Quantification and analysis of novel protein biomarkers for application in early-stage disease and toxin exposure detection
Dinh, Trinh.
2017
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Abstract: Early detection of diseases and exposure to toxins can provide timely access to medical care and support, improve clinical outcomes, increase survival rate, and might greatly reduce medical costs. A number of protein molecules, such as cytokines, have been found to play significant roles in the initial host immune response to infection and exposure to toxins and have been identified as p... read moreromising biomarker candidates for disease and toxicity diagnostics. Most of these current technologies are limited by sensitivities in the pico Molar (pM) range or above, making the biomarkers undetectable until later stages of the disease or intoxication progression. Therefore, a sensitive detection method is needed for early diagnosis in order to provide early treatment and to prevent transmission of potential life-threatening diseases and intoxication. This dissertation is composed of three chapters that describe the development of single-molecule arrays (Simoa) technology for early-stage detection. Chapter 2 presents the analysis of the physiological baseline of cytokine panels, enabling further research studies on the predictive role of cytokines in health and disease. Chapters 3 and 4 detail the ultrasensitive detection of ricin toxin and botulinum neurotoxin in human biological samples, providing clinically actionable information in a timeframe where there is only a short window for intervention. Chapter 5 further evaluates the Simoa assay performance by using antigen-antibody binding kinetics to simplify the assay optimization process while maximizing its performance.
Thesis (Ph.D.)--Tufts University, 2017.
Submitted to the Dept. of Chemistry.
Advisor: David Walt.
Committee: Charles Sykes, Krishna Kumar, and Charles Shoemaker.
Keyword: Chemistry.read less - ID:
- xg94j2308
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