Date of Award
Doctor of Philosophy (PhD)
Physics & Astronomy
Alan T. Johnson
The need for scalable, rapid, sensitive, label-free detection of small biomolecules and chemicals such as proteins, nucleic acids or market drugs is central to the field of biomolecular and chemical sensing. Detection of these biomolecules and chemicals is relevant for early disease diagnostics and therapeutic drug monitoring to prolong lifespans, treat patients in a brief timeframe, and decrease medical costs. Various ailments, such as cancers, are the source of up-regulation or down-regulation of certain biomolecules, or “biomarkers” in human fluids, and are indicative of the presence of the disease when compared to human fluids from a healthy subject. By detecting these biomarkers in low concentrations, or by tracking their change in concentration in human samples, scientists could create an effective early disease diagnostics tool that would be used at the point-of-care. In parallel, detection of market drugs in human samples could replace the need for more expensive and time-consuming analytical techniques such as liquid chromatography-mass spectrometry (LC-MS).
The work presented here explores the necessary proof-of-concept for the creation of point-of-care devices for medical diagnostics and therapeutic drug monitoring. It details the process of synthetic nucleic acid detection down to attomolar concentrations, the detection of single base-pair mismatches in nucleic acid strands, and drug target detection in concentrations (1-10 ng/mL) far less than those found in human fluid, the latter for the purpose of therapeutic drug monitoring or “drug compliance” testing. Such sensitivity could only be achieved with the nanomaterial graphene, a two-dimensional allotrope of carbon with the highest electron mobility at room temperature of any material currently known, and with exceptional robustness and biocompatibility. The work here is based on the use of graphene field-effect transistors, or GFETs, for nucleic acid and drug target sensing, and further explores the various uses of graphene for protein and pH sensing, as well as binding of protein-nanoparticle assemblies and neuropeptide-receptor binding, through either rigid or flexible substrates.
Vishnubhotla, Ramya, "Bio-Functionalized Graphene Field-Effect Transistors For The Detection Of Nucleic Acids And Drug Targets" (2018). Publicly Accessible Penn Dissertations. 2867.