P3HT-based organic field effect transistor for low-cost, label-free detection of immunoglobulin G.

Currently, organic field effect transistors (OFETs) are widely used in the field of biodetection because of their inherent gain amplification function and good biocompatibility. However, the vast majority of OFET biosensors have disadvantages including a long preparation cycle, complicated processing and expensive materials. Thus, this paper proposes a simple and inexpensive preparation method for label-free detection of immunoglobulin G (IgG). In this work an active dielectric bilayer field effect transistor with 3D-printed silver source and drain electrodes was used. The active layer was modified by physically adsorbing an anti-IgG antibody on P3HT as a recognition element and then sealed with bovine serum albumin (BSA) to prevent nonspecific adsorption. The carrier mobility of the bilayer dielectric layer active field effect transistor reached 4.6 × 10-2 cm2/Vs, and the dynamic detection range for IgG spanned 6 orders of magnitude with a detection limit of 2.9 Picomolar (pM). Controlled experiments demonstrated that the developed sensor has high selectivity for IgG. Overall, this easy-to-operate and low-cost OFET biosensor has broad commercialization prospects and lays the foundation for the early clinical detection of disease-causing biomolecules.

Selective Ion Sensing in Artificial Sweat Using Low-Cost Reduced Graphene Oxide Liquid-Gated Plastic Transistors.

Health monitoring is experiencing a radical shift from clinic-based to point-of-care and wearable technologies, and a variety of nanomaterials and transducers have been employed for this purpose. 2D materials (2DMs) hold enormous potential for novel electronics, yet they struggle to meet the requirements of wearable technologies. Here, aiming to foster the development of 2DM-based wearable technologies, reduced graphene oxide (rGO)-based liquid-gated transistors (LGTs) for cation sensing in artificial sweat endowed with distinguished performance and great potential for scalable manufacturing is reported. Laser micromachining is employed to produce flexible transistor test patterns employing rGO as the electronic transducer. Analyte selectivity is achieved by functionalizing the transistor channel with ion-selective membranes (ISMs) via a simple casting method. Real-time monitoring of K+ and Na+ in artificial sweat is carried out employing a gate voltage pulsed stimulus to take advantage of the fast responsivity of rGO. The sensors show excellent selectivity toward the target analyte, low working voltages (<0.5 V), fast (5-15 s), linear response at a wide range of concentrations (10 µm to 100 mm), and sensitivities of 1 µA/decade. The reported strategy is an important step forward toward the development of wearable sensors based on 2DMs for future health monitoring technologies.

Antidelaminating, Thermally Stable, and Cost-Effective Flexible Kapton Platforms for Nitrate Sensors, Mercury Aptasensors, Protein Sensors, and p-Type Organic Thin-Film Transistors.

The inkjet printing of metal electrodes on polymer films is a desirable manufacturing process due to its simplicity but is limited by the lack of thermal stability and serious delaminating flaws in various aqueous and organic solutions. Kapton, adopted worldwide due to its superior thermal durability, allows the high-temperature sintering of nanoparticle-based metal inks. By carefully selecting inks (Ag and Au) and Kapton substrates (Kapton HN films with a thickness of 135 µm and a thermal resistance of up to 400 °C) with optimal printing parameters and simplified post-treatments (sintering), outstanding film integrity, thermal stability, and antidelaminating features were obtained in both aqueous and organic solutions without any pretreatment strategy (surface modification). These films were applied in four novel devices: a solid-state ion-selective (IS) nitrate (NO3-) sensor, a single-stranded DNA (ssDNA)-based mercury (Hg2+) aptasensor, a low-cost protein printed circuit board (PCB) sensor, and a long-lasting organic thin-film transistor (OTFT). The IS NO3- sensor displayed a linear sensitivity range between 10-4.5 and 10-1 M (r2 = 0.9912), with a limit of detection of 2 ppm for NO3-. The Hg2+ sensor exhibited a linear correlation (r2 = 0.8806) between the change in the transfer resistance (RCT) and the increasing concentration of Hg2+. The protein PCB sensor provided a label-free method for protein detection. Finally, the OTFT demonstrated stable performance, with mobility values in the linear (µlin) and saturation (µsat) regimes of 0.0083 ± 0.0026 and 0.0237 ± 0.0079 cm2 V-1 S-1, respectively, and a threshold voltage (Vth) of -6.75 ± 3.89 V.

Facile and cost-effective liver cancer diagnosis by water-gated organic field-effect transistors.

The rise of mortality rate caused by hepatocellular carcinoma accelerates requirements of biosensors for early liver cancer diagnosis and treatment to improve the clinical prognosis and prolong the survival of patients. However, how to realize label-free, low-cost, easy and fast-detection is the major challenge in the design of biosensors. Water-gated organic field-effect transistors efficiently bridge the gap between semiconductor devices and biological systems, leading to an organic device suitable for health or body signal monitoring. Herein, a kind of high-performance water-gated organic field-effect transistor is developed through the optimization process. This method provides a label-free general sensing platform for the determination of liver cancer biomarker alpha-fetoprotein in 45 minutes, much quicker than traditional methods such as the enzyme-linked immunosorbent assay for several hours. In addition, with the detection limit lower than the cut-off value as well as the ability to achieve quantitative detection, this novel water-gated organic field-effect transistor enables a much broader analysis of other biomarkers in cancer patient samples.

Trace-Level, Multi-Gas Detection for Food Quality Assessment Based on Decorated Silicon Transistor Arrays.

Multiplexed gas detection at room temperature is critical for practical applications, such as for tracking the complex chemical environments associated with food decomposition and spoilage. An integrated array of multiple silicon-based, chemical-sensitive field effect transistors (CSFETs) is presented to realize selective, sensitive, and simultaneous measurement of gases typically associated with food spoilage. CSFETs decorated with sensing materials based on ruthenium, silver, and silicon oxide are used to obtain stable room-temperature responses to ammonia (NH3 ), hydrogen sulfide (H2 S), and humidity, respectively. For example, one multi-CSFET sensor signal changes from its baseline by 13.34 in response to 1 ppm of NH3 , 724.45 under 1 ppm H2 S, and 23.46 under 80% relative humidity, with sensitive detection down to 10 ppb of NH3 and H2 S. To demonstrate this sensor for practical applications, the CSFET sensor array is combined with a custom-printed circuit board into a compact, fully integrated, and portable system to conduct real-time monitoring of gases generated by decomposing food. By using existing silicon-based manufacturing methodologies, this room-temperature gas sensing array can be fabricated reproducibly and at low cost, making it an attractive platform for ambient gas measurement needed in food safety applications.

High correlation between radiation dose estimates for 256-slice CT obtained by highly parallelized hybrid Monte Carlo computation and solid-state metal-oxide semiconductor field-effect transistor measurements in physical anthropomorphic phantoms.

PURPOSE: Accurate, patient-specific radiation dosimetry for CT scanning is critical to optimize radiation doses and balance dose against image quality. While Monte Carlo (MC) simulation is often used to estimate doses from CT, comparison of estimates to experimentally measured values is lacking for advanced CT scanners incorporating novel design features. We aimed to compare radiation dose estimates from MC simulation to doses measured in physical anthropomorphic phantoms using metal-oxide semiconductor field-effect transistors (MOSFETs) in a 256-slice CT scanner. METHODS: Fifty MOSFETs were placed in organs within tissue-equivalent anthropomorphic adult and pediatric radiographic phantoms, which were scanned using a variety of chest, cardiac, abdomen, brain, and whole-body protocols on a 256-slice system. MC computations were performed on voxelized CT reconstructions of the phantoms using a highly parallel MC tool developed specifically for diagnostic X-ray energies and rapid computation. Doses were compared between MC estimates and physical measurements. RESULTS: The average ratio of MOSFET to MC dose in the in-field region was close to 1 (range, 0.96-1.12; mean ± SD, 1.01 ± 0.04), indicating outstanding agreement between measured and simulated doses. The difference between measured and simulated doses tended to increase with distance from the in-field region. The error in the MC simulations due to the limited number of simulated photons was less than 1%. The errors in the MOSFET dose determinations in the in-field region for a single scan were mainly due to the calibration method and were typically about 6% (8% if the error in the reading of the ionization chamber that was used for the MOSFET calibration was included). CONCLUSIONS: Radiation dose estimation using a highly parallelized MC method is strongly correlated with experimental measurements in physical adult and infant anthropomorphic phantoms for a wide range of scans performed on a 256-slice CT scanner. Incorporation into CT scanners of radiation-dose distribution estimation, employing the scanner's reconstructed images of the patient, may offer the potential for accurate patient-specific CT dosimetry.

Rapid detection of single E. coli bacteria using a graphene-based field-effect transistor device.

Contamination of surface and drinking water due to the presence of Escherichia coli bacteria is a major cause of water-borne disease outbreak. To address unmet challenges for practical pathogen detection in contaminated samples, we report fabrication of thermally reduced graphene oxide-based field-effect transistor (rGO FET) passivated with an ultrathin layer of Al2O3 for real-time detection of E. coli bacteria. The sensor could detect a single E. coli cell within 50 s in a 1 µL sample volume. The ultrathin layer of Al2O3 acted as a barrier between rGO and potential interferents present in the sample. E. coli specific antibodies anchored on gold nanoparticles acted as probes for selective capture of E. coli. The high density of negative charge on the surface of E. coli cells strongly modulates the concentration of majority charge carriers in the rGO monolayer, thereby allowing real-time monitoring of E. coli concentration in a given sample. With a low detection limit of single cell, the FET sensor had a linear range of 1-100 CFU in 1 µL volume of sample (i.e., 103 to 105 CFU/ mL). The biosensor with good selectivity and rapid detection was further successfully demonstrated for E. coli sensing in river water. The rGO-based FET sensor provides a low cost and label-free approach, and can be mass produced for detection of a broad spectrum of pathogens in water or other liquid media.

Risk stratification of heart failure from one drop of blood using hand-held biosensor for BNP detection.

Continued risk assessment by evaluating cardiac biomarkers in healthy and unhealthy individuals can lower the mortality rate of cardiovascular diseases (CVDs). In this research, we have developed a hand-held biosensor system to rapidly screen for brain natriuretic peptide (BNP) from a single drop of whole blood. The sensor methodology is based on extended gate design of electrical double layer (EDL) field effect transistor (FET), that can directly detect BNP in whole blood, without extensive sample pre-treatments, thereby eliminating the limitations of charge screening in high ionic strength solutions. A simple sensor array chip is fabricated to integrate with the MOSFET sensor system. Sensing characteristics are elucidated using purified BNP samples in 1 × PBS (with 4% BSA), spiked BNP samples in whole blood and clinical whole blood samples. The blood cells can be gravitationally separated without the use of any external actuation. The sensor exhibits very high sensitivity over wide dynamic range of detection. The sensing characteristics are not adversely affected by the presence of background proteins or blood cells, even without gravitational blood cell separation. Thus, the biosensor system can allow users to perform rapid whole blood diagnostics with minimal user protocols, in 5 min. The features of high sensitivity, cost-effectiveness and convenience of usage empower this technology to revolutionize the mobile diagnostics and healthcare industry.

ZIF-67 derived porous Co3O4 hollow nanopolyhedron functionalized solution-gated graphene transistors for simultaneous detection of glucose and uric acid in tears.

Biomarkers in tears have attracted much attention in daily healthcare sensing and monitoring. Here, highly sensitive sensors for simultaneous detection of glucose and uric acid are successfully constructed based on solution-gated graphene transistors (SGGTs) with two separate Au gate electrodes, modified with GOx-CHIT and BSA-CHIT respectively. The sensitivity of the SGGT is dramatically improved by co-modifying the Au gate with ZIF-67 derived porous Co3O4 hollow nanopolyhedrons. The sensing mechanism for glucose sensor is attributed to the reaction of H2O2 generated by the oxidation of glucose near the gate, while the sensing mechanism for uric acid is due to the direct electro-oxidation of uric acid molecules on the gate. The optimized glucose and uric acid sensors show the detection limits both down to 100nM, far beyond the sensitivity required for non-invasive detection of glucose and uric acid in tears. The glucose and uric acid in real tear samples was quantitatively detected at 323.2 ± 16.1µM and 98.5 ± 16.3µM by using the functionalized SGGT device. Due to the low-cost, high-biocompatibility and easy-fabrication features of the ZIF-67 derived porous Co3O4 hollow nanopolyhedron, they provide excellent electrocatalytic nanomaterials for enhancing sensitivity of SGGTs for a broad range of disease-related biomarkers.

Flow-assisted Dielectrophoresis: A Low Cost Method for the Fabrication of High Performance Solution-processable Nanowire Devices.

Flow-assisted dielectrophoresis (DEP) is an efficient self-assembly method for the controllable and reproducible positioning, alignment, and selection of nanowires. DEP is used for nanowire analysis, characterization, and for solution-based fabrication of semiconducting devices. The method works by applying an alternating electric field between metallic electrodes. The nanowire formulation is then dropped onto the electrodes which are on an inclined surface to create a flow of the formulation using gravity. The nanowires then align along the gradient of the electric field and in the direction of the liquid flow. The frequency of the field can be adjusted to select nanowires with superior conductivity and lower trap density. In this work, flow-assisted DEP is used to create nanowire field effect transistors. Flow-assisted DEP has several advantages: it allows selection of nanowire electrical properties; control of nanowire length; placement of nanowires in specific areas; control of orientation of nanowires; and control of nanowire density in the device. The technique can be expanded to many other applications such as gas sensors and microwave switches. The technique is efficient, quick, reproducible, and it uses a minimal amount of dilute solution making it ideal for the testing of novel nanomaterials. Wafer scale assembly of nanowire devices can also be achieved using this technique, allowing large numbers of samples for testing and large-area electronic applications.

Versatile transduction scheme based on electrolyte-gated organic field-effect transistor used as immunoassay readout system.

We report on an innovative heterogeneous bisphenol A (BPA) immunoassay based on an electrolyte-gated organic field-effect transistor whose organic semiconductor is poly(2,5-bis(3-tetradecylthiophen-2-yl)thieno[3,2-b]thiophene) co-crystallized with an alkyl derivative of bisphenol A. A decrease of the transistor output current is first observed upon antibody specific binding onto the organic semiconductor. Upon bisphenol A addition, the competitive dissociation of the antibody from the semiconductor surface leads to an opposite increase of the output current. We present here a proof-of-concept for bisphenol A detection; the device could be readily adapted to other small organic molecules of interest and is a promising tool for simple, low-cost, portable and easy-to-use biosensors.

Printed organo-functionalized graphene for biosensing applications.

Graphene is a highly promising material for biosensors due to its excellent physical and chemical properties which facilitate electron transfer between the active locales of enzymes or other biomaterials and a transducer surface. Printing technology has recently emerged as a low-cost and practical method for fabrication of flexible and disposable electronics devices. The combination of these technologies is promising for the production and commercialization of low cost sensors. In this review, recent developments in organo-functionalized graphene and printed biosensor technologies are comprehensively covered. Firstly, various methods for printing graphene-based fluids on different substrates are discussed. Secondly, different graphene-based ink materials and preparation methods are described. Lastly, biosensing performances of printed or printable graphene-based electrochemical and field effect transistor sensors for some important analytes are elaborated. The reported printed graphene based sensors exhibit promising properties with good reliability suitable for commercial applications. Among most reports, only a few printed graphene-based biosensors including screen-printed oxidase-functionalized graphene biosensor have been demonstrated. The technology is still at early stage but rapidly growing and will earn great attention in the near future due to increasing demand of low-cost and disposable biosensors.

Bioelectronic Nose Using Odorant Binding Protein-Derived Peptide and Carbon Nanotube Field-Effect Transistor for the Assessment of Salmonella Contamination in Food.

Salmonella infection is the one of the major causes of food borne illnesses including fever, abdominal pain, diarrhea, and nausea. Thus, early detection of Salmonella contamination is important for our healthy life. Conventional detection methods for the food contamination have limitations in sensitivity and rapidity; thus, the early detection has been difficult. Herein, we developed a bioelectronic nose using a carbon nanotube (CNT) field-effect transistor (FET) functionalized with Drosophila odorant binding protein (OBP)-derived peptide for easy and rapid detection of Salmonella contamination in ham. 3-Methyl-1-butanol is known as a specific volatile organic compound, generated from the ham contaminated with Salmonella. We designed and synthesized the peptide based on the sequence of the Drosophila OBP, LUSH, which specifically binds to alcohols. The C-terminus of the synthetic peptide was modified with three phenylalanine residues and directly immobilized onto CNT channels using the π-π interaction. The p-type properties of FET were clearly maintained after the functionalization using the peptide. The biosensor detected 1 fM of 3-methyl-1-butanol with high selectivity and successfully assessed Salmonella contamination in ham. These results indicate that the bioelectronic nose can be used for the rapid detection of Salmonella contamination in food.

Current trends in nanomaterial embedded field effect transistor-based biosensor.

Recently, as metal-, polymer-, and carbon-based biocompatible nanomaterials have been increasingly incorporated into biosensing applications, with various nanostructures having been used to increase the efficacy and sensitivity of most of the detecting devices, including field effect transistor (FET)-based devices. These nanomaterial-based methods also became the ideal for the amalgamation of biomolecules, especially for the fabrication of ultrasensitive, low-cost, and robust FET-based biosensors; these are categorically very successful at binding the target specified entities in the confined gated micro-region for high functionality. Furthermore, the contemplation of nanomaterial-based FET biosensors to various applications encompasses the desire for detection of many targets with high selectivity, and specificity. We assess how such devices have empowered the achievement of elevated biosensor performance in terms of high sensitivity, selectivity and low detection limits. We review the recent literature here to illustrate the diversity of FET-based biosensors, based on various kinds of nanomaterials in different applications and sum up that graphene or its assisted composite based FET devices are comparatively more efficient and sensitive with highest signal to noise ratio. Lastly, the future prospects and limitations of the field are also discussed.

A straightforward strategy toward large BN-embedded π-systems: synthesis, structure, and optoelectronic properties of extended BN heterosuperbenzenes.

A straightforward strategy has been used to construct large BN-embedded π-systems simply from azaacenes. BN heterosuperbenzene derivatives, the largest BN heteroaromatics to date, have been synthesized in three steps. The molecules exhibit curved π-surfaces, showing two different conformations which are self-organized into a sandwich structure and further packed into a π-stacking column. The assembled microribbons exhibit good charge transport properties and photoconductivity, representing an important step toward the optoelectronic applications of BN-embedded aromatics.

Highly specific and sensitive non-enzymatic determination of uric acid in serum and urine by extended gate field effect transistor sensors.

A potentiometric non-enzymatic sensor using off-chip extended-gate field effect transistor (EGFET) with a ferrocenyl-alkanethiol modified gold electrode is demonstrated for determining the uric acid concentration in human serum and urine. Hexacyanoferrate (II) and (III) ions are used as redox reagent. This potentiometric sensor measures the interface potential on the ferrocene immobilized gold electrode, which is modulated by the redox reaction between uric acid and hexacyanoferrate ions. The device shows a near Nernstian response to uric acid and is highly specific. The interference that comes from glucose, bilirubin, ascorbic acid and hemoglobin is negligible in normal concentration range of these interferents. The sensor also exhibits excellent long term reliability. This extended gate field effect transistor based sensors can be used as a point of care UA testing tool, due to the small size, low cost, and low sample volume consumption.

Flexible polymer transistors with high pressure sensitivity for application in electronic skin and health monitoring.

Flexible pressure sensors are essential parts of an electronic skin to allow future biomedical prostheses and robots to naturally interact with humans and the environment. Mobile biomonitoring in long-term medical diagnostics is another attractive application for these sensors. Here we report the fabrication of flexible pressure-sensitive organic thin film transistors with a maximum sensitivity of 8.4 kPa(-1), a fast response time of <10 ms, high stability over >15,000 cycles and a low power consumption of <1 mW. The combination of a microstructured polydimethylsiloxane dielectric and the high-mobility semiconducting polyisoindigobithiophene-siloxane in a monolithic transistor design enabled us to operate the devices in the subthreshold regime, where the capacitance change upon compression of the dielectric is strongly amplified. We demonstrate that our sensors can be used for non-invasive, high fidelity, continuous radial artery pulse wave monitoring, which may lead to the use of flexible pressure sensors in mobile health monitoring and remote diagnostics in cardiovascular medicine.

Indium-tin-oxide thin film transistor biosensors for label-free detection of avian influenza virus H5N1.

As continuous outbreak of avian influenza (AI) has become a threat to human health, economic development and social stability, it is urgently necessary to detect the highly pathogenic avian influenza H5N1 virus quickly. In this study, we fabricated indium-tin-oxide thin-film transistors (ITO TFTs) on a glass substrate for the detecting of AI H5N1. The ITO TFT is fabricated by a one-shadow-mask process in which a channel layer can be simultaneously self-assembled between ITO source/drain electrodes during magnetron sputtering deposition. Monoclonal anti-H5N1 antibodies specific for AI H5N1 virus were covalently immobilized on the ITO channel by (3-glycidoxypropyl)trimethoxysilane. The introduction of target AI H5N1 virus affected the electronic properties of the ITO TFT, which caused a change in the resultant threshold voltage (VT) and field-effect mobility. The changes of ID-VG curves were consistent with an n-type field effect transistor behavior affected by nearby negatively charged AI H5N1 viruses. The transistor based sensor demonstrated high selectivity and stability for AI H5N1 virus sensing. The sensor showed linear response to AI H5N1 in the concentrations range from 5×10(-9) g mL(-1) to 5×10(-6) g mL(-1) with a detection limit of 0.8×10(-10) g mL(-1). Moreover, the ITO TFT biosensors can be repeatedly used through the washing processes. With its excellent electric properties and the potential for mass commercial production, ITO TFTs can be promising candidates for the development of label-free biosensors.

Monte Carlo investigation of I-125 interseed attenuation for standard and thinner seeds in prostate brachytherapy with phantom validation using a MOSFET.

PURPOSE: In permanent seed implant prostate brachytherapy the actual dose delivered to the patient may be less than that calculated by TG-43U1 due to interseed attenuation (ISA) and differences between prostate tissue composition and water. In this study the magnitude of the ISA effect is assessed in a phantom and in clinical prostate postimplant cases. Results are compared for seed models 6711 and 9011 with 0.8 and 0.5 mm diameters, respectively. METHODS: A polymethyl methacrylate (PMMA) phantom was designed to perform ISA measurements in a simple eight-seed arrangement and at the center of an implant of 36 seeds. Monte Carlo (MC) simulation and experimental measurements using a MOSFET dosimeter were used to measure dose rate and the ISA effect. MC simulations of 15 CT-based postimplant prostate treatment plans were performed to compare the clinical impact of ISA on dose to prostate, urethra, rectum, and the volume enclosed by the 100% isodose, for 6711 and 9011 seed models. RESULTS: In the phantom, ISA reduced the dose rate at the MOSFET position by 8.6%-18.3% (6711) and 7.8%-16.7% (9011) depending on the measurement configuration. MOSFET measured dose rates agreed with MC simulation predictions within the MOSFET measurement uncertainty, which ranged from 5.5% to 7.2% depending on the measurement configuration (k = 1, for the mean of four measurements). For 15 clinical implants, the mean ISA effect for 6711 was to reduce prostate D90 by 4.2 Gy (3%), prostate V100 by 0.5 cc (1.4%), urethra D10 by 11.3 Gy (4.4%), rectal D2cc by 5.5 Gy (4.6%), and the 100% isodose volume by 2.3 cc. For the 9011 seed the mean ISA effect reduced prostate D90 by 2.2 Gy (1.6%), prostate V100 by 0.3 cc (0.7%), urethra D10 by 8.0 Gy (3.2%), rectal D2cc by 3.1 Gy (2.7%), and the 100% isodose volume by 1.2 cc. Differences between the MC simulation and TG-43U1 consensus data for the 6711 seed model had a similar impact, reducing mean prostate D90 by 6 Gy (4.2%) and V100 by 0.6 cc (1.8%). CONCLUSIONS: ISA causes the delivered dose in prostate seed implant brachytherapy to be lower than the dose calculated by TG-43U1. MC simulation of phantom seed arrangements show that dose at a point can be reduced by up to 18% and this has been validated using a MOSFET dosimeter. Clinical simulations show that ISA reduces DVH parameter values, but the reduction is less for thinner seeds.