Quantification and analysis of novel protein biomarkers for application in early-stage disease and toxin exposure detection
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 ... read moreas promising 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