Date of Award
Spring 2024
Document Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Department
Mechanical Engineering & Materials Science (ENAS)
First Advisor
Kyriakides, Themis
Abstract
Innovations in materials and process development in recent decades have enabled surface engineering at the nanoscale, which provides a pathway to improvement in the performance and longevity of biomedical implants and biosensors. One such novel class of materials is bulk metallic glass. As an amorphous metal, bulk metallic glass can be molded with after initial casting to produce high-precision features by elevating the material above the glass transition temperature, Tg, via the process of thermoplastic forming (TPF). Thus, BMGs enable a unique pathway to molding nano-scale structures in air at comparably low processing temperatures. Platinum-base BMG alloys (Pt-BMGs) are of particular interest for potential use as biomaterials. Nanopatterned Pt-BMG substrates with arrays of nanorods ranging from 55 nm – 200 nm in nominal diameter were fabricated using TPF, and the interaction of several different cell types associated with FBR with the nanopatterned Pt-BMG substrates was evaluated. The Pt-BMG alloy was determined to be biocompatible, and the response to the range of nanotopographies differed by cell type. For all cell types, the cells demonstrated the ability to sense and respond to the nanotopography, which influenced cell function and morphology. Nanopattern-cell interactions for fibroblast cells on Pt-BMG substrates were investigated using FIB-SEM; this revealed a mechanosensing mechanism of the cells which was associated with nanorod bending across the cell radius. Analysis of cellular traction force showed how varying the mechanical properties and design of the nanotopography on a surface can influence cell behavior. Nanorod bending near the cell perimeter was confirmed by examining live fibroblast cells with intact cell membranes using confocal microscopy with reflectance of the nanorods in order to concurrently image the nanopattern-cell interaction at both the micro- and nano-scales. Nanopatterned Pt-BMGs were also identified as potential electrode architecture for electrochemical biosensing applications due to the PT-BMG alloy’s chemistry combined with the increase in electrode surface area associated with the nanorods. Glucose was selected as the target biological molecule, and Pt-BMG substrates nanopatterned with 200 nm diameter nanorods were functionalized with glucose oxidase enzyme to be utilized as biosensor electrodes. The Pt-BMG electrodes were successfully demonstrated to function as electrochemical glucose biosensors. In order to assess the impact of electrode surface area on sensor performance, two nanotopographies were evaluated: 200 nm Pt-BMG arrays fabricated using the same protocol as the prior cell study (25 kN applied force during TPF), and a second 200 nm Pt-BMG nanopattern which were created using a lower applied force during TPF (7 KN) in order to produce nanorods with reduced height. When compared to a flat Pt-BMG control, the nanopatterned electrodes both exhibited an increase in sensor electrical signal and sensitivity. The Pt-BMG electrodes with the taller nanorods – and therefore greater surface area – demonstrated an order of magnitude increase in sensitivity. The nanopatterned electrodes with shorter nanorods also resulted in more than three times the sensitivity compared to the flat control. Nanopatterned biosensor electrodes with optimized sensor performance and biocompatibility were next pursued to expand upon the initial demonstration of Pt-BMG nanopatterned biosensor electrodes. By transitioning from TPF of Pt-BMGs for fabricating nanopatterned electrodes to using materials and processes that are used for semiconductor manufacturing, the precision of the nanotopography was improved while also scaling up the electrode size. The transition to semiconductor-compatible processing also enabled agility in the nanopattern design, and arrays of nanorods oriented with different center-to-center spacing were designed in order to assess the impact of nanorod pitch on sensor performance. The nanorod composition and architecture were also re-engineered to enhance electrochemical sensing capability. A hybrid nanorod structure consisting of an electroplated gold core encapsulated by a thin platinum film enabled reliable electrochemical detection with improved electrical signal using biocompatible materials. Cell-nanopattern interaction was again evaluated using fibroblast cells. The hybrid gold-platinum nanopatterned electrodes were demonstrated to successfully detect glucose with greater signal and sensitivity compared to an unpatterned platinum control electrode. Nanorod spacing was also observed to impact sensor performance; the optimal sensor performance was found to be dependent on nanorod density in addition to total effective surface area. When normalized for effective surface area, the performance of the hybrid gold-platinum nanorods exceeded that of the nanopatterned Pt-BMG electrodes for both sensor signal and sensitivity.
Recommended Citation
Kinser, Emily R., "Nanopatterned Electrochemical Biosensor Electrodes with Enhanced Signal and Sensitivity" (2024). Yale Graduate School of Arts and Sciences Dissertations. 1290.
https://elischolar.library.yale.edu/gsas_dissertations/1290
