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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.
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.
Efficient and Adaptive Error Recovery in a Micro-Electrode-Dot-Array Digital Microfluidic Biochip
(2018-03-01)
Li, Zipeng
;
Lai, Kelvin Yi-Tse
;
McCrone, John
;
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.
Droplet Size-Aware and Error-Correcting Sample Preparation Using Micro-Electrode-Dot-Array Digital Microfluidic Biochips
(2017-12-01)
Li, Zipeng
;
Lai, Kelvin Yi-Tse
;
Chakrabarty, Krishnendu
;
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.
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.
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.
Design of a Micro-Electrode Cell for Programmable Lab-on-CMOS Platform
(2016)
Ho, Yingchieh
;
Wang, Gary
;
Lai, Kelvin Yi-Tse
;
Lug, Yi-Wen
;
Liu, Keng-Ming
This paper presents a programmable lab-on-CMOS (LoCMOS) with micro-electrode cell array. Array structure is suitable for programmable like CMOS VLSIs. In order to improve the utilization, each micro-electrode cell is composed of actuation and sensing circuit. In addition, a CMOS-compatible extended drain MOSFET (EDMOS) is adopted under a 3V supply. This LoCMOS platform is composed of 1,800 microelectrodes with exploiting EDMOS to enable droplet actuations. Through its field programmability, the chip can successfully perform all microfluidic operations, droplet moving/cutting/mixing on a 2-dimenional microelectrode cell array. Implemented in 0.35um standard CMOS process, the LoCMOS platform demonstrates microfluidic functions and droplet detection. Measured results show successfully for actuation and real-time droplet location sensing.
A 3.3V 15.6b 6.1pJ/0.02% RH with 10ms Response Humidity Sensor for Respiratory Monitoring
(2014)
Lai, Kelvin Yi-Tse
;
Yang, Yu-Tao
;
Chen, Bang-Jing
;
Shen, Chun-Jen
;
Shiu, Ming-Feng
An event-driven and energy-efficient humidity sensor for environment detection and healthcare monitoring is presented. A differential CMOS-MEMS humidity device and proportion-based capacitance-to-digit readout circuit are proposed to overcome PVT variations, and in the meantime to improve sensitivity, response time, and conversion energy. This chip achieves 15.6b 20-90 % RH at 1KS/s, 6.1pJ per 0.02% RH of sensitivity, and 10ms fast response time in TSMC 0.35-mu m CMOS MEMS process. With variations in temperature and voltage, our proposal can minimize the errors from 40% RH to 0.2% RH and 50% RH to 0.1% RH, making it very suitable for wearable respiratory monitoring.
Built-In Self-Test for Micro-Electrode-Dot-Array Digital Microfluidic Biochips
(2016)
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. 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.

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