Microfluidic very large-scale integration for biochips: Technology, testing and fault-tolerant design

Abstract

Abstract-Microfluidic biochips are replacing the conventional biochemical analyzers by integrating all the necessary functions for biochemical analysis using microfluidics. Biochips are used in many application areas, such as, in vitro diagnostics, drug discovery, biotech and ecology. The focus of this paper is on continuous-flow biochips, where the basic building block is a microvalve. By combining these microvalves, more complex units such as mixers, switches, multiplexers can be built, hence the name of the technology, "microfluidic Very Large-Scale Integration" (mVLSI). A roadblock in the deployment of microfluidic biochips is their low reliability and lack of test techniques to screen defective devices before they are used for biochemical analysis. Defective chips lead to repetition of experiments, which is undesirable due to high reagent cost and limited availability of samples. This paper presents the state-of-the-art in the mVLSI platforms and emerging research challenges in the area of continuous-flow microfluidics, focusing on testing techniques and fault-tolerant design.

Computer-Aided Design of Microfluidic Circuits

“…By utilizing the concepts of flow paths and cut-sets, Liu and colleagues (61) designed an optimized methodology for fault detection in FPVAs. For general continuous microfluidic designs, Araci and colleagues (62) proposed a faulttolerant design strategy with which failed valves or channels can be managed. Their approach was to introduce redundancy so as to allow for application execution on a failed device.…”

Experimental Study on SPR Array Sensing Chip Integrated with Microvalves

“…Quake et al used pneumatic microfluidic chips to realize the large-scale integration of thousands of microvalves and hundreds of reactors on microfluidic chips, with a density of thousands of microvalves per square centimeter, which became an important technological breakthrough in the field of microfluidic chips [ 15 ]. Araci et al proposed the ultra-large-scale integration of pneumatic microfluidic chips with a density of millions of microvalves per square centimeter [ 16 ]. Lee et al studied the relationship between the closing performance of pneumatic membrane valves and the shape of the flow channels [ 17 ].…”

Volume management for fault-tolerant continuous-flow microfluidics

“…This can be costly because of the reduced manufacturing yield, the need to redo lengthy experiments, using expensive reagents, and can be safety-critical, e.g., in case of a cancer misdiagnosis. Researchers have started to propose fault models and test techniques for continuous flow biochips [2]. Six typical defects: Block, leak, misalignment, faulty pumps, degradation of valves and dimensional errors have been identified.…”