Date of Award

5-7-2020

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Physics and Astronomy

First Advisor

Alexandru Biris

Second Advisor

Vladimir Zharov

Abstract

Photoacoustic (PA) flow cytometry (PAFC) is a powerful diagnostic method that has vast potential in clinical diagnosis of cancer, infections, and cardiovascular disorders by providing highly sensitive detection and enumeration of individual circulating cells or particles associated with presence and progression of a disease. This promising diagnostic tool commonly uses solid-state lasers as the illuminating light sources. However, these lasers are usually expensive and bulky, limiting their usage in many clinical applications. Low-cost, portable, high-power pulsed diode lasers can be used as potential alternative sources for PAFC due to their high efficiency, and availability in a wide spectral range of near infrared (NIR) wavelengths. However, little progress has been made in application of laser diodes with PAFC. Thus, the main focus of this dissertation is to utilize diode lasers in PAFC for noninvasive, rapid detection of single circulating particles and cells in blood vessels. In this novel PAFC platform, one of the key requirements is to deliver the smallest focused linear beam possible with high power efficiency in order to adequately illuminate circulating micro targets in blood vessels. A variety of unique optical schemes have been developed using group lenses, single fiber, fibers array or liquid guide fiber. However, some of these schemes are simple and compact, containing only two optical elements, thus, these schemes are considered very suitable for PAFC use in clinical applications. We explored using an array of transducers with diode lasers in PAFC instead of a single transducer to demonstrate the further increase in sensitive detection of individual targets in small veins. Additionally, we developed a new two-color PAFC platform based on two-spectral diode lasers for real-time detection of infected red blood cells (iRBCs) with malaria hemozoin. This new system demonstrated increased diagnostic specificity for the early, noninvasive diagnosis of malaria in vitro and in vivo. Finally, a portable PAFC diagnostic device with a handheld probe was developed. We found that this integrated fiber-based device has a high capability for detection and identification of circulating blood clots (CBCs) in deep large vessels at the early stage of stroke disease. This new platform drastically lessens the cost and improves the portability, facilitating the applicability of PAFC in clinics.

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