On-Line Testing of Lab-on-Chip Using Digital Microfluidic Compactors1Yang Zhao and Krishnendu ChakrabartyDepartment of Electrical and Computer EngineeringDuke UniversityDurham, NC 27708, USA{yz61, krish}@ee.duke.eduAbstractDependability is an important system attribute for mi-crofluidic lab-on-chip devices. On-line testing offers apromising method for detecting defects, fluidic abnormal-ities, and bioassay malfunctions during chip operation.However, previous techniques for reading test outcomes andanalyzing pulse sequences are cumbersome, sensitive tothe calibration of capacitive sensors, and error-prone. Wepresent a built-in self-test (BIST) method for on-line test-ing of digital microfluidic lab-on-chip. This method uti-lizes microfluidic compactors based on droplet-based ANDgates, which are implemented using digital microfluidics.Dynamic reconfiguration of these compactors ensures lowarea overhead and it allows BIST to be interleaved withbioassays in functional mode.1. IntroductionMicrofluidic-based lab-on-chips are being advocatedfor applications such as immunoassays, clinical diagnosisand high-throughput DNA sequencing [1]. An especiallypromising technology platform is based on the principleof electrowetting-on-dielectric. Discrete droplets of nano-liter volumes can be manipulated in a “digital” manner un-der clock control on a two-dimensional array of electrodes(“unit cells”). Hence this technology is referred to as “digi-tal microfluidics” [2].An emerging application of microfluidics lies in the useof droplets for microfluidic computing. Microfluidic com-puting inherits the advantages of both microfluidics forsensing and computing for information processing [5]. Itcan potentially enhance microfluidic technology throughdirect incorporation of computing functions on-chip with1This work was supported in part by the National Science Foundationunder grant CCF-0541055.other primary sensing functions. Digital microfluidics of-fers a promising enabling technique for on-chip logic func-tionality and for integrating sensing, computing, and on-linemonitoring.A prototype lab-on-chip has been developed for gene se-quencing through synthesis [1], which targets the simulta-neous execution of 106 fluidic operations and the process-ing of billions of droplets. Other lab-on-chip systems arebeing designed for protein crystallization, which requiresthe concurrent execution of hundreds of operations [17]. Acommercially available droplet-based lab-on-chip embedsmore than 600,000 20 µmby20µm electrodes with inte-grated optical detectors [8]. Recent years have thereforeseen growing interest in design-automation and test tech-niques for the digital microfluidic platform [7, 10, 11, 14].Test techniques for other microfluidic platforms have alsobeen developed [4].Microfluidics-based lab-on-chip devices are expected tobe deployed for safety-critical biomedical applications suchas point-of care diagnostics, health assessment and screen-ing for infectious diseases. Therefore, dependability is anessential system attribute for lab-on-chip. An increase inthe density and area of microfluidics-based lab-on-chip willlead to high defect densities, thereby reducing yield. Thesesystems need to be tested adequately not only after fabri-cation, but also continuously during in-field operation. On-line testing, which allows testing and normal biochemicalassays to run simultaneously on a microfluidic system, cantherefore play an important role. It facilitates built-in self-test (BIST) of microfluidics-based lab-on-chip systems andmakes them less dependent on costly manual maintenanceon a regular basis.A cost-effective test method for digital microfluidic sys-tems was first described in [13]. Likely physical defectsin such systems were analyzed and faults were classifiedas being either catastrophic or parametric. Further detailson defects and fault models are presented in [15]. Faultscan be detected by electrically controlling and tracking themotion of test droplets. In [12], a concurrent testing tech-14th IEEE International On-Line Testing Symposium 2008978-0-7695-3264-6/08 $25.00 © 2008 IEEEDOI 10.1109/IOLTS.2008.4521314th IEEE International On-Line Testing Symposium 2008978-0-7695-3264-6/08 $25.00 © 2008 IEEEDOI 10.1109/IOLTS.2008.45213Authorized licensed use limited to: University of North Carolina at Charlotte. Downloaded on January 18, 2010 at 21:02 from IEEE Xplore. Restrictions apply.nique is presented for detecting catastrophic faults in digitalmicrofluidics. A parallel scan-like testing methodology ofstructural test is proposed for digital microfluidic devicesin [15]. A diagnosis method based on test outcomes hasalso been proposed to locate both single and multiple de-fect sites. In [16], several techniques are proposed for thefunctional testing of droplet-based microfluidic lab-on-chip.These techniques address fundamental biochip operationssuch as droplet dispensing, droplet transportation, mixing,splitting, and capacitive sensing.Previous test methods for the digital microfluidic plat-form use capacitive-sensing circuits to read and analyzetest outcomes [12, 15, 16]. After reading the test-outcomedroplets in a consecutive manner, the capacitive sensing cir-cuit generates a pulse-sequence corresponding to the detec-tion of these droplets. This approach requires an additionalstep to analyze the pulse sequence to determine whether themicrofluidic array-under-test is defective. The reading oftest outcomes and the analysis of pulse sequences increasetest time; the latter procedure is especially prone to errorsarising from inaccuracies in sensor calibration. The com-plexity of the capacitive-sensing circuit and the need forpulse-sequence analysis make previously proposed testingmethods less practical, especially for field operation.In this paper, we propose an on-line testing methodfor digital microfluidic lab-on-chip. This method uti-lizes microfluidic compactors based on AND gates imple-mented using digital microfluidics. Using the principleof electrowetting-on-dielectric, we implement AND gatethrough basic droplet-handling operations such as trans-portation, merging, and splitting. The same input-outputinterpretation enables the cascading of gates for the imple-mentation of additional logic functions. The microfluidiccompactor can compress the test-outcome droplets into onedroplet that can be detected using a simple photo-diode de-tector, thereby avoiding the need for a
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