, Pages 460: Microfluidics: A Novel Approach for
           Dehydration Protein Droplets

    • Authors: Van Nhat Pham, Dimitri Radajewski, Isaac Rodríguez-Ruiz, Sebastien Teychene
      First page: 460
      Abstract: The equation of state of colloids plays an important role in the modelling and comprehension of industrial processes, defining the working conditions of processes such as drying, filtration, and mixing. The determination of the equation is based on the solvent equilibration, by dialysis, between the colloidal suspension and a reservoir with a known osmotic pressure. In this paper, we propose a novel microfluidic approach to determine the equation of state of a lysozyme solution. Monodispersed droplets of lysozyme were generated in the bulk of a continuous 1-decanol phase using a flow-focusing microfluidic geometry. In this multiphasic system and in the working operation conditions, the droplets can be considered to act as a permeable membrane system. A water mass transfer flow occurs by molecule continuous diffusion in the surrounding 1-decanol phase until a thermodynamic equilibrium is reached in a few seconds to minutes, in contrast with the standard osmotic pressure measurements. By changing the water saturation of the continuous phase, the equation of state of lysozyme in solution was determined through the relation of the osmotic pressure between protein molecules and the volume fraction of protein inside the droplets. The obtained equation shows good agreement with other standard approaches reported in the literature.
      Citation: Biosensors
      PubDate: 2021-11-16
      DOI: 10.3390/bios11110460
      Issue No: Vol. 11, No. 11 (2021)
  • Biosensors, Vol. 11, Pages 461: Highly Sensitive Surface Plasmon Resonance

    • Authors: Wang, Wang, Shao, Liao, Wang
      First page: 461
      Abstract: A surface-plasmon-resonance-based fiber device is proposed for highly sensitive relative humidity (RH) sensing and human breath monitoring. The device is fabricated by using a polyvinyl alcohol (PVA) film and gold coating on the flat surface of a side-polished polymer optical fiber. The thickness and refractive index of the PVA coating are sensitive to environmental humidity, and thus the resonant wavelength of the proposed device exhibits a redshift as the RH increases. Experimental results demonstrate an average sensitivity of 4.98 nm/RH% across an ambient RH ranging from 40% to 90%. In particular, the sensor exhibits a linear response between 75% and 90% RH, with a sensitivity of 10.15 nm/RH%. The device is suitable for human breath tests and shows an average wavelength shift of up to 228.20 nm, which is 10 times larger than that of a silica-fiber-based humidity sensor. The corresponding response and recovery times are determined to be 0.44 s and 0.86 s, respectively. The proposed sensor has significant potential for a variety of practical applications, such as intensive care and human health analysis.
      Citation: Biosensors
      PubDate: 2021-11-17
      DOI: 10.3390/bios11110461
      Issue No: Vol. 11, No. 11 (2021)
  • Biosensors, Vol. 11, Pages 462: A Double-Deck Structure of Reduced
           Graphene Oxide Modified Porous Ti3C2Tx Electrode towards Ultrasensitive
           and Simultaneous Detection of Dopamine and Uric Acid

    • Authors: Yangguang Zhu, Qichen Tian, Xiufen Li, Lidong Wu, Aimin Yu, Guosong Lai, Li Fu, Qiuping Wei, Dan Dai, Nan Jiang, He Li, Chen Ye, Cheng-Te Lin
      First page: 462
      Abstract: Considering the vital physiological functions of dopamine (DA) and uric acid (UA) and their coexistence in the biological matrix, the development of biosensing techniques for their simultaneous and sensitive detection is highly desirable for diagnostic and analytical applications. Therefore, Ti3C2Tx/rGO heterostructure with a double-deck layer was fabricated through electrochemical reduction. The rGO was modified on a porous Ti3C2Tx electrode as the biosensor for the detection of DA and UA simultaneously. Debye length was regulated by the alteration of rGO mass on the surface of the Ti3C2Tx electrode. Debye length decreased with respect to the rGO electrode modified with further rGO mass, indicating that fewer DA molecules were capable of surpassing the equilibrium double layer and reaching the surface of rGO to achieve the voltammetric response of DA. Thus, the proposed Ti3C2Tx/rGO sensor presented an excellent performance in detecting DA and UA with a wide linear range of 0.1–100 μM and 1–1000 μM and a low detection limit of 9.5 nM and 0.3 μM, respectively. Additionally, the proposed Ti3C2Tx/rGO electrode displayed good repeatability, selectivity, and proved to be available for real sample analysis.
      Citation: Biosensors
      PubDate: 2021-11-18
      DOI: 10.3390/bios11110462
      Issue No: Vol. 11, No. 11 (2021)
  • Biosensors, Vol. 11, Pages 463: Superior Non-Invasive Glucose Sensor Using
           Bimetallic CuNi Nanospecies Coated Mesoporous Carbon

    • Authors: Ahmed Bahgat Radwan, Sreedevi Paramparambath, John-John Cabibihan, Abdulaziz Khalid Al-Ali, Peter Kasak, Rana A. Shakoor, Rayaz A. Malik, Said A. Mansour, Kishor Kumar Sadasivuni
      First page: 463
      Abstract: The assessment of blood glucose levels is necessary for the diagnosis and management of diabetes. The accurate quantification of serum or plasma glucose relies on enzymatic and nonenzymatic methods utilizing electrochemical biosensors. Current research efforts are focused on enhancing the non-invasive detection of glucose in sweat with accuracy, high sensitivity, and stability. In this work, nanostructured mesoporous carbon coupled with glucose oxidase (GOx) increased the direct electron transfer to the electrode surface. A mixed alloy of CuNi nanoparticle-coated mesoporous carbon (CuNi-MC) was synthesized using a hydrothermal process followed by annealing at 700 °C under the flow of argon gas. The prepared catalyst’s crystal structure and morphology were explored using X-ray diffraction and high-resolution transmission electron microscopy. The electrocatalytic activity of the as-prepared catalyst was investigated using cyclic voltammetry (CV) and amperometry. The findings show an excellent response time of 4 s and linear range detection from 0.005 to 0.45 mM with a high electrode sensitivity of 11.7 ± 0.061 mA mM cm−2 in a selective medium.
      Citation: Biosensors
      PubDate: 2021-11-18
      DOI: 10.3390/bios11110463
      Issue No: Vol. 11, No. 11 (2021)
  • Biosensors, Vol. 11, Pages 464: Progress of Microfluidic Continuous
           Separation Techniques for Micro-/Nanoscale Bioparticles

    • Authors: Choe, Kim, Kim
      First page: 464
      Abstract: Separation of micro- and nano-sized biological particles, such as cells, proteins, and nucleotides, is at the heart of most biochemical sensing/analysis, including in vitro biosensing, diagnostics, drug development, proteomics, and genomics. However, most of the conventional particle separation techniques are based on membrane filtration techniques, whose efficiency is limited by membrane characteristics, such as pore size, porosity, surface charge density, or biocompatibility, which results in a reduction in the separation efficiency of bioparticles of various sizes and types. In addition, since other conventional separation methods, such as centrifugation, chromatography, and precipitation, are difficult to perform in a continuous manner, requiring multiple preparation steps with a relatively large minimum sample volume is necessary for stable bioprocessing. Recently, microfluidic engineering enables more efficient separation in a continuous flow with rapid processing of small volumes of rare biological samples, such as DNA, proteins, viruses, exosomes, and even cells. In this paper, we present a comprehensive review of the recent advances in microfluidic separation of micro-/nano-sized bioparticles by summarizing the physical principles behind the separation system and practical examples of biomedical applications.
      Citation: Biosensors
      PubDate: 2021-11-18
      DOI: 10.3390/bios11110464
      Issue No: Vol. 11, No. 11 (2021)
  • Biosensors, Vol. 11, Pages 465: ZnO Tips Dotted with Au
           Nanoparticles—Advanced SERS Determination of Trace Nicotine

    • Authors: Jiaying Cao, Yan Zhai, Wanxin Tang, Xiaoyu Guo, Ying Wen, Haifeng Yang
      First page: 465
      Abstract: Long-term exposure to nicotine causes a variety of human diseases, such as lung damage/adenocarcinoma, nausea and vomiting, headache, incontinence and heart failure. In this work, as a surface-enhanced Raman scattering (SERS) substrate, zinc oxide (ZnO) tips decorated with gold nanoparticles (AuNPs) are fabricated and designated as ZnO/Au. Taking advantage of the synergistic effect of a ZnO semiconductor with morphology of tips and AuNPs, the ZnO/Au-based SERS assay for nicotine demonstrates high sensitivity and the limit of detection 8.9 × 10−12 mol/L is reached, as well as the corresponding linear dynamic detection range of 10−10–10−6 mol/L. Additionally, the signal reproducibility offered by the SERS substrate could realize the reliable determination of trace nicotine in saliva.
      Citation: Biosensors
      PubDate: 2021-11-19
      DOI: 10.3390/bios11110465
      Issue No: Vol. 11, No. 11 (2021)
  • Biosensors, Vol. 11, Pages 466: Reagentless D-Tagatose Biosensors Based on
           the Oriented Immobilization of Fructose Dehydrogenase onto Coated Gold
           Nanoparticles- or Reduced Graphene Oxide-Modified Surfaces: Application in
           a Prototype Bioreactor

    • Authors: Šakinytė, Butkevičius, Gurevičienė, Stankevičiūtė, Meškys, Razumienė
      First page: 466
      Abstract: As electrode nanomaterials, thermally reduced graphene oxide (TRGO) and modified gold nanoparticles (AuNPs) were used to design bioelectrocatalytic systems for reliable D-tagatose monitoring in a long-acting bioreactor where the valuable sweetener D-tagatose was enzymatically produced from a dairy by-product D-galactose. For this goal D-fructose dehydrogenase (FDH) from Gluconobacter industrius immobilized on these electrode nanomaterials by forming three amperometric biosensors: AuNPs coated with 4-mercaptobenzoic acid (AuNP/4-MBA/FDH) or AuNPs coated with 4-aminothiophenol (AuNP/PATP/FDH) monolayer, and a layer of TRGO on graphite (TRGO/FDH) were created. The immobilized FDH due to changes in conformation and spatial orientation onto proposed electrode surfaces catalyzes a direct D-tagatose oxidation reaction. The highest sensitivity for D-tagatose of 0.03 ± 0.002 μA mM–1cm–2 was achieved using TRGO/FDH. The TRGO/FDH was applied in a prototype bioreactor for the quantitative evaluation of bioconversion of D-galactose into D-tagatose by L-arabinose isomerase. The correlation coefficient between two independent analyses of the bioconversion mixture: spectrophotometric and by the biosensor was 0.9974. The investigation of selectivity showed that the biosensor was not active towards D-galactose as a substrate. Operational stability of the biosensor indicated that detection of D-tagatose could be performed during six hours without loss of sensitivity.
      Citation: Biosensors
      PubDate: 2021-11-19
      DOI: 10.3390/bios11110466
      Issue No: Vol. 11, No. 11 (2021)
  • Biosensors, Vol. 11, Pages 467: Label-Free Surface Enhanced Raman
           Scattering (SERS) on Centrifugal Silver Plasmonic Paper (CSPP): A Novel
           Methodology for Unprocessed Biofluids Sampling and Analysis

    • Authors: Alessandro Esposito, Alois Bonifacio, Valter Sergo, Stefano Fornasaro
      First page: 467
      Abstract: Label-free SERS is a powerful bio-analytical technique in which molecular fingerprinting is combined with localized surface plasmons (LSPs) on metal surfaces to achieve high sensitivity. Silver and gold colloids are among the most common nanostructured substrates used in SERS, but since protein-rich samples such as serum or plasma can hinder the SERS effect due to protein–substrate interactions, they often require a deproteinization step. Moreover, SERS methods based on metal colloids often suffer from a poor reproducibility. Here, we propose a paper-based SERS sampling method in which unprocessed human serum samples are first soaked on paper strips (0.4 × 2 cm2), and then mixed with colloidal silver nanoparticles by centrifugation to obtain a Centrifugal Silver Plasmonic Paper (CSPP). The CSPP methodology has the potential to become a promising tool in bioanalytical SERS applications: it uses common colloidal substrates but without the need for sample deproteinization, while having a good reproducibility both in terms of overall spectral shape (r > 0.96) and absolute intensity (RSD < 10%). Moreover, this methodology allows SERS analysis more than one month after serum collection on the paper strip, facilitating storage and handling of clinical samples (including shipping from clinical sites to labs).
      Citation: Biosensors
      PubDate: 2021-11-21
      DOI: 10.3390/bios11110467
      Issue No: Vol. 11, No. 11 (2021)
  • Biosensors, Vol. 11, Pages 468: Hot-Band-Absorption-Induced Anti-Stokes
           Fluorescence of Aggregation-Induced Emission Dots and the Influence on the
           Nonlinear Optical Effect

    • Authors: Yuhuang Zhang, Jing Zhou, Shiyi Peng, Wenbin Yu, Xiaoxiao Fan, Wen Liu, Zikang Ye, Ji Qi, Zhe Feng, Jun Qian
      First page: 468
      Abstract: Hot-band absorption (HBA)-induced anti-Stokes fluorescence (ASF) with longer-wavelength excitation is one effective pathway to deep penetration and low autofluorescence in intravital fluorescence imaging, raising demands for fluorophores with broad spectra, high absorption, and strong emission. However, typical fluorescent dyes display some emission quenching when their concentration is increased in order to obtain brighter fluorescence. In this work, the HBA-induced ASF of aggregation-induced emission (AIE) dots is reported. BPN-BBTD dots were synthesized and confirmed with a fluorescence enhancement and a considerable ASF intensity. In addition, the mechanism of ASF and the HBA process of BPN-BBTD dots were carefully validated and discussed. To obtain the full advantages of the long-wavelength excitation and the short fluorescence lifetime in deep-tissue bioimaging, a large-depth ASF confocal microscopic imaging of in vivo cerebral vasculature was conducted under the excitation of a 980 nm continuous wave laser after intravenous injection of BPN-BBTD dots. Meanwhile, the 3D structure of the cerebrovascular network was successfully reconstructed.
      Citation: Biosensors
      PubDate: 2021-11-22
      DOI: 10.3390/bios11110468
      Issue No: Vol. 11, No. 11 (2021)
  • Biosensors, Vol. 11, Pages 469: Accuracy of the Electronic Nose Breath
           Tests in Clinical Application: A Systematic Review and Meta-Analysis

    • Authors: Hsiao-Yu Yang, Wan-Chin Chen, Rodger-Chen Tsai
      First page: 469
      Abstract: (1) Background: An electronic nose applies a sensor array to detect volatile biomarkers in exhaled breath to diagnose diseases. The overall diagnostic accuracy remains unknown. The objective of this review was to provide an estimate of the diagnostic accuracy of sensor-based breath tests for the diagnosis of diseases. (2) Methods: We searched the PubMed and Web of Science databases for studies published between 1 January 2010 and 14 October 2021. The search was limited to human studies published in the English language. Clinical trials were not included in this review. (3) Results: Of the 2418 records identified, 44 publications were eligible, and 5728 patients were included in the final analyses. The pooled sensitivity was 90.0% (95% CI, 86.3–92.8%, I2 = 47.7%), the specificity was 88.4% (95% CI, 87.1–89.5%, I2 = 81.4%), and the pooled area under the curve was 0.93 (95% CI 0.91–0.95). (4) Conclusion: The findings of our review suggest that a standardized report of diagnostic accuracy and a report of the accuracy in a test set are needed. Sensor array systems of electronic noses have the potential for noninvasiveness at the point-of-care in hospitals. Nevertheless, the procedure for reporting the accuracy of a diagnostic test must be standardized.
      Citation: Biosensors
      PubDate: 2021-11-22
      DOI: 10.3390/bios11110469
      Issue No: Vol. 11, No. 11 (2021)
  • Biosensors, Vol. 11, Pages 470: Recent Advances in Electrical Impedance
           Sensing Technology for Single-Cell Analysis

    • Authors: Zhao Zhang, Xiaowen Huang, Ke Liu, Tiancong Lan, Zixin Wang, Zhen Zhu
      First page: 470
      Abstract: Cellular heterogeneity is of significance in cell-based assays for life science, biomedicine and clinical diagnostics. Electrical impedance sensing technology has become a powerful tool, allowing for rapid, non-invasive, and label-free acquisition of electrical parameters of single cells. These electrical parameters, i.e., equivalent cell resistance, membrane capacitance and cytoplasm conductivity, are closely related to cellular biophysical properties and dynamic activities, such as size, morphology, membrane intactness, growth state, and proliferation. This review summarizes basic principles, analytical models and design concepts of single-cell impedance sensing devices, including impedance flow cytometry (IFC) to detect flow-through single cells and electrical impedance spectroscopy (EIS) to monitor immobilized single cells. Then, recent advances of both electrical impedance sensing systems applied in cell recognition, cell counting, viability detection, phenotypic assay, cell screening, and other cell detection are presented. Finally, prospects of impedance sensing technology in single-cell analysis are discussed.
      Citation: Biosensors
      PubDate: 2021-11-22
      DOI: 10.3390/bios11110470
      Issue No: Vol. 11, No. 11 (2021)
  • Biosensors, Vol. 11, Pages 384: Application of Functionalized Graphene
           Oxide Based Biosensors for Health Monitoring: Simple Graphene Derivatives
           to 3D Printed Platforms

    • Authors: Agnivo Gosai, Kamil Reza Khondakar, Xiao Ma, Md. Azahar Ali
      First page: 384
      Abstract: Biosensors hold great potential for revolutionizing personalized medicine and environmental monitoring. Their construction is the key factor which depends on either manufacturing techniques or robust sensing materials to improve efficacy of the device. Functional graphene is an attractive choice for transducing material due to its various advantages in interfacing with biorecognition elements. Graphene and its derivatives such as graphene oxide (GO) are thus being used extensively for biosensors for monitoring of diseases. In addition, graphene can be patterned to a variety of structures and is incorporated into biosensor devices such as microfluidic devices and electrochemical and plasmonic sensors. Among biosensing materials, GO is gaining much attention due to its easy synthesis process and patternable features, high functionality, and high electron transfer properties with a large surface area leading to sensitive point-of-use applications. Considering demand and recent challenges, this perspective review is an attempt to describe state-of-the-art biosensors based on functional graphene. Special emphasis is given to elucidating the mechanism of sensing while discussing different applications. Further, we describe the future prospects of functional GO-based biosensors for health care and environmental monitoring with a focus on additive manufacturing such as 3D printing.
      Citation: Biosensors
      PubDate: 2021-10-10
      DOI: 10.3390/bios11100384
      Issue No: Vol. 11, No. 10 (2021)
  • Biosensors, Vol. 11, Pages 385: Applications of Microfluidics in Liquid
           Crystal-Based Biosensors

    • Authors: Deng, Han, Yang
      First page: 385
      Abstract: Liquid crystals (LCs) with stimuli-responsive configuration transition and optical anisotropic properties have attracted enormous interest in the development of simple and label-free biosensors. The combination of microfluidics and the LCs offers great advantages over traditional LC-based biosensors including small sample consumption, fast analysis and low cost. Moreover, microfluidic techniques provide a promising tool to fabricate uniform and reproducible LC-based sensing platforms. In this review, we emphasize the recent development of microfluidics in the fabrication and integration of LC-based biosensors, including LC planar sensing platforms and LC droplets. Fabrication and integration of LC-based planar platforms with microfluidics for biosensing applications are first introduced. The generation and entrapment of monodisperse LC droplets with different microfluidic structures, as well as their applications in the detection of chemical and biological species, are then summarized. Finally, the challenges and future perspectives of the development of LC-based microfluidic biosensors are proposed. This review will promote the understanding of microfluidic techniques in LC-based biosensors and facilitate the development of LC-based microfluidic biosensing devices with high performance.
      Citation: Biosensors
      PubDate: 2021-10-12
      DOI: 10.3390/bios11100385
      Issue No: Vol. 11, No. 10 (2021)
  • Biosensors, Vol. 11, Pages 386: Portable and Label-Free Quantitative
           Loop-Mediated Isothermal Amplification (LF-qLamp) for Reliable COVID-19
           Diagnostics in Three Minutes of Reaction Time: Arduino-Based Detection
           System Assisted by a pH Microelectrode

    • Authors: Mario Moisés Alvarez, Sergio Bravo-González, Everardo González-González, Grissel Trujillo-de Santiago
      First page: 386
      Abstract: Loop-mediated isothermal amplification (LAMP) has been recently studied as an alternative method for cost-effective diagnostics in the context of the current COVID-19 pandemic. Recent reports document that LAMP-based diagnostic methods have a comparable sensitivity and specificity to that of RT-qPCR. We report the use of a portable Arduino-based LAMP-based amplification system assisted by pH microelectrodes for the accurate and reliable diagnosis of SARS-CoV-2 during the first 3 min of the amplification reaction. We show that this simple system enables a straightforward discrimination between samples containing or not containing artificial SARS-CoV-2 genetic material in the range of 10 to 10,000 copies per 50 µL of reaction mix. We also spiked saliva samples with SARS-CoV-2 synthetic material and corroborated that the LAMP reaction can be successfully monitored in real time using microelectrodes in saliva samples as well. These results may have profound implications for the design of real-time and portable quantitative systems for the reliable detection of viral pathogens including SARS-CoV-2.
      Citation: Biosensors
      PubDate: 2021-10-13
      DOI: 10.3390/bios11100386
      Issue No: Vol. 11, No. 10 (2021)
  • Biosensors, Vol. 11, Pages 387: Noncontact Optical Measurement of Aqueous
           Humor Glucose Levels and Correlation with Serum Glucose Levels in Rabbit

    • Authors: Yih-Shiou Hwang, Eugene Yu-Chuan Kang, Chia-Rui Shen, Wei-Hsin Hong, Wei-Chi Wu
      First page: 387
      Abstract: The noninvasive measurement of serum glucose levels has been investigated for the monitoring of blood sugar control in diabetes. In our study, we aimed to develop a novel noncontact glucometer (NCGM) utilizing an optical approach to measure the intraocular aqueous humor glucose levels in the anterior chamber of rabbit eyes. The NCGM consists of a hybrid optical system that simultaneously measures near-infrared absorption and the polarized rotatory distribution of glucose molecules in the aqueous humor. In vitro optical measurements demonstrated that NCGM measurements had high precision and repeatability for different glucose levels, including 50 mg/dL (14.36%), 100 mg/dL (−4.05%), 200 mg/dL (−5.99%), 300 mg/dL (4.86%), 400 mg/dL (−2.84%), 500 mg/dL (−0.11%), and 600 mg/dL (4.48%). In the rabbit experiments, we found a high correlation between aqueous glucose levels and serum glucose levels, with a mean difference of 8 mg/dL. According to the testing results, the in vivo NCGM measurement of aqueous humor glucose levels also displayed a high correlation with serum glucose levels, with a mean difference of 29.2 mg/dL. In conclusion, aqueous humor glucose levels were accurately measured using the NCGM, and the results correlated with serum glucose levels.
      Citation: Biosensors
      PubDate: 2021-10-13
      DOI: 10.3390/bios11100387
      Issue No: Vol. 11, No. 10 (2021)
  • Biosensors, Vol. 11, Pages 388: Microfluidic Lab-on-a-Chip Based on
           UHF-Dielectrophoresis for Stemness Phenotype Characterization and
           Discrimination among Glioblastoma Cells

    • Authors: Elisa Lambert, Rémi Manczak, Elodie Barthout, Sofiane Saada, Elena Porcù, Francesca Maule, Barbara Bessette, Giampietro Viola, Luca Persano, Claire Dalmay, Fabrice Lalloué, Arnaud Pothier
      First page: 388
      Abstract: Glioblastoma (GBM) is one of the most aggressive solid tumors, particularly due to the presence of cancer stem cells (CSCs). Nowadays, the characterization of this cell type with an efficient, fast and low-cost method remains an issue. Hence, we have developed a microfluidic lab-on-a-chip based on dielectrophoresis (DEP) single cell electro-manipulation to measure the two crossover frequencies: fx01 in the low-frequency range (below 500 kHz) and fx02 in the ultra-high-frequency range (UHF, above 50 MHz). First, in vitro conditions were investigated. An U87-MG cell line was cultured in different conditions in order to induce an undifferentiated phenotype. Then, ex vivo GBM cells from patients’ primary cell culture were passed through the developed microfluidic system and characterized in order to reflect clinical conditions. This article demonstrates that the usual exploitation of low-frequency range DEP does not allow the discrimination of the undifferentiated GBM cells from the differentiated one. However, the presented study highlights the use of UHF-DEP as a relevant discriminant parameter. The proposed microfluidic lab-on-a-chip is able to follow the kinetics of U87-MG phenotype transformation in a CSC enrichment medium and the cancer stem cells phenotype acquirement.
      Citation: Biosensors
      PubDate: 2021-10-13
      DOI: 10.3390/bios11100388
      Issue No: Vol. 11, No. 10 (2021)
  • Biosensors, Vol. 11, Pages 389: Brain–Computer Interfacing Using
           Functional Near-Infrared Spectroscopy (fNIRS)

    • Authors: Paulmurugan, Vijayaragavan, Ghosh, Padmanabhan, Gulyás
      First page: 389
      Abstract: Functional Near-Infrared Spectroscopy (fNIRS) is a wearable optical spectroscopy system originally developed for continuous and non-invasive monitoring of brain function by measuring blood oxygen concentration. Recent advancements in brain–computer interfacing allow us to control the neuron function of the brain by combining it with fNIRS to regulate cognitive function. In this review manuscript, we provide information regarding current advancement in fNIRS and how it provides advantages in developing brain–computer interfacing to enable neuron function. We also briefly discuss about how we can use this technology for further applications.
      Citation: Biosensors
      PubDate: 2021-10-13
      DOI: 10.3390/bios11100389
      Issue No: Vol. 11, No. 10 (2021)
  • Biosensors, Vol. 11, Pages 390: Theoretical Model for a Highly Sensitive
           Near Infrared Biosensor Based on Bloch Surface Wave with Dirac Semimetal

    • Authors: Qiwen Zheng, Yamei Liu, Wenguang Lu, Xiaoyu Dai, Haishan Tian, Leyong Jiang
      First page: 390
      Abstract: In this work, we present a theoretical model of a near-infrared sensitive refractive index biosensor based on the truncate 1D photonic crystal (1D PC) structure with Dirac semimetal. This highly sensitive near-infrared biosensor originates from the sharp reflectance peak caused by the excitation of Bloch surface wave (BSW) at the interface between the Dirac semimetal and 1D PC. The sensitivity of the biosensor model is sensitive to the Fermi energy of Dirac semimetal, the thickness of the truncate layer and the refractive index of the sensing medium. By optimizing the structural parameters, the maximum refractive index sensitivity of the biosensor model can surpass 17.4 × 103/RIU, which achieves a certain competitiveness compared to conventional surface plasmon resonance (SPR) or BSW sensors. Considering that bulk materials are easier to handle than two-dimensional materials in manufacturing facilities, we judge that 3D Dirac semimetal and its related devices will provide a strong competitor and alternative to graphene-based devices.
      Citation: Biosensors
      PubDate: 2021-10-14
      DOI: 10.3390/bios11100390
      Issue No: Vol. 11, No. 10 (2021)
  • Biosensors, Vol. 11, Pages 391: Oxygen Saturation Behavior by Pulse
           Oximetry in Female Athletes: Breaking Myths

    • Authors: Pilar Martín-Escudero, Ana María Cabanas, Manuel Fuentes-Ferrer, Mercedes Galindo-Canales
      First page: 391
      Abstract: The myths surrounding women’s participation in sport have been reflected in respiratory physiology. This study aims to demonstrate that continuous monitoring of blood oxygen saturation during a maximal exercise test in female athletes is highly correlated with the determination of the second ventilatory threshold (VT2) or anaerobic threshold (AnT). The measurements were performed using a pulse oximeter during a maximum effort test on a treadmill on a population of 27 healthy female athletes. A common behavior of the oxygen saturation evolution during the incremental exercise test characterized by a decrease in saturation before the aerobic threshold (AeT) followed by a second significant drop was observed. Decreases in peripheral oxygen saturation during physical exertion have been related to the athlete’s physical fitness condition. However, this drop should not be a limiting factor in women’s physical performance. We found statistically significant correlations between the maximum oxygen uptake and the appearance of the ventilatory thresholds (VT1 and VT2), the desaturation time, the total test time, and between the desaturation time and the VT2. We observed a relationship between the desaturation time and the VT2 appearance. Indeed, a linear regression model between the desaturation time and the VT2 appearance can predict 80% of the values in our sample. Besides, we suggest that pulse oximetry is a simple, fairly accurate, and non-invasive technique for studying the physical condition of athletes who perform physical exertion.
      Citation: Biosensors
      PubDate: 2021-10-14
      DOI: 10.3390/bios11100391
      Issue No: Vol. 11, No. 10 (2021)
  • Biosensors, Vol. 11, Pages 392: On-Site Detection of Carcinoembryonic
           Antigen in Human Serum

    • Authors: Tohid Mahmoudi, Mohammad Pourhassan-Moghaddam, Behnaz Shirdel, Behzad Baradaran, Eden Morales-Narváez, Hamed Golmohammadi
      First page: 392
      Abstract: Real-time connectivity and employment of sustainable materials empowers point-of-care diagnostics with the capability to send clinically relevant data to health care providers even in low-resource settings. In this study, we developed an advantageous kit for the on-site detection of carcinoembryonic antigen (CEA) in human serum. CEA sensing was performed using cellulose-based lateral flow strips, and colorimetric signals were read, processed, and measured using a smartphone-based system. The corresponding immunoreaction was reported by polydopamine-modified gold nanoparticles in order to boost the signal intensity and improve the surface blocking and signal-to-noise relationship, thereby enhancing detection sensitivity when compared with bare gold nanoparticles (up to 20-fold in terms of visual limit of detection). Such lateral flow strips showed a linear range from 0.05 to 50 ng/mL, with a visual limit of detection of 0.05 ng/mL and an assay time of 15 min. Twenty-six clinical samples were also tested using the proposed kit and compared with the gold standard of immunoassays (enzyme linked immunosorbent assay), demonstrating an excellent correlation (R = 0.99). This approach can potentially be utilized for the monitoring of cancer treatment, particularly at locations far from centralized laboratory facilities.
      Citation: Biosensors
      PubDate: 2021-10-14
      DOI: 10.3390/bios11100392
      Issue No: Vol. 11, No. 10 (2021)
  • Biosensors, Vol. 11, Pages 393: Biomechanical and Physiological Evaluation
           of a Multi-Joint Exoskeleton with Active-Passive Assistance for Walking

    • Authors: Wujing Cao, Zhewen Zhang, Chunjie Chen, Yong He, Dashuai Wang, Xinyu Wu
      First page: 393
      Abstract: How to improve the walking efficiency while ensuring the wearability is an important issue of lower limb exoskeletons. Active devices can provide greater forces, while the passive devices have advantage in weight. We presented a multi-joint exoskeleton with active hip extension assistance and passive ankle plantarflexion assistance in this work. An admittance controller based on a feedforward model was proposed to track the desired active force of the hip extension. An underfoot clutch mechanism was adapted to realize the passive ankle plantarflexion assistance. To assess the efficacy of the multi-joint exoskeleton in assisting walking, we conducted comprehensive experiments to evaluate the force tracking performance, lower limb muscle activities and metabolic cost. The results demonstrated that: (i) The average tracking error of the peak hip extension assistance force from three subjects was less than 3%. (ii) The reductions of normalized root-mean-square EMG in the lateral soleus, medial soleus and gluteus maximus of eight subjects achieved 15.33%, 11.11%, and 3.74%, respectively. (iii) The average metabolic cost of six subjects was reduced by 10.41% under exoskeleton on (EO) condition comparing to the condition of walking with no exoskeleton (NE). This work proved that the concept of the multi-joint exoskeleton with active-passive assistance can improve the walking efficiency.
      Citation: Biosensors
      PubDate: 2021-10-15
      DOI: 10.3390/bios11100393
      Issue No: Vol. 11, No. 10 (2021)
  • Biosensors, Vol. 11, Pages 394: Liquid Biopsy-Based Biosensors for MRD
           Detection and Treatment Monitoring in Non-Small Cell Lung Cancer (NSCLC)

    • Authors: Parvaneh Sardarabadi, Amir Asri Kojabad, Davod Jafari, Cheng-Hsien Liu
      First page: 394
      Abstract: Globally, non-small cell lung cancer (NSCLC) is the leading cause of cancer deaths. Despite advancements in chemotherapy and targeted therapies, the 5-year survival rate has remained at 16% for the past forty years. Minimal residual disease (MRD) is described as the existence of either isolated tumour cells or circulating tumour cells in biological liquid of patients after removal of the primary tumour without any clinical signs of cancer. Recently, liquid biopsy has been promising as a non-invasive method of disease monitoring and treatment guidelines as an MRD marker. Liquid biopsy could be used to detect and assess earlier stages of NSCLC, post-treatment MRD, resistance to targeted therapies, immune checkpoint inhibitors (ICIs) and tumour mutational burden. MRD surveillance has been proposed as a potential marker for lung cancer relapse. Principally, biosensors provide the quantitative analysis of various materials by converting biological functions into quantifiable signals. Biosensors are usually operated to detect antibodies, enzymes, DNA, RNA, extracellular vesicles (EVs) and whole cells. Here, we present a category of biosensors based on the signal transduction method for identifying biosensor-based biomarkers in liquid biopsy specimens to monitor lung cancer treatment.
      Citation: Biosensors
      PubDate: 2021-10-15
      DOI: 10.3390/bios11100394
      Issue No: Vol. 11, No. 10 (2021)
  • Biosensors, Vol. 11, Pages 395: Topographical Vacuum Sealing of 3D-Printed
           Multiplanar Microfluidic Structures

    • Authors: Benjamin Heidt, Renato Rogosic, Nils Leoné, Eduardo J. S. Brás, Thomas J. Cleij, Jules A. W. Harings, Hanne Diliën, Kasper Eersels, Bart van Grinsven
      First page: 395
      Abstract: We demonstrate a novel way of creating three-dimensional microfluidic channels capable of following complex topographies. To this end, substrates with open channels and different geometries were 3D-printed, and the open channels were consecutively closed with a thermoplastic using a low-resolution vacuum-forming approach. This process allows the sealing of channels that are located on the surface of complex multiplanar topographies, as the thermoplastic aligns with the surface-shape (the macrostructure) of the substrate, while the microchannels remain mostly free of thermoplastic as their small channel size resists thermoplastic inflow. This new process was analyzed for its capability to consistently close different substrate geometries, which showed reliable sealing of angles >90°. Furthermore, the thermoplastic intrusion into channels of different widths was quantified, showing a linear effect of channel width and percentage of thermoplastic intrusion; ranging from 43.76% for large channels with 2 mm width to only 5.33% for channels with 500 µm channel width. The challenging sealing of substrate ‘valleys’, which are created when two large protrusions are adjacent to each other, was investigated and the correlation between protrusion distance and height is shown. Lastly, we present three application examples: a serpentine mixer with channels spun around a cuboid, increasing the usable surface area; a cuvette-inspired flow cell for a 2-MXP biosensor based on molecular imprinted polymers, fitting inside a standard UV/Vis-Spectrophotometer; and an adapter system that can be manufactured by one-sided injection molding and is self-sealed before usage. These examples demonstrate how this novel technology can be used to easily adapt microfluidic circuits for application in biosensor platforms.
      Citation: Biosensors
      PubDate: 2021-10-15
      DOI: 10.3390/bios11100395
      Issue No: Vol. 11, No. 10 (2021)
  • Biosensors, Vol. 11, Pages 396: Malignancies and Biosensors: A Focus on
           Oral Cancer Detection through Salivary Biomarkers

    • Authors: Goldoni, Scolaro, Boccalari, Dolci, Scarano, Inchingolo, Ravazzani, Muti, Tartaglia
      First page: 396
      Abstract: Oral cancer is among the deadliest types of malignancy due to the late stage at which it is usually diagnosed, leaving the patient with an average five-year survival rate of less than 50%. The booming field of biosensing and point of care diagnostics can, in this regard, play a major role in the early detection of oral cancer. Saliva is gaining interest as an alternative biofluid for non-invasive diagnostics, and many salivary biomarkers of oral cancer have been proposed. While these findings are promising for the application of salivaomics tools in routine practice, studies on larger cohorts are still needed for clinical validation. This review aims to summarize the most recent development in the field of biosensing related to the detection of salivary biomarkers commonly associated with oral cancer. An introduction to oral cancer diagnosis, prognosis and treatment is given to define the clinical problem clearly, then saliva as an alternative biofluid is presented, along with its advantages, disadvantages, and collection procedures. Finally, a brief paragraph on the most promising salivary biomarkers introduces the sensing technologies commonly exploited to detect oral cancer markers in saliva. Hence this review provides a comprehensive overview of both the clinical and technological advantages and challenges associated with oral cancer detection through salivary biomarkers.
      Citation: Biosensors
      PubDate: 2021-10-15
      DOI: 10.3390/bios11100396
      Issue No: Vol. 11, No. 10 (2021)
  • Biosensors, Vol. 11, Pages 397: Computer Simulation of a Surface Charge
           Nanobiosensor with Internal Signal Integration

    • Authors: Dmitry Dyubo, Oleg Yu. Tsybin
      First page: 397
      Abstract: The ionized states of molecular analytes located on solid surfaces require profound investigation and better understanding for applications in the basic sciences in general, and in the design of nanobiosensors, in particular. Such ionized states are induced by the interactions of molecules between them in the analyzed substance and with the target surface. Here, computer simulations using COMSOL Multiphysics software show the effect of surface charge density and distribution on the output generation in a dynamic PIN diode with gate control. This device, having built-in potential barriers, has a unique internal integration of output signal generation. The identified interactions showed the possibility of a new design for implementing a nanobiosensor based on a dynamic PIN diode in a mode with surface charge control.
      Citation: Biosensors
      PubDate: 2021-10-16
      DOI: 10.3390/bios11100397
      Issue No: Vol. 11, No. 10 (2021)
  • Biosensors, Vol. 11, Pages 398: Electrical Impedance of Upper Limb Enables
           Robust Wearable Identity Recognition against Variation in Finger Placement
           and Environmental Factors

    • Authors: Hyung Wook Noh, Joo Yong Sim, Chang-Geun Ahn, Yunseo Ku
      First page: 398
      Abstract: Most biometric authentication technologies commercialized in various fields mainly rely on acquired images of structural information, such as fingerprints, irises, and faces. However, bio-recognition techniques using these existing physical features are always at risk of template forgery threats, such as fake fingerprints. Due to the risk of theft and duplication, studies have recently been attempted using the internal structure and biological characteristics of the human body, including our previous works on the ratiometric biological impedance feature. However, one may still question its accuracy in real-life use due to the artifacts from sensing position variability and electrode–skin interfacing noise. Moreover, since the finger possesses more severe thermoregulatory vasomotion and large variability in the tissue properties than the core of the body, it is necessary to mitigate the harsh changes occurring at the peripheral extremities of the human body. To address these challenges, we propose a biometric authentication method through robust feature extraction from the upper-limb impedance acquired based on a portable wearable device. In this work, we show that the upper limb impedance features obtained from wearable devices are robust against undesirable factors such as finger placement deviations and day-to-day physiological changes, along with ratiometric impedance features. Overall, our upper-limb impedance-based analysis in a dataset of 1627 measurement from 33 subjects lowered the classification error rate from 22.38% to 4.3% (by a factor of 5), and further down to 2.4% (by a factor of 9) when combined with the ratiometric features.
      Citation: Biosensors
      PubDate: 2021-10-16
      DOI: 10.3390/bios11100398
      Issue No: Vol. 11, No. 10 (2021)
  • Biosensors, Vol. 11, Pages 399: Investigating the Regulation of Neural
           Differentiation and Injury in PC12 Cells Using Microstructure Topographic

    • Authors: Sun, Li, Gong, Hu, Ge, Wu, Gao
      First page: 399
      Abstract: In this study, we designed and manufactured a series of different microstructure topographical cues for inducing neuronal differentiation of cells in vitro, with different topography, sizes, and structural complexities. We cultured PC12 cells in these microstructure cues and then induced neural differentiation using nerve growth factor (NGF). The pheochromocytoma cell line PC12 is a validated neuronal cell model that is widely used to study neuronal differentiation. Relevant markers of neural differentiation and cytoskeletal F-actin were characterized. Cellular immunofluorescence detection and axon length analysis showed that the differentiation of PC12 cells was significantly different under different isotropic and anisotropic topographic cues. The expression differences of the growth cone marker growth-associated protein 43 (GAP-43) and sympathetic nerve marker tyrosine hydroxylase (TH) genes were also studied in different topographic cues. Our results revealed that the physical environment has an important influence on the differentiation of neuronal cells, and 3D constraints could be used to guide axon extension. In addition, the neurotoxin 6-hydroxydopamine (6-OHDA) was used to detect the differentiation and injury of PC12 cells under different topographic cues. Finally, we discussed the feasibility of combining the topographic cues and the microfluidic chip for neural differentiation research.
      Citation: Biosensors
      PubDate: 2021-10-16
      DOI: 10.3390/bios11100399
      Issue No: Vol. 11, No. 10 (2021)
  • Biosensors, Vol. 11, Pages 400: Self-Referenced Refractive Index
           Biosensing with Graphene Fano Resonance Modes

    • Authors: Xiaoyu Dai, Banxian Ruan, Yuanjiang Xiang
      First page: 400
      Abstract: A hybrid structure composed of periodic monolayer graphene nanoribbons and a dielectric multilayer structure was designed to generate a Fano resonance (FR). The strong interaction between the surface plasmon resonance of graphene and the dielectric waveguide mode results in the FR. The finite element method is utilized to investigate the behaviors of the FR, and it matches well with the theoretical calculations using rigorous coupled wave theory. The results demonstrate that the profile of the FR can be passively tuned by the period of the graphene nanoribbons and actively tuned by the Fermi level of the graphene. The decoupled nature of the FR gives it potential applications as a self-calibrated refractive index biosensor, and the sensitivity can reach as high as 4.615 μm/RIU. Thus, this work provides a new idea for an excellent self-referencing refractive index biosensor.
      Citation: Biosensors
      PubDate: 2021-10-17
      DOI: 10.3390/bios11100400
      Issue No: Vol. 11, No. 10 (2021)
  • Biosensors, Vol. 11, Pages 401: Dielectrophoretic and Electrical Impedance
           Differentiation of Cancerous Cells Based on Biophysical Phenotype

    • Authors: Ina Turcan, Iuliana Caras, Thomas Gabriel Schreiner, Catalin Tucureanu, Aurora Salageanu, Valentin Vasile, Marioara Avram, Bianca Tincu, Marius Andrei Olariu
      First page: 401
      Abstract: Here, we reported a study on the detection and electrical characterization of both cancer cell line and primary tumor cells. Dielectrophoresis (DEP) and electrical impedance spectroscopy (EIS) were jointly employed to enable the rapid and label-free differentiation of various cancer cells from normal ones. The primary tumor cells that were collected from two colorectal cancer patients and cancer cell lines (SW-403, Jurkat, and THP-1), and healthy peripheral blood mononuclear cells (PBMCs) were trapped first at the level of interdigitated microelectrodes with the help of dielectrophoresis. Correlation of the cells dielectric characteristics that was obtained via electrical impedance spectroscopy (EIS) allowed evident differentiation of the various types of cell. The differentiations were assigned to a “dielectric phenotype” based on their crossover frequencies. Finally, Randles equivalent circuit model was employed for highlighting the differences with regard to a series group of charge transport resistance and constant phase element for cancerous and normal cells.
      Citation: Biosensors
      PubDate: 2021-10-17
      DOI: 10.3390/bios11100401
      Issue No: Vol. 11, No. 10 (2021)
  • Biosensors, Vol. 11, Pages 402: Enhanced Plasmonic Biosensor Utilizing
           Paired Antibody and Label-Free Fe3O4 Nanoparticles for Highly Sensitive
           and Selective Detection of Parkinson’s α-Synuclein in Serum

    • Authors: Samuel Husin Surya Mandala, Tai-Jan Liu, Chiung-Mei Chen, Kuo-Kang Liu, Mochamad Januar, Ying-Feng Chang, Chao-Sung Lai, Kuo-Hsuan Chang, Kou-Chen Liu
      First page: 402
      Abstract: Parkinson’s disease (PD) is an acute and progressive neurodegenerative disorder, and diagnosis of the disease at its earliest stage is of paramount importance to improve the life expectancy of patients. α-Synuclein (α-syn) is a potential biomarker for the early diagnosis of PD, and there is a great need to develop a biosensing platform that precisely detects α-syn in human body fluids. Herein, we developed a surface plasmon resonance (SPR) biosensor based on the label-free iron oxide nanoparticles (Fe3O4 NPs) and paired antibody for the highly sensitive and selective detection of α-syn in serum samples. The sensitivity of the SPR platform is enhanced significantly by directly depositing Fe3O4 NPs on the Au surface at a high density to increase the decay length of the evanescent field on the Au film. Moreover, the utilization of rabbit-type monoclonal antibody (α-syn-RmAb) immobilized on Au films allows the SPR platform to have a high affinity-selectivity binding performance compared to mouse-type monoclonal antibodies as a common bioreceptor for capturing α-syn molecules. As a result, the current platform has a detection limit of 5.6 fg/mL, which is 20,000-fold lower than that of commercial ELISA. The improved sensor chip can also be easily regenerated to repeat the α-syn measurement with the same sensitivity. Furthermore, the SPR sensor was applied to the direct analysis of α-syn in serum samples. By using a format of paired α-syn-RmAb, the SPR sensor provides a recovery rate in the range from 94.5% to 104.3% to detect the α-syn in diluted serum samples precisely. This work demonstrates a highly sensitive and selective quantification approach to detect α-syn in human biofluids and paves the way for the future development in the early diagnosis of PD.
      Citation: Biosensors
      PubDate: 2021-10-18
      DOI: 10.3390/bios11100402
      Issue No: Vol. 11, No. 10 (2021)
  • Biosensors, Vol. 11, Pages 403: Biometric Identification of Taxodium spp.
           and Their Hybrid Progenies by Electrochemical Fingerprints

    • Authors: Yuhong Zheng, Da Wang, Xiaolong Li, Ziyang Wang, Qingwei Zhou, Li Fu, Yunlong Yin, David Creech
      First page: 403
      Abstract: The use of electrochemical fingerprints for plant identification is an emerging application in biosensors. In this work, Taxodium ascendens, T. distichum, T. mucronatum, and 18 of their hybrid progenies were collected for this purpose. This is the first attempt to use electrochemical fingerprinting for the identification of plant hybrid progeny. Electrochemical fingerprinting in the leaves of Taxodium spp. was recorded under two conditions. The results showed that the electrochemical fingerprints of each species and progeny possessed very suitable reproducibility. These electrochemical fingerprints represent the electrochemical behavior of electrochemically active substances in leaf tissues under specific conditions. Since these species and progenies are very closely related to each other, it is challenging to identify them directly using a particular electrochemical fingerprinting. Therefore, electrochemical fingerprints measured under different conditions were used to perform pattern recognition. We can identify different species and progenies by locating the features in different pattern maps. We also performed a phylogenetic study with data from electrochemical fingerprinting. The results proved that the electrochemical classification results and the relationship between them are closely related.
      Citation: Biosensors
      PubDate: 2021-10-18
      DOI: 10.3390/bios11100403
      Issue No: Vol. 11, No. 10 (2021)
  • Biosensors, Vol. 11, Pages 404: Chronic Study on Brainwave Authentication
           in a Real-Life Setting: An LSTM-Based Bagging Approach

    • Authors: Liuyin Yang, Arno Libert, Marc M. Van Van Hulle
      First page: 404
      Abstract: With the advent of the digital age, concern about how to secure authorized access to sensitive data is increasing. Besides traditional authentication methods, there is an interest in biometric traits such as fingerprints, the iris, facial characteristics, and, recently, brainwaves, primarily based on electroencephalography (EEG). Current work on EEG-based authentication focuses on acute recordings in laboratory settings using high-end equipment, typically equipped with 64 channels and operating at a high sampling rate. In this work, we validated the feasibility of EEG-based authentication in a real-world, out-of-laboratory setting using a commercial dry-electrode EEG headset and chronic recordings on a population of 15 healthy people. We used an LSTM-based network with bootstrap aggregating (bagging) to decode our recordings in response to a multitask scheme consisting of performed and imagined motor tasks, and showed that it improved the performance of the standard LSTM approach. We achieved an authentication accuracy, false acceptance rate (FAR), and false rejection rate (FRR) of 92.6%, 2.5%, and 5.0% for the performed motor task; 92.5%, 2.6%, and 4.9% for the imagined motor task; and 93.0%, 1.9%, and 5.1% for the combined tasks, respectively. We recommend the proposed method for time- and data-limited scenarios.
      Citation: Biosensors
      PubDate: 2021-10-18
      DOI: 10.3390/bios11100404
      Issue No: Vol. 11, No. 10 (2021)
  • Biosensors, Vol. 11, Pages 405: A Review of Capillary Pressure Control
           Valves in Microfluidics

    • Authors: Shaoxi Wang, Xiafeng Zhang, Cong Ma, Sheng Yan, David Inglis, Shilun Feng
      First page: 405
      Abstract: Microfluidics offer microenvironments for reagent delivery, handling, mixing, reaction, and detection, but often demand the affiliated equipment for liquid control for these functions. As a helpful tool, the capillary pressure control valve (CPCV) has become popular to avoid using affiliated equipment. Liquid can be handled in a controlled manner by using the bubble pressure effects. In this paper, we analyze and categorize the CPCVs via three determining parameters: surface tension, contact angle, and microchannel shape. Finally, a few application scenarios and impacts of CPCV are listed, which includes how CPVC simplify automation of microfluidic networks, work with other driving modes; make extensive use of microfluidics by open channel, and sampling and delivery with controlled manners. The authors hope this review will help the development and use of the CPCV in microfluidic fields in both research and industry.
      Citation: Biosensors
      PubDate: 2021-10-19
      DOI: 10.3390/bios11100405
      Issue No: Vol. 11, No. 10 (2021)
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