High Throughput Microfluidics for Ultrasensitive Blood-Based Diagnostics / Nishal Shah.

Format:

Book

Thesis/Dissertation

Author/Creator:

Shah, Nishal, author.

Contributor:

University of Pennsylvania. Bioengineering, degree granting institution.

Language:

English

Subjects (All):

Bioengineering.

Nanotechnology.

Materials science.

Bioengineering--Penn dissertations.

Penn dissertations--Bioengineering.

Local Subjects:

Bioengineering.

Nanotechnology.

Materials science.

Bioengineering--Penn dissertations.

Penn dissertations--Bioengineering.

Physical Description:

1 online resource (110 pages)

Contained In:

Dissertations Abstracts International 84-09B.

Place of Publication:

[Philadelphia, Pennsylvania] : University of Pennsylvania, 2022.

Ann Arbor : ProQuest Dissertations & Theses, 2022

Language Note:

English

Summary:

Ultrasensitive diagnostic assays have made it to the bench in recent years and helped improve the clinical landscape in many diseases. These assays can target nucleic acids, proteins, extracellular vesicles or whole cells down to the single particle, thus allowing for early detection and continuous monitoring of cancers and infectious diseases. However, the two primary limitations to these technologies are that 1. they require complicated and lossy sample processing steps to remove biological background from and 2. their throughput is limited to single-particle analysis to maximize sensitivity. As a result, we have developed two platform technologies that can be used with blood-based liquid biopsies for detection of rare targets at a much higher throughput than is currently being implemented. We first demonstrate the ability of graphene Hall sensors to detect magnetic particles directly from blood. Using a process compatible with CMOS technology used in integrated circuits, we demonstrate long-term stability and high sensitivity in a hybrid microfluidic-microelectronic chip for eventual application with rare cell detection from whole blood. We then developed a digital droplet ELISA platform for the ultrasensitive detection of p24, a highly-conserved HIV protein, that can improve the limit of detection by greater than 2 orders of magnitude. Using a cellphone- based imaging platform for high throughput droplet detection, this platform could easily be implemented for continuous at-home monitoring of p24 in HIV patients on antiretroviral therapies at risk of virological rebound. Together, these projects lay the groundwork for ultrasensitive diagnostic tests that can be accomplished with minimal processing sample and maximum throughput. Although we present two applications of these platforms, they can easily be extended for detection of multiple biomarker modalities across clinical applications. Additionally, by combining advancements in microfluidics and microelectronics into fully integrated assays, these platforms can be used as point-of-care tools for optimal disease management in a personalized manner.

Notes:

Source: Dissertations Abstracts International, Volume: 84-09, Section: B.

Advisors: Issadore, David A.; Committee members: Cohen, Yale E.; Collman, Ronald G.; Gross, Robert; Johnson, A. Charlie.

Department: Bioengineering.

Ph.D. University of Pennsylvania 2022.

Local Notes:

School code: 0175

ISBN:

9798374413953

Access Restriction:

Restricted for use by site license.

This item is not available from ProQuest Dissertations & Theses.