Enhancing Electrochemical Sensing through Molecular Engineering of Reduced Graphene Oxide-Solution Interfaces and Remote Floating-Gate FET Analysis.

Two-dimensional nanomaterials such as reduced graphene oxide (rGO) have captured significant attention in the realm of field-effect transistor (FET) sensors due to their inherent high sensitivity and cost-effective manufacturing. Despite their attraction, a comprehensive understanding of rGO-solution interfaces (specifically, electrochemical interfacial properties influenced by linker molecules and surface chemistry) remains challenging, given the limited capability of analytical tools to directly measure intricate solution interface properties. In this study, we introduce an analytical tool designed to directly measure the surface charge density of the rGO-solution interface leveraging the remote floating-gate FET (RFGFET) platform. Our methodology involves characterizing the electrochemical properties of rGO, which are influenced by adhesion layers between SiO2 and rGO, such as (3-aminopropyl)trimethoxysilane (APTMS) and hexamethyldisilazane (HMDS). The hydrophilic nature of APTMS facilitates the acceptance of oxygen-rich rGO, resulting in a noteworthy pH sensitivity of 56.8 mV/pH at the rGO-solution interface. Conversely, hydrophobic HMDS significantly suppresses the pH sensitivity from the rGO-solution interface, attributed to the graphitic carbon-rich surface of rGO. Consequently, the carbon-rich surface facilitates a denser arrangement of 1-pyrenebutyric acid N-hydroxysuccinimide ester linkers for functionalizing capturing probes on rGO, resulting in an enhanced sensitivity of lead ions by 32% in our proof-of-concept test.

Rapid, Sensitive, Label-Free Electrical Detection of SARS-CoV-2 in Nasal Swab Samples.

Rapid diagnosis of coronavirus disease 2019 (COVID-19) is key for the long-term control of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) amid renewed threats of mutated SARS-CoV-2 around the world. Here, we report on an electrical label-free detection of SARS-CoV-2 in nasopharyngeal swab samples directly collected from outpatients or in saliva-relevant conditions by using a remote floating-gate field-effect transistor (RFGFET) with a 2-dimensional reduced graphene oxide (rGO) sensing membrane. RFGFET sensors demonstrate rapid detection (<5 min), a 90.6% accuracy from 8 nasal swab samples measured by 4 different devices for each sample, and a coefficient of variation (CV) < 6%. Also, RFGFET sensors display a limit of detection (LOD) of pseudo-SARS-CoV-2 that is 10 000-fold lower than enzyme-linked immunosorbent assays, with a comparable LOD to that of reverse transcription-polymerase chain reaction (RT-PCR) for patient samples. To achieve this, comprehensive systematic studies were performed regarding interactions between SARS-CoV-2 and spike proteins, neutralizing antibodies, and angiotensin-converting enzyme 2, as either a biomarker (detection target) or a sensing probe (receptor) functionalized on the rGO sensing membrane. Taken together, this work may have an immense effect on positioning FET bioelectronics for rapid SARS-CoV-2 diagnostics.

Bioinspired Plasmo-virus for Point-of-Care SARS-CoV-2 Detection.

Directly identifying the presence of the virus in infected hosts with an appropriate speed and sensitivity permits early epidemic management even during the presymptomatic incubation period of infection. Here, we synthesize a bioinspired plasmo-virus (BPV) particle for rapid and sensitive point-of-care (POC) detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) via a self-assembled plasmonic nanoprobe array on spike proteins. The BPV enables strong near-infrared (NIR) extinction peaks caused by plasmonic nanogaps. We quantify SARS-CoV-2 in viral transport medium (VTM) at low titers within 10 min with a limit of detection (LOD) of 1.4 × 101 pfu/mL, which is 103 times more sensitive than the current gold-standard method. The high-sensitivity and high-speed POC detection may be widely used for the timely, individualized diagnosis of infectious agents in low-resource settings.

Remote Floating-Gate Field-Effect Transistor with 2-Dimensional Reduced Graphene Oxide Sensing Layer for Reliable Detection of SARS-CoV-2 Spike Proteins.

Despite intensive research of nanomaterials-based field-effect transistors (FETs) as a rapid diagnostic tool, it remains to be seen for FET sensors to be used for clinical applications due to a lack of stability, reliability, reproducibility, and scalability for mass production. Herein, we propose a remote floating-gate (RFG) FET configuration to eliminate device-to-device variations of two-dimensional reduced graphene oxide (rGO) sensing surfaces and most of the instability at the solution interface. Also, critical mechanistic factors behind the electrochemical instability of rGO such as severe drift and hysteresis were identified through extensive studies on rGO-solution interfaces varied by rGO thickness, coverage, and reduction temperature. rGO surfaces in our RFGFET structure displayed a Nernstian response of 54 mV/pH (from pH 2 to 11) with a 90% yield (9 samples out of total 10), coefficient of variation (CV) < 3%, and a low drift rate of 2%, all of which were calculated from the absolute measurement values. As proof-of-concept, we demonstrated highly reliable, reproducible, and label-free detection of spike proteins of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a saliva-relevant media with concentrations ranging from 500 fg/mL to 5 µg/mL, with an R2 value of 0.984 and CV < 3%, and a guaranteed limit of detection at a few pg/mL. Taken together, this new platform may have an immense effect on positioning FET bioelectronics in a clinical setting for detecting SARS-CoV-2.

Understanding, discovery, and synthesis of 2D materials enabled by machine learning.

Machine learning (ML) is becoming an effective tool for studying 2D materials. Taking as input computed or experimental materials data, ML algorithms predict the structural, electronic, mechanical, and chemical properties of 2D materials that have yet to be discovered. Such predictions expand investigations on how to synthesize 2D materials and use them in various applications, as well as greatly reduce the time and cost to discover and understand 2D materials. This tutorial review focuses on the understanding, discovery, and synthesis of 2D materials enabled by or benefiting from various ML techniques. We introduce the most recent efforts to adopt ML in various fields of study regarding 2D materials and provide an outlook for future research opportunities. The adoption of ML is anticipated to accelerate and transform the study of 2D materials and their heterostructures.

Few-Layer MoS2 Photodetector Arrays for Ultrasensitive On-Chip Enzymatic Colorimetric Analysis.

Enzymatic colorimetric analysis of metabolites provides signatures of energy conversion and biosynthesis associated with disease onsets and progressions. Miniaturized photodetectors based on emerging two-dimensional transition metal dichalcogenides (TMDCs) promise to advance point-of-care diagnosis employing highly sensitive enzymatic colorimetric detection. Reducing diagnosis costs requires a batched multisample assay. The construction of few-layer TMDC photodetector arrays with consistent performance is imperative to realize optical signal detection for a miniature batched multisample enzymatic colorimetric assay. However, few studies have promoted an optical reader with TMDC photodetector arrays for on-chip operation. Here, we constructed 4 × 4 pixel arrays of miniaturized molybdenum disulfide (MoS2) photodetectors and integrated them with microfluidic enzyme reaction chambers to create an optoelectronic biosensor chip device. The fabricated device allowed us to achieve arrayed on-chip enzymatic colorimetric detection of d-lactate, a blood biomarker signifying the bacterial translocation from the intestine, with a limit of detection that is 1000-fold smaller than the clinical baseline, a 10 min assay time, high selectivity, and reasonably small variability across the entire arrays. The enzyme (Ez)/MoS2 optoelectronic biosensor unit consistently detected d-lactate in clinically important biofluids, such as saliva, urine, plasma, and serum of swine and humans with a wide detection range (10-3-103 µg/mL). Furthermore, the biosensor enabled us to show that high serum d-lactate levels are associated with the symptoms of systemic infection and inflammation. The lensless, optical waveguide-free device architecture should readily facilitate development of a monolithically integrated hand-held module for timely, cost-effective diagnosis of metabolic disorders in near-patient settings.

Integrated on-site collection and detection of airborne microparticles for smartphone-based micro-climate quality control.

The rapid emergence of air-mediated diseases in a micro-climate demands on-site monitoring of airborne microparticles. The on-site detection of airborne microparticles becomes more challenging as the particles are highly localized and change dynamically over time. However, most existing monitoring systems rely on time-consuming sample collection and centralized off-site analysis. Here, we report a smartphone-based integrated microsystem for on-site collection and detection that enables real-time detection of indoor airborne microparticles with high sensitivity. The collection device, inspired by the Venturi effect, was designed to collect airborne microparticles without requiring an additional power supply. Our systematic analysis showed that the collection device was able to collect microparticles with consistent negative pressure, regardless of the particle concentration in the air sample. By incorporating a microfluidic-biochip based on inertial force to trap particles and an optoelectronic photodetector into a miniaturized device with a smartphone, we demonstrate real-time and sensitive detection of the collected airborne microparticles, such as Escherichia coli, Bacillus subtilis, Micrococcus luteus, and Staphylococcus with a particle-density dynamic range of 103-108 CFU mL-1. Because of its capabilities of minimal-power sample collection, high sensitivity, and rapid detection of airborne microparticles, this integrated platform can be readily adopted by the government and industrial sectors to monitor indoor air contamination and improve human healthcare.

Inkjet-defined site-selective (IDSS) growth for controllable production of in-plane and out-of-plane MoS2 device arrays.

Along with the increasing interest in MoS2 as a promising electronic material, there is also an increasing demand for nanofabrication technologies that are compatible with this material and other relevant layered materials. In addition, the development of scalable nanofabrication approaches capable of directly producing MoS2 device arrays is an imperative task to speed up the design and commercialize various functional MoS2-based devices. The desired fabrication methods need to meet two critical requirements. First, they should minimize the involvement of resist-based lithography and plasma etching processes, which introduce unremovable contaminations to MoS2 structures. Second, they should be able to produce MoS2 structures with in-plane or out-of-plane edges in a controlled way, which is key to increase the usability of MoS2 for various device applications. Here, we introduce an inkjet-defined site-selective (IDSS) method that meets these requirements. IDSS includes two main steps: (i) inkjet printing of microscale liquid droplets that define the designated sites for MoS2 growth, and (ii) site-selective growth of MoS2 at droplet-defined sites. Moreover, IDSS is capable of generating MoS2 with different structures. Specifically, an IDSS process using deionized (DI) water droplets mainly produces in-plane MoS2 features, whereas the processes using graphene ink droplets mainly produce out-of-plane MoS2 features rich in exposed edges. Using out-of-plane MoS2 structures, we have demonstrated the fabrication of miniaturized on-chip lithium ion batteries, which exhibit reversible lithiation/delithiation capacity. This IDSS method could be further expanded as a scalable and reliable nanomanufacturing method for generating miniaturized on-chip energy storage devices.

An Integrated Plasmo-Photoelectronic Nanostructure Biosensor Detects an Infection Biomarker Accompanying Cell Death in Neutrophils.

Bacterial infections leading to sepsis are a major cause of deaths in the intensive care unit. Unfortunately, no effective methods are available to capture the early onset of infectious sepsis near the patient with both speed and sensitivity required for timely clinical treatment. To fill the gap, the authors develop a highly miniaturized (2.5 × 2.5 µm2 ) plasmo-photoelectronic nanostructure device that detected citrullinated histone H3 (CitH3), a biomarker released to the blood circulatory system by neutrophils. Rapidly detecting CitH3 with high sensitivity has the great potential to prevent infections from developing life-threatening septic shock. To this end, the author's device incorporates structurally engineered arrayed hemispherical gold nanoparticles that are functionalized with high-affinity antibodies. A nanoplasmonic resonance shift induces a photoconduction increase in a few-layer molybdenum disulfide (MoS2 ) channel, and it provides the sensor signal. The device achieves label-free detection of serum CitH3 with a 5-log dynamic range from 10-4 to 101 ng mL and a sample-to-answer time <20 min. Using this biosensor, the authors longitudinally measure the dynamic CitH3 profiles of individual living mice in a sepsis model at high resolution over 12 hours. The developed biosensor may be poised for future translation to personalized management of systemic bacterial infections.

Rubbing-Induced Site-Selective Growth of MoS2 Device Patterns.

The superior electronic and mechanical properties of two-dimensional layered transition-metal dichalcogenides could be exploited to make a broad range of devices with attractive functionalities. However, the nanofabrication of such layered material-based devices still needs resist-based lithography and plasma etching processes for patterning layered materials into functional device features. Such patterning processes lead to unavoidable contaminations, to which the transport characteristics of atomically thin-layered materials are very sensitive. More seriously, such lithography-introduced contaminants cannot be safely eliminated by conventional semiconductor cleaning approaches. This challenge seriously retards the manufacturing of large arrays of layered material-based devices with consistent characteristics. Toward addressing this challenge, we introduce a rubbing-induced site-selective growth method capable of directly generating few-layer MoS2 device patterns without the need of any additional patterning processes. This method consists of two critical steps: (i) a damage-free mechanical rubbing process for generating microscale triboelectric charge patterns on a dielectric surface and (ii) site-selective deposition of MoS2 within rubbing-induced charge patterns. Our microscopy characterizations in combination with finite element analysis indicate that the field magnitude distribution within triboelectric charge patterns determines the morphologies of grown MoS2 patterns. In addition, the MoS2 line patterns produced by the presented method have been implemented for making arrays of working transistors and memristors. These devices exhibit a high yield and good uniformity in their electronic properties over large areas. The presented method could be further developed into a cost-efficient nanomanufacturing approach for producing functional device patterns based on various layered materials.

MoS2 Memristors Exhibiting Variable Switching Characteristics toward Biorealistic Synaptic Emulation.

Memristors based on 2D layered materials could provide biorealistic ionic interactions and potentially enable construction of energy-efficient artificial neural networks capable of faithfully emulating neuronal interconnections in human brains. To build reliable 2D-material-based memristors suitable for constructing working neural networks, the memristive switching mechanisms in such memristors need to be systematically analyzed. Here, we present a study on the switching characteristics of the few-layer MoS2 memristors made by mechanical printing. First, two types of dc-programmed switching characteristics, termed rectification-mediated and conductance-mediated behaviors, are observed among different MoS2 memristors, which are attributed to the modulation of MoS2/metal Schottky barriers and redistribution of vacancies, respectively. We also found that an as-fabricated MoS2 memristor initially exhibits an analog pulse-programmed switching behavior, but it can be converted to a quasi-binary memristor with an abrupt switching behavior through an electrical stress process. Such a transition of switching characteristics is attributed to field-induced agglomeration of vacancies at MoS2/metal interfaces. The additional Kelvin probe force microscopy, Auger electron spectroscopy analysis, and electronic characterization results support this hypothesis. Finally, we fabricated a testing device consisting of two adjacent MoS2 memristors and demonstrated that these two memristors can be ionically coupled to each other. This device interconnection scheme could be exploited to build neural networks for emulating ionic interactions among neurons. This work advances the device physics for understanding the memristive properties of 2D-material-based memristors and serves as a critical foundation for building biorealistic neuromorphic computing systems based on such memristors.

Cyclewise Operation of Printed MoS2 Transistor Biosensors for Rapid Biomolecule Quantification at Femtomolar Levels.

Field-effect transistors made from MoS2 and other emerging layered semiconductors have been demonstrated to be able to serve as ultrasensitive biosensors. However, such nanoelectronic sensors still suffer seriously from a series of challenges associated with the poor compatibility between electronic structures and liquid analytes. These challenges hinder the practical biosensing applications that demand rapid, low-noise, highly specific biomolecule quantification at femtomolar levels. To address such challenges, we study a cyclewise process for operating MoS2 transistor biosensors, in which a series of reagent fluids are delivered to the sensor in a time-sequenced manner and periodically set the sensor into four assay-cycle stages, including incubation, flushing, drying, and electrical measurement. Running multiple cycles of such an assay can acquire a time-dependent sensor response signal quantifying the reaction kinetics of analyte-receptor binding. This cyclewise detection approach can avoid the liquid-solution-induced electrochemical damage, screening, and nonspecific adsorption to the sensor and therefore improves the transistor sensor's durability, sensitivity, specificity, and signal-to-noise ratio. These advantages in combination with the inherent high sensitivity of MoS2 biosensors allow for rapid biomolecule quantification at femtomolar levels. We have demonstrated the cyclewise quantification of Interleukin-1ß in pure and complex solutions (e.g., serum and saliva) with a detection limit of ∼1 fM and a total detection time ∼23 min. This work leverages the superior properties of layered semiconductors for biosensing applications and advances the techniques toward realizing fast real-time immunoassay for low-abundance biomolecule detection.

Biotunable Nanoplasmonic Filter on Few-Layer MoS2 for Rapid and Highly Sensitive Cytokine Optoelectronic Immunosensing.

Monitoring of the time-varying immune status of a diseased host often requires rapid and sensitive detection of cytokines. Metallic nanoparticle-based localized surface plasmon resonance (LSPR) biosensors hold promise to meet this clinical need by permitting label-free detection of target biomolecules. These biosensors, however, continue to suffer from relatively low sensitivity as compared to conventional immunoassay methods that involve labeling processes. Their response speeds also need to be further improved to enable rapid cytokine quantification for critical care in a timely manner. In this paper, we report an immunobiosensing device integrating a biotunable nanoplasmonic optical filter and a highly sensitive few-layer molybdenum disulfide (MoS2) photoconductive component, which can serve as a generic device platform to meet the need of rapid cytokine detection with high sensitivity. The nanoplasmonic filter consists of anticytokine antibody-conjugated gold nanoparticles on a SiO2 thin layer that is placed 170 µm above a few-layer MoS2 photoconductive flake device. The principle of the biosensor operation is based on tuning the delivery of incident light to the few-layer MoS2 photoconductive flake thorough the nanoplasmonic filter by means of biomolecular surface binding-induced LSPR shifts. The tuning is dependent on cytokine concentration on the nanoplasmonic filter and optoelectronically detected by the few-layer MoS2 device. Using the developed optoelectronic biosensor, we have demonstrated label-free detection of IL-1ß, a pro-inflammatory cytokine, with a detection limit as low as 250 fg/mL (14 fM), a large dynamic range of 106, and a short assay time of 10 min. The presented biosensing approach could be further developed and generalized for point-of-care diagnosis, wearable bio/chemical sensing, and environmental monitoring.