Fischell Department of Bioengineering Theses and Dissertations
Permanent URI for this collectionhttp://hdl.handle.net/1903/6628
Browse
2 results
Search Results
Item Microsystems Integration Towards Point-of-Care Monitoring of Clozapine Treatment for Adherence, Efficacy, and Safety(2017) Winkler, Thomas E.; Ghodssi, Reza; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Schizophrenia is a challenging and complex disorder with 30–50% of patients not responding to first line antipsychotic treatment. Clozapine is the only antipsychotic approved by the FDA for treatment-resistant schizophrenia and is the most effective antipsychotic medication currently available. Yet, clozapine remains underutilized because of the requirements for frequent invasive and burdensome monitoring to 1) titrate doses to achieve effective blood levels, as well as 2) monitor white blood cells on a weekly basis for the first six months due to risk of agranulocytosis, a rare but potentially fatal side effect of clozapine. These blood draws, and the time lag in receiving reports from central labs, can add several more visits to the caregivers' treatment plan, which may not be feasible for the patient nor the treatment team. This contributes to a very low prescription rate for clozapine, making it one of the most underutilized evidence-based treatments in the field of mental health. The objective of this work is to progress toward a point-of-care approach to monitor both white blood cells and clozapine within a clinical setting. This would significantly lower the burden associated with clozapine treatment by allowing both tests to be performed rapidly during a single doctor's office visit or at the pharmacy. Specifically, I have developed and studied novel clozapine detection schemes based on electrochemical signal amplification in chitosan-based films. Moreover, I have investigated impedance cytometry coupled with hydrodynamic focusing and osmotic lysis to provide label- and reagent-free differential white blood cell counting capabilities. Finally, I have integrated the components in a microsystem capable of concurrent sensing of both biomarkers in whole blood samples. This proof-of-concept device lays the foundation for a fully integrated and automated lab-on-a-chip for point-of-care or even at-home testing to ensure treatment adherence, efficacy, and safety. This will allow for broader use of clozapine by increasing convenience to patients as well as medical professionals, thus improving the lives of people affected by schizophrenia through personalized medicine.Item Bridging the biology-electronics communication gap with redox signaling(2015) Gordonov, Tanya; Bentley, William E; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Electronic and biological systems both have the ability to sense, respond to, and communicate relevant data. This dissertation aims to facilitate communication between the two and create bio-hybrid devices that can process the breadths of both electronic and biological information. We describe the development of novel methods that bridge this bi-directional communication gap through the use of electronically and biologically relevant redox molecules for controlled and quantitative information transfer. Additionally, we demonstrate that the incorporation of biological components onto microelectronic systems can open doors for improved capabilities in a variety of fields. First, we describe the original use of redox molecules to electronically control the activity of an enzyme on a chip. Using biofabrication techniques, we assembled HLPT, a fusion protein which generates the quorum sensing molecule autoinducer-2, on an electrodeposited chitosan film on top of an electrode. This allows the electrode to controllably oxidize the enzyme in situ through a redox mediator, acetosyringone. We successfully showed that activity decrease and bacterial quorum sensing response are proportional to the input charge. To engineer bio-electronic communication with cells, we first aimed for better characterizing an electronic method for measuring cell response. We engineered Escherichia coli (E.coli) cells to respond to autoinducer-2 by producing the β-galactosidase enzyme. We then investigated an existing electrochemical method for detecting β-galactosidase activity by measuring a redox-active product of the cleavage of the added substrate molecule PAPG. In our novel findings, the product, PAP, was found to be produced at a rate that correlated with the standard spectrophotometric method for measuring β-galactosidase, the Miller assay, in both whole live and lysed cells. Conversely, to translate electronic signals to something cells can understand, we used pyocyanin, a redox drug which oxidizes the E.coli SoxR protein and allows transcription from the soxS promoter. We utilized electronic control of ferricyanide, an electron acceptor, to amplify the production of a reporter from soxS. With this novel method, we show that production of reporter depends on the frequency and amplitude of electronic signals, and investigate the method’s metabolic effects. Overall, the work in this dissertation makes strides towards the greater goal of creating multi-functional bio-hybrid devices.