Highly Scalable, Uniform, and Sensitive Biosensors Based on Top-Down Indium Oxide Nanoribbons and Electronic Enzyme-Linked Immunosorbent Assay

Abstract

Nanostructure field-effect transistor (FET) biosensors have shown great promise for ultra sensitive biomolecular detection. Top-down assembly of these sensors increases scalability and device uniformity but faces fabrication challenges in achieving the small dimensions needed for sensitivity. We report top-down fabricated indium oxide (In2O3) nanoribbon FET biosensors using highly scalable radio frequency (RF) sputtering to create uniform channel thicknesses ranging from 50 to 10 nm. We combine this scalable sensing platform with amplification from electronic enzyme-linked immunosorbent assay (ELISA) to achieve high sensitivity to target analytes such as streptavidin and human immunodeficiency virus type 1 (HIV-1) p24 proteins. Our approach circumvents Debye screening in ionic solutions and detects p24 protein at 20 fg/mL (about 250 viruses/mL or about 3 orders of magnitude lower than commercial ELISA) with a 35% conduction change in human serum. The In2O3 nanoribbon biosensors have 100% device yield and use a simple 2 mask photolithography process. The electrical properties of 50 In2O3 nanoribbon FETs showed good uniformity in on-state current, on/off current ratio, mobility, and threshold voltage. In addition, the sensors show excellent pH sensitivity over a broad range (pH 4 to 9) as well as over the physiological-related pH range (pH 6.8 to 8.2). With the demonstrated sensitivity, scalability, and uniformity, the In2O3 nanoribbon sensor platform makes great progress toward clinical testing, such as for early diagnosis of acquired immunodeficiency syndrome (AIDS).

Flexible Multiplexed In2O3 Nanoribbon Aptamer-Field-Effect Transistors for Biosensing

“…Recently, a number of types of flexible electronics, including displays ( Lewis et al., 2004 ; Park et al., 2009 ), photovoltaics ( Fan et al., 2009 ), and wearable biosensors ( Rim, et al., 2015 ; Liu et al., 2018a ), have been fabricated using metal oxides in their structures. The In 2 O 3 FETs are well suited to wearable or implantable sensing applications versus a variety of other metal oxides, such as indium-gallium-zinc oxide (IGZO) and ZnO, as the latter are unstable under physiological conditions ( Aroonyadet et al., 2015 ; Jin et al., 2015 ). For example, ZnO nanoribbon FETs dissolve completely after 14 h of exposure to phosphate buffer saline (PBS).…”

High performance indium oxide nanoribbon FETs: mitigating devices signal variation from batch fabrication

“…Nanostructured FET based sensors have attracted extensive attention in chemical and biological sensing because of their direct signal transduction, exquisite sensitivity, and point-ofcare integration capability. [1][2][3][4] Preferred materials for nano FET sensors construction include silicon (Si), [5][6][7][8] oxide semiconductors, [9][10][11][12] III-V materials, [13][14][15] and carbon based materials. [16][17][18] While Si-based nanoFETs (e.g.…”

“…nanowires and nanoribbons) have been studied extensively, 6,7,[19][20][21][22] signicant recent research has focussed on semiconducting metal oxides towards better device performance and more scalable fabrication. [9][10][11][12][23][24][25][26] Of the studied oxides, In 2 O 3 displays excellent features for sensing applications. For instance, excellent sensing performance for nanoscale In 2 O 3 based FET sensors has been demonstrated for different bio/chemical/gas sensing applications.…”

“…For instance, excellent sensing performance for nanoscale In 2 O 3 based FET sensors has been demonstrated for different bio/chemical/gas sensing applications. [9][10][11]16,24,27 Importantly, economical fabrication processes are available for nanoscale In 2 O 3 FETs in large scale regardless of their substrate types (hard 9,10 or exible 28,29 substrates). This makes In 2 O 3 FETs readily compatible with point-of-care and wearable applications that typically require cost effectiveness in addition to the sensor's performance.…”

Electronic Biosensors Based on III-Nitride Semiconductors

“…Devices relying on this mechanism of detection include those containing functionalized metal, insulator, and semiconductor surfaces. In addition, sensors composed of nanoscopic entities have been achieved (8,9). To date, electronic biosensors using semiconductorbased field-effect-transistors (FETs) with a chemically modified channel surface as a transducer are the most promising and practical.…”