UCLA

Analysis of biomarkers, biomolecular indicators of medical conditions, is fundamental to the diagnosis and the medicinal research of various diseases and other human physiological conditions. These biomarkers are usually found in complex biological samples and almost always require multi-step sample processing before the key information of the relevant biomarkers could be extracted for analysis. The sample processing procedures are associated with the performance metrics of the assay, such as the sensitivity and accuracy of the result, and therefore is critical to the reliability of the diagnosis result or the goal of the research missions. Furthermore, such sample processing procedures often start with a limited volume available from the subjects and involve a series of technical steps tailored towards the target biomarkers resulting in process complexity.

The application of microfluidic platform technologies to biological sample processing and corresponding assays demonstrated great potential in advancing biomarker analysis, both in simplifying assay processes by means such as miniaturization, automation, and cost reduction; and in improving assay performance on metrics such as sensitivity, assay time, throughput, etc.

This work explores microfluidic solutions to improving sample processing procedures, especially by means of process automation; and enhancing the sensitivity metrics of assay performances, targeting the analysis of single entities. The first two chapters covers the development of digitalized affinity assays for single-molecule detection, where we achieved counting of single enzyme reactions using a novel lab-on-a-particle assay mechanism. We demonstrated digital counting of β-galactosidase enzyme at a femtomolar detection limit with a dynamic range of 3 orders of magnitude using standard benchtop equipment and experiment techniques. The third chapter presents an innovative ferrobot platform to address process automation for sample processing. This electromagnetic platform is capable of performing massively parallelized and sequential fluidic operations cross-collaboratively to complete pipelined bioassays with high efficiency and flexibility. In the fourth and final chapter, we established a multiferroic system deployed for time-lapse single-cell functional profiling, featuring both single entity analysis capacity and automation potential.