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Showing papers on "Biochip published in 2021"


Journal ArticleDOI
TL;DR: By systematically inserting the protospacer-adjacent-motif (PAM) sequence, the universality of the CRISPR/Cas12a based SNP detection was improved and the sensitivity and specificity was improved.
Abstract: Single nucleotide polymorphisms (SNPs) are associated with many human diseases, so accurate and efficient SNP detection is of great significance for early diagnosis and clinical prognosis. This report proposes a universal and high-fidelity genotyping method in microfluidic point-of-care equipment based on the clustered regularly interspaced short palindromic repeat (CRISPR) system. Briefly, by systematically inserting the protospacer-adjacent-motif (PAM) sequence, we improved the universality of the CRISPR/Cas12a based SNP detection; by removing the complementary ssDNA and introducing an additional nucleotide mismatch, we improved the sensitivity and specificity. We preloaded the CRISPR/Cas12a reagents into the point-of-care biochip for automating the process, increasing the stability and long-term storage. This biochip enables us to rapidly and conveniently detect the genotypes within 20 min. In a practical application, the CRISPR/Cas12a biochip successfully distinguished three genotypes (homozygous wild type; the homozygous mutant type; and the heterozygous mutant type) of the CYP1A1*2 (A4889G, rs1048943), CYP2C19*2 (G681A, rs4244285), CYP2C9*3 (A1075C, rs1057910), and CYP2C19*3 (G636A, rs4986893) genes related to multiple cancers from 17 clinical blood samples. This CRISPR/Cas12a-based SNP genotyping method, being universal, accurate, and sensitive, will have broad applications in molecular diagnostics and clinical research.

51 citations


Journal ArticleDOI
Chu Yujin1, Yakun Gao1, Wei Tang1, Le Qiang1, Yingkuan Han1, Jianwei Gao1, Yu Zhang1, Hong Liu1, Lin Han1 
TL;DR: In this paper, the authors developed an attomolar-level ultrasensitive, rapid, and multiple-miRNA simultaneous detection platform enabled by nanomaterial locally assembled microfluidic biochips.
Abstract: Non-invasive early diagnosis is of great significance in disease pathologic development and subsequent medical treatments, and microRNA (miRNA) detection has attracted critical attention in early cancer screening and diagnosis. High-throughput, sensitive, economic, and fast miRNA sensing platforms are necessary to realize the low-concentration miRNA detection in clinical diagnosis and biological studies. Here, we developed an attomolar-level ultrasensitive, rapid, and multiple-miRNA simultaneous detection platform enabled by nanomaterial locally assembled microfluidic biochips. This platform presents a large linear detection regime of 1 aM-10 nM, an ultralow detection limit of 0.146 aM with no amplification, a short detection time of 35 min with multiplex miRNA sensing capability, and a small sample volume consumption of 2 μL. The detection results of five miRNAs in real samples from breast cancer patients and healthy humans indicate its excellent capacity for practical applications in early cancer diagnosis. The proposed ultrasensitive, rapid, and multiple-miRNA detection microfluidic biochip platform is a universal miRNA detection approach and an important and valuable tool in early cancer screening and diagnosis as well as biological studies.

37 citations


Journal ArticleDOI
01 Jan 2021
TL;DR: Its application in developing cancer preclinical models, detecting cancer biomarkers, screening anti-cancer drugs, exploring tumor heterogeneity and producing nano-drugs is introduced.
Abstract: Microfluidic chip is not a chip in the traditional sense. It is technologies that control fluids at the micro level. As a burgeoning biochip, microfluidic chips integrate multiple disciplines, including physiology, pathology, cell biology, biophysics, engineering mechanics, mechanical design, materials science, and so on. The application of microfluidic chip has shown tremendous promise in the field of cancer therapy in the past three decades. Various types of cell and tissue cultures, including 2D cell culture, 3D cell culture and tissue organoid culture could be performed on microfluidic chips. Patient-derived cancer cells and tissues can be cultured on microfluidic chips in a visible, controllable, and high-throughput manner, which greatly advances the process of personalized medicine. Moreover, the functionality of microfluidic chip is greatly expanding due to the customizable nature. In this review, we introduce its application in developing cancer preclinical models, detecting cancer biomarkers, screening anti-cancer drugs, exploring tumor heterogeneity and producing nano-drugs. We highlight the functions and recent development of microfluidic chip to provide references for advancing cancer diagnosis and treatment.

32 citations


Journal ArticleDOI
TL;DR: In this paper, the authors present a review of the lithographic methods that are capable of large-scale and mass fabrication of biochips and biosensors, including those allowing patterning of large areas from 10 cm2 to m2, maintaining cost effectiveness, high throughput (>100 cm2 h-1), high resolution (from micrometer down to nanometer scale), accuracy, and reproducibility.
Abstract: Since the early 2000s, extensive research has been performed to address numerous challenges in biochip and biosensor fabrication in order to use them for various biomedical applications. These biochips and biosensor devices either integrate biological elements (e.g., DNA, proteins or cells) in the fabrication processes or experience post fabrication of biofunctionalization for different downstream applications, including sensing, diagnostics, drug screening, and therapy. Scalable lithographic techniques that are well established in the semiconductor industry are now being harnessed for large-scale production of such devices, with additional development to meet the demand of precise deposition of various biological elements on device substrates with retained biological activities and precisely specified topography. In this review, the lithographic methods that are capable of large-scale and mass fabrication of biochips and biosensors will be discussed. In particular, those allowing patterning of large areas from 10 cm2 to m2, maintaining cost effectiveness, high throughput (>100 cm2 h-1), high resolution (from micrometer down to nanometer scale), accuracy, and reproducibility. This review will compare various fabrication technologies and comment on their resolution limit and throughput, and how they can be related to the device performance, including sensitivity, detection limit, reproducibility, and robustness.

24 citations


Journal ArticleDOI
Chunhua Wang1, Chao Wang1, Jiaoyan Qiu1, Jianwei Gao1, Hong Liu1, Yu Zhang1, Lin Han1 
TL;DR: In this article, a space-encoding microfluidic biochip was developed for high-throughput, rapid, sensitive, simultaneous quantitative detection of SARS-CoV-2 antigen proteins and IgG/IgM antibodies in serum.
Abstract: COVID-19 is now a severe threat to global health. Facing this pandemic, we developed a space-encoding microfluidic biochip for high-throughput, rapid, sensitive, simultaneous quantitative detection of SARS-CoV-2 antigen proteins and IgG/IgM antibodies in serum. The proposed immunoassay biochip integrates the advantages of graphene oxide quantum dots (GOQDs) and microfluidic chip and is capable of conducting multiple SARS-CoV-2 antigens or IgG/IgM antibodies of 60 serum samples simultaneously with only 2 μL sample volume of each patient. Fluorescence intensity of antigens and IgG antibody detection at emission wavelength of ~680 nm was used to quantify the target concentration at excitation wavelength of 632 nm, and emission wavelength of ~519 nm was used during the detection of IgM antibodies at excitation wavelength of 488 nm. The method developed has a large linear quantification detection regime of 5 orders of magnitude, an ultralow detection limit of ~0.3 pg/mL under optimized conditions, and less than 10-min qualitative detection time. The proposed biosensing platform will not only greatly facilitate the rapid diagnosis of COVID-19 patients, but also provide a valuable screening approach for infected patients, medical therapy, and vaccine recipients.

19 citations


Journal ArticleDOI
TL;DR: A distributed channel-storage architecture (DCSA) to cache fluid samples inside flow channels temporarily and confirm that the execution efficiency of a bioassay can be improved significantly, while the number of valves in the biochip can be reduced accordingly.
Abstract: Flow-based microfluidic biochips have attracted much attention in the EDA community due to their miniaturized size and execution efficiency. Previous research, however, still follows the traditional computing model with a dedicated storage unit, which actually becomes a bottleneck of the performance of biochips. In this article, we propose a distributed channel-storage architecture (DCSA) to cache fluid samples inside flow channels temporarily. Since distributed storage can be accessed more efficiently than a dedicated storage unit and channels can switch between the roles of transportation and storage easily, biochips with this architecture can achieve a higher execution efficiency even with fewer resources. Furthermore, we also address the flow-path planning that enables the manipulation of actual fluid transportation/caching on a chip. The simulation results confirm that the execution efficiency of a bioassay can be improved significantly, while the number of valves in the biochip can be reduced accordingly. Also, flow paths for transportation tasks can be constructed and planned automatically with minimum extra resources.

17 citations


Journal ArticleDOI
TL;DR: In this article, the authors present recent advances in the design automation of biochips, involving CAD techniques for architectural synthesis, wash optimization, testing, fault diagnosis, and fault-tolerant design.
Abstract: As one of the most promising lab-on-a-chip systems, flow-based microfluidic biochips are being increasingly used for automatically executing various laboratory procedures in biology and biochemistry, such as enzyme-linked immunosorbent assay, point-of-care diagnosis, and so on. As manufacturing technology advances, the characteristic dimensions of biochip systems keep shrinking, and tens of thousands of microvalves can now be integrated into a coin-sized microfluidic platform, making the conventional manual-based chip design no longer applicable. Accordingly, computer-aided design (CAD) of microfluidics has attracted considerable research interest in the EDA community over the past decade. This review article presents recent advances in the design automation of biochips, involving CAD techniques for architectural synthesis, wash optimization, testing, fault diagnosis, and fault-tolerant design. With the help of these CAD tools, chip designers can be released from the burden of complex, large-scale design tasks. Meanwhile, new chip architectures can be explored automatically to open new doors to meet requirements from future large-scale biological experiments and medical diagnosis. We discuss key trends and directions for future research that are related to enable microfluidics to reach its full potential, thus further advancing the development and progression of the microfluidics industry.

14 citations


Journal ArticleDOI
12 Mar 2021
TL;DR: In this article, a simple yet efficient platform integrating a portable and low-cost custom-made detector and a novel microwell array biochip for rapid and accurate detection of SARS-CoV-2 is presented.
Abstract: Sensitive detection of SARS-CoV-2 is of great importance for inhibiting the current pandemic of COVID-19. Here, we report a simple yet efficient platform integrating a portable and low-cost custom-made detector and a novel microwell array biochip for rapid and accurate detection of SARS-CoV-2. The instrument exhibits expedited amplification speed that enables colorimetric read-out within 25 minutes. A polymeric chip with a laser-engraved microwell array was developed to process the reaction between the primers and the respiratory swab RNA extracts, based on reverse transcriptase loop-mediated isothermal amplification (RT-LAMP). To achieve clinically acceptable performance, we synthesized a group of six primers to identify the conserved regions of the ORF1ab gene of SARS-CoV-2. Clinical trials were conducted with 87 PCR-positive and 43 PCR-negative patient samples. The platform demonstrated both high sensitivity (95.40%) and high specificity (95.35%), showing potentials for rapid and user-friendly diagnosis of COVID-19 among many other infectious pathogens.

14 citations


Journal ArticleDOI
TL;DR: In this article, a standard operating procedure (SOP) for the switchSENSE method is presented, which aims to guide new users through the process of a switchSense measurement, covering sample preparation, instrument and biochip handling as well as data acquisition and analysis.
Abstract: There is currently a large panel of technologies available to address molecular interactions in vitro. Each technology presents individual advantages and drawbacks, and it becomes challenging to choose which technology will be best suited for a molecular interaction of interest. Approaches can be broadly categorized as either microfluidic surface-bound methods (such as Surface Plasmon Resonance (SPR) or switchSENSE) or in-solution methods (such as Isothermal Titration Calorimetry (ITC) or MicroScale Thermophoresis (MST)). In-solution methods are advantageous in terms of sample preparation and ease of use as none of the binding partners are subjected to immobilization. On the other hand, surface-based techniques require only small amounts of immobilized interaction partner and provide off-rate characterization as unbound analytes can be removed from the surface to observe analyte dissociation. Here, a standard operating procedure (SOP) for the switchSENSE method is presented, which aims to guide new users through the process of a switchSENSE measurement, covering sample preparation, instrument and biochip handling as well as data acquisition and analysis. This guide will help researchers decide whether switchSENSE is the right method for their application as well as supporting novice users to get the most information out of a switchSENSE measurement. switchSENSE technology offers the unique advantage of a controlled DNA-based ligand surface within a microfluidic channel which allows the user to distribute specifically up to two different ligand molecules on the surface at a customized density and ratio. The technology offers multi-parameter characterization of binding kinetics, affinity, enzymatic activity, and changes in protein conformation.

11 citations


Journal ArticleDOI
TL;DR: This article forms the first practical system level design and wash optimization problem for microfluidic biochips with distributed channel storage architecture, considering high-level synthesis, physical design, and wash optimized simultaneously, and presents a top-down design flow to solve this problem systematically.
Abstract: System-architecture design optimization of flow-based microfluidic biochips has been extensively investigated over the past decade. Most of the prior work, however, is still based on chip architectures with dedicated storage units and this, not only limits the performance of biochips, but also increases their fabrication cost. To overcome this limitation, a distributed channel-storage architecture can be implemented, where fluid samples can be cached temporarily in flow channels instead of using a dedicated storage. This new concept of fluid storage, however, requires a careful arrangement of fluid samples to enable the channels to fulfill their dual functions. Moreover, to avoid cross-contamination between fluidic flows, wash operations are necessary to remove the residue left in flow channels. In this paper, we formulate the first system level design and wash optimization problem for microfluidic biochips with distributed channel storage, considering high-level synthesis, physical design, and wash optimization simultaneously. Given the protocol of a biochemical application and the corresponding design requirements, our goal is to generate a chip architecture with minimized cost. Meanwhile the bioassay can be executed efficiently with an optimized wash scheme. Experimental results confirm that our approach leads to short completion time of bioassays, low chip cost, and high wash efficiency.

11 citations


Journal ArticleDOI
TL;DR: In this paper, the authors present an approach to generate 3D multilayer tissue models in microfluidic platforms, including a dermal and an epidermal compartment.
Abstract: Microfluidic-based tissues-on-chips (TOCs) have thus far been restricted to modelling simple epithelia as a single cell layer, but likely due to technical difficulties, no TOCs have been reported to include both an epithelial and a stromal component despite the biological importance of the stroma for the structure and function of human tissues. We present, for the first time, a novel approach to generate 3D multilayer tissue models in microfluidic platforms. As a proof of concept, we modelled skin, including a dermal and an epidermal compartment. To accomplish this, we developed a parallel flow method enabling the deposition of bilayer tissue in the upper chamber, which was subsequently maintained under dynamic nutrient flow conditions through the lower chamber, mimicking the function of a blood vessel. We also designed and built an inexpensive, easy-to-implement, versatile, and robust vinyl-based device that overcomes some of the drawbacks present in PDMS-based chips. Preliminary tests indicate that this biochip will allow the development and maintenance of multilayer tissues, which opens the possibility of better modelling of the complex cell–cell and cell–matrix interactions that exist in and between the epithelium and mesenchyme, allowing for better-grounded tissue modelling and drug screening.

Journal ArticleDOI
TL;DR: A nano-integrated portable enzymatic microfluidic electrochemical biochip was developed for single-step point-of-care testing of creatinine and holds promise to become a practical device for medical diagnosis, especially POCT.

Journal ArticleDOI
TL;DR: In this article, a facile functionalization strategy is developed for excellent charge-transport thin films by suppressing the gelation of diketopyrrolopyrrole (DPP)-based polymer semiconductors with the addition of the glutaraldehyde cross-linking agent.
Abstract: In recent years, organic field-effect transistors (OFETs) have shown great potential for advanced protein biochips due to their inherent biocompatibility and high-throughput detectability. However, the development of OFET-based protein biochips is still at an early stage. On the one hand, single-biomarker determination is not sufficient for the diagnosis of cancer; thus, simultaneous monitoring of electrical signals toward multi-biomarkers is widely concerned and explored. On the other hand, an optimized functionalization strategy for efficient protein immobilization is another key to make OFET-based protein biochips accessible with improved detection performance. Herein, a facile functionalization strategy is developed for excellent charge-transport thin films by suppressing the gelation of diketopyrrolopyrrole (DPP)-based polymer semiconductors with the addition of the glutaraldehyde cross-linking agent. Besides, functional groups are introduced on the device surface for efficient attachment of antibodies as receptors via a condensation reaction, enabling simultaneous determination of α-fetoprotein biomarker and carcinoembryonic antigen biomarker with improved sensitivity and reliability. Therefore, the proposed high-throughput OFET-based protein biochip has the potential to be widely utilized in early liver cancer diagnosis.

Journal ArticleDOI
10 Feb 2021
TL;DR: The development of a microfluidic-based cell biochip device that enables the administration of nanoparticles under laminar flow to cells of the immune system to assess their cytotoxicity is presented, suggesting that commonly employed static platforms might not be well-suited to perform toxicological screening of nanomaterials and may lead to an underestimation of cytotoxic responses.
Abstract: Nanomaterials are widely used in industrial and clinical settings due to their unique physical and chemical properties. However, public health and environmental concerns have emerged owing to their undesired toxicity and ability to trigger immune responses. This paper presents the development of a microfluidic-based cell biochip device that enables the administration of nanoparticles under laminar flow to cells of the immune system to assess their cytotoxicity. The exposure of human B lymphocytes to 10 nm silver nanoparticles under fluid flow led to a 3-fold increase in toxicity compared to static conditions, possibly indicating enhanced cell–nanoparticle interactions. To investigate whether the administration under flow was the main contributing factor, we compared and validated the cytotoxicity of the same nanoparticles in different platforms, including the conventional well plate format and in-house fabricated microfluidic devices under both static and dynamic flow conditions. Our results suggest that commonly employed static platforms might not be well-suited to perform toxicological screening of nanomaterials and may lead to an underestimation of cytotoxic responses. The simplicity of the developed flow system makes this setup a valuable tool to preliminary screen nanomaterials.

Journal ArticleDOI
TL;DR: Dip-pen nanolithography is an emerging and attractive surface modification technique that has the capacity to directly and controllably write micro/nano-array patterns on diverse substrates.

Journal ArticleDOI
TL;DR: In this paper, the authors developed a magneto-optical biochip based on the Cotton-Mouton effect of γ-Fe2O3@Au core/shell magnetic nanoparticles for the detection of spike glycoprotein S of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
Abstract: Background In the past decades, different diseases and viruses, such as Ebola, MERS and COVID-19, impacted the human society and caused huge cost in different fields. With the increasing threat from the new or unknown diseases, the demand of rapid and sensitive assay method is more and more urgent. Results In this work, we developed a magneto-optical biochip based on the Cotton-Mouton effect of γ-Fe2O3@Au core/shell magnetic nanoparticles. We performed a proof-of-concept experiment for the detection of the spike glycoprotein S of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The assay was achieved by measuring the magneto-optical Cotton-Mouton effect of the biochip. This magneto-optical biochip can not only be used to detect SARS-CoV-2 but also can be easily modified for other diseases assay. Conclusion The assay process is simple and the whole testing time takes only 50 min including 3 min for the CM rotation measurement. The detection limit of our method for the spike glycoprotein S of SARS-CoV-2 is estimated as low as 0.27 ng/mL (3.4 pM).

Journal ArticleDOI
TL;DR: PathDriver+ as mentioned in this paper integrates the actual fluid manipulations into both high-level synthesis and physical design of microfluidic biochips, which has never been considered in prior work.
Abstract: Continuous-flow microfluidic biochips have attracted high research interest over the past years. Inside such a chip, fluid samples of milliliter volumes are efficiently transported between devices (e.g., mixers, heaters, etc.) to automatically perform various laboratory procedures in biology and biochemistry. Each transportation task, however, requires an exclusive flow path composed of multiple contiguous microchannels during its execution period. Excess/waste fluids, in the meantime, should be discarded by independent flow paths connected to waste ports. All these paths are etched in a very tiny chip area using multilayer soft lithography and driven by flow ports connecting with external pressure sources, forming a highly integrated chip architecture that determines the final performance of biochips. In this paper, we propose a new and practical design flow called PathDriver+ for the architecture design of microfluidic biochips, integrating the actual fluid manipulations into both high-level synthesis and physical design, which has never been considered in prior work. With this design flow, highly efficient chip architectures with a flow-path network that enables the actual fluid transportation and removal can be constructed automatically. Meanwhile, fluid volume management between devices and flowpath minimization are realized for the first time, thus ensuring the correctness of assay outcomes while reducing the complexity of chip architectures. Additionally, diagonal channel routing is implemented to fundamentally improve the chip performance. The tradeoff between the numbers of channel intersections and fluidic ports is evaluated to further reduce the fabrication cost of biochips. Experimental results on multiple benchmarks confirm that the proposed design flow leads to high assay execution efficiency and low overall chip cost.

Journal ArticleDOI
Li Gao1, Qiuxiang Lv1, Ni Xia1, Yuanwei Lin1, Feng Lin, Bangxing Han2 
TL;DR: In this article, a series of simple, low-cost, and highly sensitive biochips based on a graphene oxide (GO)/DNA hybrid was developed for Hg2+ detection.

Journal ArticleDOI
TL;DR: A new microelectrode cell (MC) design is presented such that the droplet-sensing operation can be enabled/disabled for individual MCs and a wear-leveling synthesis method is proposed to ensure uniform utilization of MCs on MEDA.
Abstract: A digital microfluidic biochip (DMFB) enables the miniaturization of immunoassays, point-of-care clinical diagnostics, DNA sequencing, and other laboratory procedures in biochemistry. A recent generation of biochips uses a micro-electrode-dot-array (MEDA) architecture, which provides fine-grained control of droplets and seamlessly integrates microelectronics and microfluidics using CMOS technology and a TSMC fabrication process. To ensure that bioassays are carried out on MEDA biochips efficiently, high-level synthesis algorithms have recently been proposed. However, as in the case of conventional DMFBs, microelectrodes are likely to fail when they are heavily utilized, and previous methods fail to consider reliability issues. In this article, we first present a new microelectrode cell (MC) design such that the droplet-sensing operation can be enabled/disabled for individual MCs. Next, “partial update” and “partial sensing” operations are presented based on an IEEE Std. 1687 IJTAG network design. Finally, wear-leveling synthesis method is proposed to ensure uniform utilization of MCs on MEDA. A comprehensive set of simulation results demonstrate the effectiveness of the proposed hardware design and design automation methods.

Journal ArticleDOI
TL;DR: In this paper, the authors proposed an authentication mechanism with an error control mechanism that provides reliability, authentication, trustworthy and safety for both storage and communication of GDS, i.e., Graphical Design System, file generally used for DMF biochip layouts.
Abstract: Among recent technological advances, microfluidic biochips have been leading a prominent solution for healthcare and miniaturized bio-laboratories with the assurance of high sensitivity and reconfigurability. On increasing more unreliable communication networks day-by-day, technological shifts in the fields of communication and security are now converging. In today's cyber threat landscape, these microfluidic biochips are ripe targets of powerful cyber-attacks from different hackers or cyber-criminals. Hence, securing such systems is of paramount importance. This paper presents the security aspects of digital microfluidic (DMF) biochip layout to protect the confidentiality of layout data from unscrupulous people and man-in-the-middle attacks. We propose an authentication mechanism with an error control mechanism that provides reliability, authentication, trustworthy and safety for both storage and communication of GDS, i.e., Graphical Design System, file generally used for DMF biochip layouts. Simulation results articulate the efficacy of the proposed security model without the overhead of the bioprotocol completion time. The proposed scheme, which used AES as an encryption algorithm with a 256-bit encryption key, has also shown a speedup of 6.0 (with 85% efficiency) faster than the prior efficient scheme. We hope to develop a secure layout design flow for DMF biochips to achieve better resistance to any attack.

Journal ArticleDOI
TL;DR: In this article, a combination of electrochemiluminescence (ECL) and bipolar electrochemistry (BPE) was used to map in real-time the oxidation of silicon in microchannels.
Abstract: This work depicts the original combination of electrochemiluminescence (ECL) and bipolar electrochemistry (BPE) to map in real-time the oxidation of silicon in microchannels We fabricated model silicon-PDMS microfluidic chips, optionally containing a restriction, and monitored the evolution of the surface reactivity using ECL BPE was used to remotely promote ECL at the silicon surface inside microfluidic channels The effects of the fluidic design, the applied potential and the resistance of the channel (controlled by the fluidic configuration) on the silicon polarization and oxide formation were investigated A potential difference down to 6 V was sufficient to induce ECL, which is two orders of magnitude less than in classical BPE configurations Increasing the resistance of the channel led to an increase in the current passing through the silicon and boosted the intensity of ECL signals Finally, the possibility of achieving electrochemical reactions at predetermined locations on the microfluidic chip was investigated using a patterning of the silicon oxide surface by etched micrometric squares This ECL imaging approach opens exciting perspectives for the precise understanding and implementation of electrochemical functionalization on passivating materials In addition, it may help the development and the design of fully integrated microfluidic biochips paving the way for development of original bioanalytical applications

Journal ArticleDOI
TL;DR: In this paper, the authors proposed a routing scheme for functional droplets specifically targeted for intelligent cross-contamination avoidance, which effectively reduces both intra and inter sub-problem cross contaminations.
Abstract: Recent advances in microfluidics and microfabrication technology enabled the emergence of a new microelectrode-dot-array (MEDA) architecture for microfluidic biochips. The MEDA-based design allows dynamic routing with variable-sized droplets. The cross contamination avoidance between droplets of different biomolecules subjected for analysis and detection on MEDA architecture poses a major design challenge for development of MEDA-based biochips. In this article, we propose a precise technique for droplet routing with minimal cross contamination for MEDA-based biochips. Here we first evaluate the probability of cross contamination between any two droplets within the 2-D MEDA layout. Thereby, we propose a routing scheme for functional droplets specifically targeted for intelligent cross-contamination avoidance. As evident from the experimental results, the proposed technique effectively reduces both intra and inter subproblem cross contaminations. Experiment results shows considerable improvements over contemporary works.

Journal ArticleDOI
Huanhuan Shi1, Kaixuan Nie1, Bo Dong1, Mengqiu Long1, Zhengchun Liu1 
TL;DR: An automated synthesis system for in situ preparation of biochip with peptide backbone based on the microfluidic mixer and micro reaction chamber that indicates that this system may provide a new alternative for low-cost in situ synthesis of bio chip.
Abstract: Biochips have become a sophisticated analytical device in the fields of biochemical sensing and genetic analysis. However, the cumbersome preparation process and the high production cost limit the versatility of its application. Herein, we have developed an automated synthesis system for in situ preparation of biochip with peptide backbone based on the microfluidic mixer and micro reaction chamber. The microfluidic mixer was used as a key component to perform the real-time activation of the carboxylic groups, leading to an instant coupling reaction of monomers with high efficiency. The repeating synthesis procedure was realized without too much manual intervention with the help of flow control system based on programmable logical controller and LabVIEW. The real-time monitoring of synthesis process was realized using a low-cost solar cell coupled with simple ultraviolet absorption device. The photodeprotection experiment revealed that an exposure time of 4 min with 20 mW/cm2 ultraviolet (UV) light at 365nm was sufficient for the complete removal of 2-(2-nitrophenyl) propyloxycarbonyl (NPPOC) groups from the synthetic sites in N, N-dimethylformamide (DMF). The practical capability performance of this synthesis system was further demonstrated by the synthesis of four cycles of aminocaproic acid, and the stepwise yield of coupling was measured to be about 96%, which was comparable with the result from literature, and indicated that this system may provide a new alternative for low-cost in situ synthesis of biochip.

Journal ArticleDOI
TL;DR: In this paper, the authors presented a novel neuronal network on a chip device, including a chamber, fabricated from PDMS, vinyl and glass connected to a microfluidic platform to perfuse the continuous flow of culture medium.
Abstract: Cultured neuronal networks (CNNs) are a robust model to closely investigate neuronal circuits' formation and monitor their structural properties evolution. Typically, neurons are cultured in plastic plates or, more recently, in microfluidic platforms with potentially a wide variety of neuroscience applications. As a biological protocol, cell culture integration with a microfluidic system provides benefits such as accurate control of cell seeding area, culture medium renewal, or lower exposure to contamination. The objective of this report is to present a novel neuronal network on a chip device, including a chamber, fabricated from PDMS, vinyl and glass connected to a microfluidic platform to perfuse the continuous flow of culture medium. Network growth is compared in chips and traditional Petri dishes to validate the microfluidic chip performance. The network assessment is performed by computing relevant topological measures like the number of connected neurons, the clustering coefficient, and the shortest path between any pair of neurons throughout the culture's life. The results demonstrate that neuronal circuits on a chip have a more stable network structure and lifespan than developing in conventional settings, and therefore this setup is an advantageous alternative to current culture methods. This technology could lead to challenging applications such as batch drug testing of in vitro cell culture models. From the engineering perspective, a device's advantage is the chance to develop custom designs more efficiently than other microfluidic systems.

Book ChapterDOI
01 Jan 2021
TL;DR: In this paper, the authors proposed a generalized electrochemiluminescence (ECL) and light-initiated chemiluminecence (LiC) for biomedical analysis.
Abstract: Chemiluminescence (CL) is an important detection method, and has been widely used in the field of biomedical analysis. The generalized CL comprises electrochemiluminescence (ECL) and light-initiated chemiluminescence (LiC). ECL contains two processes of electrochemical reaction and CL reaction, and can be applied to detection of nucleic acids, proteins, cells, and some small molecules. In recent years, a growing number of ECL luminescent substances have been reported, and many technologies have been developed for integrating with ECL. This indicates that ECL has great potential in biomedical applications. LiC is an immunoassay method that combines labeling and luminescence techniques. It has a simple principle and some distinct features and advantages compared with other immunoassay technologies. With the advance of the LiC, many related instruments and reagents have been developed, which promotes the application of LiC in biomedicine. CL is widely used in biological detection and can be used for in vitro diagnosis of many diseases, such as diabetes and thyroid disease. The development of biochips, especially microfluidic biochips, enrich the application of CL in in vitro detection. The chip development for enzyme substrate, nucleic acid, protein, cell, and others make it possible to complete large-scale biomedical detection rapidly and efficiently. For in vivo detection, CL can also be applied in many areas. With the development of advanced CL technologies, some researchers try to apply the in vivo CL technologies to cells, tissues, and individuals, and some satisfactory results have been achieved. In short, CL technologies have been recognized by more and more scholars, and their applications have a great significance in the development of biomedicine.

Journal ArticleDOI
TL;DR: In this paper, an open-well microfluidic system facilitated with coplanar-electrodes-enabled optoelectrokinetic concentration and magnetic particles was developed to overcome the challenges of close-form configuration of biochips and the required use of low electric conductivity limit their practicability.

Book ChapterDOI
01 Jan 2021
TL;DR: In this paper, an overview of optical DNA biochips as well as the Network Time Protocol (NTP) protocol deployment for synchronization among the collection database and the optical biochip automaton via the ASTM Elecsys protocol for better real-time detection with diagnosis of genetically mutated cancer.
Abstract: DNA biochip technology (especially in the optical field) can study a large amount of nucleic acid records at high throughput. It makes viable the simultaneous scrutiny of quite a few of tens of thousands of genes belonging to a healthy or diseased biological sample in terms of its genome (DNA). This article overviews optical DNA biochips as well as the Network Time Protocol (NTP) protocol deployment for synchronization among the collection database and the optical biochip automaton via the ASTM Elecsys protocol for better real-time detection with diagnosis of genetically mutated cancer. The present study utilizes the UNIX Server platform and NTP to synchronize communication between servers and optical DNA. Section 7.4 brings in automates.

Journal ArticleDOI
TL;DR: An inter-laboratory collaborative study was performed to evaluate the performance of the Biochip Array Technology (BAT) Myco 7 method as discussed by the authors, which is a method which simultaneously and quantitatively quantitatively analyzes the performance.
Abstract: An inter-laboratory collaborative study was performed to evaluate the performance of the Biochip Array Technology (BAT) Myco 7 method. The Myco 7 Array is a method which simultaneously and quantita...

Journal ArticleDOI
TL;DR: A hybrid artificial bee colony (ABC) algorithm using generalized N‐point crossover (GNX) based scheduling of DMFB operations is proposed and results show that the proposed ABC‐GNX produces a higher number of optimal completion times and faster execution times than existing algorithms.
Abstract: Digital microfluidic biochips (DMFBs) are designed to efficiently carry out biochemical and biomedical analysis in a miniaturized way. DMFBs offer various advantages over traditional laboratory techniques and reduces cost, and increases automation and software programmability. Scheduling of microfluidic operations is the first and essential step in the fluidic‐level synthesis of DMFBs, while the other two are the module placement and droplet routing. Scheduling DMFB operations is a multiconstrained optimization problem, and the particular decision problem is NP‐complete. We propose a hybrid artificial bee colony (ABC) algorithm using generalized N‐point crossover (GNX) based scheduling of DMFB operations. Proposed ABC‐GNX perturbs through search space, evaluates various schedules possible, and returns the best schedule among the evaluated schedules. Simple list scheduling based heuristic algorithms can explore a single schedule based on the sequence generated by the priority function. Iterative improvement based search algorithms explore the search space and evaluate more schedules, but the proposed ABC‐GNX algorithm produces optimal solutions in shorter execution times. Simulation results show that the proposed ABC‐GNX produces a higher number of optimal completion times and faster execution times than existing algorithms.

Proceedings ArticleDOI
13 Jun 2021
TL;DR: In this article, a 1024-pixel CMOS biochip for multiplex polymerase chain reaction application is presented, which includes 137dB DDR photosensors and an integrated emission filter with OD~6 to perform real-time fluorescence-based measurements.
Abstract: A 1024-pixel CMOS biochip for multiplex polymerase chain reaction application is presented. Biosensing pixels include 137dB DDR photosensors and an integrated emission filter with OD~6 to perform real-time fluorescence-based measurements while thermocycling the reaction chamber with heating and cooling rates of > ±10°C/s. The surface of the CMOS IC is biofunctionalized with DNA capturing probes. The biochip is integrated into a fluidic consumable enabling loading of extracted nucleic acid samples and the detection of upper respiratory pathogens, including SARS-CoV-2.