Low-Cost Electronic Microfluidics for Multiplexed Point-of-Care Biomarker Detection
Name
kikkeri-kkikkeri-phd-eecs-2024-thesis.pdf
Description
Thesis PDF
Size
4.43 MB
Format
Adobe PDF
Checksum (MD5)
a60113be12b1c806e34de0e10b486f15
Author(s)
Kikkeri, Kruthika
Advisor(s)
Voldman, Joel
Date Issued
May 2024
Publisher
Massachusetts Institute of Technology
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.
MIT Department
Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science
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