Ultrasensitive Detection of Ribonucleic Acid Biomarkers Using Portable Sensing Platforms Based on Organic Electrochemical Transistors.

The analysis of ribonucleic acid (RNA) plays an important role in the early diagnosis of diseases and will greatly benefit patients with a higher cure rate. However, the low abundance of RNA in physiological environments requires ultrahigh sensitivity of a detection technology. Here, we construct a portable and smart-phone-controlled biosensing platform based on disposable organic electrochemical transistors for ultrasensitive analysis of microRNA (miRNA) biomarkers within 1 h. Due to their inherent amplification function, the devices can detect miRNA cancer biomarkers from little-volume solutions with concentrations down to 10-14 M. The devices can distinguish blood miRNA expression levels at different cancer stages using a 4T1 mouse tumor model. The technique for ultrasensitive and fast detection of RNA biomarkers with high selectivity opens a window for mobile diagnosis of various diseases with low cost.

Functionalized Organic Thin Film Transistors for Biosensing.

The rise of organic bioelectronics efficiently bridges the gap between semiconductor devices and biological systems, leading to flexible, lightweight, and low-cost organic bioelectronic devices suitable for health or body signal monitoring. The introduction of organic semiconductors in the devices can soften the boundaries between microelectronic systems and dynamically active cells and tissues. Therefore, organic bioelectronics has attracted much attention recently due to the unique properties and promising applications. Organic thin film transistors (OTFTs), owing to their inherent capability of amplifying received signals, have emerged as one of the state-of-the-art biosensing platforms. The advantages of organic semiconductors in terms of synthetic freedom, low temperature solution processing, biocompatibility, and mechanical flexibility render OTFTs ideal transducers for wearable electronics, e-skin, and implantable devices. How to realize highly sensitive, selective, rapid, and efficient signal capture and extraction of biological recognition events is the major challenge in the design of biosensors. OTFTs are prone to converting the presence or change of target analytes into specific electrical signals even in complex biological systems. More importantly, OTFT sensors can be conveniently functionalized with chemical or biological modifications and exhibit substantially improved device sensitivity and selectivity as well as other analytical figure of merits, including calibration range, linearity, and accuracy. However, the stability and reproducibility of the organic devices need to be further improved. In this Account, we first introduce the unique features of OTFTs for bioelectronic applications. Two typical OTFT configurations, including organic electrochemical transistor (OECT) and electrolyte gated organic field effect transistor (EGOFET), are highlighted in their sensing applications mainly due to the operation of the devices in electrolytes and the combination of ionic and electronic charge transports in the devices. These devices are potentiometric transducers with low working voltages (<1 V) and high sensitivity, and are thus suitable for wearable applications with low power consumption. Second, the functionalization strategies on channel materials, electrolytes, and gate electrodes based on various modification methods and sensing mechanisms are discussed in sequence. In an OECT- or EGOFET-based biosensor, the device performance is particularly sensitive to the physical properties of the two interfaces, including channel/electrolyte and gate/electrolyte interfaces. Any change in the potential drop or capacitance of either interface can influence the channel current substantially. Therefore, the functionalization of the interfaces is critical to the sensing performance. In particular, when an electrochemically active material is modified on the interfaces, the reaction of the analyte catalyzed by the modified material can influence the interface potential and lead to a channel current response much stronger than that of a conventional electrochemical measurement. So the biosensors are much more sensitive than typical analytical methods due to the signal amplification of the transistors. Third, the processing techniques including screen printing and inkjet printing and the possibility for mass production are discussed. The applications of organic transistors in wearable electronics and healthcare monitoring systems, especially the fabric OECT-based biosensors for noninvasive detection, are presented. It is expected that the versatile organic transistors will enable various compact, flexible and disposable biosensors compatible with wearable electronics.

Antioxidant Grain Passivation for Air-Stable Tin-Based Perovskite Solar Cells.

Tin-based perovskites with excellent optoelectronic properties and suitable band gaps are promising candidates for the preparation of efficient lead-free perovskite solar cells (PSCs). However, it is challenging to prepare highly stable and efficient tin-based PSCs because Sn2+ in perovskites can be easily oxidized to Sn4+ upon air exposure. Here we report the fabrication of air-stable FASnI3 solar cells by introducing hydroxybenzene sulfonic acid or its salt as an antioxidant additive into the perovskite precursor solution along with excess SnCl2 . The interaction between the sulfonate group and the Sn2+ ion enables the in situ encapsulation of the perovskite grains with a SnCl2 -additive complex layer, which results in greatly enhanced oxidation stability of the perovskite film. The corresponding PSCs are able to maintain 80 % of the efficiency over 500 h upon air exposure without encapsulation, which is over ten times longer than the best result reported previously. Our results suggest a possible strategy for the future design of efficient and stable tin-based PSCs.

Perovskite Solar Cell-Gated Organic Electrochemical Transistors for Flexible Photodetectors with Ultrahigh Sensitivity and Fast Response.

Photodetectors (PDs) are the building block of various imaging and sensing applications. However, commercially available PDs based on crystalline inorganic semiconductors cannot meet the requirements of emerging wearable/implantable applications due to their rigidity and fragility, which creates the need for flexible devices. Here, a high-performance flexible PD is presented by gating an organic electrochemical transistor (OECT) with a perovskite solar cell. Due to the ultrahigh transconductance of the OECT, the device demonstrates a high gain of ≈106 , a fast response time of 67 µs and an ultrahigh detectivity of 6.7 × 1017 Jones to light signals under a low working voltage (≤0.6 V). Thanks to the ultrahigh sensitivity and fast response, the device can track photoplethysmogram signals and peripheral oxygen saturation under ambient light and even provide contactless remote sensing, offering a low-power and convenient way for continuous vital signs monitoring. This work offers a novel strategy for realizing high-performance flexible PDs that are promising for low-power, user-friendly and wearable optoelectronics.

High-Performance Tin-Lead Mixed-Perovskite Solar Cells with Vertical Compositional Gradient.

Sn-Pb mixed perovskites with bandgaps in the range of 1.1-1.4 eV are ideal candidates for single-junction solar cells to approach the Shockley-Queisser limit. However, the efficiency and stability of Sn-Pb mixed-perovskite solar cells (PSCs) still lag far behind those of Pb-based counterparts due to the easy oxidation of Sn2+ . Here, a reducing agent 4-hydrazinobenzoic acid is introduced as an additive along with SnF2 to suppress the oxidation of Sn2+ . Meanwhile, a vertical Pb/Sn compositional gradient is formed spontaneously after an antisolvent treatment due to different solubility and crystallization kinetics of Sn- and Pb-based perovskites and it can be finely tuned by controlling the antisolvent temperature. Because the band structure of a perovskite is dependent on its composition, graded vertical heterojunctions are constructed in the perovskite films with a compositional gradient, which can enhance photocarrier separation and suppress carrier recombination in the resultant PSCs. Under optimal fabrication conditions, the Sn-Pb mixed PSCs show power conversion efficiency up to 22% along with excellent stability during light soaking.

Highly sensitive detection of caspase-3 activity based on peptide-modified organic electrochemical transistor biosensors.

Caspase-3 is an important proteolytic enzyme that cleaves several key substrates in apoptotic processes, resulting in DNA fragmentation, the degradation of nuclear proteins, and the formation of apoptotic bodies. However, it is challenging to detect caspase-3 due to its low expression levels in cells. In this work, organic electrochemical transistors (OECTs) are used in the detection of caspase-3 for the first time. A self-assembled monolayer of the peptide is bonded to the Au gate electrode (GE) of an OECT via gold-sulphur bonds. It is found that the transfer curve of the transistor shifts to a lower gate voltage due to the modulation of the surface potential of the GE by the peptides. Then, the device is used in the detection of caspase-3 in aqueous solutions and shows a detection limit of 0.1 pM. Due to its high sensitivity, the device can detect caspase-3 in induced apoptotic HeLa cells. The system is low-cost, conveniently used and applicable for biological and medical monitoring where caspase-3 detection and quantification are required.

Ultrafast, sensitive, and portable detection of COVID-19 IgG using flexible organic electrochemical transistors.

The outbreak of COVID-19 and its continued spread have seriously threatened public health. Antibody testing is essential for infection diagnosis, seroepidemiological analysis, and vaccine evaluation. However, convenient, fast, and accurate antibody detection remains a challenge in this protracted battle. Here, we report an ultrafast, low-cost, label-free, and portable SARS-CoV-2 immunoglobulin G (IgG) detection platform based on organic electrochemical transistors (OECTs), which can be remotely controlled by a mobile phone. To enable faster detection, voltage pulses are applied on the gate electrode of the OECT to accelerate binding between the antibody and antigen. By optimizing ion concentrations and pH values of test solutions, we realize specific detection of SARS-CoV-2 IgG in several minutes with a detectable region from 10 fM to 100 nM, which encompasses the range of serum SARS-CoV-2 IgG levels in humans. These portable sensors show promise for use in diagnosis and prognosis of COVID-19.

2D materials for conducting holes from grain boundaries in perovskite solar cells.

Grain boundaries in organic-inorganic halide perovskite solar cells (PSCs) have been found to be detrimental to the photovoltaic performance of devices. Here, we develop a unique approach to overcome this problem by modifying the edges of perovskite grain boundaries with flakes of high-mobility two-dimensional (2D) materials via a convenient solution process. A synergistic effect between the 2D flakes and perovskite grain boundaries is observed for the first time, which can significantly enhance the performance of PSCs. We find that the 2D flakes can conduct holes from the grain boundaries to the hole transport layers in PSCs, thereby making hole channels in the grain boundaries of the devices. Hence, 2D flakes with high carrier mobilities and short distances to grain boundaries can induce a more pronounced performance enhancement of the devices. This work presents a cost-effective strategy for improving the performance of PSCs by using high-mobility 2D materials.

Organic electrochemical transistor for sensing of sialic acid in serum samples.

Sialic acid usually locates at the terminal of glycoproteins and glycolipids on cell surface. Compared to normal cells, cancer cells generally express much more sialic acid residues, and the sialylation of cell surface proteins or lipids is related to the progression of tumors, which leads to high expression of serum sialic acid in cancer patients. This work used an organic electrochemical transistor as the sensing platform to design a simple and suitable device for sensitive and convenient detection of sialic acid level in serum samples. The transistor-based biosensor consisted of three typical drain/source/gate Au electrodes on a glass substrate and a polymer membrane to serve as conducting channel between source electrode and drain electrode. The gate electrode was modified with carboxylated multi-wall carbon nanotubes to covalently bind 3-aminobenzeneboronic acid, which specifically recognized sialic acid to change the effect gate voltage of the transistor, and thus produced the signal of drain-source channel current for sensitive detection of sialic acid ranging from 0.1 to 7 mM. The novel biosensor possessed excellent specificity for distinguishing normal and cancer people. The detection results of serum samples from lung cancer patients demonstrated the excellent performance of the transistor-based biosensor, showing the potential application in clinical diagnose.

Lead-Free Perovskite/Organic Semiconductor Vertical Heterojunction for Highly Sensitive Photodetectors.

In recent years, photodetectors based on organic-inorganic lead halide perovskites have been studied extensively. However, the inclusion of lead in those materials can cause severe human health and environmental problems, which is undesirable for practical applications. Here, we report high-performance photodetectors with a tin-based perovskite/PEDOT:PSS vertical heterojunction. The device demonstrates a broadband photoresponse from NIR to UV. The maximum responsivity and gain are up to 2.6 × 106 A/W and 4.7 × 106, respectively. Moreover, a much shorter response time and higher detectivity can be achieved by reducing the thickness of PEDOT:PSS. The outstanding performance is due to the excellent optoelectronic properties of the perovskite and the photogating effect originating from the heterojunction. Furthermore, devices fabricated on flexible substrates can demonstrate not only high sensitivity but also excellent bending stability. This work opens up the opportunity of using lead-free perovskite in highly sensitive photodetectors with vertical heterojunctions.

Gradient 2D/3D Perovskite Films Prepared by Hot-Casting for Sensitive Photodetectors.

2D Ruddlesden-Popper perovskites have attracted wide attention recently because of tunable optoelectronic properties and have been used as alternatives to their 3D counterparts in various optoelectronic devices. Here, a series of (PEA)2(MA) n -1Pb n I3 n +1 perovskite thin films is designed and fabricated by a convenient hot-casting method to obtain gradient n in the films, which leads to the formation of vertical heterojunctions that can enhance charge separation in the films under light illumination. Based on a single gradient perovskite film, a highly sensitive and stable photodetector with a responsivity up to 149 AW-1 and a specific detectivity of 2 × 1012 Jones is obtained. This work paves a way to realizing high-performance optoelectronic devices with enhanced charge separation by introducing compositional gradient in a perovskite film.

Organic electrochemical transistor arrays for real-time mapping of evoked neurotransmitter release in vivo.

Though neurotransmitters are essential elements in neuronal signal transduction, techniques for in vivo analysis are still limited. Here, we describe an organic electrochemical transistor array (OECT-array) technique for monitoring catecholamine neurotransmitters (CA-NTs) in rat brains. The OECT-array is an active sensor with intrinsic amplification capability, allowing real-time and direct readout of transient CA-NT release with a sensitivity of nanomolar range and a temporal resolution of several milliseconds. The device has a working voltage lower than half of that typically used in a prevalent cyclic voltammetry measurement, and operates continuously in vivo for hours without significant signal drift, which is inaccessible for existing methods. With the OECT-array, we demonstrate simultaneous mapping of evoked dopamine release at multiple striatal brain regions in different physiological scenarios, and reveal a complex cross-talk between the mesolimbic and the nigrostriatal pathways, which is heterogeneously affected by the reciprocal innervation between ventral tegmental area and substantia nigra pars compacta.

Cells in the nervous system pass messages using a combination of electrical and chemical signals. When an electrical impulse reaches the end of one cell, it triggers the release of chemicals called neurotransmitters, which pass the message along. Neurotransmitters can be either activating or inhibitory, determining whether the next cell fires its own electrical signal or remains silent. Currently, researchers lack effective methods for measuring neurotransmitters directly. Instead, methods mainly focus on electrical recordings, which can only tell when cells are active. One new approach is to use miniature devices called organic electrochemical transistors. Transistors are common circuit board components that can switch or amplify electrical signals. Organic electrochemical transistors combine these standard components with a semi-conductive material and a flexible membrane. When they interact with certain biological molecules, they release electrons, inducing a voltage. This allows organic electrochemical transistors to detect and measure neurotransmitter release. So far, the technology has been shown to work in tissue isolated from a brain, but no-one has used it to detect neurotransmitters inside a living brain. Xie, Wang et al. now present a new device that can detect the release of the neurotransmitter, dopamine, in real-time in living rats. The device is a miniature microarray of transistors fixed to a blade-shaped film. Xie, Wang et al. implanted this device into the brain of an anaesthetised rat and then stimulated nearby brain cells using an electrode. The device was able to detect the release of the neurotransmitter dopamine, despite there being a range of chemicals released inside the brain. It was sensitive to tiny amounts of the neurotransmitter and could distinguish bursts that were only milliseconds apart. Finally, Xie, Wang et al. also implanted the array across two connected brain areas to show that it was possible to watch different brain regions at the same time. This is the first time that transistor arrays have measured neurotransmitter release in a living brain. The new device works at low voltage, so can track brain cell activity for hours, opening the way for brand new neuroscience experiments. In the future, adaptations could extend the technology even further. More sensors could give higher resolution results, different materials could detect different neurotransmitters, and larger arrays could map larger brain areas.

Sn-Based Perovskite for Highly Sensitive Photodetectors.

Organic-inorganic hybrid perovskites have emerged as promising functional materials for high-performance photodetectors. However, the toxicity of Pb and the lack of internal gain mechanism in typical perovskites significantly hinder their practical applications. Herein, a low-voltage and high-performance photodetector based on a single layer of lead-free Sn-based perovskite film is reported. The device shows broadband response from ultraviolet to near-infrared light with a responsivity up to 105 A W-1 and a high gain at a low operating voltage. The outstanding performance is attributed to the high hole mobility, p-doping nature, and excellent optoelectronic properties of the Sn-based perovskite. Moreover, the device is assembled on a flexible substrate and demonstrates both high sensitivity and good bending stability. This work demonstrates a route for realizing nontoxic, low-cost, and high-performance perovskite photodetectors with a simple device structure.

PEDOT:PSS for Flexible and Stretchable Electronics: Modifications, Strategies, and Applications.

Substantial effort has been devoted to both scientific and technological developments of wearable, flexible, semitransparent, and sensing electronics (e.g., organic/perovskite photovoltaics, organic thin-film transistors, and medical sensors) in the past decade. The key to realizing those functionalities is essentially the fabrication of conductive electrodes with desirable mechanical properties. Conductive polymers (CPs) of poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) have emerged to be the most promising flexible electrode materials over rigid metallic oxides and play a critical role in these unprecedented devices as transparent electrodes, hole transport layers, interconnectors, electroactive layers, or motion-sensing conductors. Here, the current status of research on PEDOT:PSS is summarized including various approaches to boosting the electrical conductivity and mechanical compliance and stability, directly linked to the underlying mechanism of the performance enhancements. Along with the basic principles, the most cutting edge-progresses in devices with PEDOT:PSS are highlighted. Meanwhile, the advantages and plausible problems of the CPs and as-fabricated devices are pointed out. Finally, new perspectives are given for CP modifications and device fabrications. This work stresses the importance of developing CP films and reveals their critical role in the evolution of these next-generation devices featuring wearable, deformable, printable, ultrathin, and see-through characteristics.

AC Measurements Using Organic Electrochemical Transistors for Accurate Sensing.

Organic electrochemical transistors (OECTs) have been successfully employed for a variety of applications , especially chemical and biological sensing. Although the device response to analytes can be directly monitored by measuring steady-state channel currents of the devices, it is challenging to obtain stable signals with high signal-to-noise ratios. In this work, we developed a novel method for electrochemical sensing by measuring both the transconductance and the phase of the AC channel current for the first time. Then we successfully realized highly sensitive ion strength sensors and dopamine sensors based on the AC method. Our results indicate that the AC method is more sensitive than typical DC methods and can provide more stable data in sensing applications. Considering that the sensors can be conveniently integrated with AC circuits, this technology is expected to find broad applications in the future.

The Influence of Fiber Cross-Section on Fabric Far-Infrared Properties.

Far-infrared radiation (FIR) possesses various promising properties that are beneficial to an individuals' health. Exploring the interaction between fiber shapes and FIR performance is thought to be a significant means to develop highly-efficient FIR textile products. In this study, a non-additive triangular polyamide (PA) fiber showed excellent FIR properties in both theoretical simulation and experimental verification aspects. The triangular PA fiber affords a higher probability to facilitate large optical path difference, improving both FIR absorption and emission. Textiles woven with the specific triangular PA fiber achieved a remarkable emissivity of 91.85% and temperature difference of 2.11 Celsius, which is obviously superior to the reference circular fiber (86.72%, 1.52 Celsius). Considering the low cost, environmental stability, facile fabrication, as well as being environmentally friendly, this non-additive triangular PA fiber has great potential for high-performance and cost-effective FIR textiles in the future.

Organic Electrochemical Transistors for the Detection of Cell Surface Glycans.

Cell surface glycans play critical roles in diverse biological processes, such as cell-cell communication, immunity, infection, development, and differentiation. Their expressions are closely related to cancer growth and metastasis. This work demonstrates an organic electrochemical transistor (OECT)-based biosensor for the detection of glycan expression on living cancer cells. Herein, mannose on human breast cancer cells (MCF-7) as the target glycan model, poly dimethyl diallyl ammonium chloride-multiwall carbon nanotubes (PDDA-MWCNTs) as the loading interface, concanavalin A (Con A) with active mannose binding sites, aptamer and horseradish peroxidase co-immobilized gold nanoparticles (HRP-aptamer-Au NPs) as specific nanoprobes are used to fabricate the OECT biosensor. In this strategy, PDDA-MWCNT interfaces can enhance the loading of Con A, and the target cells can be captured through Con A via active mannose binding sites. Thus, the expression of cell surface can be reflected by the amount of cells captured on the gate. Specific nanoprobes are introduced to the captured cells to produce an OECT signal because of the reduction of hydrogen peroxide catalyzed by HRP conjugated on Au nanoparticles, while the aptamer on nanoprobes can selectively recognize the MCF-7 cells. It is reasonable that more target cells are captured on the gate electrode, more HRP-nanoprobes are loaded thus a larger signal response. The device shows an obvious response to MCF-7 cells down to 10 cells/µL and can be used to selectively monitor the change of mannose expression on cell surfaces upon a treatment with the N-glycan inhibitor. The OECT-based biosensor is promising for the analysis of glycan expressions on the surfaces of different types of cells.

Fabric Organic Electrochemical Transistors for Biosensors.

Flexible fabric biosensors can find promising applications in wearable electronics. However, high-performance fabric biosensors have been rarely reported due to many special requirements in device fabrication. Here, the preparation of organic electrochemical transistors (OECTs) on Nylon fibers is reported. By introducing metal/conductive polymer multilayer electrodes on the fibers, the OECTs show very stable performance during bending tests. The devices with functionalized gates are successfully used as various biosensors with high sensitivity and selectivity. The fiber-based OECTs are woven together with cotton yarns successfully by using a conventional weaving machine, resulting in flexible and stretchable fabric biosensors with high performance. The fabric sensors show much more stable signals in the analysis of moving aqueous solutions than planar devices due to a capillary effect in fabrics. The fabric devices are integrated in a diaper and remotely operated by using a mobile phone, offering a unique platform for convenient wearable healthcare monitoring.

Highly Sensitive Detection of Protein Biomarkers with Organic Electrochemical Transistors.

The analysis of protein biomarkers is of great importance in the diagnosis of diseases. Although many convenient and low-cost electrochemical approaches have been extensively investigated, they are not sensitive enough in the detection of protein biomarkers with low concentrations in physiological environments. Here, this study reports a novel organic-electrochemical-transistor-based biosensor that can successfully detect cancer protein biomarkers with ultrahigh sensitivity. The devices are operated by detecting electrochemical activity on gate electrodes, which is dependent on the concentrations of proteins labeled with catalytic nanoprobes. The protein sensors can specifically detect a cancer biomarker, human epidermal growth factor receptor 2, down to the concentration of 10-14 g mL-1 , which is several orders of magnitude lower than the detection limits of previously reported electrochemical approaches. Moreover, the devices can successfully differentiate breast cancer cells from normal cells at various concentrations. The ultrahigh sensitivity of the protein sensors is attributed to the inherent amplification function of the organic electrochemical transistors. This work paves a way for developing highly sensitive and low-cost biosensors for the detection of various protein biomarkers in clinical analysis in the future.