Graduation Year

2020

Document Type

Dissertation

Degree

Ph.D.

Degree Name

Doctor of Philosophy (Ph.D.)

Degree Granting Department

Biomedical Engineering

Major Professor

Anna Pyayt, Ph.D.

Committee Member

Robert Frisina, Ph.D.

Committee Member

Steven Saddow, Ph.D.

Committee Member

Sandy Westerheide, Ph.D.

Committee Member

Piyush Koria, Ph.D.

Keywords

Aggregation, Convection, Isolation, Microfluid, Thermal-plasmonic

Abstract

Contemporary biomedical technologies introduce many new instruments that are important for diagnosis and treatment of the patients. Instrument that can do rapid detection of bacterial infections, and further direct medical practitioner to prescribe optimal antibiotics is highly desirable. But unfortunately, this instrument is not available yet. Ideally, this instrument has to be portable to be used at point-of-care. This means it has to be small and inexpensive, but still highly accurate. Another critical requirement for the instrument is that the test results have to be available promptly. Because in case of such complications of bacterial infections as sepsis, each additional hour needed for the test decreases patient’s chance of survival. Traditional treatment of bacterial infections is relied on empirical prescription of antibiotics. This kind of treatment is very imprecise and may incur side effects in long term. Meanwhile, optimal prescription of antibiotics for treating bacterial infection relies on the body fluids tests of patient. Whereas the test often includes bacteria culture followed by antibiotic susceptibility testing. These steps are very time-consuming and as a consequence, which may cause a negative impact on patient’s chance of survival. The goal of this project is to address the fundamental challenges of optimal antibiotic prescription and develop new instrument for rapid concentration and analysis of bacteria.

This dissertation introduces an innovative approach to bacterial analysis based on a new Opto-Fluidic Manipulation (OFM) technology that we proposed and published in several reputable journals. OFM can be integrated with microfluidics for careful and gentle manipulation of micro and nano-scale objects in miniature fluid samples. We designed and optimized special bi-layer metallic substrates that can efficiently absorb laser light, locally heat fluids for couple of degrees and generate microscopic currents. These micro-currents can be used to concentrate and project particles, sort them based on their size, capture bacteria, and many other interesting applications.

We demonstrated that OFM does not damage live cells, bacteria, and it can be used to carefully isolate desired type of the bacterial cells from fluid samples for further analysis. In addition to that, we showed that isolated live bacteria can be used for rapid antibiotic susceptibility testing. This way we can potentially isolate bacteria from a biological sample and identify the optimal antibiotic under one hour, in comparison with the traditional approaches that can often take from 24 to 72hours.

There are seven chapters in this dissertation. Briefly, chapter one and two explain the mechanism of OFM and optimization process of the integrated chip fabrication. Chapters three, four and five present a system derives from a combination of Opto-Fluidic chip and auxiliary components and various tests of the system with different types of particles. Chapter six demonstrates our latest results on micro-mixing application of OFM that can be used for accelerated antigen-antibody-based sensing. Finally, there are several other projects that I have participated in during Ph.D. study. I briefly discuss my contribution to each project focusing on development of different biomedical devices. Future development of these biomedical instruments might enable many important applications for better, more affordable, and precise healthcare.

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