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 BioChip JournalJournal Prestige (SJR): 0.412 Citation Impact (citeScore): 1Number of Followers: 0      Hybrid journal (It can contain Open Access articles) ISSN (Print) 1976-0280 - ISSN (Online) 2092-7843 Published by Springer-Verlag  [2626 journals]
• Orientation Control of the Molecular Recognition Layer for Improved
Sensitivity: a Review
• Abstract: Abstract Biosensors have been used in various fields of biological analysis, such as for quantification of analytes and the study of molecule-molecule interactions. Orientation control of the molecular recognition layer is one of the easiest and most effective ways to improve the sensitivity of biosensors. In this review, the orientation control of molecular recognition molecules, such as antibodies, aptamers, and enzymes, is discussed. The review compares the improvement in the sensitivity and binding activity of biosensors achieved through orientation control with that achieved through random orientation. Immobilization methods of antibodies for orientation control are first discussed, with a focus on immobilization of the fragment crystallizable region of antibodies, which is the most studied technique. Covalent and non-covalent immobilization strategies are also discussed, and their effect on the sensitivity of biosensors is summarized. Lastly, the orientation control of other molecular recognition molecules (aptamers and enzymes) was discussed and the applications of molecular recognition molecules as biosensors are discussed.
PubDate: 2019-03-01

• Recent Developments of Chip-based Phenotypic Antibiotic Susceptibility
Testing
• Abstract: Abstract Antibiotic susceptibility testing (AST), the screening of effective types and dosages of antibiotics, has become significantly important in the antimicrobial- resistance era over the last few decades. In order to overcome the limitations of conventional AST methods, several recent studies have developed AST platforms which exhibit the advantages of microfluidics. They demonstrated the performance of the platforms by determining effective antimicrobials for bacterial strains and their minimum inhibitory concentrations within hours. In this review, we cover recent developments of on-chip approaches for measurements of bacterial growth as well as for dilutions of antibiotic concentrations. We also discuss Point-of-Care AST devices that employ inexpensive materials and simple working principles to operate screenings near the site of care, which can potentially bring current laboratory- limited assays to clinical standards. All thing considered, emerging microfluidic AST devices have the potential to be decent alternatives to commonplace macro-scale AST methods.
PubDate: 2019-03-01

• A Minireview on Inertial Microfluidics Fundamentals: Inertial Particle
Focusing and Secondary Flow
• Abstract: Abstract In 1961, Segre and Silberberg first reported the tubular pinch effect and numerous theoretical studies were subsequently published to explain the inertial particle migration phenomenon. Presently, as fluid mechanics meets micro- and nanotechnology, theoretical studies on intrinsic particle migration and flow phenomena associated with inertia are being experimentally tested and validated. This collective study on the fluid-particle-structure phenomena in microchannels involving fluid inertia is called, “inertial microfluidics”. Beyond theoretical studies, now inertial microfluidics has been gaining much attention from various research fields ranging from biomedicine to industry. Despite the positive contributions, there is still a lack of clear understanding of intrinsic inertial effects in microchannels. Therefore, this minireview introduces the mechanisms and underlying physics in inertial microfluidic systems with specific focuses on inertial particle migration and secondary flow, and outlines the opportunities provided by inertial microfluidics, along with an outlook on the field.
PubDate: 2019-03-01

• Functional Microparticle R&D for IVD and Cell Therapeutic Technology:
Large-Scale Commercialized Products
• Abstract: Abstract The global R&D of functional materials have become more prominent and are expected to increase with a high growth rate through 2022. High demand due to current and emerging applications, superior structural properties, and the development of advanced fabrication methods is accelerating and driving the functional materials market. The functional materials are segmented based on application into construction composites, medical technology, cosmetics & personal care, oil & gas, automotive, life science & technology, and other categories. In particular, the use of microparticles as functional materials is continually increasing in the field of medicine and the healthcare industry. Nanotechnology for diagnosis, monitoring, drug delivery, treatment and control of biological systems is the leading application in the microparticle market, causing the growing demand for new types of microparticles. Furthermore, growing medical and healthcare industries will increase the worldwide demand for new functional microparticles in biomedical technology applications. This review paper will discuss the main aspects of state-of-the-art functional microparticles research, while demonstrating the broad variety of applications in the fields of diagnostics and therapy, especially in large-scale commercialized products related to magnetic microparticles in IVD and to microcarriers in cell therapeutics.
PubDate: 2019-03-01

• Nanomaterial-modified Hybrid Platforms for Precise Electrochemical
Detection of Dopamine
• Abstract: Abstract Dopamine belongs to the class of catecholamine neurotransmitters which have vital roles in the human central nervous system. Due to its importance in signal transmission in the nervous system, the abnormal release of dopamine is critical for the development of a number of neurological diseases/disorders, including Parkinson’s diseases, attention deficit hyperactivity disorder, and even drug addiction. Hence, there is an utmost need to develop platforms for the quantitative detection of dopamine in the human body in a rapid, sensitive, and label-free manner. A variety of nanomaterials have been explored and integrated into dopamine sensing platforms; in particular, electrochemical sensors can enhance both the sensitivity and selectivity toward dopamine, with promising results. The aim of this review is to summarize recent research on nanomaterial-modified dopamine electrochemical sensor platforms, particularly those that use nanoparticle-, graphene composite-, and transition metal dichalcogenide-modified electrodes. The information presented in this review might motivate the discovery or extension of nanomaterials with beneficial properties for the development of biosensors to detect various neurotransmitters including dopamine.
PubDate: 2019-03-01

• Microfluidic Fabrication of Encoded Hydrogel Microparticles for
Application in Multiplex Immunoassay
• Abstract: Abstract Recent interests in comprehensive protein surveys and protein biomarker studies have led to an increased demand for simultaneous measurement of multiple proteins in a single sample. Among various multiplex techniques, bead-based immunoassays, which use encoded particles attached with capture probes, have demonstrated distinct advantages of fluid-phase kinetics, high precision, and flexible target selection. In particular, encoded hydrogel particles composed of porous, hydrophilic, three-dimensional polymers have received positive attention because they enhance the binding kinetics of proteins, reduce protein denaturation, and increase the loading density of capture probes. Microfluidic techniques have been extensively used to fabricate the encoded hydrogel particles for multiplex immunoassays, enabling mass-production of highly monodisperse particles with complex morphologies in mild synthesis conditions. In this paper, we review microfluidic techniques available for the synthesis of encoded hydrogel particles and the important design parameters that determine the particles’ immunoassay performance. We also discuss currently reported multiplex immunoassay platforms that are based on encoded hydrogel particles.
PubDate: 2019-03-01

• Consideration of the Mechanical Properties of Hydrogels for Brain Tissue
Engineering and Brain-on-a-chip
• Abstract: Abstract To present a more physiologically relevant microenvironment for cells, hydrogel-based threedimensional culture platforms have been widely adopted. As noted by multiple pioneering reports, the neural cells are sensitive with the change of mechanical properties of the microenvironment. Therefore, in the context of brain tissue engineering and brain-on-a-chip, there is a need to consider the brain-tissue-specific mechanical properties of hydrogels. In this review, we overview the influence the mechanical properties of hydrogel on the behavior of brain tissue cells. For this purpose, in addition to the stiffness, the viscoelasticity and degradability of hydrogels are considered to be mechanical cues, and we summarize how those mechanical properties can affect cell behavior, such as viability, proliferation, differentiation, and spreading. Consideration of the brain tissue-specific mechanical microenvironment may guide the design of 3D cell culture platforms for brain tissue engineering and brain- on-a-chip.
PubDate: 2019-03-01

• Current Immunotherapy Approaches for Malignant Melanoma
• Abstract: Abstract Melanoma is one of the skin cancers caused by various causes. Since the patients often do not feel pain that melanoma is mistaken for benign skin diseases. However, melanoma has the risk of multiplying rapidly and spreading easily through metastasis. It is important to treat it through chemo- or radiotherapy after surgical resection. Immunotherapy is a relatively new cancer treatment, which has shown longer survival rates than conventional cancer treatments in some cases. Cytokines or immune checkpoint blockers are the common immunotherapy strategies for melanoma. However, there are still melanoma patients who have not been benefited by immunotherapies. To overcome the limitations of current immunotherapy approaches, studies are underway to find new immunomodulators and various combinational immunotherapies. In this review, the existing treatments for melanoma are introduced and efforts to find optimal immunotherapy conditions for melanoma treatment have been summarized. Attempts to study the immunotherapy of melanoma with biochip technologies that simulate the body's microenvironment have also been summarized.
PubDate: 2019-03-01

• Fabrication Strategies of 3D Plasmonic Structures for SERS
• Abstract: Abstract Recent advancements in fabricating plasmonic nanostructures have markedly lessened the limitations of conventional optical sensors, in terms of sensitivity, tunability, photostability, and in vivo applicability. The sophisticated design of diverse metallic nanoparticles and formation of two- or threedimensional (3D) assemblies have enhanced the performance of plasmon-based sensing and imaging applications. Especially, the creation of highly localized electromagnetic fields (i.e., hot-spots) in the multidimensional plasmonic structures has enabled ultrasensitive detection of biomolecules at low concentrations via surface-enhanced Raman scattering (SERS). In this review, we summarize representative approaches to obtain 3D plasmonic structures categorized by the fabrication strategies. These include colloidal synthesis of plasmonic nanoparticles with multiple hot-spots and post-integration of the nanoparticles into 3D templates, and self-integration in the course of constructing 3D structures. We also describe notable structural benefits in sensing applications, especially for SERS, that take advantages of such 3D plasmonic nanostructures.
PubDate: 2019-03-01

• In Vitro Reconstruction of Brain Tumor Microenvironment
• Abstract: Abstract The cancer cells in brain tumors interact with their microenvironment, which includes stromal cells, the extracellular matrix (ECM), and the physical properties of tissues. The reciprocal interaction between cancer cells and the surrounding microenvironment regulates the biological behavior of cancer cells. To improve our understanding of the progression of brain tumors, it is useful to construct physiologically relevant brain tumor models. Consequently, versatile in vitro tumor models ranging from simplistic two-dimensional (2D) cultures to three-dimensional (3D) cultures have been developed to mimic the microenvironments of the brain. This review covers the recent progress in the in vitro reconstruction of brain tumor microenvironments.
PubDate: 2019-03-01

• Detection of Bacillus Cereus Using Bioluminescence Assay with Cell
Wall-binding Domain Conjugated Magnetic Nanoparticles
• Abstract: Abstract Bacillus cereus can cause blood infections (i.e., sepsis). Its early detection is very important for treating patients. However, an antibody with high binding affinity to B. cereus is not currently available. Bacteriophage cell wall-binding domain (CBD) has strong and specific binding affinity to B. cereus. Here, we report the improvement in the sensitivity of an ATP bioluminescence assay for B. cereus detection using CBD-conjugated magnetic nanoparticles (CBDMNPs). The assay was able to detect as few as 10 colony forming units (CFU) per mL and 103 CFU per mL in buffer and blood. CBD-MNPs did not show any cross-reactivity with other microorganisms. These results demonstrate the feasibility of the ATP assay for the detection of B. cereus.
PubDate: 2018-12-01

• An Integrated Approach of CNT Front-end Amplifier towards Spikes
Monitoring for Neuro-prosthetic Diagnosis
• Abstract: Abstract The future neuro-prosthetic devices would be required spikes data monitoring through sub-nanoscale transistors that enables to neuroscientists and clinicals for scalable, wireless and implantable applications. This research investigates the spikes monitoring through integrated CNT front-end amplifier for neuro-prosthetic diagnosis. The proposed carbon nanotube-based architecture consists of front-end amplifier (FEA), integrate fire neuron and pseudo resistor technique that observed high electrical performance through neural activity. A pseudo resistor technique ensures large input impedance for integrated FEA by compensating the input leakage current. While carbon nanotube based FEA provides low-voltage operation with directly impacts on the power consumption and also give detector size that demonstrates fidelity of the neural signals. The observed neural activity shows amplitude of spiking in terms of action potential up to 80 μV while local field potentials up to 40 mV by using proposed architecture. This fully integrated architecture is implemented in Analog cadence virtuoso using design kit of CNT process. The fabricated chip consumes less power consumption of 2 μW under the supply voltage of 0.7 V. The experimental and simulated results of the integrated FEA achieves 60 GΩ of input impedance and input referred noise of 8.5 nv/ $$\rm\sqrt{Hz}$$ over the wide bandwidth. Moreover, measured gain of the amplifier achieves 75 dB midband from range of 1 KHz to 35 KHz. The proposed research provides refreshing neural recording data through nanotube integrated circuit and which could be beneficial for the next generation neuroscientists.
PubDate: 2018-12-01

• Fabrication of Multi-layered Macroscopic Hydrogel Scaffold Composed of
Multiple Components by Precise Control of UV Energy
• Abstract: Abstract Hydrogel scaffolds composed of multiple components are promising platform in tissue engineering as a transplantation materials or artificial organs. Here, we present a new fabrication method for implementing multi-layered macroscopic hydrogel scaffold composed of multiple components by controlling height of hydrogel layer through precise control of ultraviolet (UV) energy density. Through the repetition of the photolithography process with energy control, we can form several layers of hydrogel with different height. We characterized UV energy-dependent profiles with single-layered PEGDA posts photocrosslinked by the modular methodology and examined the optical effect on the fabrication of multi-layered, macroscopic hydrogel structure. Finally, we successfully demonstrated the potential applicability of our approach by fabricating various macroscopic hydrogel constructs composed of multiple hydrogel layers.
PubDate: 2018-12-01

• Organic-Inorganic Hybrid Nanoflowers as Potent Materials for Biosensing
and Biocatalytic Applications
• Abstract: Abstract Flower-shaped organic-inorganic hybrid nanostructures, termed nanoflowers, have received considerable recent attention as they possess greatly enhanced activity, stability, durability, and even selectivity of entrapped organic biomolecules, which are much better than those from the conventional methods. They can be synthesized simply via co-incubation of organic and inorganic components in aqueous buffer at room temperature and yield hierarchical nanostructures with large surface-to-volume ratios, allowing for low-cost production by easy scale-up, as well as the high loading capacity of biomolecules without severe mass transfer limitations. Since a pioneering study reported on hybrid nanoflowers prepared with protein and copper sulfate, many other organic and inorganic components, which endow nanoflowers with diverse functionalities, have been employed. Thanks to these features, they have been applied in a diverse range of areas, including biosensors and biocatalysis. To highlight the progress of research on organic-inorganic hybrid nanoflowers, this review discusses their synthetic methods and mechanisms, structural and biological characteristics, as well as recent representative applications. Current challenges and future directions toward the design and development of multi-functional nanoflowers for their widespread utilization in biotechnology are also discussed.
PubDate: 2018-12-01

• Genomic Susceptibility Analysis for Atopy Disease Using Cord Blood DNA in
a Small Cohort
• Abstract: Abstract Atopic disease is caused by a complex combination of environmental factors and genetic factors, and studies on influence of exposure to various environmental factors on atopic diseases are continuously reported. However, the exact cause of atopic dermatitis is not yet known. Our study was conducted to analyse the association of SNPs with the development of atopic disease in a small cohort. Samples were collected from the Mothers’ and Children’s Environmental Health (MOCEH) study and 192 cord blood DNA samples were used to identify incidence of atopy due to influence of exposure to environmental factors. Genetic elements were analysed using a precision medicine research (PMR) array designed with various SNPs for personalized medicine. Case-control analysis of atopy disease revealed 253 significant variants (p<0.0001) and SNPs on five genes (CARD11, ZNF365, KIF3A, DMRTA1, and SFMBT1) were variants identified in previous atopic studies. These results are important to confirm the genetic mutation that may lead to the onset of foetal atopy due to maternal exposure to harmful environmental factors. Our results also suggest that a small-scale genome-wide association analysis is beneficial to confirm specific variants as direct factors in the development of atopy.
PubDate: 2018-12-01

• Inertial Microfluidics-Based Cell Sorting
• Abstract: Abstract Inertial microfluidics has attracted significant attention in recent years due to its superior benefits of high throughput, precise control, simplicity, and low cost. Many inertial microfluidic applications have been demonstrated for physiological sample processing, clinical diagnostics, and environmental monitoring and cleanup. In this review, we discuss the fundamental mechanisms and principles of inertial migration and Dean flow, which are the basis of inertial microfluidics, and provide basic scaling laws for designing the inertial microfluidic devices. This will allow end-users with diverse backgrounds to more easily take advantage of the inertial microfluidic technologies in a wide range of applications. A variety of recent applications are also classified according to the structure of the microchannel: straight channels and curved channels. Finally, several future perspectives of employing fluid inertia in microfluidic-based cell sorting are discussed. Inertial microfluidics is still expected to be promising in the near future with more novel designs using various shapes of cross section, sheath flows with different viscosities, or technologies that target micron and submicron bioparticles.
PubDate: 2018-12-01

• Development of the Microfluidic Device to Regulate Shear Stress Gradients
• Abstract: Abstract Shear stress occurs in flowing liquids, especially at the interface of a flowing liquid and a stationary solid phase. Thus, it occurs inside the artery system of the human body, where it is responsible for a number of biological functions. The shear stress level generally remains less than 70 dyne/cm2 in the whole circulatory system, but in the stenotic arteries, which are constricted by 95%, a shear stress greater than 1,000 dyne/cm2 can be reached. Methods of researching the effects of shear stress on cells are of large interest to understand these processes. Here, we show the development of a microfluidic device for generating shear stress gradients. The performance of the shear stress gradient generator was theoretically simulated prior to experiments. Through simple manipulations of the liquid flow, the shape and magnitude of the shear stress gradients can be manipulated. Our microfluidic device consisted of five portions divided by arrays of micropillars. The generated shear stress gradient has five distinct levels at 8.38, 6.55, 4.42, 2.97, and 2.24 dyne/cm2. Thereafter, an application of the microfluidic device was demonstrated testing the effect of shear stress on human umbilical vein endothelial cells.
PubDate: 2018-12-01

• An Ultrasensitive FRET-based DNA Sensor via the Accumulated QD System
• Abstract: Abstract Förster resonance energy transfer (FRET) is extremely sensitive to the separation distance between the donor and the acceptor which is ideal for probing such biological phenomena. Also, FRET-based probes have been developing for detecting an unamplified, low-abundance of target DNA. Here we describe the development of FRET based DNA sensor based on an accumulated QD system for detecting KRAS G12D mutation which is the most common mutation in cancer. The accumulated QD system consists of the polystyrene beads which surface is modified with carboxyl modified QDs. The QDs are sandwich-hybridized with DNA of a capture probe, a reporter probe with Texas-red, and a target DNA by EDC-NHS coupling. Because the carboxyl modified QDs are located closely to each other in the accumulated QDs, these neighboring QDs are enough to transfer the energy to the acceptor dyes. Therefore the FRET factor in the bead system is enhancing by the additional increase of 29.2% as compared to that in a single QD system. These results suggest that the accumulated nanobead probe with conjugated QDs can be used as ultrasensitive DNA nanosensors detecting the mutation in the various cancers.
PubDate: 2018-12-01

• Clinical Evaluation of a Low-pain Long Microneedle for Subcutaneous
Insulin Injection
• Abstract: Abstract Microneedles (MNs) are being developed to overcome the limitations of the conventional hypodermic needle, e.g. the injection pain. In this study, we conducted an analysis of clinical pain and bleeding at the site of MN insertion and evaluated the insulin pharmacodynamic profile compared with parameters obtained with a conventional pen needle. MN insertion into the skin of 25 healthy adults or 15 patients with type 2 diabetes (T2D) revealed significantly less pain relative to a conventional hypodermic pen needle, thus reducing pain scores from 2.1±1.9 to 1.3±1.4 (mean±standard deviation [SD]). Besides, no bleeding was observed when the MN was used. In the insulin pharmacodynamic assay, no significant differences were observed in the blood glucose-lowering effect between the pen needle and MN. Based on these results, the MN is expected to be a good substitute for conventional hypodermic pen needles and improve the quality of life of patients by significantly reducing the pain associated with insulin treatment.
PubDate: 2018-12-01

• Development of Colorimetric Paper Sensor for Pesticide Detection Using
Competitive-inhibiting Reaction
• Abstract: Abstract Contamination by pesticides is an ever-increasing problem associated with fields of environmental management and healthcare. Accordingly, appropriate treatments are in demand. Pesticide detection methods have been researched extensively, aimed at making the detection convenient, fast, cost-effective, and easy to use. Among the various detecting strategies, paper-based assay is potent for real-time pesticide sensing due to its unique advantages including disposability, light weight, and low cost. In this study, a paper-based sensor for chlorpyrifos, an organophosphate pesticide, has been developed by layering three sheets of patterned plates. In colorimetric quantification of pesticides, the blue color produced by the interaction between acetylcholinesterase and indoxyl acetate is inhibited by the pesticide molecules present in the sample solutions. With the optimized paper-based sensor, the pesticide is sensitively detected (limit of detection=8.60 ppm) within 5 min. Furthermore, the shelf life of the device is enhanced to 14 days after from the fabrication, by treating trehalose solution onto the deposited reagents. We expect the paper-based device to be utilized as a first-screening analytic device for water quality monitoring and food analysis.
PubDate: 2018-12-01

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