Metal-Oxide FET Biosensor for Point-of-Care Testing: Overview and Perspective

Abstract

Metal-oxide semiconducting materials are promising for building high-performance field-effect transistor (FET) based biochemical sensors. The existence of well-established top-down scalable manufacturing processes enables the reliable production of cost-effective yet high-performance sensors, two key considerations toward the translation of such devices in real-life applications. Metal-oxide semiconductor FET biochemical sensors are especially well-suited to the development of Point-of-Care testing (PoCT) devices, as illustrated by the rapidly growing body of reports in the field. Yet, metal-oxide semiconductor FET sensors remain confined to date, mainly in academia. Toward accelerating the real-life translation of this exciting technology, we review the current literature and discuss the critical features underpinning the successful development of metal-oxide semiconductor FET-based PoCT devices that meet the stringent performance, manufacturing, and regulatory requirements of PoCT.

Keywords: field effect transistor sensor; metal-oxide; point-of-care testing; regulatory pathway; semiconductor materials.

Figure 6

(a) A TiO2 thin film-based biosensor’s surface functionalization process involves silanization with APTES, reaction with bifunctional linker (glutaraldehyde), and covalent antibody conjugation. Reprinted from Ref. [144] with permission from Elsevier. Copyright © 2017, Elsevier BV All rights reserved. (b) Schematic diagram of FET-based In₂O₃ NW biosensors for the prostate-specific antigen (PSA). Monoclonal antibodies (Abs) are anchored to the surface of the NWs and serve as specific recognition groups for PSA. (c) Reaction sequence for the functionalization of In₂O₃ NW:  i, 3-phosphonopropionic acid deposition; ii, DCC and N-hydroxysuccinimide activation; iii, PSA-Abs incubation. Reprinted from Ref. [142] with permission from ACS. Copyright © 2005, American Chemical Society.

Figure 7

(a) Schematic of the 3D-printed hydrostatic pressure-driven PoC sample processing platform performing filtration and washing on chip. American Chemical Society Copyright © 2022 [37]. (b) Schematic of SiNWs microfluidic purification chip performing protein purification, then photocleaving the crosslinker to release the purified protein into the sensing area. Adopted from Ref. [151] (c) Schematic showing Pyrene-modified graphene functionalized with thiol–PEG, then with the F(ab′)2 antibody fragment against the thyroid-stimulating hormone. Reprinted from Ref. [168] with permission from Advanced Materials Technologies Copyright © 2018. (d) Schematic of a graphene FET device with PEG and a small-molecule spacer for non-specific and specific detection of the analyte directly in physiological samples [167]. (e) Schematic model of AlGaN/GaN HEMT with the gate electrode functionalized with respective antibody/aptamer and measurement of impedance to allow novel sensing method in the physiological sample directly. Reprinted from Ref. [76] with permission from Springer Nature Copyright © 2017.

Figure 1

Illustration of a typical PoCT-based metal-oxide field-effect transistor biosensor and its operation process.

Figure 2

(a) Oxidation process of D-glucose by glucose oxidase enzyme produces protons that can modify the surface potential of an indium oxide FET; (b) Indium oxide FET electrical response to D-glucose concentrations in human diabetic tears (lower range) and blood (upper range), lower range, and upper range, respectively. Adapted from [78]. Copyright © 2015, American Chemical Society; (c) Different regimes of FET operation.

Figure 3

Vapor-phase-grown nanostructures: (a) ZnO nanowires; (b) SnO₂ nanobelts; Reproduced from Ref. [83] with permission from The Royal Society of Chemistry. (c) An example of randomly distributed In₂O₃ NWs between source and drain during device integration. Reprinted with permission from Ref. [94]. Copyright © 2015, American Chemical Society.

Figure 4

(a) Photograph of a 3-inch wafer with top-down fabricated In₂O₃ nanoribbon FT biosensors. Inset shows a magnified image of a nanoribbon chip composed of four subgroups of six nanoribbon FETs; (b) SEM micrograph of the nanoribbon FETs showing identical device channels precisely positioned on the source and drain areas, reproduced with permission from Ref. [23]. Copyright © 2015, American Chemical Society.

Figure 5

Examples of solution-synthesized nanostructures: (a) 600 tilted cross-sectional FE-SEM images of vertical ZnO NWs grown on a reduced graphene/PDMS substrate. Reprinted with permission from the Royal Society of Chemistry (Ref. [116]); (b) HR-TEM image of SnO₂ nanorods. Reprinted with permission from Ref. [123]; (c) TEM images of ZnO nanorods. Reprinted with permission from Ref. [122].

Figure 8

Development, validation, and regulatory pathway of a biosensor PoCT technology and their interconnection. Abbreviation: US FDA—United States Food and Drug Administration, EU CE—European Conformite Europeenne, AU TGA—Australia Therapeutic Goods Administration, JP PMDA—Japan Pharmaceuticals and Medical Devices Agency.