Showing papers on "Biochip published in 2017"

Microfluidic hydrodynamic trapping for single cell analysis: mechanisms, methods and applications

Abstract: The development of hydrodynamic-based microfluidic biochips has been increasing over the years. In this technique, the cells or particles are trapped in a particular region for single cell analysis (SCA) usually without any application of external force fields such as optical, electrical, magnetic or acoustic. There is a need to explore the insights of SCA in the cell's natural state and development of these techniques is highly essential for that study. Researchers have highlighted the vast potential field that needs to be explored to develop biochip devices to suit market/researcher demands. Hydrodynamic microfluidics facilitates the development of passive lab-on-chip applications. This review gives an account of the recent advances in this field, along with their mechanisms, methods and applications.

Naked eye detection of multiple tumor-related mRNAs from patients with photonic-crystal micropattern supported dual-modal upconversion bioprobes

Abstract: Development of a portable device for the detection of multiple mRNAs is a significant need in the early diagnosis of cancer. We have designed a biochip-based mRNA detection device by combining a hydrophilic–hydrophobic micropattern with upconversion luminescence (UCL) probes. The device achieves highly sensitive detection, using the naked eye, of multiple mRNAs among patient samples. The high sensitivity is attributed to enrichment of the target concentration and a fluorescence enhancement effect. In addition, since the photonic crystal (PC) dot biochip is functionalized with dual-wavelength excitation UCL probes, two kinds of mRNAs in the heterogeneous biological samples are detected simultaneously, and the corresponding luminescence signals are captured using an unmodified camera phone. The biochip-based mRNA detection device reported here demonstrates that multiple mRNAs extracted from patient samples can be simultaneously and sensitively detected in a visual way without sophisticated instrumentation. Therefore, this device is promising for real-time detection of multiple biomarkers in patient samples, and it is anticipated that it will provide a powerful tool for convenient early diagnosis of cancer.

Microporous Nanocomposite Enabled Microfluidic Biochip for Cardiac Biomarker Detection

Abstract: This paper demonstrates an ultrasensitive microfluidic biochip nanoengineered with microporous manganese-reduced graphene oxide nanocomposite for detection of cardiac biomarker, namely human cardiac troponin I. In this device, the troponin sensitive microfluidic electrode consisted of a thin layer of manganese-reduced graphene oxide (Mn3O4-RGO) nanocomposite material. This nanocomposite thin layer was formed on surface of a patterned indium tin oxide substrate after modification with 3-aminopropyletriethoxysilane and was assembled with a polydimethylsiloxane-based microfluidic system. The nanoengineered microelectrode was functionalized with antibodies specific to cardiac troponin I. The uniformly distributed flower-shaped nanostructured manganese oxide (nMn3O4) onto RGO nanosheets offered large surface area for enhanced loading of antibody molecules and improved electrochemical reaction at the sensor surface. This microfluidic device showed an excellent sensitivity of log [87.58] kΩ/(ng mL–1)/cm2 for qua...

Droplet Size-Aware High-Level Synthesis for Micro-Electrode-Dot-Array Digital Microfluidic Biochips

Abstract: A digital microfluidic biochip (DMFB) is an attractive technology platform for automating laboratory procedures in biochemistry. In recent years, DMFBs based on a microelectrode-dot-array (MEDA) architecture have been demonstrated. However, due to the inherent differences between today's DMFBs and MEDA, existing synthesis solutions for biochemistry mapping cannot be utilized for MEDA biochips. We present the first synthesis approach that can be used for MEDA biochips. We first present a general analytical model for droplet velocity and validate it experimentally using a fabricated MEDA biochip. We then present the proposed 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. Simulation results using benchmarks and experimental results using a fabricated MEDA biochip demonstrate the effectiveness of the proposed synthesis technique.

Control-Layer Routing and Control-Pin Minimization for Flow-Based Microfluidic Biochips

Abstract: Recent advances in flow-based microfluidic biochips have enabled the emergence of lab-on-a-chip devices for bimolecular recognition and point-of-care disease diagnostics. However, the adoption of flow-based biochips is hampered today by the lack of computer-aided design tools. Manual design procedures not only delay product development but they also inhibit the exploitation of the design complexity that is possible with current fabrication techniques. In this paper, we present the first practical problem formulation for automated control-layer design in flow-based microfluidic very large-scale integration (mVLSI) biochips and propose a systematic approach for solving this problem. Our goal is to find an efficient routing solution for control-layer design with a minimum number of control pins. The pressure-propagation delay, an intrinsic physical phenomenon in mVLSI biochips, is minimized in order to reduce the response time for valves, decrease the pattern set-up time, and synchronize valve actuation. Two fabricated flow-based devices and six synthetic benchmarks are used to evaluate the proposed optimization method. Compared with manual control-layer design and a baseline approach, the proposed approach leads to fewer control pins, better timing behavior, and shorter channel length in the control layer.

Synthesis of Cyberphysical Digital-Microfluidic Biochips for Real-Time Quantitative Analysis

Abstract: Considerable effort has recently been directed toward the implementation of molecular bioassays on digital-microfluidic biochips (DMFBs). However, today’s solutions suffer from the drawback that multiple sample pathways are not supported and on-chip reconfigurable devices are not efficiently exploited. As a result, impractical manual intervention is needed to process protocols for gene-expression analysis. To overcome this problem, we first describe our benchtop experimental studies to understand gene-expression analysis and its relationship to the biochip design specification. We then introduce an integrated framework for quantitative gene-expression analysis using DMFBs. The proposed framework includes: 1) a spatial-reconfiguration technique that incorporates resource-sharing specifications into the synthesis flow; 2) an interactive firmware that collects and analyzes sensor data based on quantitative polymerase chain reaction; and 3) a real-time resource-allocation scheme that responds promptly to decisions about the protocol flow received from the firmware layer. This framework is combined with cyberphysical integration to develop the first design-automation framework for quantitative gene expression. Simulation results show that our adaptive framework efficiently utilizes on-chip resources to reduce time-to-result without sacrificing the chip’s lifetime.

Testing microfluidic Fully Programmable Valve Arrays (FPVAs)

Abstract: Fully Programmable Valve Array (FPVA) has emerged as a new architecture for the next-generation flow-based microfluidic biochips. This 2D-array consists of regularly-arranged valves, which can be dynamically configured by users to realize microfluidic devices of different shapes and sizes as well as interconnections. Additionally, the regularity of the underlying structure renders FPVAs easier to integrate on a tiny chip. However, these arrays may suffer from various manufacturing defects such as blockage and leakage in control and flow channels. Unfortunately, no efficient method is yet known for testing such a general-purpose architecture. In this paper, we present a novel formulation using the concept of flow paths and cut-sets, and describe an ILP-based hierarchical strategy for generating compact test sets that can detect multiple faults in FPVAs. Simulation results demonstrate the efficacy of the proposed method in detecting manufacturing faults with only a small number of test vectors.

Exact routing for micro-electrode-dot-array digital microfluidic biochips

Abstract: Digital microfluidics is an emerging technology that provide fluidic-handling capabilities on a chip. One of the most important issues to be considered when conducting experiments on the corresponding biochips is the routing of droplets. A recent variant of biochips uses a micro-electrode-dot-array (MEDA) which yields a finer controllability of the droplets. Although this new technology allows for more advanced routing possibilities, it also poses new challenges to corresponding CAD methods. In contrast to conventional microfluidic biochips, droplets on MEDA biochips may move diagonally on the grid and are not bound to have the same shape during the entire experiment. In this work, we present an exact routing method that copes with these challenges while, at the same time, guarantees to find the minimal solution with respect to completion time. For the first time, this allows for evaluating the benefits of MEDA biochips compared to their conventional counterparts as well as a quality assessment of previously proposed routing methods in this domain.

BioChipWork: Reverse Engineering of Microfluidic Biochips

Abstract: Microfluidic biochip is an emerging platform that has wide applications in areas of immunoassays, DNA sequencing and point-of-care health service. This paper presents BioChipWork, the first practical framework for automatic reverse engineering and IP piracy of microfluidic biochips. Our work targets two types of presently available microfluidic biochips which are characterized based on working mechanisms: flow-based microfluidic biochip (FMFB) and droplet-based microlfuidic biochip (DMFB). More specifically, BioChipWork identifies two practical sets of reverse engineering attacks and demonstrates the attacks using our developed algorithm and an open source synthesis tool. In the first attack, the attacker extracts the hardware layout of the pertinent FMFB based on image analysis. In the second attack, the attacker reconstructs the proprietary protocol mapped onto the DMFB by analyzing the actuation sequence or the video frames recorded by the CCD camera. The proposed reverse engineering attacks are non-intrusive, scalable and easy to implement, rendering the IP of authentic owners in danger. As countermeasures to obscure the functional layout and reduce information leakage from side-channels, we suggest novel biochip camouflaging and obfuscation techniques.

Transport or Store?: Synthesizing Flow-based Microfluidic Biochips using Distributed Channel Storage

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 paper, we propose the first architectural synthesis framework considering distributed storage constructed temporarily from transportation channels to cache fluid samples 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 distributed computing architecture can achieve a higher execution efficiency even with fewer resources Experimental results confirm that the execution efficiency of a bioassay can be improved by up to 28% while the number of valves in the biochip can be reduced effectively

Hamming-distance-based valve-switching optimization for control-layer multiplexing in flow-based microfluidic biochips

Abstract: Flow-based microfluidic biochips have progressed significantly in the past decade. Thanks to innovations in multilayer soft lithography (MSL) fabrication technology, the integration of thousands of microvalves along with large-scale networks of microchannels on a chip has been enabled. This progress has even been compared to the evolution of VLSI circuits following Moore's Law. In flow-based microfluidic biochips, microvalves are critical components to control the fluidic transportation for complex operations. To activate the open/close states of a microvalve, off-chip control pins are required. Due to the tremendous increase of the number of microvalves, a software-programmable microfluidic platform has been proposed to reduce the number of off-chip control pins, which integrates a microfluidic multiplexer on a separate control layer to control the array of microvalves. The multiplexer needs to be switched when the states of microvalves are changed between every two adjacent time slots. High switching frequency will make the multiplexer vulnerable and decrease the chip's reliability. We observe that different switching orders of microvalves lead to different switching frequencies of a multiplexer. Based on this observation, this paper proposes the first Hamming-distance-based switching order optimization method for microvalves to enhance the reliability of the multiplexer. Experimental results show that our method can significantly reduce the switching frequency of multiplexer, and the solution is very close to the theoretical optimal lower bound.

Transport or Store? Synthesizing Flow-based Microfluidic Biochips using Distributed Channel Storage

Abstract: Flow-based microfluidic biochips have attracted much atten- tion 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 bio- chips. In this paper, we propose the first architectural synthe- sis framework considering distributed storage constructed tem- porarily from transportation channels to cache fluid samples. 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 dis- tributed computing architecture can achieve a higher execution efficiency even with fewer resources. Experimental results con- firm that the execution efficiency of a bioassay can be improved by up to 28% while the number of valves in the biochip can be reduced effectively.

Droplet Size-Aware and Error-Correcting Sample Preparation Using Micro-Electrode-Dot-Array Digital Microfluidic Biochips

Abstract: Sample preparation in digital microfluidics refers to the generation of droplets with target concentrations for on-chip biochemical applications In recent years, digital microfluidic biochips (DMFBs) have been adopted as a platform for sample preparation However, there remain two major problems associated with sample preparation on a conventional DMFB First, only a (1:1) mixing/splitting model can be used, leading to an increase in the number of fluidic operations required for sample preparation Second, only a limited number of sensors can be integrated on a conventional DMFB; as a result, the latency for error detection during sample preparation is significant To overcome these drawbacks, we adopt a next generation DMFB platform, referred to as micro-electrode-dot-array (MEDA), for sample preparation We propose the first sample-preparation method that exploits the MEDA-specific advantages of fine-grained control of droplet sizes and real-time droplet sensing Experimental demonstration using a fabricated MEDA biochip and simulation results highlight the effectiveness of the proposed sample-preparation method

Synthesis of Error-Recovery Protocols for Micro-Electrode-Dot-Array Digital Microfluidic Biochips

Abstract: A digital microfluidic biochip (DMFB) is an attractive technology platform for various biomedical applications. However, a conventional DMFB is limited by: (i) the number of electrical connections that can be practically realized, (ii) constraints on droplet size and volume, and (iii) the need for special fabrication processes and the associated reliability/yield concerns. To overcome the above challenges, DMFBs based on a micro-electrode-dot-array (MEDA) architecture have been proposed and fabricated recently. Error recovery is of key interest for MEDA biochips due to the need for system reliability. Errors are likely to occur during droplet manipulation due to defects, chip degradation, and the uncertainty inherent in biochemical experiments. In this paper, we first formalize error-recovery objectives, and then synthesize optimal error-recovery protocols using a model based on Stochastic Multiplayer Games (SMGs). We also present a global error-recovery technique that can update the schedule of fluidic operations in an adaptive manner. Using three representative real-life bioassays, we show that the proposed approach can effectively reduce the bioassay completion time and increase the probability of success for error recovery.

Security Implications of Cyberphysical Flow-Based Microfluidic Biochips

Abstract: Flow-based microfluidic biochips are revolutionizing biochemical research by automating complex protocols and reducing sample and reagent consumption Integration of these biochips with sensors, actuators, and intelligent control have compounded these benefits while increasing reliability And, many flow-based platforms have successfully transitioned to the marketplace, demonstrating their utility through several recent scientific publications However, these microfluidic technologies and platforms have unintended security and trust implications that threaten their continued success We survey cyberphysical flow-based microfluidic platforms and perform a security assessment We then describe an attack on digital polymerase chain reactions and how such attacks undermine research integrity

Performance Improvements and Congestion Reduction for Routing-Based Synthesis for Digital Microfluidic Biochips

Abstract: Routing-based synthesis for digital microfluidic biochips yields faster assay execution times compared to module-based synthesis. We show that routing-based synthesis can lead to deadlocks and livelocks in specific cases, and that dynamically detecting them and adjusting the probabilities associated with different droplet movements can alleviate the situation. We also introduce methods to improve the efficiency of wash droplet routing during routing-based synthesis, and to support nonreconfigurable modules, such as integrated heaters and detectors. We obtain increases in success rates when dealing with resource-constrained chips and reductions in average assay execution time.

Microfluidic biochips for simple impedimetric detection of thrombin based on label-free DNA aptamers

Abstract: This paper presents a proof-of-concept microfluidic aptamer-based sensor for thrombin point-of-care testing using electrochemical impedance spectroscopy. The disposable biosensor is composed of a polydimethylsiloxane (PDMS) channel layer over a glass substrate. The substrate surface has an Au working electrode and a Pt reference/counter electrode. In this study, human thrombin was used as a biomarker for disease diagnosis. An unlabeled aptamer specific to thrombin was immobilized on a working electrode and electrochemical impedance was measured as thrombin was injected into the biosensor. Thrombin was detected by measuring change in impedance. The proposed biochip had a detection range of 0.1–100,000 ng mL−1 for thrombin concentration and a limit of detection of 0.1 ng mL−1. The results indicated that our biochip could be an effective tool for other molecular diagnostic systems.

Ultrafast Laser Fabrication of Functional Biochips: New Avenues for Exploring 3D Micro- and Nano-Environments

Abstract: Lab-on-a-chip biological platforms have been intensively developed during the last decade since emerging technologies have offered possibilities to manufacture reliable devices with increased spatial resolution and 3D configurations. These biochips permit testing chemical reactions with nanoliter volumes, enhanced sensitivity in analysis and reduced consumption of reagents. Due to the high peak intensity that allows multiphoton absorption, ultrafast lasers can induce local modifications inside transparent materials with high precision at micro- and nanoscale. Subtractive manufacturing based on laser internal modification followed by wet chemical etching can directly fabricate 3D micro-channels in glass materials. On the other hand, additive laser manufacturing by two-photon polymerization of photoresists can grow 3D polymeric micro- and nanostructures with specific properties for biomedical use. Both transparent materials are ideal candidates for biochips that allow exploring phenomena at cellular levels while their processing with a nanoscale resolution represents an excellent opportunity to get more insights on biological aspects. We will review herein the laser fabrication of transparent microfluidic and optofluidic devices for biochip applications and will address challenges associated with their potential. In particular, integrated micro- and optofluidic systems will be presented with emphasis on the functionality for biological applications. It will be shown that ultrafast laser processing is not only an instrument that can tailor appropriate 3D environments to study living microorganisms and to improve cell detection or sorting but also a tool to fabricate appropriate biomimetic structures for complex cellular analyses. New advances open now the avenue to construct miniaturized organs of desired shapes and configurations with the goal to reproduce life processes and bypass in vivo animal or human testing.

Pressure-Aware Control Layer Optimization for Flow-Based Microfluidic Biochips

Abstract: Flow-based microfluidic biochips are attracting increasing attention with successful biomedical applications. One critical issue with flow-based microfluidic biochips is the large number of microvalves that require peripheral control pins. Even using the broadcasting addressing scheme, i.e., one control pin controls multiple microvalves simultaneously, thousands of microvalves would still require hundreds of control prins, which is unrealistic. To address this critical challenge in control scalability, the control-layer multiplexer is introduced to effectively reduce the number of control pins into log scale of the number of microvalves. There are two practical design issues with the control-layer multiplexer: (1) the reliability issue caused by the frequent control-valve switching, and (2) the pressure degradation problem caused by the control-valve switching without pressure refreshing from the pressure source. This paper addresses these two design issues by the proposed Hamming-distance-based switching sequence optimization method and the XOR-based pressure refreshing method. Simulation results demonstrate the effectiveness and efficiency of the proposed methods with an average 77.2% (maximum 89.6%) improvement in total pressure refreshing cost, and an average 88.5% (maximum 90.0%) improvement in pressure deviation.

Diagonal Component Expansion for Flow-Layer Placement of Flow-Based Microfluidic Biochips

Abstract: Continuous flow-based microfluidic devices have seen a huge increase in interest because of their ability to automate and miniaturize biochemistry and biological processes, as well as their promise of creating a programmable platform for chemical and biological experimentation. The major hurdle in the adoption of these types of devices is in the design, which is largely done by hand using tools such as AutoCAD or SolidWorks, which require immense domain knowledge and are hard to scale. This paper investigates the problem of automated physical design for continuous flow-based microfluidic very large scale integration (mVLSI) biochips, starting from a netlist specification of the flow layer. After an initial planar graph embedding, vertices in the netlist are expanded into two-dimensional components, followed by fluid channel routing. A new heuristic, DIagonal Component Expansion (DICE) is introduced for the component expansion step. Compared to a baseline expansion method, DICE improves area utilization by a factor of 8.90x and reduces average fluid routing channel length by 47.4%.

Nonlithographic Fabrication of Plastic-Based Nanofibers Integrated Microfluidic Biochip for Sensitive Detection of Infectious Biomarker.

Abstract: We report fabrication of a fully integrated plastic based microfluidic biochip for biosensing application. The microfluidic channels were fabricated by tune transfer method and integrated with the prefunctionalized sensing platform. This approach to assembling microchannels into prefunctionalized sensing substrate facilitates controlled functionalization and prevents damages on the functionalized surface. The sensing platform comprised a three-electrode system, in which the sensing electrode was integrated with antibody immobilized carbon nanotubes-zinc oxide (C-ZnO) nanofibers. Electrospinning technique was used to synthesize C-ZnO nanofibers and the surface of the nanofibers was covalently conjugated with histidine rich protein II antibodies (AntiHRP II) toward detection of infectious malarial specific antigen, namely histidine-rich protein II (HRP II). The analytical performance of the fabricated biochip was evaluated by differential pulse voltammetry method. The device exhibited a high sensitivity of ...

Characterization of paraben substituted cyclotriphosphazenes, and a DNA interaction study with a real-time electrochemical profiling based biosensor

Abstract: This paper describes an amperometric method for studying DNA-drug candidate interactions. It uses an automatted electrochemical biosensor (MiSens®) based on real-time electrochemical profiling and gold nanoparticles. A biochip was prepared from a 10 x 20 mm silicon dioxide wafer. The biochip surface is modified with a self-assembled monolayer and integrated into the microfluidic system. All the steps of the DNA-drug interaction assay have been performed during fluid flow. Biotinylated surface DNA has been captured on a NeutrAvidin -modified biochip surface. Hybridization of the complementary target sequence and biotinylated detection probe to the surface DNA strand was studied with and without the addition of newly synthesised drug candidates. NeutrAvidin and enzyme modified gold nanoparticles were then injected to bind to the biochip surface. The real-time reading of the amperometric response during the substrate injection results in the biosensor signal. The DNA interaction analysis was exemplarily applied to test the activity of paraben-substituted cyclotriphosphazenes as potential anticancer agents. Two of the synthesised compounds were identified that are capable of inducing DNA damage by 27 and 34%, respectively.

Design rules for combined label-free and fluorescence Bloch surface wave biosensors.

Abstract: We report on the fabrication and physical characterization of optical biosensors implementing simultaneous label-free and fluorescence detection and taking advantage of the excitation of Bloch surface waves at a photonic crystal’s truncation interface. Two types of purposely designed one-dimensional photonic crystals on molded organic substrates with micro-optics were fabricated. These crystals feature either high or low finesse of the Bloch surface wave resonances and were tested on the same optical readout system. The experimental results show that designing biochips with a large resonance quality factor does not necessarily lead in the real case to an improvement of the biosensor performance. The conditions for optimal biochip design and operation of the complete bio-sensing platform are established.

Advances in Testing Techniques for Digital Microfluidic Biochips

Abstract: With the advancement of digital microfluidics technology, applications such as on-chip DNA analysis, point of care diagnosis and automated drug discovery are common nowadays. The use of Digital Microfluidics Biochips (DMFBs) in disease assessment and recognition of target molecules had become popular during the past few years. The reliability of these DMFBs is crucial when they are used in various medical applications. Errors found in these biochips are mainly due to the defects developed during droplet manipulation, chip degradation and inaccuracies in the bio-assay experiments. The recently proposed Micro-electrode-dot Array (MEDA)-based DMFBs involve both fluidic and electronic domains in the micro-electrode cell. Thus, the testing techniques for these biochips should be revised in order to ensure proper functionality. This paper describes recent advances in the testing technologies for digital microfluidics biochips, which would serve as a useful platform for developing revised/new testing techniques for MEDA-based biochips. Therefore, the relevancy of these techniques with respect to testing of MEDA-based biochips is analyzed in order to exploit the full potential of these biochips.

Label-Free Biochips for Accurate Detection of Prostate Cancer in the Clinic: Dual Biomarkers and Circulating Tumor Cells.

Abstract: Purpose: Early diagnosis of prostate cancer (PCa) is essential for the prevention of metastasis and for early treatment; therefore, we aimed to develop a simple, accurate, and multi-analyte assay system for early PCa diagnosis in this study. Experimental design: We fabricated three kinds of biochips then integrated into microfluidic device for simultaneous detection of vascularendothelial growth factor (VEGF), prostate-specific antigen (PSA), and PCa circulating tumor cells (CTC) in human serum for accurate diagnosis of PCa. Then the integrated device can be put in the ELISA reader for signal analysis after sample incubation, no necessary of further fluorescence staining or microscopy counting. Result: The integrated device has wide liner detection ranges (0.05-25 ng/mL for both PSA and VEGF, and 5-300 cells/mL for PCa CTC), as well as high levels of sensitivity and selectivity, and demonstrated a high correlation with an enzyme-linked immunosorbent assay for sample detection in patients. Also, the presented biochips could maintain their stability when stored at 37°C for 49 days without significant differences in the red-shift (<5%). Conclusions: We have successfully developed a multi-analyte sensing system for rapid and easy detection of PSA, VEGF, and PC3 cells in PCa samples using label-free glass-based chips. This method presents the advantages of a broad working range, high specificity, label-free, high-speed, stability, and low cost detection method for point-of-care testing of PCa.

Sample Preparation on Micro-Electrode-Dot-Array Digital Microfluidic Biochips

Abstract: Sample preparation in digital microfluidics refers to the generation of droplets with target concentrations for onchip biochemical applications. In recent years, digital microfluidic biochips (DMFBs) have been adopted as a platform for sample preparation. However, there remain one major problem associated with sample preparation on a conventional DMFB. For conventional DMFBs, only a (1:1) mixing/splitting model can be used, leading to an increase in the number of fluidic operations required for sample preparation. To overcome the drawback, we adopt a next generation DMFB platform, referred to as micro-electrode-dot-array (MEDA), for sample preparation. We propose the first sample preparation method that exploits the MEDA-specific advantages of fine-grained control of droplet sizes and real-time droplet sensing. Experimental demonstration using a fabricated MEDA biochip and simulation results highlight the effectiveness of the proposed sample-preparation method.

System-level integration of active silicon photonic biosensors

Abstract: Biosensors based on silicon photonic integrated circuits have attracted a growing interest in recent years. The use of sub-micron silicon waveguides to propagate near-infrared light allows for the drastic reduction of the optical system size, while increasing its complexity and sensitivity. Using silicon as the propagating medium also leverages the fabrication capabilities of CMOS foundries, which offer low-cost mass production. Researchers have deeply investigated photonic sensor devices, such as ring resonators, interferometers and photonic crystals, but the practical integration of silicon photonic biochips as part of a complete system has received less attention. Herein, we present a practical system-level architecture which can be employed to integrate the aforementioned photonic biosensors. We describe a system based on 1 mm2 dies that integrate germanium photodetectors and a single light coupling device. The die are embedded into a 16x16 mm2 epoxy package to enable microfluidic and electrical integration. First, we demonstrate a simple process to mimic Fan-Out Wafer-level-Packaging, which enables low-cost mass production. We then characterize the photodetectors in the photovoltaic mode, which exhibit high sensitivity at low optical power. Finally, we present a new grating coupler concept to relax the lateral alignment tolerance down to ± 50 μm at 1-dB (80%) power penalty, which should permit non-experts to use the biochips in a“plug-and-play” style. The system-level integration demonstrated in this study paves the way towards the mass production of low-cost and highly sensitive biosensors, and can facilitate their wide adoption for biomedical and agro-environmental applications.