Design, fabrication, and characterization of field-effect and impedance based biosensors.

摘要

Highly sensitive biological sensors are important to the development of biological and medical science. The purpose of this work is to develop highly sensitive AlGaN/GaN heterostructure field-effect transistors (HFETs) and silicon on insulator (SOI) nanowire biosensors. Impedance based lipid membrane characterization is also discussed.;Due to chemical inertness in biological buffer solutions and highly localized carriers, AlGaN/GaN heterostructures are ideal for high-sensitivity field-effect biosensors. The AlGaN/GaN HFET biosensor is firstly designed based on modification of conventional AlGaN/GaN heterostructure high electron mobility transistors (HEMTs) by substituting the metal gate electrode for biomolecule immobilization (ssDNA or ssPNA for ssDNA detection and antibody for protein detection) and the formation of a reservoir for applying solutions. A silanization and biotinylation procedure was developed to immobilize the streptavidin (SA) on the AlGaN surface. The devices show reasonable performance prior to any optimization. With feasibility demonstrated, the device sensitivity is further improved in three aspects. The first is to optimize AlGaN oxidization methods. Inductively coupled plasma (ICP) plasma has been found to produce the highest surface protein coverage and the best electrical properties (i.e. less surface trap density). The second is to operate devices in the subthreshold regime. In this regime, the drain current versus the gate voltage follows a semilog relationship. The biomolecule introduced an effective voltage shift that results in much higher current change. The results with subthreshold regime operation have shown a sensitivity improvement of seven orders of magnitude. The third method is to recess the AlGaN barrier so that a much smaller gate voltage is necessary to bias the device at the subthreshold regime. With this strategy, the noise induced by the gate current and ion movements is reduced while signal-to-noise ratio is increased. The substhreshold swing is 74.4 mV/decade, which is largely improved. The SA detection limit is lowered one order of magnitude compared to the subthreshold regime operation. To extend the application of AlGaN/GaN protein sensors, anti monokine-induced interferon gamma (MIG) IgG is immobilized on silanized AlGaN surfaces for MIG detection. The sensors have shown reasonable detection limits for clinical applications. To model and improve the device performance, a two-dimensional analysis has been developed for planar AlGaN/GaN biosensors. Because analytical solutions are not available, numerical simulations are needed.;Besides the AlGaN/GaN heterostructure, an SOI structure was also developed for nanowire biosensors. To avoid ion drifting in silicon dioxide, oxide-free surface modification process was developed and characterized for better chemical stability in biological buffer. For fabrication, e-beam lithography and plasma dry etching processing have been developed. The minimum nanowire width is 30 nm. Theoretical analysis has been developed for modeling ideal three-dimensional cylindrical nanowires. Numerical simulations with Silvaco software were used to verify the effects of device dimension and the doping level. Both theoretical and numerial simulation show that the nanowires with lower doping levels, smaller widths (or diameters) have higher sensitivities. Theoretical analysis also shows that lower buffer ionic concentration has higher sensitivity. Numerical modeling shows that longer nanowire widths have higher sensitivity.;In addition to the field-effect biosensors, impedance based measurements are very sensitive to the surface molecular structure change. Electrochemical impedance spectroscopy (EIS) was used to characterize the qualities of tethered bilayer lipid membranes (tBLMs) on planar gold surfaces and gold surfaces with nanopores. Nanopores fabricated from topdown technologies are with well-defined shapes and dimensions, which benefits the understanding of dimension-related EIS characteristics. tBLMs with artificially-introduced defects were characterized to simulate the channel opening in the cell membranes. Equivalent circuit models have been developed to explain the EIS behavior of gold surfaces with well defined nanopores.;In this work, field-effect AlGaN/GaN HFET biosensors have been designed for the detection of proteins. With the optimization of oxidization methods and operating the device in subthreshold regime, the sensitivity is largely improved. SOI based nanowire biosensors are also being developed. The fabrication process and the surface modification procedure have been established. Theoretical and numerical analysis have been developed to predict and improve the device performance. Besides, EIS characterizations of tBLMs with well-defined nanopores are developed to study the cell membrane channel opening, which will be used in drug/gene delivery applications.