Showing papers on "Biochip published in 2019"

All-in-one microfluidic device for on-site diagnosis of pathogens based on an integrated continuous flow PCR and electrophoresis biochip

Abstract: Current continuous flow polymerase chain reaction (CF-PCR) microfluidic chips require external precision syringe pumps and off-line methods (e.g., electrophoresis and hybridization) to detect PCR products, resulting in complex operations and possible cross-contamination and consequently CF-PCR is still confined to laboratories. Herein, a portable all-in-one microfluidic device is fabricated for rapid diagnosis of pathogens based on an integrated CF-PCR and electrophoresis biochip. A new method was proposed for automatic sample injection into the chip which can substitute the costly external precision syringe pump. It not only achieves rapid DNA amplification and on-site PCR product detection, but also realizes automatic sample injection. As an application, three periodontal pathogens (e.g., Porphyromonas gingivalis, Treponema denticola and Tannerela forsythia) were successfully amplified in the device. Treponema denticola was amplified in as short as 2'31'', and detection of PCR products was completed within 3'43''. The minimum number of bacteria that can be amplified was 125 cfu per μl. The all-in-one device has the potential to be applied in point-of-care nucleic acid testing for diseases.

Highly Sensitive Detection of Bladder Cancer-Related miRNA in Urine Using Time-Gated Luminescent Biochip.

Abstract: Detection of biomarkers in complex samples is a significant health plan strategy for medical diagnosis, therapy monitoring, and health management. However, high background noise resulting from impurities and other analytes in complex samples has hampered the improvement of detection sensitivity and accuracy. Herein, an ultralow background biochip based on time-gated luminescent probes supported by photonic crystals (PCs) was successfully developed for detection of bladder cancer (BC)-related miRNA biomarkers with high sensitivity and specificity in urine samples. Coupled with the time-gated luminescence of long-lifetime luminescence probes and the luminescence-enhanced capability of PCs, the short-lived autofluorescence can be efficiently removed; thus, the detection sensitivity will be significantly improved. Benefiting from these merits, a detection limit of 26.3 fM is achieved. Furthermore, the biochip exhibits excellent performance in urinary miRNA detection, and good recoveries are also obtained. The developed biochip possesses unique properties of ultralow background and luminescence enhancement, thus offering a suitable tool for the detection of BC-related miRNA in urine. With rational design of probe sequences, the biochip holds great potential for many other biomarkers in real patient samples, making it valuable in areas such as medical diagnosis and disease evaluation.

Characterization of four functional biocompatible pressure-sensitive adhesives for rapid prototyping of cell-based lab-on-a-chip and organ-on-a-chip systems.

Abstract: In the advent of affordable photo- and soft-lithography using polydimethylsiloxane (PDMS), low cost multi-step microfabrication methods have become available to a broad scientific community today. Although these methods are frequently applied for microfluidic prototype production in academic and industrial settings, fast design iterations and rapid prototyping within a few minutes with a high degree of flexibility are nearly impossible. To reduce microfluidic concept-to-chip time and costs, a number of alternative rapid prototyping techniques have recently been introduced including CNC micromachining, 3D printing and plotting out of numeric CAD designs as well as micro-structuring of thin PDMS sheets and pressure sensitive adhesives. Although micro-structuring of pressure sensitive adhesives promises high design flexibility, rapid fabrication and simple biochip assembly, most adhesives are toxic for living biological systems. Since an appropriate bio-interface and proper biology-material interaction is key for any cell chip and organ-on-a-chip system, only a limited number of medical-grade materials are available for microfluidic prototyping. In this study, we have characterized four functional biomedical-grade pressure sensitive adhesives for rapid prototyping (e.g. less than 1 hour) applications including structuring precision, physical and optical properties as well as biocompatibilities. While similar biocompatibility was found for all four adhesives, significant differences in cutting behavior, bonding strength to glass and polymers as well as gas permeability was observed. Practical applications included stability testing of multilayered, membrane-integrated organ-on-a-chip devices under standard cell culture conditions (e.g. 2–3 weeks at 37 °C and 100% humidity) and a shear-impact up to 5 dynes/cm2. Additionally, time- and shear-dependent uptake of non-toxic fluorescently labelled nanoparticles on human endothelial cells are demonstrated using micro-structured adhesive-bonded devices. Our results show that (a) both simple and complex microdevices can be designed, fabricated and tested in less than 1 hour, (b) these microdevices are stable for weeks even under physiological shear force conditions and (c) can be used to maintain cell monolayers as well as 3D cell culture systems.

Portable tumor biosensing of serum by plasmonic biochips in combination with nanoimprint and microfluidics

Abstract: Abstract Plasmonic sensing has a great potential in the portable detection of human tumor markers, among which the carcinoembryonic antigen (CEA) is one of the most widely used in clinical medicine. Traditional plasmonic and non-plasmonic methods for CEA biosensing are still not suitable for the fast developing era of Internet of things. In this study, we build up a cost-effective plasmonic immunochip platform for rapid portable detection of CEA by combining soft nanoimprint lithography, microfluidics, antibody functionalization, and mobile fiber spectrometry. The plasmonic gold nanocave array enables stable surface functionality, high sensitivity, and simple reflective measuring configuration in the visible range. The rapid quantitative CEA sensing is implemented by a label-free scheme, and the detection capability for the concentration of less than 5 ng/ml is achieved in clinical experiments, which is much lower than the CEA cancer diagnosis threshold of 20 ng/ml and absolutely sufficient for medical applications. Clinical tests of the chip on detecting human serums demonstrate good agreement with conventional medical examinations and great advantages on simultaneous multichannel detections for high-throughput and multi-marker biosensing. Our platform provides promising opportunities on low-cost and compact medical devices and systems with rapid and sensitive tumor detection for point-of-care diagnosis and mobile healthcare.

Micro-Electrode-Dot-Array Digital Microfluidic Biochips: Technology, Design Automation, and Test Techniques

Abstract: Digital microfluidic biochips (DMFBs) are being increasingly used for DNA sequencing, point-of-care clinical diagnostics, and immunoassays. DMFBs based on a micro-electrode-dot-array (MEDA) architecture have recently been proposed, and fundamental droplet manipulations, e.g., droplet mixing and splitting, have also been experimentally demonstrated on MEDA biochips. There can be thousands of microelectrodes on a single MEDA biochip, and the fine-grained control of nanoliter volumes of biochemical samples and reagents is also enabled by this technology. MEDA biochips offer the benefits of real-time sensitivity, lower cost, easy system integration with CMOS modules, and full automation. This review paper first describes recent design tools for high-level synthesis and optimization of map bioassay protocols on a MEDA biochip. It then presents recent advances in scheduling of fluidic operations, placement of fluidic modules, droplet-size-aware routing, adaptive error recovery, sample preparation, and various testing techniques. With the help of these tools, biochip users can concentrate on the development of nanoscale bioassays, leaving details of chip optimization and implementation to software tools.

MiniControl: Synthesis of Continuous-Flow Microfluidics with Strictly Constrained Control Ports

Abstract: Recent advances in continuous-flow microfluidics have enabled highly integrated lab-on-a-chip biochips. These chips can execute complex biochemical applications precisely and efficiently within a tiny area, but they require a large number of control ports and the corresponding control logic to generate required pressure patterns for flow control, which, consequently, offset their advantages and prevent their wide adoption. In this paper, we propose the first synthesis flow called MiniControl, for continuous-flow microfluidic biochips (CFMBs) under strict constraints for control ports, incorporating high-level synthesis and physical design simultaneously, which has never been considered in previous work. With the maximum number of allowed control ports specified in advance, this synthesis flow generates a biochip architecture with high execution efficiency. Moreover, the overall cost of a CFMB can be reduced and the tradeoff between control logic and execution efficiency of biochemical applications can be evaluated for the first time. Experimental results demonstrate that MiniControl leads to high execution efficiency and low overall platform cost, while satisfying the given control port constraint strictly.

Triggerable H2O2-Cleavable Switch of Paper-Based Biochips Endows Precision of Chemometer/Ratiometric Electrochemical Quantification of Analyte in High-Efficiency Point-of-Care Testing.

Abstract: In this work, a triggerable H2O2-cleavable fluid switch mediated paper-based biochip, being amenable to multiplexing and quantitative analysis with the dual-response output of visual screening and ...

Optimized protocol for the hepatic differentiation of induced pluripotent stem cells in a fluidic microenvironment.

Abstract: In the present study, we evaluated the performance of different protocols for the hepatic differentiation of human-induced pluripotent stem cells (hiPSCs) in microfluidic biochips. Strategies for complete and partial on-chip differentiation were tested. Unlike full on-chip differentiation, the transfer of iPSCs from Petri dishes to biochips during the differentiation process produced a heterogeneous tissue with enhanced hepatic features compared with control cultures in Petri dishes. The tissue in biochips was constituted of cells expressing either stabilin-1 or albumin, while no stabilin-1 was detected in controls. Functional analysis also revealed double the production rate for albumin in biochips (about 2,000 ng per day per 106 cells). Besides this, tissues obtained in biochips and controls exhibited the metabolism of a specific bile acid. Whole transcriptome analysis with nanoCAGE exhibited a differential expression of 302 genes between control and biochip cultures and a higher degree of hepatic differentiation in biochips, together with increased promoter motif activity for typical liver transcription factors such as estrogen related receptor alpha ( ESRRA), hepatic nuclear factor 1 ( HNF1A), hepatic nuclear factor 4 ( HNF4A), transcription factor 4 ( TCF4), and CCAAT enhancer binding protein alpha ( CEBPA). Gene set enrichment analysis identified several pathways related to the extracellular matrix, tissue reorganization, hypoxia-inducible transcription factor, and glycolysis that were differentially modulated in biochip cultures. However, the presence of CK19/ALB-positive cells and the ɑ-fetoprotein levels measured in the cultures still reflect primitive differentiation patterns. Overall, we identified key parameters for improved hepatic differentiation on-chip, including the maturation stage of hepatic progenitors, inoculation density, adhesion time, and perfusion flow rate. Optimization of these parameters further led to establish a protocol for reproducible differentiation of hiPSCs into hepatocyte-like cells in microfluidic biochips with significant improvements over Petri dish cultures.

Optimising the supercritical angle fluorescence structures in polymer microfluidic biochips for highly sensitive pathogen detection: a case study on Escherichia coli.

Abstract: In this paper, we present, to the best of our knowledge, for the first time, in-depth theoretical analysis and experimental results for the optimisation of supercritical angle fluorescence (SAF) structures in polymer microfluidic chips fabricated from a combination of micro-milling and polymer injection-moulding techniques for their application in the highly-sensitive detection of pathogens. In particular, we address experimentally and theoretically the relationship between the supercritical angle and the heights of the SAF structures embedded in the microfluidic chips to obtain optimised results where the highest fluorescence intensity is collected, and hence determining the optimised limit of detection (LOD). Together with theoretical modelling, we experimentally fabricate microarrays of SAF structures with different heights varying from zero to the order of 300 μm in cyclic olefin copolymer (COC) microfluidic chips. The results show that for fluorophores at the interface of air and COC, the highest fluorescence intensities are obtained at SAF structures with a 163 μm height for a milling tool with a 97.4 μm diameter, which is in excellent agreement with our modelling. A fluorescence LOD of 5.42 × 104 molecules is achieved when using such SAF structures. The solid-phase polymerase chain reaction (SP-PCR) on these SAF structures permits sensitive pathogen detection (3.37 × 102 copies of the E. coli genome per μL) on-chip. These results especially are of interest for applications in hypersensitive pathogen detection as well as in assisting the design of devices for point-of-care applications. Findings on the height optimization of SAF structures also advance our understanding of SAF detection techniques and provide insights into the development of fluorescence microscopy.

The Surface Science of Microarray Generation-A Critical Inventory.

Abstract: Microarrays are powerful tools in biomedical research and have become indispensable for high-throughput multiplex analysis, especially for DNA and protein analysis. The basis for all microarray processing and fabrication is surface modification of a chip substrate and many different strategies to couple probe molecules to such substrates have been developed. We present here a critical assessment of typical biochip generation processes from a surface science point of view. While great progress has been made from a molecular biology point of view on the development of qualitative assays and impressive results have been obtained on the detection of rather low concentrations of DNA or proteins, quantitative chip-based assays are still comparably rare. We argue that lack of stable and reliable deposition chemistries has led in many cases to suboptimal quantitative reproducibility, impeded further progress in microarray development and prevented a more significant penetration of microarray technology into the diagnostic market. We suggest that surface-attached hydrogel networks might be a promising strategy to achieve highly sensitive and quantitatively reproducible microarrays.

An open-space microfluidic chip with fluid walls for online detection of VEGF via rolling circle amplification.

Abstract: Despite traditional poly-dimethyl siloxane (PDMS) microfluidic devices having great potential in various biological studies, they are limited by sophisticated fabrication processes and low utilization. An easily controlled microfluidic platform with high efficiency and low cost is desperately required. In this work, we present an open-space microfluidic chip with fluid walls, integrating cell culture and online semi-quantitative detection of vascular endothelial growth factor (VEGF) via rolling circle amplification (RCA) reaction. In comparison with conventional co-culture detecting platforms, this method features the prominent advantages of saving reagents and time, a simplified chip fabrication process, and avoiding additional assistance for online detection with the help of an interfacial tension valve. On such a multi-functional microfluidic chip, cells (human umbilical vein endothelial cells and malignant glioma cells) could maintain regular growth and cell viability. VEGF could be detected with excellent specificity and good linearity in the range of 10-250 pg mL-1. Meanwhile, VEGF secreted by malignant glioma cells was also detected online and obviously increased when cells were stimulated by deferoxamine (DFO) to mimic a hypoxic microenvironment. The designed biochip with fluid walls provides a new perspective for micro-total analysis and could be promisingly applied in future clinical diagnosis and drug analysis.

Miniaturized electrochemiluminescent biochip prepared on gold nanoparticles-loaded mesoporous silica film for visual detection of hydrogen peroxide released from living cells

Abstract: Au nanoparticles (NPs) has been widely used for the detection of intracellular H2O2 to enhance the electron transfer process. But AuNPs are easy to aggregate in the live cells environment. Herein we report a rapid, reliable and low-cost electrochemiluminescent (ECL) biochip integrated by AuNPs-loaded mesoporous silica film (MSF) to detect H2O2 released by macrophage cells. The MSF was employed as a template to load AuNPs within the nanochannels to avoid aggregation. H2O2 could be catalyzed by AuNPs to promote the ECL reaction of luminol molecules in solution. The ECL intensity was significantly enhanced, and the peak potential was negatively shifted by 400 mV due to the excellent electrocatalytic ability of AuNPs. The integrated biochip demonstrated good reproducibility, with a wide linear range of 0.1–200 μM and an LOD of 25.3 nM. The reliability was evaluated by applying for the assessment of antioxidant activity of resveratrol using RAW 264.7 macrophage model. The AuNPs-loaded MSF integrated biochip can be easily adapted to the development of improved devices in biosensing, lab-on-a-chip, and nanofluidic systems.

Security Assessment of Micro-Electrode-Dot-Array Biochips

Abstract: Digital microfluidic biochips (DMFBs) are versatile, reconfigurable systems for manipulating discrete fluid droplets. Building on the success of DMFBs, platforms based on “sea-of-electrodes,” the micro-electrode-dot-array (MEDA), has been proposed to further increase scalability and reconfigurability. Research has shown that DMFBs are susceptible to actuation tampering attacks which alter control signals and result in fluid manipulation; such attacks have yet to be studied in the context of MEDA biochips. In this paper, we assess the security of MEDA biochips under such attacks, and further argue that it is inherently a more secure platform than traditional DMFBs. First, we identify a new class of actuation tampering attacks specific to MEDA biochips: the micro-droplet attack. We show that this new attack is stealthy as it produces a subtler difference in results compared to traditional DMFBs. We then illustrate our findings through a case study of an MEDA biochip implementing a glucose measurement assay. Second, we enumerate the system features required to secure an MEDA biochip against actuation tampering attacks and show that these features are naturally implemented in MEDA.

Design and Manufacturing of a Disposable, Cyclo-Olefin Copolymer, Microfluidic Device for a Biosensor †

Abstract: This contribution outlines the design and manufacturing of a microfluidic device implemented as a biosensor for retrieval and detection of bacteria RNA. The device is fully made of Cyclo-Olefin Copolymer (COC), which features low auto-fluorescence, biocompatibility and manufacturability by hot-embossing. The RNA retrieval was carried on after bacteria heat-lysis by an on-chip micro-heater, whose function was characterized at different working parameters. Carbon resistive temperature sensors were tested, characterized and printed on the biochip sealing film to monitor the heating process. Off-chip and on-chip processed RNA were hybridized with capture probes on the reaction chamber surface and identification was achieved by detection of fluorescence tags. The application of the mentioned techniques and materials proved to allow the development of low-cost, disposable albeit multi-functional microfluidic system, performing heating, temperature sensing and chemical reaction processes in the same device. By proving its effectiveness, this device contributes a reference to show the integration potential of fully thermoplastic devices in biosensor systems.

Ultra-sensitive detection of uranyl ions with a specially designed high-efficiency SERS-based microfluidic device

Abstract: The uranyl ion (UO22+) poses high risks to human health and the environment, hence its detection and monitoring is of utmost significance. However, the development of an ultra-sensitive, high-efficiency and convenient approach for on-site detection of UO22+ remains a challenge. Herein, a reliable and reusable surface-enhanced Raman spectroscopy (SERS)-based microfluidic biosensor was developed for rapid detection of UO22+ in real samples. The detection protocol involved the reaction of 5′-Rhodamine B (RhB)-labeled double-stranded DNA for UO22+-specific DNAzyme-cleavage reaction in a U-shaped micro-channel. Then, the reaction products were delivered into three parallel samples for high-throughput tests by SERS biochips, where 3D ZnO-Ag mesoporous nanosheet arrays (MNSs) were modified with a single-stranded DNA (ssDNA). The ssDNA was sequence-complementary with the 5′-RhB-labeled cleaved-stranded DNA (csDNA) from the reaction products. By the hybridization of ssDNA and csDNA, the signal probe RhB was fixed close to the surface of the ZnO-Ag MNSs to enhance the Raman signal. The limit of detection for UO22+ with the microfluidic-SERS biosensor was 3.71× 10−15 M. An over 20,000-fold selectivity towards UO22+ response was also achieved in the presence of 15 other metal ions. The high-throughput microfluidic-SERS biosensor operated well for practical UO22+ detection, with excellent recoveries in contaminated river and tap water from 95.2% to 106.3% (relative standard deviation (RSD) n =6). Although the SERS-based microfluidic biosensor developed in this study was deployed for the detection of UO22+, the reusable and high-efficiency system may be expanded to the detection of other analytes on-site.

An Electrochemical Fiveplex Biochip Assay Based on Anti-Idiotypic Antibodies for Fast On-Site Detection of Bioterrorism Relevant Low Molecular Weight Toxins.

Abstract: Modern threats of bioterrorism force the need for multiple detection of biothreat agents to determine the presence or absence of such agents in suspicious samples. Here, we present a rapid electrochemical fiveplex biochip screening assay for detection of the bioterrorism relevant low molecular weight toxins saxitoxin, microcystin-LR, T-2 toxin, roridin A and aflatoxin B1 relying on anti-idiotypic antibodies as epitope-mimicking reagents. The proposed method avoids the use of potentially harmful toxin-protein conjugates usually mandatory for competitive immunoassays. The biochip is processed and analyzed on the automated and portable detection platform pBDi within 13.4 min. The fiveplex biochip assay revealed toxin group specificity to multiple congeners. Limits of detection were 1.2 ng/mL, 1.5 ng/mL, 0.4 ng/mL, 0.5 ng/mL and 0.6 ng/mL for saxitoxin, microcystin-LR, T-2 toxin, roridin A or aflatoxin B1, respectively. The robustness of the fiveplex biochip for real samples was demonstrated by detecting saxitoxin, microcystin-LR, HT-2 toxin, roridin A and aflatoxin B1 in contaminated human blood serum without elaborate sample preparation. Recovery rates were between 52–115% covering a wide concentration range. Thus, the developed robust fiveplex biochip assay can be used on-site to quickly detect one or multiple low molecular weight toxins in a single run.

Toward Secure Microfluidic Fully Programmable Valve Array Biochips

Abstract: The fully programmable valve array (FPVA) is a general-purpose programmable flow-based microfluidic platform, akin to the VLSI field-programmable gate array (FPGA). FPVAs are dynamically reconfigurable and, hence, are suitable in a broad spectrum of applications involving immunoassays and cell analysis. Since these applications are safety critical, addressing security concerns is vital for the success and adoption of FPVAs. This study evaluates the security of FPVA biochips. We show that FPVAs are vulnerable to malicious operations similar to digital and flow-based microfluidic biochips. FPVAs are further prone to new classes of attacks—tunneling and deliberate aging. This study establishes security metrics and describes possible attacks on real-life bioassays. Furthermore, we study the use of machine learning (ML) techniques to detect and classify attacks based on the golden and real-time biochip state. In order to boost the classifier’s performance, we propose a smart checkpointing mechanism. Experimental results are presented to showcase: 1) best-fit ML model classifier; 2) performance of different tradeoffs in checkpointing; and 3) effectiveness of the proposed smart checkpointing scheme.

Desieve the Attacker: Thwarting IP Theft in Sieve-Valve-based Biochips

Abstract: Researchers develop bioassays following rigorous experimentation in the lab that involves considerable fiscal and highly-skilled-person-hour investment. Previous work shows that a bioassay implementation can be reverse engineered by using images or video and control signals of the biochip. Hence, techniques must be devised to protect the intellectual property (IP) rights of the bioassay developer. This study is the first step in this direction and it makes the following contributions: (1) it introduces use of a sieve-valve as a security primitive to obfuscate bioassay implementations; (2) it shows how sieve-valves can be used to obscure biochip building blocks such as multiplexers and mixers; (3) it presents design rules and security metrics to design and measure obfuscated biochips. We assess the cost-security trade-offs associated with this solution and demonstrate practical sieve-valve based obfuscation on real-life biochips.

Bio-O-Pump: a novel portable microfluidic device driven by osmotic pressure

Abstract: The concepts of lab on a chip, miniaturised fluidic systems, and biochips entail the use of a fluid to perform analogue or digital operations. The temporal and spatial fluidic drive and control in microfluidic systems usually involves a complex pump, tubing, and connection system. Reducing the number of external components is crucial for use by scientists without an engineering background. In this paper, we present a novel pump-free device that uses an osmotic-pressure-driven flow to control and modulate fluid flow in microfluidic networks. The flow rate was regulated by controlling the osmotic area and the concentration of the draw solution, which comprised an easily accessible solution of electrolytes such as commercial sterile saline buffer and sodium chloride solution. The Bio-O-Pump can continuously generate liquid movement up to a flow rate of 4.88 mL h−1 over 1 h. This research also presents a single cell trapping application for biomedical uses.

Efficient Generation of Dilution Gradients With Digital Microfluidic Biochips

Abstract: Digital microfluidic biochips (DMFBs) are now being extensively used to automate several biochemical laboratory protocols such as clinical analysis, point-of-care diagnostics, or DNA sequencing. In many biological assays, e.g., bacterial susceptibility tests and cellular response analysis, samples, or reagents are required in multiple concentration (or dilution) factors, satisfying certain gradient patterns such as linear, exponential, or parabolic. Dilution gradients are traditionally prepared using continuous-flow microfluidic devices. Unfortunately, most of them suffer from inflexibility and nonprogrammability, and they require large volumes of costly stock-solutions. DMFBs, on the other hand, are shown to produce, more efficiently, samples with multiple dilution factors. However, none of the existing DMFB-based algorithms utilize the properties of the gradient-profile while optimizing reactant-cost and sample-preparation time. In this paper, we explore the underlying combinatorial attributes of different gradients and harnessed them for efficient production of the desired concentration profile. For linear gradients, we present theoretical results concerning the number of mix-split operations and waste production, and prove an upper bound on on-chip storage requirement. A cost-effective method for generating a wide class of exponential gradients is also proposed. Finally, in order to handle a complex-shaped gradient, we posit a digital-geometric technique to approximate it with a sequence of linear gradients. Experimental results on various gradient-profiles are presented in support of the proposed method.

Droplet Size-Aware High-Level Synthesis

Abstract: Due to the inherent differences between today’s digital microfluidic biochips and micro-electrode-dot-array (MEDA) biochips, existing synthesis solutions for biochemistry mapping cannot be utilized for MEDA biochips. This chapter presents the first synthesis approach that can be used for MEDA biochips. A general analytical model for droplet velocity is proposed and experimentally validated using fabricated MEDA biochips. A synthesis method targeting reservoir placement, operation scheduling, module placement, routing of droplets of various sizes, and diagonal movement of droplets in a two-dimensional array is then presented for MEDA biochips. Simulation results using benchmarks and experimental results using a fabricated MEDA biochip demonstrate the effectiveness of the proposed synthesis technique.

Randomized Checkpoints: A Practical Defense for Cyber-Physical Microfluidic Systems

Abstract: Attacks on cyber-physical microfluidic systems have emerged as a rising threat and call for an immediate solution. In this article, the authors survey different attacks on digital microfluidic biochips and propose to use randomized checkpoints as hardware-based countermeasures to address security vulnerabilities. —Ujjwal Guin, Auburn University

Two-dimensional computational method for generating planar electrode patterns with enhanced volumetric electric fields and its application to continuous dielectrophoretic bacterial capture

Abstract: An array of microfabricated interdigitated electrodes (IDEs) is one of the most commonly used forms of electrode geometry for dielectrophoretic manipulation of biological particles in microfluidic biochips owing to simplicity of fabrication and ease of analysis. However, the dielectrophoretic force dramatically reduces as the distance from the electrode surface increases; therefore, the effective region is usually close to the electrode surface for a given electric potential difference. Here, we present a novel two-dimensional computational method for generating planar electrode patterns with enhanced volumetric electric fields, which we call the "microelectrode discretization (MED)" method. It involves discretization and reconstruction of planar electrodes followed by selection of the electrode pattern that maximizes a novel objective function, factor S, which is determined by the electric potentials on the electrode surface alone. In this study, IDEs were used as test planar electrodes. Two arrays of IDEs and respective MED-optimized electrodes were implemented in microfluidic devices for the selective capture of Escherichia coli against 1 μm-diameter polystyrene beads, and we experimentally observed that 1.4 to 35.8 times more bacteria were captured using the MED-optimized electrodes than the IDEs (p < 0.0016), with a bacterial purity against the beads of more than 99.8%. This simple design method offered simplicity of fabrication, highly enhanced electric field, and uniformity of particle capture, and can be used for many dielectrophoresis-based sensors and microfluidic systems.

Sample preparation for multiple-reactant bioassays on micro-electrode-dot-array biochips

Abstract: Sample preparation, as a key procedure in many biochemical protocols, mixes various samples and/or reagents into solutions that contain the target concentrations. Digital microfluidic biochips (DMFBs) have been adopted as a platform for sample preparation because they provide automatic procedures that require less reactant consumption and reduce human-induced errors. However, traditional DMFBs only utilize the (1:1) mixing model, i.e., only two droplets of the same volume can be mixed at a time, which results in higher completion time and the wastage of valuable reactants. To overcome this limitation, a next-generation micro-electrode-dot-array (MEDA) architecture that provides flexibility of mixing multiple droplets of different volumes in a single operation was proposed. In this paper, we present a generic multiple-reactant sample preparation algorithm that exploits the novel fluidic operations on MEDA biochips. Simulated experiments show that the proposed method outperforms existing methods in terms of saving reactant cost, minimizing the number of operations, and reducing the amount of waste.