Concurrent testing of droplet-based microfluidic systems for multiplexed biomedical assays

We present a concurrent testing methodology for detecting catastrophic faults in droplet-based microfluidic systems and investigate the related problems of test planning and resource optimization. We apply this methodology to a droplet-based microfluidic array that was fabricated and used to perform multiplexed glucose and lactate assays. The test approach interleaves test application with the biomedical assays and prevents resource conflicts. We show that an integer linear programming model can be used to minimize testing time for a given hardware overhead due to droplet dispensing sources and capacitive sensing circuitry. The proposed approach is therefore directed at ensuring high reliability and availability of bio-MEMS and lab-on-a-chip systems, as they are increasingly deployed for safety-critical applications.

[1]  R. Fair,et al.  Electrowetting-based actuation of liquid droplets for microfluidic applications , 2000 .

[2]  Cornelis A. Grimbergen,et al.  Robotics in minimally invasive surgery , 2004, 2004 IEEE International Conference on Systems, Man and Cybernetics (IEEE Cat. No.04CH37583).

[3]  Brian N. Johnson,et al.  An integrated nanoliter DNA analysis device. , 1998, Science.

[4]  Fei Su,et al.  Testing of droplet-based microelectrofluidic systems , 2003, International Test Conference, 2003. Proceedings. ITC 2003..

[5]  R. Fair,et al.  CLINICAL DIAGNOSTICS ON HUMAN WHOLE BLOOD, PLASMA, SERUM, URINE, SALIVA, SWEAT, AND TEARS ON A DIGITAL MICROFLUIDIC PLATFORM , 2003 .

[6]  Z. Memish,et al.  Bioterrorism--a new challenge for public health. , 2003, International journal of antimicrobial agents.

[7]  Hans G. Kerkhoff.  Testing philosophy behind the micro analysis system , 1999, Design, Test, Integration, and Packaging of MEMS/MOEMS.

[8]  R. Fair,et al.  A digital microfluidic biosensor for multianalyte detection , 2003, The Sixteenth Annual International Conference on Micro Electro Mechanical Systems, 2003. MEMS-03 Kyoto. IEEE.

[9]  R. Fair,et al.  Electrowetting-based actuation of droplets for integrated microfluidics. , 2002, Lab on a chip.

[10]  Albert K. Henning,et al.  Microfluidic MEMS , 1998, 1998 IEEE Aerospace Conference Proceedings (Cat. No.98TH8339).

[11]  S. Cho,et al.  Towards digital microfluidic circuits: creating, transporting, cutting and merging liquid droplets by electrowetting-based actuation , 2002, Technical Digest. MEMS 2002 IEEE International Conference. Fifteenth IEEE International Conference on Micro Electro Mechanical Systems (Cat. No.02CH37266).

[12]  E.L. Lawler,et al.  Optimization and Approximation in Deterministic Sequencing and Scheduling: a Survey , 1977 .

[13]  Hans G. Kerkhoff,et al.  Testable design and testing of micro-electro-fluidic arrays , 2003, Proceedings. 21st VLSI Test Symposium, 2003..

[14]  A K Saeed,et al.  Bioterrorism and biodefence. , 2001, Journal of Ayub Medical College, Abbottabad : JAMC.

[15]  Salvador Mir,et al.  Extending fault-based testing to microelectromechanical systems , 1999, ETW.

[16]  N. F. de Rooij,et al.  Microfluidics meets MEMS , 2003, Proc. IEEE.

[17]  W Menz,et al.  Microstructure technologies and their potential in medical applications. , 1994, Minimally invasive neurosurgery : MIN.

[18]  Hans G. Kerkhoff,et al.  Fault Modeling and Fault Simulation in Mixed Micro-Fluidic Microelectronic Systems , 2001, J. Electron. Test..

[19]  F. Dietrich,et al.  INVESTIGATION OF ELECTROWETTING-BASED MICROFLUIDICS FOR REAL-TIME PCR API’LICATIONS , 2003 .

[20]  Bernhard H Weigl,et al.  Microfluidic technologies in clinical diagnostics. , 2002, Clinica chimica acta; international journal of clinical chemistry.

[21]  R. D. Blanton,et al.  Development of a MEMS testing methodology , 1997, Proceedings International Test Conference 1997.

[22]  H. Hull,et al.  Smallpox and bioterrorism: public-health responses. , 2003, Journal of Laboratory and Clinical Medicine.

[23]  S. Shoji.  Microfabrication technologies and micro-flow devices for chemical and bio-chemical micro flow systems , 1999, Digest of Papers. Microprocesses and Nanotechnology '99. 1999 International Microprocesses and Nanotechnology Conference.

[24]  Phil Paik,et al.  Rapid droplet mixers for digital microfluidic systems. , 2003, Lab on a chip.

[25]  R. D. Blanton,et al.  Analysis of failure sources in surface-micromachined MEMS , 2000, Proceedings International Test Conference 2000 (IEEE Cat. No.00CH37159).