Low-Cost Electronic Microfluidics for Multiplexed Point-of-Care Biomarker Detection

Abstract

As we have seen in recent years, point-of-care (PoC) systems are vital elements in healthcare, as they can aid in disease detection, monitoring, and treatment, and even inform public policy. However, while qualitative (yes/no) PoC sensors are abundant (i.e. pregnancy tests, rapid COVID19 tests), low-cost, automated, quantitative PoC platforms are limited. Yet, given the importance of quantitative biomarker detection for nuanced analysis of patient health for chronic and fast acting diseases, there remains a persistent need for PoC systems capable of cost-effective detection of low abundance markers in blood. This thesis explores methodology for development of an automated low-cost system for the measurement of protein biomarkers in blood. By prioritizing accessibility, affordability, and automation, I focus on addressing unmet needs in PoC platform development which often prevent translation of these systems to PoC settings. Focusing primarily on cytokine biomarkers, notably IL-6, this thesis proposes modular solutions designed for seamless integration into existing clinical workflows. Chapter 2 introduces a sample-to-answer PoC workflow, consolidating blood testing steps through at-site sample collection, on-chip blood-to-plasma separation, and a bead-based electrochemical assay. Leveraging microfluidics and electronics, this system offers a rapid 30-minute assay time. It was validated by measuring spiked IL-6 concentrations in human blood, with applications demonstrated in CAR-T patient monitoring and small molecule detection for drug regulation. Chapter 3 introduces Microfluidics via Inkjet-Printing and Xurography (MINX), the first rapid prototyping technique which combines tape-based microfluidics with multiplexed electrodes. MINX was employed to fabricate low-cost PoC biosensors for detecting cytokine biomarkers. In Chapter 4, this modular fabrication method was extended to create the first integrated PoC system featuring tape-based microfluidic valves for automated fluidic and electrical controls. This MINX PoC platform was validated through detection of IL-6 in human plasma. Finally, Chapter 5 outlines future directions, emphasizing real-time dynamic control to enhance assay tunability. These advancements in PoC platforms hold promise for improving protein biomarker detection accessibility and affordability.