Date of Award

Spring 5-4-2021

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Physics and Astronomy

First Advisor

A. G. Unil Perera

Second Advisor

Ritu Aneja

Third Advisor

Vadim Apalkov

Fourth Advisor

Mukesh Dhamala

Fifth Advisor

Yuan Liu

Sixth Advisor

Didier Merlin

Seventh Advisor

Gengsheng Qin

Abstract

The fundamental vibrational modes of biological constituents in the tissues and the complex body fluids coincide with optical frequencies in the infrared region. Therefore, spatially resolved molecular compositions and interaction information within the biological materials can be extracted non-destructively using IR radiation without the use of labels or probes. However, the feasibility of this technique to elucidate constituent molecular compositions and interactions within the diagnostic mediums is not well explored. This study demonstrates an application of infrared (IR) spectroscopy of sera for monitoring inflammatory bowel diseases (IBD) and various cancers. Using samples from experimental mice and human patients, the power of IR spectroscopy in structural studies of proteins and other complex band contours are explored to find spectral signatures.

Two experimental models of IBD; interleukin 10 knockouts (IL10-/-) and Dextran Sodium Sulfate (DSS) induced mouse shows diagnostic accuracy with 80-100% sensitivity and specificity values. Importantly, the findings of human IBD patients’ serum also show promising results resembling our proofs-of-concept investigations of mouse models. Maximum values of sensitivity and specificity are 100% and 86%, respectively, in human samples. Similarly, in cancer studies, the EL4 mouse model of non-Hodgkin lymphoma (NHL) and a B16 mouse model of the subcutaneous melanoma are used to extract a snapshot of tumor-associated alteration in the serum. The study of both cancer-bearing mouse models in wild types (WT) and their corresponding control types emphasizes the diagnostic potential of this approach as a screening technique for the NHL and melanoma skin cancer. The breast cancer (BC) -associated protein conformational alteration in the serum samples shows the sensitivity and the specificity of identifying spectral signatures were both 90%. All in all, IR spectroscopy of serum samples accompanied by spectral analysis technique shows some promising results for disease diagnostics. The brief outlook of the fundamentals of the infrared detection technique and their applicability for the development of portable spectroscopy is also provided.

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