Development of a microfluidic fluorescence immunosensor for Point-of-Care diagnostics
Rapid and affordable point-of-care (POC) diagnostics with superior sensitivity are urgently needed in many scenarios of our society from home health care and disease outbreaks to doctors’ practice and biodefense. Currently, most critical diagnostic tests are still conducted in clinical laboratories with enzyme-linked immunosorbent assay (ELISA). Although ELISA provides a quantitative, specific and sensitive detection approach for analyzing a plethora of biological agents, it often requires relatively long incubation times and multi-step fluid handling by highly trained personnel, which therefore is not suitable for POC diagnostics. Over the past two decades, microfluidics, given its superior abilities to manipulate small volumes of liquid in an automated fashion, has shown a tremendous potential to bring conventional clinical diagnosis to the POC. It is a rapidly advancing research field with many exciting achievements and unfulfilled promises. “The Holy Grail” of microfluidics-based POC diagnostics is to offer a hand-held/portable, self-calibrating, automated, and inexpensive device that is capable of performing rapid, specific, sensitive, and quantitative tests for biomolecules using minimal raw samples at resource-poor settings.^ Keeping this aim in mind, the research conducted in this dissertation focuses on exploring novel solutions and developing essential components that can be beneficial to microfluidics-based POC diagnostics. Chapter 1 presents an ultrafast quantitative heterogeneous immunoassay (HEI) with pre-functionalized microfluidic poly(dimethylsiloxane) (PDMS) chips. In chapter 2, a method to further simplify the multi-step HEI is demonstrated with microchips. For the first time, the blocking process is eliminated from a HEI. Chapter 3 demonstrates a planar labyrinth micromixer that can be readily integrated into lab-on-a-chip devices where passive mixing is needed. Chapter 4 presents a picomolar-level sensitivity microfluidic fluorescence biosensor using a low-cost high-power light-emitting diode. A fluorescence amplification method by using biofunctional self-priming microstructures is also demonstrated with the sensor. In Chapter 5, a portable and automated immunosensor with an on-cartridge microfluidic valveless sequential loading system (ì-VSLS) is reported. The ì-VSLS enables an automation of a multi-step HEI with only one sample loading step by a user. Chapter 6 shows the potential of further enhancing the sensitivity of microfluidic immunosensors by using magnetic nanoparticles encapsulated in hyperbranched protein networks.^
Engineering, Biomedical|Engineering, Mechanical
"Development of a microfluidic fluorescence immunosensor for Point-of-Care diagnostics"
Dissertations and Master's Theses (Campus Access).