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Ultra-Sensitive AlGaN/GaN HFET Biosensors: Performance Enhancement, Clinical and Food Safety Applications

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2014, Doctor of Philosophy, Ohio State University, Electrical and Computer Engineering.
Among a variety of sensing mechanisms and device architectures, field effect transistor (FET) based devices hold great promise to function as a biosensor that can directly convert biomolecular interactions to electrical signals with significant advantages including low cost, rapid and label-free detection, and high sensitivity. However, it is challenging to detect biomarkers at ultralow concentrations with high specificity in physiological buffers with a high ionic strength. III-nitride semiconductor materials have attracted considerable interest for biosensing applications due to their unique properties, such as chemical inertness, non-toxicity, and excellent thermal stability. In particular, III-nitride FETs are ion-impermeable and highly stable in electrolytes, making them ideal for detection at ultralow concentrations in fluids with high ionic strengths. The objective of this Ph.D. research is to develop easy-to-use biosensing devices with high sensitivity, specificity, and stability based on wide bandgap III-nitride semiconductors for detection of proteins, DNA hybridization, and bacteria. The research highlights and key innovations are summarized as below: (1) We first showed that AlGaN/GaN based FET biosensors have the highest signal-to-noise ratio (SNR) and lowest normalized drain current noise power spectra compared to reported FET biosensors based on other materials, including silicon, carbon nanotube and graphene. The results suggest that AlGaN/GaN FET biosensors have the advantages in nature over other biosensing materials in low frequency noise (LFN). Therefore, AlGaN/GaN based FET biosensors have the potential of achieving a higher sensitivity than sensors made of other semiconductor materials. (2) As a proof of principle, gate-recessed AlGaN/GaN heterostructure FET (HFET) biosensors with a sensitivity of 16 aM (i.e., 5 molecules in the sensing gate area) were demonstrated for detection of streptavidin proteins. The recessed devices operate naturally in the subthreshold regime without applying a bias to the reference electrode, which leads to a significantly higher SNR and a lower LFN power density than non-recessed or under-recessed AlGaN/GaN FET devices. To the best of our knowledge, the detection limit we demonstrated is the lowest ever reported on any planar FET biosensors under physiological conditions. We attribute the enhancement of device sensitivity to the enhancement of SNR by recessed AlGaN/GaN HFET biosensors. (3) After the optimization of device design and architectures, we applied the AlGaN/GaN HFET biosensors for detection of a clinically-relevant protein biomarker, monokine induced by gamma interferon (MIG or CXCL9), a biomarker that has been identified as the early-stage diagnostics of transplantation rejection. We successfully demonstrated nanomole (nM) level sensitivity using AlGaN/GaN HFET biosensors in physiological buffer (PBS), murine serum, and urine samples. Furthermore, we developed a needle device with a miniaturized AlGaN/GaN HFET biosensor chip embedded for in vivo detection of CXCL9 in a mouse’s liver. A mouse undergoing graft-versus-host-disease exhibited a significant current change (the current change ratio was more than 95%) compared to a normal mouse, on which the current change ratio was less than 5%. To the best of our knowledge, this is the first demonstration of FET based sensors employed for biodetection in tissues. (4) At last, as a demonstration of potential applications on food safety to achieve rapid, low-cost, and reliable pathogen detection, we explored Escherichia coli detection using AlGaN/GaN HFET biosensors. We developed a novel two-step method in which devices immobilized with anti-IHF antibodies are first used to capture DNABII proteins and break the biofilm surrounding E. coli, followed by the detection of newly released E. Coli after biofilm breakage through AlGaN/GaN HFET biosensors immobilized with anti-E. Coli IgG.
Wu Lu (Advisor)
Leonard Brillson (Committee Member)
Siddharth Rajan (Committee Member)
Gregg Hadley (Committee Member)
173 p.

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Citations

  • Wang, Y. (2014). Ultra-Sensitive AlGaN/GaN HFET Biosensors: Performance Enhancement, Clinical and Food Safety Applications [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1409017537

    APA Style (7th edition)

  • Wang, Yuji. Ultra-Sensitive AlGaN/GaN HFET Biosensors: Performance Enhancement, Clinical and Food Safety Applications. 2014. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1409017537.

    MLA Style (8th edition)

  • Wang, Yuji. "Ultra-Sensitive AlGaN/GaN HFET Biosensors: Performance Enhancement, Clinical and Food Safety Applications." Doctoral dissertation, Ohio State University, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=osu1409017537

    Chicago Manual of Style (17th edition)