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

Abstract

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.

Testing and Diagnosis of Realistic Defects in Digital Microfluidic Biochips

“…In addition, we investigate the problem of fault diagnosis. We apply this methodology to a real-life biochip performing multiplexed biochemical assays, and compare our results with the results reported in [20].…”

“…It is based on a graph model of the microfluidic array and a problem formulation based on Hamiltonian paths in a graph. An efficient concurrent testing method that interleaves test application with a set of bioassays was proposed in [20]. Reconfiguration and defect tolerance techniques for biochips were described in [17,21].…”

“…For example, a common defect seen in fabricated microfluidic arrays is a short-circuit between two adjacent electrodes [18]. It was assumed in [18][19][20] that this defect causes a droplet to be stuck at one of the two electrodes irrespective of the orientation of liquid flow. No attempt was made in prior work to experimentally validate this assumption.…”

“…Experiments show however that the effect of this short-circuit defect on droplet flow depends on whether the droplet flow path is perpendicular to the two shorted electrodes or aligned with them. A test procedure for such defects should therefore not only test single cells as in [18][19][20], but it should also focus on pairs of cells and the traversal of droplets from one cell to all its neighbors. In addition, no systematic attempt has been made to relate defects to fault models and observable errors.…”

Design of Fault-Tolerant and Dynamically-Reconfigurable Microfluidic Biochips

“…This cost-effective test methodology facilitates on-line testing, which allows fault testing and biochemical assays to run simultaneously on a microfluidicsbased biochip [14].…”