High-speed and large-scale intrinsically stretchable integrated circuits.

Intrinsically stretchable electronics with skin-like mechanical properties have been identified as a promising platform for emerging applications ranging from continuous physiological monitoring to real-time analysis of health conditions, to closed-loop delivery of autonomous medical treatment1-7. However, current technologies could only reach electrical performance at amorphous-silicon level (that is, charge-carrier mobility of about 1 cm2 V-1 s-1), low integration scale (for example, 54 transistors per circuit) and limited functionalities8-11. Here we report high-density, intrinsically stretchable transistors and integrated circuits with high driving ability, high operation speed and large-scale integration. They were enabled by a combination of innovations in materials, fabrication process design, device engineering and circuit design. Our intrinsically stretchable transistors exhibit an average field-effect mobility of more than 20 cm2 V-1 s-1 under 100% strain, a device density of 100,000 transistors per cm2, including interconnects and a high drive current of around 2 µA µm-1 at a supply voltage of 5 V. Notably, these achieved parameters are on par with state-of-the-art flexible transistors based on metal-oxide, carbon nanotube and polycrystalline silicon materials on plastic substrates12-14. Furthermore, we realize a large-scale integrated circuit with more than 1,000 transistors and a stage-switching frequency greater than 1 MHz, for the first time, to our knowledge, in intrinsically stretchable electronics. Moreover, we demonstrate a high-throughput braille recognition system that surpasses human skin sensing ability, enabled by an active-matrix tactile sensor array with a record-high density of 2,500 units per cm2, and a light-emitting diode display with a high refreshing speed of 60 Hz and excellent mechanical robustness. The above advancements in device performance have substantially enhanced the abilities of skin-like electronics.

Multi-project wafers for flexible thin-film electronics by independent foundries.

Flexible and large-area electronics rely on thin-film transistors (TFTs) to make displays1-3, large-area image sensors4-6, microprocessors7-11, wearable healthcare patches12-15, digital microfluidics16,17 and more. Although silicon-based complementary metal-oxide-semiconductor (CMOS) chips are manufactured using several dies on a single wafer and the multi-project wafer concept enables the aggregation of various CMOS chip designs within the same die, TFT fabrication is currently lacking a fully verified, universal design approach. This increases the cost and complexity of manufacturing TFT-based flexible electronics, slowing down their integration into more mature applications and limiting the design complexity achievable by foundries. Here we show a stable and high-yield TFT platform for the fabless manufacturing of two mainstream TFT technologies, wafer-based amorphous indium-gallium-zinc oxide and panel-based low-temperature polycrystalline silicon, two key TFT technologies applicable to flexible substrates. We have designed the iconic 6502 microprocessor in both technologies as a use case to demonstrate and expand the multi-project wafer approach. Enabling the foundry model for TFTs, as an analogy of silicon CMOS technologies, can accelerate the growth and development of applications and technologies based on these devices.

Robust chemical analysis with graphene chemosensors and machine learning.

Ion-sensitive field-effect transistors (ISFETs) have emerged as indispensable tools in chemosensing applications1-4. ISFETs operate by converting changes in the composition of chemical solutions into electrical signals, making them ideal for environmental monitoring5,6, healthcare diagnostics7 and industrial process control8. Recent advancements in ISFET technology, including functionalized multiplexed arrays and advanced data analytics, have improved their performance9,10. Here we illustrate the advantages of incorporating machine learning algorithms to construct predictive models using the extensive datasets generated by ISFET sensors for both classification and quantification tasks. This integration also sheds new light on the working of ISFETs beyond what can be derived solely from human expertise. Furthermore, it mitigates practical challenges associated with cycle-to-cycle, sensor-to-sensor and chip-to-chip variations, paving the way for the broader adoption of ISFETs in commercial applications. Specifically, we use data generated by non-functionalized graphene-based ISFET arrays to train artificial neural networks that possess a remarkable ability to discern instances of food fraud, food spoilage and food safety concerns. We anticipate that the fusion of compact, energy-efficient and reusable graphene-based ISFET technology with robust machine learning algorithms holds the potential to revolutionize the detection of subtle chemical and environmental changes, offering swift, data-driven insights applicable across a wide spectrum of applications.

Artificial neuromorphic cognitive skins based on distributed biaxially stretchable elastomeric synaptic transistors.

Cephalopod (e.g., squid, octopus, etc.) skin is a soft cognitive organ capable of elastic deformation, visualizing, stealth, and camouflaging through complex biological processes of sensing, recognition, neurologic processing, and actuation in a noncentralized, distributed manner. However, none of the existing artificial skin devices have shown distributed neuromorphic processing and cognition capabilities similar to those of a cephalopod skin. Thus, the creation of an elastic, biaxially stretchy device with embedded, distributed neurologic and cognitive functions mimicking a cephalopod skin can play a pivotal role in emerging robotics, wearables, skin prosthetics, bioelectronics, etc. This paper introduces artificial neuromorphic cognitive skins based on arrayed, biaxially stretchable synaptic transistors constructed entirely out of elastomeric materials. Systematic investigation of the synaptic characteristics such as the excitatory postsynaptic current, paired-pulse facilitation index of the biaxially stretchable synaptic transistor under various levels of biaxial mechanical strain sets the operational foundation for stretchy distributed synapse arrays and neuromorphic cognitive skin devices. The biaxially stretchy arrays here achieved neuromorphic cognitive functions, including image memorization, long-term memorization, fault tolerance, programming, and erasing functions under 30% biaxial mechanical strain. The stretchy neuromorphic imaging sensory skin devices showed stable neuromorphic pattern reinforcement performance under both biaxial and nonuniform local deformation.

Mass Production of Carbon Nanotube Transistor Biosensors for Point-of-Care Tests.

Low-dimensional semiconductor-based field-effect transistor (FET) biosensors are promising for label-free detection of biotargets while facing challenges in mass fabrication of devices and reliable reading of small signals. Here, we construct a reliable technology for mass production of semiconducting carbon nanotube (CNT) film and FET biosensors. High-uniformity randomly oriented CNT films were prepared through an improved immersion coating technique, and then, CNT FETs were fabricated with coefficient of performance variations within 6% on 4-in. wafers (within 9% interwafer) based on an industrial standard-level process. The CNT FET-based ion sensors demonstrated threshold voltage standard deviations within 5.1 mV at each ion concentration, enabling direct reading of the concentration information based on the drain current. By integrating bioprobes, we achieved detection of biosignals as low as 100 aM through a plug-and-play portable detection system. The reliable technology will contribute to commercial applications of CNT FET biosensors, especially in point-of-care tests.

Mimicking the retinal neuron functions by a photoresponsive single transistor with a double gate.

To realize a low-cost neuromorphic visual system, employing an artificial neuron capable of mimicking the retinal neuron functions is essential. A photoresponsive single transistor neuron composed of a vertical silicon nanowire is proposed. Similar to retinal neurons, various photoresponsive characteristics of the single transistor neuron can be modulated by light intensity as well as wavelength and have a high responsivity to green light like the human eye. The device is designed with a cylindrical surrounding double-gate structure, enclosed by an independently controlled outer gate and inner gate. The outer gate has the function of selectively inhibiting neuron activity, which can mimic lateral inhibition of amacrine cells to ganglion cells, and the inner gate can be utilized for the adjustment of the firing threshold voltage, which can be used to mimic the regulation of photoresponsivity by horizontal cells for adaptive visual perception. Furthermore, a myelination function that controls the speed of information transmission is obtained according to the inherent asymmetric source/drain structure of a vertical silicon nanowire. This work can enable photoresponsive neuronal function using only a single transistor, providing a promising hardware implementation for building miniaturized neuromorphic vision systems at low cost.

A Drug Molecule-Modified Graphene Field-Effect Transistor Nanosensor for Rapid, Label-Free, and Ultrasensitive Detection of Estrogen Receptor α Protein.

Estrogen receptor α (ERα) is an important biomarker in breast cancer diagnosis and treatment. Sensitive and accurate detection of ERα protein expression is crucial in guiding selection of an appropriate therapeutic strategy to improve the effectiveness and prognosis of breast cancer treatment. Herein, we report a liquid-gated graphene field-effect transistor (FET) biosensor that enables rapid, sensitive, and label-free detection of the ERα protein by employing a novel drug molecule as a capture probe. The drug molecule was synthesized and subsequently immobilized onto the sensing surface of the fabricated graphene FET, which was able to distinguish the ERα-positive from the ERα-negative protein. The developed sensor not only demonstrated a low detection limit (LOD: 2.62 fM) but also achieved a fast response to ERα protein samples within 30 min. Moreover, depending on the relationship between the change of dirac point and the ERα protein concentrations, the dissociation constant (Kd) was estimated to be 7.35 ± 0.06 pM, indicating that the drug probe-modified graphene FET had a good affinity with ERα protein. The nanosensor was able to analyze ERα proteins from 36 cell samples lysates. These results show that the graphene FET sensor was able to differentiate between ERα-positive and ERα-negative cells, indicating a promising biosensor for the ultrasensitive and rapid detection of ERα protein without antibody labeling.

Extended-Gate FET Biosensor Based on GaN Micropillar Array and Polycrystalline Layer: Application to Hg2+ Detection in Human Urine.

Owing to the separation of field-effect transistor (FET) devices from sensing environments, extended-gate FET (EGFET) biosensor features high stability and low cost. Herein, a highly sensitive EGFET biosensor based on a GaN micropillar array and polycrystalline layer (GMP) was fabricated, which was prepared by using simple one-step low-temperature MOCVD growth. In order to improve the sensitivity and detection limit of EGFET biosensor, the surface area and the electrical conductivity of extended-gate electrode can be increased by the micropillar array and the polycrystalline layer, respectively. The designed GMP-EGFET biosensor was modified with l-cysteine and applied for Hg2+ detection with a low limit of detection (LOD) of 1 ng/L, a high sensitivity of -16.3 mV/lg(µg/L) and a wide linear range (1 ng/L-24.5 µg/L). In addition, the detection of Hg2+ in human urine was realized with an LOD of 10 ng/L, which was more than 30 times lower than that of reported sensors. To our knowledge, it is the first time that GMP was used as extended-gate of EGFET biosensor.

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.

Cascading CRISPR/Cas and Nanozyme for Enhanced Organic Photoelectrochemical Transistor Detection with Triple Signal Amplification.

Innovative signal amplification and transduction play pivotal roles in bioanalysis. Herein, cascading CRISPR/Cas and the nanozyme are integrated with electronic amplification in an organic photoelectrochemical transistor (OPECT) to enable triple signal amplification, which is exemplified by the miRNA-triggered CRISPR/Cas13a system and polyoxometalate nanozyme for OPECT detection of miRNA-21. The CRISPR/Cas13a-enabled release of glucose oxidase could synergize with peroxidase-like SiW12 to induce catalytic precipitation on the photogate, inhibiting the interfacial mass transfer and thus the significant suppression of the channel current. The as-developed OPECT sensor demonstrates good sensitivity and selectivity for miRNA-21 detection, with a linear range from 1 fM to 10 nM and an ultralow detection limit of 0.53 fM. This study features the integration of bio- and nanoenzyme cascade and electronic triple signal amplification for OPECT detection.

Dual Engine Boosts Organic Photoelectrochemical Transistor for Enhanced Modulation and Bioanalysis.

Organic photoelectrochemical transistor (OPECT) has shown substantial potential in the development of next-generation bioanalysis yet is limited by the either-or situation between the photoelectrode types and the channel types. Inspired by the dual-photoelectrode systems, we propose a new architecture of dual-engine OPECT for enhanced signal modulation and its biosensing application. Exemplified by incorporating the CdS/Bi2S3 photoanode and Cu2O photocathode within the gate-source circuit of Ag/AgCl-gated poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) channel, the device shows enhanced modulation capability and larger transconductance (gm) against the single-photoelectrode ones. Moreover, the light irritation upon the device effectively shifts the peak value of gm to zero gate voltage without degradation and generates larger current steps that are advantageous for the sensitive bioanalysis. Based on the as-developed dual-photoelectrode OPECT, target-mediated recycling and etching reactions are designed upon the CdS/Bi2S3, which could result in dual signal amplification and realize the sensitive microRNA-155 biodetection with a linear range from 1 fM to 100 pM and a lower detection limit of 0.12 fM.

Molecule Engineering Metal-Organic Framework-Based Organic Photoelectrochemical Transistor Sensor for Ultrasensitive Bilirubin Detection.

The functionalization of metal-organic frameworks (MOFs) with organic small molecules by in situ postsynthetic modification has garnered considerable attention. However, the precise engineering of recognition sites using this method remains rarely explored in optically controlled bioelectronics. Herein, employing the Schiff base reaction to embed the small molecule (THBA) into a Zr-MOF, we fabricated a hydroxyl-rich MOF on the surface of titanium dioxide nanorod arrays (U6H@TiO2 NRs) to develop light-sensitive gate electrodes with tailored recognition capabilities. The U6H@TiO2 NR gate electrodes were integrated into organic photoelectrochemical transistor (OPECT) sensing systems to tailor a sensitive device for bilirubin (I-Bil) detection. In the presence of I-Bil, coordination effects, hydrogen bonding, and π-π interactions facilitated strong binding between U6H@TiO2 NRs and the target I-Bil. The electron-donating property of I-Bil influenced the gate voltage, enabling precise control of the channel status and modulation of the channel current. The OPECT device exhibited exceptional analytical performance toward I-Bil with wide linearity ranging from 1 × 10-16 to 1 × 10-9 M and a low limit detection of 0.022 fM. Leveraging the versatility of small molecules for boosting the functionalization of materials, this work demonstrates the great potential of the small molecule family for OPECT bioanalysis and holds promise for the advancement of OPECT sensors.

Enzymatically Mediated In Situ Generation of Z-Scheme Bi2S3/Bi2MoO6 Heterojunction-Based Organic Photoelectrochemical Transistor for METTL3/METTL14 Detection.

The OPECT biosensing platform, which connects optoelectronics and biological systems, offers significant amplification and more possibilities for research in biological applications. In this work, a homogeneous organic photoelectrochemical transistor (OPECT) biosensor based on a Bi2S3/Bi2MoO6 heterojunction was constructed to detect METTL3/METTL14 protein activity. The METTL3/METTL14 complex enzyme was used to catalyze adenine (A) on an RNA strand to m6A, protecting m6A-RNA from being cleaved by an E. coli toxin (MazF). Alkaline phosphatase (ALP) catalyzed the conversion of Na3SPO3 to H2S through an enzymatic reaction. Due to the adoption of the strategy of no fixation on the electrode, the generated H2S was easy to diffuse to the surface of the ITO electrode. The Bi2S3/Bi2MoO6 heterojunction was formed in situ through a chemical replacement reaction with Bi2MoO6, improving photoelectric conversion efficiency and realizing signal amplification. Based on this "signal on" mode, METTL3/METTL14 exhibited a wide linear range (0.00001-25 ng/µL) between protein concentration and photocurrent intensity with a limit of detection (LOD) of 7.8 fg/µL under optimal experimental conditions. The applicability of the developed method was evaluated by investigating the effect of four plasticizers on the activity of the METTL3/METTL14 protein, and the molecular modeling technique was employed to investigate the interaction between plasticizers and the protein.

Synergetic Enzyme-Incorporated Metal-Organic Framework and Polyoxometalate Nanozyme: Achieving Stable Tandem Catalysis for Organic Photoelectrochemical Transistor Bioanalysis.

Organic photoelectrochemical transistor (OPECT) has emerged as a promising technique for biomolecule detection, yet its operational rationale remains limited due to its short development time. This study introduces a stable tandem catalysis protocol by synergizing the enzyme-incorporated metal-organic frameworks (E-MOFs) with polyoxometalate (POM) nanozyme for sensitive OPECT bioanalysis. The zeolitic imidazolate framework-8 (ZIF-8) acts as the skeleton to protect the encapsulated glucose oxidase (GOx), allowing the stable catalytic generation of H2O2. With peroxidase-like activity, a phosphotungstic acid hydrate (PW12) is then able to utilize the H2O2 to induce the biomimetic precipitation on the photogate, ultimately resulting in the altered device characteristics for quantitative detection. This work reveals the potential and versatility of an engineered enzymatic system as a key enabler to achieve novel OPECT bioanalysis, which is believed to offer a feasible framework to explore new operational rationale in optoelectronic and bioelectronic detection.

Nanofluidic Membrane-Assisted Organic Electrochemical Transistors for Bioinspired Gustatory Sensation Based on Selective Cation Transport.

Natural organisms have evolved precise sensing systems relying on unique ion channels, which can efficiently perceive various physical/chemical stimuli based on ionic signal transmission in biological fluid environments. However, it is still a huge challenge to achieve extensive applications of the artificial counterparts as an efficient wet sensing platform due to the fluidity of the working medium. Herein, nanofluidic membranes with selective cation transport properties and solid-state organic electrochemical transistors (OECTs) with amplified signals are integrated together to mimic human gustatory sensation, achieving ionic gustatory reagent recognition and a portable configuration. Cu-HHTP nanofluidic membranes with selective cation transport through their uniform micropores are constructed first, followed by assembly with OECTs to form the designed nanofluidic membrane-assisted OECTs (nanofluidic OECTs). As a result, they can distinguish typically ionic gustatory reagents, and even ionic liquids (ILs), demonstrating enhanced gustatory perception performance under a wide concentration range (10-7-10-1 m) compared with those of conventional OECTs. The linear correlations between the response and the reagent concentration further indicate the promising potential for practical application as a next-generation sensing platform. It is suggested that nanofluidic membranes mediated intramembrane cation transport based on the steric hindrance effect, resulting in distinguishable and improved response to multiple ions.

Machine Learning Discrimination and Ultrasensitive Detection of Fentanyl Using Gold Nanoparticle-Decorated Carbon Nanotube-Based Field-Effect Transistor Sensors.

The opioid overdose crisis is a global health challenge. Fentanyl, an exceedingly potent synthetic opioid, has emerged as a leading contributor to the surge in opioid-related overdose deaths. The surge in overdose fatalities, particularly due to illicitly manufactured fentanyl and its contamination of street drugs, emphasizes the urgency for drug-testing technologies that can quickly and accurately identify fentanyl from other drugs and quantify trace amounts of fentanyl. In this paper, gold nanoparticle (AuNP)-decorated single-walled carbon nanotube (SWCNT)-based field-effect transistors (FETs) are utilized for machine learning-assisted identification of fentanyl from codeine, hydrocodone, and morphine. The unique sensing performance of fentanyl led to use machine learning approaches for accurate identification of fentanyl. Employing linear discriminant analysis (LDA) with a leave-one-out cross-validation approach, a validation accuracy of 91.2% is achieved. Meanwhile, density functional theory (DFT) calculations reveal the factors that contributed to the enhanced sensitivity of the Au-SWCNT FET sensor toward fentanyl as well as the underlying sensing mechanism. Finally, fentanyl antibodies are introduced to the Au-SWCNT FET sensor as specific receptors, expanding the linear range of the sensor in the lower concentration range, and enabling ultrasensitive detection of fentanyl with a limit of detection at 10.8 fg mL-1.

Reticular Heterojunction for Organic Photoelectrochemical Transistor Detection of Neuron-Specific Enolase.

Reticular heterojunctions on the basis of metal-organic frameworks (MOFs) and covalent organic frameworks (COFs) have sparked considerable interest in recent research endeavors, which nevertheless have seldom been studied in optoelectronic biosensing. In this work, its utilization for organic photoelectrochemical transistor (OPECT) detection of the important cancer biomarker of neuron-specific enolase (NSE) is reported. A MOF@COF@CdS quantum dots (QDs) heterojunction is rationally designed to serve as the photogating module against the polymeric channel. Linking with a sandwich complexing event, target-dependent alternation of the photogate is achieved, leading to the changed photoelectric conversion efficiency as indicated by the amplified OPECT signals. The proposed assay demonstrates good analytical performance in detecting NSE, featuring a linear detection range from 0.1 pg mL-1 to 100 ng mL-1, with a detection limit of 0.033 pg mL-1.

Polymeric integration of structure-switching aptamers on transistors for histamine sensing.

Aptamers that undergo large conformational rearrangements at the surface of electrolyte-gated field-effect transistor (EG-FETs)-based biosensors can overcome the Debye length limitation in physiological high ionic strength environments. For the sensitive detection of small molecules, carbon nanotubes (CNTs) that approach the dimensions of analytes of interest are promising channel materials for EG-FETs. However, functionalization of CNTs with bioreceptors using frequently reported surface modification strategies (e.g., π-π stacking), requires highly pristine CNTs deposited through methods that are incompatible with low-cost fabrication methods and flexible substrates. In this work, we explore alternative non-covalent surface chemistry to functionalize CNTs with aptamers. We harnessed the adhesive properties of poly-D-lysine (PDL), to coat the surface of CNTs and then grafted histamine-specific DNA aptamers electrostatically in close proximity to the CNT semiconducting channel. The layer-by-layer assembly was monitored by complementary techniques such as X-ray photoelectron spectroscopy, optical waveguide lightmode spectroscopy, and fluorescence microscopy. Surface characterization confirmed histamine aptamer integration into PDL-coated CNTs and revealed ∼5-fold higher aptamer surface coverage when using CNT networks with high surface areas. Specific aptamers assembled on EG-CNTFETs enabled histamine detection in undiluted high ionic strength solutions in the concentration range of 10 nM to 100 µM. Sequence specificity was demonstrated via parallel measurements with control EG-CNTFETs functionalized with scrambled DNA. Histamine aptamer-modified EG-CNTFETs showed high selectivity vs. histidine, the closest structural analog and precursor to histamine. Taken together, these results implied that target-specific aptamer conformational changes on CNTs facilitate signal transduction, which was corroborated by circular dichroism spectroscopy. Our work suggests that layer-by-layer polymer chemistry enables integration of structure-switching aptamers into flexible EG-CNTFETs for small-molecule biosensing.

Large-Area Interfaces for Single-Molecule Label-free Bioelectronic Detection.

Bioelectronic transducing surfaces that are nanometric in size have been the main route to detect single molecules. Though enabling the study of rarer events, such methodologies are not suited to assay at concentrations below the nanomolar level. Bioelectronic field-effect-transistors with a wide (µm2-mm2) transducing interface are also assumed to be not suited, because the molecule to be detected is orders of magnitude smaller than the transducing surface. Indeed, it is like seeing changes on the surface of a one-kilometer-wide pond when a droplet of water falls on it. However, it is a fact that a number of large-area transistors have been shown to detect at a limit of detection lower than femtomolar; they are also fast and hence innately suitable for point-of-care applications. This review critically discusses key elements, such as sensing materials, FET-structures, and target molecules that can be selectively assayed. The amplification effects enabling extremely sensitive large-area bioelectronic sensing are also addressed.

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.