Antibody Nanotweezer Constructing Bivalent Transistor-Biomolecule Interface with Spatial Tolerance.

Establishing a multivalent interface between the biointerface of a living system and electronic device is vital to building intelligent bioelectronic systems. How to achieve multivalent binding with spatial tolerance at the nanoscale remains challenging. Here, we report an antibody nanotweezer that is a self-adaptive bivalent nanobody enabling strong and resilient binding between transistor and envelope proteins at biointerfaces. The antibody nanotweezer is constructed by a DNA framework, where the nanoscale patterning of nanobodies along with their local spatial adaptivity enables simultaneous recognition of target epitopes without binding stress. As such, effective binding affinity increases by 1 order of magnitude compared with monovalent antibody. The antibody nanotweezer operating on transistor offers enhanced signal transduction, which is implemented to detect clinical pathogens, showing ∼100% overall agreement with PCR results. This work provides a perspective of engineering multivalent interfaces between biosystems with solid-state devices, holding great potential for organoid intelligence on a chip.

Electrically Oriented Antibodies on Transistor for Monitoring Several Copies of Methylated DNA.

An antibody transistor is a promising biosensing platform for the diagnosis and monitoring of various diseases. Nevertheless, the low concentration and short half-life of biomarkers require biodetection at the trace-molecule level, which remains a challenge for existing antibody transistors. Herein, we demonstrate a graphene field-effect transistor (gFET) with electrically oriented antibody probes (EOA-gFET) for monitoring several copies of methylated DNA. The electric field confines the orientation of antibody probes on graphene and diminishes the distance between graphene and methylated DNAs captured by antibodies, generating more induced charges on graphene and amplifying the electric signal. EOA-gFET realizes a limit of detection (LoD) of ∼0.12 copy µL-1, reaching the lowest LoD reported before. EOA-gFET shows a distinguishable signal for liver cancer clinical serum samples within ∼6 min, which proves its potential as a powerful tool for disease screening and diagnosis.

Chemical Sensors Based on Covalent Organic Frameworks.

Covalent organic frameworks (COFs) are a type of crystalline porous polymer composed of light elements through strong covalent bonds. COFs have attracted considerable attention due to their unique designable structures and excellent material properties. Currently, COFs have shown outstanding potential in various fields, including gas storage, pollutant removal, catalysis, adsorption, optoelectronics, and their research in the sensing field is also increasingly flourishing. In this review, we focus on COF-based sensors. Firstly, we elucidate the fundamental principles of COF-based sensors. Then, we present the primary application areas of COF-based sensors and their recent advancements, encompassing gas, ions, organic compounds, and biomolecules sensing. Finally, we discuss the future trends and challenges faced by COF-based sensors, outlining their promising prospects in the field of sensing.

Two-Dimensional Field-Effect Transistor Sensors: The Road toward Commercialization.

The evolutionary success in information technology has been sustained by the rapid growth of sensor technology. Recently, advances in sensor technology have promoted the ambitious requirement to build intelligent systems that can be controlled by external stimuli along with independent operation, adaptivity, and low energy expenditure. Among various sensing techniques, field-effect transistors (FETs) with channels made of two-dimensional (2D) materials attract increasing attention for advantages such as label-free detection, fast response, easy operation, and capability of integration. With atomic thickness, 2D materials restrict the carrier flow within the material surface and expose it directly to the external environment, leading to efficient signal acquisition and conversion. This review summarizes the latest advances of 2D-materials-based FET (2D FET) sensors in a comprehensive manner that contains the material, operating principles, fabrication technologies, proof-of-concept applications, and prototypes. First, a brief description of the background and fundamentals is provided. The subsequent contents summarize physical, chemical, and biological 2D FET sensors and their applications. Then, we highlight the challenges of their commercialization and discuss corresponding solution techniques. The following section presents a systematic survey of recent progress in developing commercial prototypes. Lastly, we summarize the long-standing efforts and prospective future development of 2D FET-based sensing systems toward commercialization.

Highly Bionic Neurotransmitter-Communicated Neurons Following Integrate-and-Fire Dynamics.

In biological neural networks, chemical communication follows the reversible integrate-and-fire (I&F) dynamics model, enabling efficient, anti-interference signal transport. However, existing artificial neurons fail to follow the I&F model in chemical communication, causing irreversible potential accumulation and neural system dysfunction. Herein, we develop a supercapacitively gated artificial neuron that mimics the reversible I&F dynamics model. Upon upstream neurotransmitters, an electrochemical reaction occurs on a graphene nanowall (GNW) gate electrode of artificial neurons. Charging and discharging the supercapacitive GNWs mimic membrane potential accumulation and recovery, realizing highly efficient chemical communication upon use of acetylcholine down to 2 × 10-10 M. By combining artificial chemical synapses with axon-hillock circuits, the output of neural spikes is realized. With the same neurotransmitter and I&F dynamics, the artificial neuron establishes chemical communication with other artificial neurons and living cells, holding promise as a basic unit to construct a neural network with compatibility to organisms for artificial intelligence and deep human-machine fusion.

Photo-Enhanced Chemo-Transistor Platform for Ultrasensitive Assay of Small Molecules.

Compared with traditional assay techniques, field-effect transistors (FETs) have advantages such as fast response, high sensitivity, being label-free, and point-of-care detection, while lacking generality to detect a wide range of small molecules since most of them are electrically neutral with a weak doping effect. Here, we demonstrate a photo-enhanced chemo-transistor platform based on a synergistic photo-chemical gating effect in order to overcome the aforementioned limitation. Under light irradiation, accumulated photoelectrons generated from covalent organic frameworks offer a photo-gating modulation, amplifying the response to small molecule adsorption including methylglyoxal, p-nitroaniline, nitrobenzene, aniline, and glyoxal when measuring the photocurrent. We perform testing in buffer, artificial urine, sweat, saliva, and diabetic mouse serum. The limit of detection is down to 10-19 M methylglyoxal, about 5 orders of magnitude lower than existing assay technologies. This work develops a photo-enhanced FET platform to detect small molecules or other neutral species with enhanced sensitivity for applications in fields such as biochemical research, health monitoring, and disease diagnosis.

Catalytic Hairpin Assembly-Enhanced Graphene Transistor for Ultrasensitive miRNA Detection.

MicroRNAs (miRNAs) have emerged as powerful biomarkers for disease diagnosis and screening. Traditional miRNA analytical techniques are inadequate for point-of-care testing due to their reliance on specialized expertise and instruments. Graphene field-effect transistors (GFETs) offer the prospect of simple and label-free diagnostics. Herein, a GFET biosensor based on tetrahedral DNA nanostructure (TDN)-assisted catalytic hairpin assembly (CHA) reaction (TCHA) has been fabricated and applied to the sensitive and specific detection of miRNA-21. TDN structures are assembled to construct the biosensing interface, facilitating CHA reaction by providing free space and preventing unwanted entanglements, aggregation, and adsorption of probes on the graphene channel. Owing to synergistic effects of TDN-assisted in situ nucleic acid amplification on the sensing surface, as well as inherent signal sensitization of GFETs, the biosensor exhibits ultrasensitive detection of miRNA-21 down to 5.67 × 10-19 M, approximately three orders of magnitude lower than that normally achieved by graphene transistors with channel functionalization of single-stranded DNA probes. In addition, the biosensor demonstrates excellent analytical performance regarding selectivity, stability, and reproducibility. Furthermore, the practicability of the biosensor is verified by analyzing targets in a complex serum environment and cell lysates, showing tremendous potential in bioanalysis and clinical diagnosis.

Artificial Nucleotide Aptamer-Based Field-Effect Transistor for Ultrasensitive Detection of Hepatoma Exosomes.

An aptamer-based field-effect transistor (Apta-FET) is a well-developed assay method with high selectivity and sensitivity. Due to the limited information density that natural nucleotide library holds, the Apta-FET faces fundamental restriction in universality to detect various types of analytes. Herein, we demonstrate a type of Apta-FET sensors based on an artificial nucleotide aptamer (AN-Apta-FET). The introduction of an artificial nucleotide increases the diversity of the potential aptamer structure and expands the analyte category of the Apta-FET. The AN-Apta-FET specifically detects hepatoma exosomes, which traditional Apta-FET fails to discriminate from other tumor-derived exosomes, with a limit of detection down to 242 particles mL-1. The AN-Apta-FET distinguishes serum samples of hepatocellular carcinoma patients within 9 min from those of healthy people, showing the potential as a comprehensive assay tool in future disease diagnosis.

The Application of Graphene Field-Effect Transistor Biosensors in COVID-19 Detection Technology: A Review.

Coronavirus disease 2019 (COVID-19) is a disease caused by the infectious agent of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2). The primary method of diagnosing SARS-CoV-2 is nucleic acid detection, but this method requires specialized equipment and is time consuming. Therefore, a sensitive, simple, rapid, and low-cost diagnostic test is needed. Graphene field-effect transistor (GFET) biosensors have become the most promising diagnostic technology for detecting SARS-CoV-2 due to their advantages of high sensitivity, fast-detection speed, label-free operation, and low detection limit. This review mainly focus on three types of GFET biosensors to detect SARS-CoV-2. GFET biosensors can quickly identify SARS-CoV-2 within ultra-low detection limits. Finally, we will outline the pros and cons of the diagnostic approaches as well as future directions.

Triple-Probe DNA Framework-Based Transistor for SARS-CoV-2 10-in-1 Pooled Testing.

Accurate and population-scale screening technology is crucial in the control and prevention of COVID-19, such as pooled testing with high overall testing efficiency. Nevertheless, pooled testing faces challenges in sensitivity and specificity due to diluted targets and increased contaminations. Here, we develop a graphene field-effect transistor sensor modified with triple-probe tetrahedral DNA framework (TDF) dimers for 10-in-1 pooled testing of SARS-CoV-2 RNA. The synergy effect of triple probes as well as the special nanostructure achieve a higher binding affinity, faster response, and better specificity. The detectable concentration reaches 0.025-0.05 copy µL-1 in unamplified samples, lower than that of the reverse transcript-polymerase chain reaction. Without a requirement of nucleic-acid amplification, the sensors identify all of the 14 positive cases in 30 nasopharyngeal swabs within an average diagnosis time of 74 s. Unamplified 10-in-1 pooled testing enabled by the triple-probe TDF dimer sensor has great potential in the screening of COVID-19 and other epidemic diseases.

Recent progress on rapid diagnosis of COVID-19 by point-of-care testing platforms.

The outbreak of COVID-19 has drawn great attention around the world. SARS-CoV-2 is a highly infectious virus with occult transmission by many mutations and a long incubation period. In particular, the emergence of asymptomatic infections has made the epidemic even more severe. Therefore, early diagnosis and timely management of suspected cases are essential measures to control the spread of the virus. Developing simple, portable, and accurate diagnostic techniques for SARS-CoV-2 is the key to epidemic prevention. The advantages of point-of-care testing technology make it play an increasingly important role in viral detection and screening. This review summarizes the point-of-care testing platforms developed by nucleic acid detection, immunological detection, and nanomaterial-based biosensors detection. Furthermore, this paper provides a prospect for designing future highly accurate, cheap, and convenient SARS-CoV-2 diagnostic technology.

Self-Expanding Molten Salt-Driven Growth of Patterned Transition-Metal Dichalcogenide Crystals.

Transition-metal dichalcogenides (TMDs) have been considered potential materials for the next generation of semiconductors. Realizing controllable growth of TMD crystals is a prerequisite for their future applications, which remains challenging. Here, we reveal a new mechanism of self-expanding molten salt-driven growth for a salt-assisted method and achieve the patterned growth of TMD single-crystal arrays with a size of hundreds of micrometers. Time-of-flight secondary ion mass spectroscopy and other spectroscopy characterizations identify the component of the molten salt solution. Microscopic characterizations reveal the existence of salt solution as an interlayer between a TMD monolayer and the silicon substrate as well as particles along the crystal edge. The edged salt solution serves as a self-expanding liquid substrate, which confines the reactive sites to the localized liquid surface, thus avoiding random nucleation. The surface reaction also assures monolayer crystal formation due to self-limiting growth. Besides, the liquid substrate affords sources and spreads itself continuously owing to the nonwetting effect on TMD crystals, thereby facilitating the continuous extension of the TMD monolayer. This work provides novel insights into the controllable synthesis of TMD monolayers and paves the way for the fabrication of TMD-based integrated functional devices.

Electrochemical Detection of a Few Copies of Unamplified SARS-CoV-2 Nucleic Acids by a Self-Actuated Molecular System.

The existing electrochemical biosensors lack controllable and intelligent merit to modulate the sensing process upon external stimulus, leading to challenges in analyzing a few copies of biomarkers in unamplified samples. Here, we present a self-actuated molecular-electrochemical system that consists of a tentacle and a trunk modification on a graphene microelectrode. The tentacle that contains a probe and an electrochemical label keeps an upright orientation, which increases recognition efficiency while decreasing the pseudosignal. Once the nucleic acids are recognized, the tentacles nearby along with the labels are spontaneously actuated downward, generating electrochemical responses under square wave voltammetry. Thus, it detects unamplified SARS-CoV-2 RNAs within 1 min down to 4 copies in 80 µL, 2-6 orders of magnitude lower than those of other electrochemical assays. Double-blind testing and 10-in-1 pooled testing of nasopharyngeal samples yield high overall agreement with reverse transcription-polymerase chain reaction results. We fabricate a portable prototype based on this system, showing great potential for future applications.

Plasma-Enhanced Chemical Vapor Deposition of Two-Dimensional Materials for Applications.

ConspectusSince the rise of two-dimensional (2D) materials, synthetic methods including mechanical exfoliation, solution synthesis, and chemical vapor deposition (CVD) have been developed. Mechanical exfoliation prepares randomly shaped materials with small size. Solution synthesis introduces impurities that degrade the performances. CVD is the most successful one for low-cost scalable preparation. However, when it comes to practical applications, disadvantages such as high operating temperature (∼1000 °C), probable usage of metal catalysts, contamination, defects, and interstices introduced by postgrowth transfer are not negligible. These are the reasons why plasma-enhanced CVD (PECVD), a method that enables catalyst-free in situ preparation at low temperature, is imperatively desirable.In this Account, we summarize our recent progress on controllable preparation of 2D materials by PECVD and their applications. We found that there was a competition between etching and nucleation and deposition in PECVD, making it highly controllable to obtain desired materials. Under different equilibrium states of the competition, various 2D materials with diverse morphologies and properties were prepared including pristine or nitrogen-doped graphene crystals, graphene quantum dots, graphene nanowalls, hexagonal boron nitride (h-BN), B-C-N ternary materials (BCxN), etc. We also used mild plasma to modify or treat 2D materials (e.g., WSe2) for desired properties.PECVD has advantages such as low temperature, transfer-free process, and industrial compatibility, which enable facile, scalable, and low-cost preparation of 2D materials with clean surfaces and interfaces directly on noncatalytic substrates. These merits significantly benefit the as-prepared materials in the applications. Field-effect transistors with high motilities were directly fabricated on graphene and nitrogen-doped graphene. By use of h-BN as the dielectric interfacial layer, both mobilities and saturated power densities of the devices were improved owing to the clean, closely contacted interface and enhanced interfacial thermal dissipation. High-quality materials and interfaces also enabled promising applications of these materials in photodetectors, pressure sensors, biochemical sensors, electronic skins, Raman enhancement, etc. To demonstrate the commercial applications, several prototypical devices were studied such as distributed pressure sensor arrays, touching module on a robot hand for braille recognition, and smart gloves for recording sign language. Finally, we discuss opportunities and challenges of PECVD as a comprehensive preparation methodology of 2D materials for future applications beyond traditional CVD.

Ultrasensitive and Regenerative Transistor Sensor Based on Dynamic Covalent Chemistry.

Field-effect transistor (FET) sensors require not only high sensitivity but also excellent regeneration ability before widespread applications are possible. Although some regenerative FETs have been reported, their lowest limit of detection (LoD) barely achieves 10-15 mol L-1. Here, we develop a graphene FET with a regenerative sensing interface based on dynamic covalent chemistry (DCvC). The LoD down to 5.0 × 10-20 mol L-1 remains even after 10 regenerative cycles, around 4-5 orders of magnitude lower than existing transistor sensors. Owing to its ultra-sensitivity, regeneration ability, and advantages such as simplicity, low cost, label-free and real-time response, the FET sensor based on DCvC is valuable in applications such as medical diagnosis, environment monitoring, etc.

Ultrasensitive Detection of SARS-CoV-2 Antibody by Graphene Field-Effect Transistors.

The fast spread of SARS-CoV-2 has severely threatened the public health. Establishing a sensitive method for SARS-CoV-2 detection is of great significance to contain the worldwide pandemic. Here, we develop a graphene field-effect transistor (g-FET) biosensor and realize ultrasensitive SARS-CoV-2 antibody detection with a limit of detection (LoD) down to 10-18 M (equivalent to 10-16 g mL-1) level. The g-FETs are modified with spike S1 proteins, and the SARS-CoV-2 antibody biorecognition events occur in the vicinity of the graphene surface, yielding an LoD of ∼150 antibodies in 100 µL full serum, which is the lowest LoD value of antibody detection. The diagnoses time is down to 2 min for detecting clinical serum samples. As such, the g-FETs leverage rapid and precise SARS-CoV-2 screening and also hold great promise in prevention and control of other epidemic outbreaks in the future.

Rapid SARS-CoV-2 Nucleic Acid Testing and Pooled Assay by Tetrahedral DNA Nanostructure Transistor.

Direct SARS-CoV-2 nucleic acid testing with fast speed and high frequency is crucial for controlling the COVID-19 pandemic. Here, direct testing of SARS-CoV-2 nucleic acid is realized by field-effect transistors (FETs) with an electro-enrichable liquid gate (LG) anchored by tetrahedral DNA nanostructures (TDNs). The applied gate bias electrostatically preconcentrates nucleic acids, while the liquid gate with TDNs provides efficient analyte recognition and signal transduction. The average diagnosis time is ∼80 s, and the limit of detection approaches 1-2 copies in 100 µL of clinical samples without nucleic acid extraction and amplification. As such, TDN-LG FETs solve the dilemma of COVID-19 testing on mass scale that diagnosis accuracy and speed undergo trade-off. In addition, TDN-LG FETs achieve unamplified 10-in-1 pooled nucleic acid testing for the first time, and the results are consistent with PCR. Thus, this technology promises on-site and wide population COVID-19 screening and ensures safe world-reopening.

Ultraprecise Antigen 10-in-1 Pool Testing by Multiantibodies Transistor Assay.

Effective screening of infectious diseases requires a fast, cheap, and population-scale testing. Antigen pool testing can increase the test rate and shorten the screening time, thus being a valuable approach for epidemic prevention and control. However, the overall percent agreement (OPA) with polymerase chain reaction (PCR) is one-half to three-quarters, hampering it from being a comprehensive method, especially pool testing, beyond the gold-standard PCR. Here, a multiantibodies transistor assay is developed for sensitive and highly precise antigen pool testing. The multiantibodies capture SARS-CoV-2 spike S1 proteins with different configurations, resulting in an antigen-binding affinity down to 0.34 fM. The limit of detection reaches 3.5 × 10-17 g mL-1SARS-CoV-2 spike S1 protein in artificial saliva, 4-5 orders of magnitude lower than existing transistor sensors. The testing of 60 nasopharyngeal swabs exhibits ∼100% OPA with PCR within an average diagnoses time of 38.9 s. Owing to its highly precise feature, a portable integrated platform is fabricated, which achieves 10-in-1 pooled screening for high testing throughput. This work solves the long-standing problem of antigen pool testing, enabling it to be a valuable tool in precise diagnoses and population-wide screening of COVID-19 or other epidemics in the future.

Direct SARS-CoV-2 Nucleic Acid Detection by Y-Shaped DNA Dual-Probe Transistor Assay.

Rapid screening of infected individuals from a large population is an effective means in epidemiology, especially to contain outbreaks such as COVID-19. The gold standard assays for COVID-19 diagnostics are mainly based on the reverse transcription polymerase chain reaction, which mismatches the requirements for wide-population screening due to time-consuming nucleic acid extraction and amplification procedures. Here, we report a direct nucleic acid assay by using a graphene field-effect transistor (g-FET) with Y-shaped DNA dual probes (Y-dual probes). The assay relies on Y-dual probes modified on g-FET simultaneously targeting ORF1ab and N genes of SARS-CoV-2 nucleic acid, enabling high a recognition ratio and a limit of detection (0.03 copy µL-1) 1-2 orders of magnitude lower than existing nucleic acid assays. The assay realizes the fastest nucleic acid testing (∼1 min) and achieves direct 5-in-1 pooled testing for the first time. Owing to its rapid, ultrasensitive, easily operated features as well as capability in pooled testing, it holds great promise as a comprehensive tool for population-wide screening of COVID-19 and other epidemics.

High-performance mid-infrared photodetection based on Bi2Se3 maze and free-standing nanoplates.

The pursuit of optoelectronic devices operating in mid-infrared regime is driven by both fundamental interests and commercial applications. The narrow bandgap (0.3 eV) of layered Bi2Se3 makes it a promising material for mid-infrared photodetection. However, the weak absorption of mid-infrared optical power and high dark current level restrict its performance. Here, a supply-control technique is applied to modulate the growth mode of Bi2Se3 crystal, and Bi2Se3 crystals with various morphologies are obtained. The nanoplates pattern transits from maze to freestanding when source mass was tuned. Due to the strong infrared absorption and photoelectric conversion efficiency of vertical Bi2Se3 nanoplates, the as-prepared vertical Bi2Se3 nanoplates/Si heterojunction shows excellent photoresponse and extremely low dark current. Among these devices based on different Bi2Se3 morphologies, freestanding nanoplates show the optimal mid-infrared characteristics, namely a photo-to-dark ratio of 2.0 × 104, a dark current of 0.21 pA, a response time of 23 ms, a specific detectivity of 6.1 × 1010 Jones (calculated) and 1.2 × 1010 Jones (measured) under 2.7 µm illumination and at room temperature. Notably, the specific detectivity of our devices are comparable to commercial InGaAs photodetectors. With the tunable- morphology growing technique and excellent photoresponding characteristics, Bi2Se3 nanomaterials are worth attention in optoelectronic field.