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Voldman, Joel Kikkeri, Kruthika Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science 2024-08-21T18:54:54Z 2024-08-21T18:54:54Z 2024-05 2024-07-10T13:01:37.601Z https://hdl.handle.net/1721.1/156298 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. Ph.D. Massachusetts Institute of Technology In Copyright - Educational Use Permitted Copyright retained by author(s) https://rightsstatements.org/page/InC-EDU/1.0/ Low-Cost Electronic Microfluidics for Multiplexed Point-of-Care Biomarker Detection Thesis application/pdf Doctoral Doctor of Philosophy Publication unknown unknown <Publication xmlns="https://www.openaire.eu/cerif-profile/1.1/" id="762c89e2-a463-42a8-a077-2388c744ba9b"> <Type xmlns="https://www.openaire.eu/cerif-profile/vocab/COAR_Publication_Types">http://purl.org/coar/resource_type/c_1843</Type> <Title>Low-Cost Electronic Microfluidics for Multiplexed Point-of-Care Biomarker Detection</Title> <PublishedIn> <Publication> </Publication> </PublishedIn> <PublicationDate>2024-05</PublicationDate> <Authors> <Author> <DisplayName>Kikkeri, Kruthika</DisplayName> <Affiliation> <OrgUnit> </OrgUnit> </Affiliation> </Author> </Authors> <Editors> </Editors> <Publishers> <Publisher> <DisplayName>Massachusetts Institute of Technology</DisplayName> <OrgUnit /> </Publisher> </Publishers> <License>https://rightsstatements.org/page/InC-EDU/1.0/</License> <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.</Abstract> <Access xmlns="http://purl.org/coar/access_right" > </Access> </Publication>