Capillary Microfluidic Chips for Point-of-Care Testing : from Research Tools to Decentralized Medical Diagnostics

Research on microfluidic devices for biological analysis has progressed sufficiently to be developed into point-of-care diagnostics products. The goal of this thesis is to improve multiple aspects of capillary-driven microfluidic devices. In particular, the objective is to provide devices with a fast time to result, that are simple to use (one-step), that can be portable, that accept a variety of samples, that operate reliably, that provide a range of detection signals, that are mass manufacturable at lost cost, and that are able to detect medically relevant biological molecules. First, we survey the evolution of microfluidic research into portable medical diagnostic devices. By looking at several gaps and opportunities in current medical diagnostics, we provide an overview of research topics that have the potential to shape the next generation of point-of-care diagnostics. Specifically we explain technologies in the order of sample interacting with different components of a device. We investigate the materials, surface treatments, sample processing, microfluidic elements (such as valves, pumps and mixers), receptors and analytes and the integration of these components into a device that might conceivably leave the laboratory for the hands of consumers. The knowledge of what is important in a point-of-care diagnostics device was used to develop a proof of concept. One of the main challenges is to make microfluidics easy to use by incorporating reagents and microfluidic elements. We integrated a number of functional elements on a chip such as a sample collector, delay valves, flow resistors, a deposition zone for detection antibodies (dAbs), a reaction chamber sealed with a polydimethylsiloxane (PDMS) substrate, and a capillary pump and vents. We further incorporated capture antibodies (cAbs), detection antibodies (dAbs) and analyte molecules for making one-step immunoassays. The integrated microfluidic chip requires only the addition of sample to trigger a sequence of events controlled by capillary forces to detect C-reactive protein (CRP), a general inflammation and cardiac marker, at a concentration of 1 ng mL-1 within 14 min using only 5 µL of human serum. The proof-of-concept is extended to easily modify several assay parameters such as the flow rates and the volumes of samples for tests, and the type of reagents and receptors for analytes. The multiparametric microfluidic chip is capable of analyzing 20 µL of human serum in 6 parallel flow paths in a range of flow rates with filling times from 10 minutes to 72 minutes. The asymmetric release of dAbs in a stream of human serum is compensated by a Dean flow mixer. Sample is equally split into 6 reaction chambers connected to flow resistances that vary flow rates, and the kinetics of capture of analyte-dAb complexes. The increased incubation time leads to a fourfold increase in detection signal in the reaction chamber with the longer incubation time. Furthermore, integrating reagents and contro