Browsing by Author "Li, Zipeng"

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Built-In Self-Test for Micro-Electrode-Dot-Array Digital Microfluidic Biochips
(2016)
Li, Zipeng
;
Lai, Kelvin Yi-Tse
;
Yu, Po-Hsien
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Chakrabarty, Krishnendu
;
Ho, Tsung-Yi
A digital microfluidic biochip (DMFB) is an attractive platform for immunoassays, point-of-care clinical diagnostics, DNA sequencing, and other laboratory procedures in biochemistry. However, today\'s DMFBs suffer from several limitations, including (i) the lack of integrated sensors for real-time detection, (ii) constraints on droplet size and the inability to vary droplet volume in a fine-grained manner, and (iii) the need for special fabrication processes and the associated reliability/yield concerns. To overcome the above limitations, DMFBs based on a micro-electrode-dot-array (MEDA) architecture have been proposed recently. Droplet manipulation on MEDA biochips has also been experimentally demonstrated. In order to ensure robust fluidic operations and high confidence in the outcome of biochemical experiments, MEDA biochips must be adequately tested before they can be used for bioassay execution. We present an efficient built-in self-test (BIST) architecture for MEDA biochips. The proposed BIST architecture can effectively detect defects in a MEDA biochip, and faulty microcells can be identified. Simulation results based on HSPICE and experiments using fabricated MEDA biochips highlight the effectiveness of the proposed BIST architecture.
Design and Optimization of 3D Digital Microfluidic Biochips for the Polymerase Chain Reaction
(2015)
Li, Zipeng
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Ho, Tsung-Yi
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Chakrabarty, Krishnendu
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資訊工程學系
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Department of Computer Science
A digital microfluidic biochip (DMFB) is an attractive technology platform for revolutionizing immunoassays, clinical diagnostics, drug discovery, DNA sequencing, and other laboratory procedures in biochemistry. In most of these applications, real-time polymerase chain reaction (PCR) is an indispensable step for amplifying specific DNA segments. In recent years, three-dimensional (3D) DMFBs that integrate photodetectors (i.e., cyberphysical DMFBs) have been developed. They offer the benefits of smaller size, higher sensitivity and quicker time-to-results. However, current DMFB design methods target optimization in only two dimensions, hence they ignore the 3D two-layer structure of a DMFB. Moreover, these techniques ignore practical constraints related to the interference between on-chip device pairs, the performance-critical PCR thermal loop, and the physical size of devices. In this paper, we describe an optimization solution for a 3D DMFB, and present a three-stage algorithm to realize a compact 3D PCR chip layout, which includes: (i) PCR thermal-loop optimization; (ii) 3D global placement based on Strong-Push-Weak-Pull (SPWP) model; (iii) constraint-aware legalization. Simulation results for four laboratory protocols demonstrate that the proposed approach is effective for the design and optimization of a 3D chip for real-time PCR.
Droplet Size-Aware and Error-Correcting Sample Preparation Using Micro-Electrode-Dot-Array Digital Microfluidic Biochips
(2017-12-01)
Li, Zipeng
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Lai, Kelvin Yi-Tse
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Chakrabarty, Krishnendu
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Ho, Tsung-Yi
;
Lee, Chen-Yi
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.
Droplet Size-Aware High-Level Synthesis for Micro-Electrode-Dot-Array Digital Microfluidic Biochips
(2017-06-01)
Li, Zipeng
;
Lai, Kelvin Yi-Tse
;
Yu, Po-Hsien
;
Chakrabarty, Krishnendu
;
Ho, Tsung-Yi
A digital microfluidic biochip (DMFB) is an attractive technology platform for automating laboratory procedures in biochemistry. In recent years, DMFBs based on a microelectrodedot- 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.
Efficient and Adaptive Error Recovery in a Micro-Electrode-Dot-Array Digital Microfluidic Biochip
(2018-03-01)
Li, Zipeng
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Lai, Kelvin Yi-Tse
;
McCrone, John
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Yu, Po-Hsien
;
Chakrabarty, Krishnendu
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 proposed. MEDA biochips can provide advantages of better capability of droplet manipulation and real-time sensing ability. However, errors are likely to occur due to defects, chip degradation, and the lack of precision inherent in biochemical experiments. Therefore, an efficient error-recovery strategy is essential to ensure the correctness of assays executed on MEDA biochips. By exploiting MEDA-specific advances in droplet sensing, we present a novel error-recovery technique to dynamically reconfigure the biochip using real-time data provided by on-chip sensors. Local recovery strategies based on probabilistic-timed-automata are presented for various types of errors. An online synthesis technique and a control flow are also proposed to connect local-recovery procedures with global error recovery for the complete bioassay. Moreover, an integer linear programming-based method is also proposed to select the optimal local-recovery time for each operation. Laboratory experiments using a fabricated MEDA chip are used to characterize the outcomes of key droplet operations. The PRISM model checker and three benchmarks are used for an extensive set of simulations. Our results highlight the effectiveness of the proposed error-recovery strategy.
Error Recovery in a Micro-Electrode-Dot-Array Digital Microfluidic Biochip
(2016)
Li, Zipeng
;
Lai, Kelvin Yi-Tse
;
Yu, Po-Hsien
;
Chakrabarty, Krishnendu
;
Pajic, Miroslav
A digital microfluidic biochip (DMFB) is an attractive technology platform for automating laboratory procedures in biochemistry. However, today\'s DMFBs suffer from several limitations: (i) constraints on droplet size and the inability to vary droplet volume in a fine-grained manner; (ii) the lack of integrated sensors for real-time detection; (iii) the need for special fabrication processes and the associated reliability/yield concerns. To overcome the above problems, DMFBs based on a micro-electrode-dot-array (MEDA) architecture have been proposed recently, and droplet manipulation on these devices has been experimentally demonstrated. Errors are likely to occur due to defects, chip degradation, and the lack of precision inherent in biochemical experiments. Therefore, an efficient error-recovery strategy is essential to ensure the correctness of assays executed on MEDA biochips. By exploiting MEDA-specific advances in droplet sensing, we present a novel error-recovery technique to dynamically reconfigure the biochip using real-time data provided by on-chip sensors. Local recovery strategies based on probabilistic-timed-automata are presented for various types of errors. A control flow is also proposed to connect local recovery procedures with global error recovery for the complete bioassay. Laboratory experiments using a fabricated MEDA chip are used to characterize the outcomes of key droplet operations. The PRISM model checker and three analytical chemistry benchmarks are used for an extensive set of simulations. Our results highlight the effectiveness of the proposed error-recovery strategy.
High-Level Synthesis for Micro-Electrode-Dot-Array Digital Microfluidic Biochips
(2016)
Li, Zipeng
;
Lai, Kelvin Yi-Tse
;
Yu, Po-Hsien
;
Ho, Tsung-Yi
;
Chakrabarty, Krishnendu
A digital microlluidic biochip (DMFB) is an attractive technology platform for automating laboratory procedures in biochemistry. However, today\'s DMFBs suffer from several limitations: (i) constraints on droplet size and the inability to vary droplet volume in a fine-grained manner; (ii) the lack of integrated sensors for real-time detection; (iii) the need for special fabrication processes and reliability/yield concerns. To overcome the above problems, DMFBs based on a micro-electrode-dot-array (MEDA) architecture have recently been demonstrated. However, due to the inherent differences between today\'s DMFBs and MEDA, existing synthesis solutions cannot he utilized for MEDA-based biochips. We present the first biochip synthesis approach that can be used for MEDA. The proposed synthesis method targets 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 co-optimization technique.
High-Level Synthesis for Micro-Electrode-Dot-Array Digital Microfluidic Biochips
(2016)
Li, Zipeng
;
Lai, Kelvin Yi-Tse
;
Yu, Po-Hsien
;
Ho, Tsung-Yi
;
Chakrabarty, Krishnendu
digital microfluidic biochip (DMFB) is an attractive technology platform for automating laboratory procedures in biochemistry. However, today\'s DMFBs suffer from several limitations: (i) constraints on droplet size and the inability to vary droplet volume in a fine-grained manner; (ii) the lack of integrated sensors for real-time detection; (iii) the need for special fabrication processes and reliability/yield concerns. To overcome the above problems, DMFBs based on a micro-electrode-dot-array (MEDA) architecture have recently been demonstrated. However, due to the inherent differences between today\'s DMFBs and MEDA, existing synthesis solutions cannot be utilized for MEDA-based biochips. We present the first biochip synthesis approach that can be used for MEDA. The proposed synthesis method targets 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 co-optimization technique.
Micro-Electrode-Dot-Array Digital Microfluidic Biochips: Technology, Design Automation, and Test Techniques
(2019-04-01)
Zhong, Zhanwei
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Li, Zipeng
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Chakrabarty, Krishnendu
;
Ho, Tsung-Yi
;
Lee, Chen-Yi
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.
Structural and Functional Test Methods for Micro-Electrode-Dot-Array Digital Microfluidic Biochips
(2018-05-01)
Li, Zipeng
;
Lai, Kelvin Yi-Tse
;
Yu, Po-Hsien
;
Chakrabarty, Krishnendu
;
Ho, Tsung-Yi
A digital microfluidic biochip (DMFB) is an attractive platform for immunoassays, point-of-care clinical diagnostics, DNA sequencing, and other laboratory procedures in biochemistry. More recently, DMFBs based on a micro-electrode-dot-array (MEDA) architecture have been proposed, and droplet manipulations on MEDA biochips have also been experimentally demonstrated. In order to ensure robust fluidic operations and high confidence in the outcome of biochemical experiments, MEDA biochips must be adequately tested before they can be used for bioassay execution. This paper presents the first approach for testing of MEDA biochips that include both CMOS circuits and microfluidic components. We first present structural test techniques to evaluate the pass/fail status of each microcell (droplet actuation, droplet maintenance, and droplet sensing) and identify faulty microcells. In order to ensure correct operation of functional units, e.g., mixers and diluters, we also present functional test techniques to address fundamental MEDA operations, such as droplet dispensing, transportation, mixing, and splitting. We evaluate the proposed test methods using simulations as well as experiments for fabricated MEDA biochips.