Defense Date

10-28-2022

Graduation Date

Fall 12-16-2022

Availability

One-year Embargo

Submission Type

dissertation

Degree Name

PhD

Department

Chemistry and Biochemistry

Committee Chair

H. M. "Skip" Kingston

Committee Member

Mihaela Rita Mihailescu

Committee Member

Stephanie Wetzel

Committee Member

Scott Faber

Keywords

Analytical Chemistry, Limit of Detection, Dried Blood Spots, Methylmalonic Acid, Mass Spectrometry

Abstract

Changes in body chemistry have long been utilized as a tool for medical diagnosis. Whether blood panel, toxin level, antigen testing or any of the myriad other tests performed annually, searching for molecules which confer health status is a long-established practice. These tests give physicians more information and allow them to make a more accurate diagnosis, from which appropriate treatment can stem. Awareness of, and the subsequent search for, biomarkers for disease states have grown substantially in the past years as analytical, biochemical, and instrumental techniques have become more precises and powerful. In an era of increasingly personalized medicine, novel techniques are necessary to ensure the accuracy and sensitivity of clinical methodology. Adding to these fields, methods were developed and optimized for the extraction, separation, and quantification of analytes. This work contains several disparate projects with this goal, ranging from the accurate quantification of a biomarker for autism spectrum disorder, methylmalonic acid, on dried blood spots from levels both above and below the limit of detection, detection of a suite of curcuminoids to determine the potential extraction efficiency curcumin from turmeric under an internal review board approved study utilizing patient blood and cerebrospinal fluid samples, and finally detection of lead isotopes in blood samples to determine potential radon exposure. Two novel proofs of concepts were developed utilizing the stable, organic molecule methylmalonic acid: quantitative dried blood spots utilizing isotope dilution mass spectrometry and a novel analytical technique for accurate quantitation below the limits of detection known as Thor’s Hammer Isotope Dilution Mass Spectrometry. These methods are instrumental for the eventual creation of at home test kits to determine the toxification of the patent and their potential response to treatment. Two other projects were the answers to problems brought to the Kingston Research Group by physicians looking for our expertise to answer: the quantitation of curcumin and detection or radon exposure. The radon exposure experiment resulted in a collaboration between the Kingston Laboratory and UPMC hospital system for method development and experimentation. The methods developed in this work have significantly improved analytically upon existing methods and have resulted in unique and unexpected collaborations.

Language

English

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