Challenges Hindering Small Molecule Detection with Floating Gate Transistor Biosensors
2023-08
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Challenges Hindering Small Molecule Detection with Floating Gate Transistor Biosensors
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2023-08
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As made evident by the COVID-19 pandemic, biological sensing enables a means of widespread monitoring of an analyte of interest. Here, a simple “yes or no” qualitative biosensor (e.g. Abbott’s BinaxNOW) provided an on-site test for people, lightening the workload and relieving wait times at testing clinics using advanced analytical instruments (e.g. PCR). The floating gate transistor (FGT) was introduced as an electrochemical platform to achieve a similar goal, with the added benefit of a quantitative response for end-use applications where concentrations are meaningful. The FGT biosensor utilizes a low voltage, high amplification signal transducer, the electrolyte-gated transistor (EGT). A floating gate electronically couples the EGT to a sensing medium while maintaining physical separation. This patent-protected technology, invented at the University of Minnesota, has been able to detect large biomolecules, including DNA and proteins. The first study aims to challenge our understanding of the FGT architecture in order to optimize the design of FGT biosensors for quasi-static sensing. Initially, FGTs were fabricated on both SiO2/Si and fused silica glass wafers to observe if charge loss experienced by the EGT was a result of parasitic capacitance between the electrodes and the p-type silicon. Our findings suggest no difference in the operation of the two types of FGTs. Alternatively, we rather attribute the perceived charge loss experienced from the sensing medium to the EGT as an uncertainty of specific capacitance values of relevant interfaces. This insight enabled predictive FGT models to be constructed without the consideration of charge loss. Further, measurement conditions were investigated along with the short and long term stability of the EGT.
The second study utilizes the predictive FGT models to design a charge-based FGT sensor for detection of glyphosate with an antibody-functionalized device. As opposed to past work with the FGT sensor, extensive characterization of the surface functionalization was carried out to guarantee antibody conjugation to gold, setting groundwork for future antibody-based devices. The resulting glyphosate FGT biosensor did not have a sufficient response to a high concentration glyphosate dosing compared to the negative controls. This was attributed to Debye length limitations from the electrolyte and perhaps poor binding affinity of the glyphosate antibody.
The third study, in turn, utilizes structure-shifting aptamers for the detection of the small molecule, serotonin. Again, the surface functionalization was characterized to guarantee aptamer immobilization on gold. The serotonin FGT biosensor responded to serotonin down to 2 µM, having dose-dependent responses; however, negative controls revealed nonspecific interactions between serotonin and the sensing surface, eliciting responses for glyphosate aptamer and MCH-only functionalized FGTs. More so, the serotonin FGT biosensor responded to a cocktail of control analytes, further revealing nonspecific small molecule-SAM interactions can elicit FGT responses. XPS characterization after stabilization in 1X PBS and serotonin sensing measurements revealed desorption of thiols from the sensing surface, indicating electrochemical instabilities.
The final study considers the electrochemical potential window as a parameter for stable FGT biosensors. Cyclic voltammetry was used to mimic the quasi-static potential windows that interrogate the sensing surface in the presence of electrolyte. Windows were applied within ±1 V for various functionalized surfaces, including the surfaces of chapter 4 and chapter 5. Stability of individual thiols contributed to the stability of the mixed monolayer, as revealed for the aptamer/MCH system. Antibody-functionalized surfaces exhibited greater stability in 1X PBS compared to aptamer/MCH-functionalized surfaces which was attributed to changes in the density and thickness of the layer. These windows can be translated to the FGT biosensor to roughly set stable operating bounds. Faster sweep rates, or less time exposed to electrochemical potentials, decreased the effective destabilization per sweep.
Although detection with an FGT biosensor has been achieved with large and charged biological molecules, it is clear the platform is stunted by additional parameters for stable and sensitive detection, especially toward small molecule analytes. Aside from parameters included in FGT models, we consider how electrochemical interrogation and the surface composition prevent or conflate signals, informing future studies to mitigate losses and enhance signals.
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University of Minnesota Ph.D. dissertation.August 2023. Major: Material Science and Engineering. Advisors: Daniel Frisbie, Kevin Dorfman. 1 computer file (PDF); xiii, 140 pages.
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Adrahtas, Demetra. (2023). Challenges Hindering Small Molecule Detection with Floating Gate Transistor Biosensors. Retrieved from the University Digital Conservancy, https://hdl.handle.net/11299/259691.
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