Ultrasensitive Assay Development toward the Early Detection of Breast Cancer
Abstract: Breast cancer is one of the most commonly diagnosed cancers in women
today, with an estimated 250,000 new cases in the United States this year. The advent of
new therapeutic strategies has vastly improved disease-free survival rates, but screening
mammography can miss up to 20% of cancer cases. This lack of clinical sensitivity prevents
early detection and in turn, timely treatment. ... read moreMoreover, current diagnostic processes used
to determine treatment plans are invasive and subjective. A quantitative, cancer
biology-focused blood test for breast cancer would provide a minimally invasive method for
screening and characterizing the disease. This blood test could also serve the purpose of
real-time monitoring of therapeutic efficacy and disease recurrence. This thesis focuses on
the development of ultrasensitive protein assays toward a blood test for the detection of
breast cancer. The technology behind the single molecule array (Simoa) assays used to
achieve ultralow limits of detection, as well as the advantages of using such a sensitive
method are described in Chapter 2. Chapter 3 details the development and preliminary
testing of singleplex cancer biomarker assays in serum. Chapter 4 describes the
incorporation of these markers and others into several multiplex assays for the
simultaneous detection of proteins in small volumes of serum. The multiplexed serum data
was then used with a multivariate classification method to evaluate the utility of an
eight-protein fingerprint for the detection of breast cancer.
Thesis (Ph.D.)--Tufts University, 2017.
Submitted to the Dept. of Chemistry.
Advisor: David Walt.
Committee: Joshua Kritzer, Samuel Thomas, and Marsha Moses.
Keywords: Chemistry, and Biology.read less