[go: up one dir, main page]
More Web Proxy on the site http://driver.im/ skip to main content
research-article

Robust In-Field Testing of Digital Microfluidic Biochips

Published: 21 September 2017 Publication History

Abstract

Microfluidic technology offers vast promise for implementing biochemistry-on-chip with diverse applications to clinical diagnosis, genome analysis, drug design, and point-of-care testing. Among various types of fluid-chips, droplet-based digital microfluidic biochips (DMFBs), which consist of a patterned array of controllable electrodes, provide the advantage of programmability, ease of fluidic operations, and versatile droplet mobility. However, because of manufacturing or field defects, electrode degradation, or dielectric breakdown, these chips may suffer from incorrect fluidic behavior. Reliability of fluidic operations is of utmost concern in DMFBs that are used to perform safety-critical bio-protocols. Various methods are deployed to test these devices, either offline or being overlapped with bioassay operations (termed as concurrent or in-field testing). The main challenge of in-field testing lies in the fact that the test must run concurrently with the execution of the normal assay without hampering the correctness of the latter. In prior work, optimal testing for droplet mobility over all electrodes was formulated in terms of finding either a Hamiltonian path or a Eulerian path in an undirected graph that represents the electrode-adjacency structure. Although these models have been studied for offline testing, no such effort was made in the area of concurrent testing. In this work, we propose, for in-field application, an SAT-based modeling and solution approach to find an optimal test plan that can be used to check droplet movement across the boundary between every pair of adjacent electrodes, which is visited by the droplets of the ongoing assay. The proposed method is robust and determines a test solution successfully regardless of the cover assay that is being executed concurrently. Experiments on several real-life assays and other test cases demonstrate the effectiveness of the method with respect to test completion time.

References

[1]
Q. Al-Gayem, H. Liu, A. Richardson, and N. Burd. 2011. Test strategies for electrode degradation in bio-fluidic microsystems. Journal of Electronic Testing: Theory and Applications 27, 1 (2011), 57--68.
[2]
S. Bhattacharjee, A. Banerjee, K. Chakrabarty, and B. B. Bhattacharya. 2014. Correctness checking of bio-chemical protocol Realizations on a digital microfluidic biochip. In International Conference on VLSI Design (VLSID’14). 504--509.
[3]
K. Chakrabarty and F. Su. 2007. Digital Microfluidic Biochips: Synthesis, Testing, and Reconfiguration Techniques. CRC Press, New York.
[4]
L. M. de Moura and N. Bjørner. 2008. Z3: An efficient SMT solver. In Proceedings of TACAS. 337--340 [Z3 is available at https://github.com/Z3Prover/z3].
[5]
N. Deo. 1994. Graph Theory with Applications to Engineering and Computer Science. Prentice-Hall of India Pvt.
[6]
T. A. Dinh, S. Yamashita, T.-Y. Ho, and K. Chakrabarty. 2015. A general testing method for digital microfluidic biochips under physical constraints. In IEEE International Test Conference (ITC’15). 1--8.
[7]
R. B. Fair, A. Khlystov, T. D. Tailor, V. Ivanov, R. D. Evans, P. B. Griffin, V. Srinivasan, V. K. Pamula, M. G. Pollack, and J. Zhou. 2007. Chemical and biological applications of digital-microfluidic devices. IEEE Design and Test of Computers 24, 1 (2007), 10--24.
[8]
M. R. Garey and D. V. Johnson. 1990. Computers and Intractability; A Guide to the Theory of NP-Completeness. W. H. Freeman 8 Co., New York.
[9]
L. Gervais, N. de Rooij, and E. Delamarche. 2011. Microfluidic chips for point-of-care immunodiagnostics. Advanced Materials 23, 24 (June2011), H151--H176.
[10]
K. Hu, B. N. Hsu, A. Madison, K. Chakrabarty, and R. Fair. 2013. Fault detection, real-time error recovery, and experimental demonstration for digital microfluidic biochips. In Proceedings of DATE. 559--564.
[11]
K. Hu, M. Ibrahim, L. Chen, Z. Li, K. Chakrabarty, and R. Fair. 2015. Experimental demonstration of error recovery in an integrated cyberphysical digital-microfluidic platform. In Proceedings of BioCAS. 1--4.
[12]
J.-D. Huang, C.-H. Liu, and T.-W. Chiang. 2012. Reactant minimization during sample preparation on digital microfluidic biochips using skewed mixing trees. In IEEE/ACM International Conference on Computer-Aided Design (ICCAD’12). 377--383.
[13]
M. J. Jebrail and A. R. Wheeler. 2010. Let’s get digital: Digitizing chemical biology with microfluidics. Current Opinion in Chemical Biology 14, 5 (2010), 574--581.
[14]
O. Keszocze, R. Wille, K. Chakrabarty, and R. Drechsler. 2015. A general and exact routing methodology for digital microfluidic biochips. In International Conference on Computer Aided Design (ICCAD’15). 874--881.
[15]
O. Keszocze, R. Wille, and R. Drechsler. 2014. Exact routing for digital microfluidic biochips with temporary blockages. In International Conference on Computer Aided Design (ICCAD’14). 405--410.
[16]
O. Keszocze, R. Wille, T. Y. Ho, and R. Drechsler. 2014. Exact one-pass synthesis of digital microfluidic biochips. In Design Automation Conference (DAC’14). 1--6.
[17]
D. Kroening and O. Strichman. 2008. Decision Procedures for Propositional Logic. Springer, Berlin, 25--57.
[18]
Y. S. Mahajan, Z. Fu, and S. Malik. 2004. Zchaff2004: An efficient SAT solver. In International Conference on Theory and Applications of Satisfiability Testing. 360--375.
[19]
D. Mitra, S. Ghoshal, H. Rahaman, K. Chakrabarty, and B. B. Bhattacharya. 2011. Test planning in digital microfluidic biochips using efficient Eulerization techniques. Journal of Electronic Testing: Theory and Applications 27, 5 (2011), 657--671.
[20]
D. Mitra, S. Ghoshal, H. Rahaman, K. Chakrabarty, and B. B. Bhattacharya. 2012. On-line error detection in digital microfluidic biochips. In Proceedings of the Asian Test Symposium. 332--337.
[21]
A. Papathanasiou and A. Boudouvis. 2005. Manifestation of the connection between dielectric breakdown strength and contact angle saturation in electrowetting. Applied Physics Letters 86 (2005), 164102.
[22]
B. Pasaniuc, R. S. Garfinkel, I. I. Mandoiu, and A. Zelikovsky. 2011. Optimal testing of digital microfluidic biochips. INFORMS Journal on Computing 23, 4 (2011), 518--529.
[23]
S. Roy, S. Kumar, P. P. Chakrabarti, B. B. Bhattacharya, and K. Chakrabarty. 2014. Demand-driven mixture preparation and droplet streaming using digital microfluidic biochips. In Design Automation Conference (DAC’14). 144:1--144:6.
[24]
R. Sista, Z. Hua, P. Thwar, A. Sudarsan, V. Srinivasan, A. Eckhardt, M. Pollack, and V. Pamula. 2008. Development of a digital microfluidic platform for point of care testing. Lab-on-a-Chip 8, 12 (2008), 2091--2104.
[25]
F. Su, W. Hwang, and K. Chakrabarty. 2006. Droplet routing in the synthesis of digital microfluidic biochips. In Design Automation Test in Europe (DATE’06) Conference, Vol. 1. 1--6.
[26]
F. Su, W. Hwang, A. Mukherjee, and K. Chakrabarty. 2007. Testing and diagnosis of realistic defects in digital microfluidic biochips. Journal of Electronic Testing: Theory and Applications 23, 5 (2007), 219--233.
[27]
F. Su, S. Ozev, and K. Chakrabarty. 2003. Testing of droplet-based microelectrofluidic systems. In International Test Conference (ITC’03). 1192--1200.
[28]
F. Su, S. Ozev, and K. Chakrabarty. 2005. Ensuring the operational health of droplet-based microelectrofluidic biosensor systems. IEEE Sensors Journal 5, 4 (2005), 763--773.
[29]
F. Su, S. Ozev, and K. Chakrabarty. 2006. Concurrent testing of digital microfluidics-based biochips. ACM Transactions on Design Automation of Electronic Systems 11, 2 (2006), 442--464.
[30]
L. Zhang, J. J. Mei, B. W. Yan, and Q. Gao. 2014. A test droplets dispensing solution for digital microfluidic biochip parallel testing. In Micro-Nano Technology XV, Vol. 609. 670--674.

Cited By

View all
  • (2022)Parallel testing optimization method of digital microfluidic biochipMeasurement10.1016/j.measurement.2022.111018194(111018)Online publication date: May-2022
  • (2019)Micro-Electrode-Dot-Array Digital Microfluidic Biochips: Technology, Design Automation, and Test TechniquesIEEE Transactions on Biomedical Circuits and Systems10.1109/TBCAS.2018.288695213:2(292-313)Online publication date: Apr-2019
  • (2018)IntroductionMicro-Electrode-Dot-Array Digital Microfluidic Biochips10.1007/978-3-030-02964-7_1(1-20)Online publication date: 15-Dec-2018

Recommendations

Comments

Please enable JavaScript to view thecomments powered by Disqus.

Information & Contributors

Information

Published In

cover image ACM Journal on Emerging Technologies in Computing Systems
ACM Journal on Emerging Technologies in Computing Systems  Volume 14, Issue 1
January 2018
289 pages
ISSN:1550-4832
EISSN:1550-4840
DOI:10.1145/3143783
  • Editor:
  • Yuan Xie
Issue’s Table of Contents
Permission to make digital or hard copies of all or part of this work for personal or classroom use is granted without fee provided that copies are not made or distributed for profit or commercial advantage and that copies bear this notice and the full citation on the first page. Copyrights for components of this work owned by others than ACM must be honored. Abstracting with credit is permitted. To copy otherwise, or republish, to post on servers or to redistribute to lists, requires prior specific permission and/or a fee. Request permissions from [email protected]

Publisher

Association for Computing Machinery

New York, NY, United States

Journal Family

Publication History

Published: 21 September 2017
Accepted: 01 July 2017
Revised: 01 May 2017
Received: 01 March 2017
Published in JETC Volume 14, Issue 1

Permissions

Request permissions for this article.

Check for updates

Author Tags

  1. Biochips
  2. digital microfluidics
  3. in-field testing

Qualifiers

  • Research-article
  • Research
  • Refereed

Funding Sources

  • INAE Chair Professorship
  • special PPEC-funded grant to Nanotechnology Research Triangle provided by Indian Statistical Institute

Contributors

Other Metrics

Bibliometrics & Citations

Bibliometrics

Article Metrics

  • Downloads (Last 12 months)20
  • Downloads (Last 6 weeks)2
Reflects downloads up to 01 Jan 2025

Other Metrics

Citations

Cited By

View all
  • (2022)Parallel testing optimization method of digital microfluidic biochipMeasurement10.1016/j.measurement.2022.111018194(111018)Online publication date: May-2022
  • (2019)Micro-Electrode-Dot-Array Digital Microfluidic Biochips: Technology, Design Automation, and Test TechniquesIEEE Transactions on Biomedical Circuits and Systems10.1109/TBCAS.2018.288695213:2(292-313)Online publication date: Apr-2019
  • (2018)IntroductionMicro-Electrode-Dot-Array Digital Microfluidic Biochips10.1007/978-3-030-02964-7_1(1-20)Online publication date: 15-Dec-2018

View Options

Login options

Full Access

View options

PDF

View or Download as a PDF file.

PDF

eReader

View online with eReader.

eReader

Media

Figures

Other

Tables

Share

Share

Share this Publication link

Share on social media