Project description:Monitoring neurochemical signaling across time scales is critical to understanding how brains encode and store information. Flexible (vs stiff) devices have been shown to improve in vivo monitoring, particularly over longer times, by reducing tissue damage and immunological responses. Here, we report our initial steps toward developing flexible and implantable neuroprobes with aptamer-field-effect transistor (FET) biosensors for neurotransmitter monitoring. A high-throughput process was developed to fabricate thin, flexible polyimide probes using microelectromechanical-system (MEMS) technologies, where 150 flexible probes were fabricated on each 4 in. Si wafer. Probes were 150 μm wide and 7 μm thick with two FETs per tip. The bending stiffness was 1.2 × 10-11 N·m2. Semiconductor thin films (3 nm In2O3) were functionalized with DNA aptamers for target recognition, which produces aptamer conformational rearrangements detected via changes in FET conductance. Flexible aptamer-FET neuroprobes detected serotonin at femtomolar concentrations in high-ionic strength artificial cerebrospinal fluid. A straightforward implantation process was developed, where microfabricated Si carrier devices assisted with implantation such that flexible neuroprobes detected physiological relevant serotonin in a tissue-hydrogel brain mimic.
Project description:Determination of the amino acid phenylalanine is important for lifelong disease management in patients with phenylketonuria, a genetic disorder in which phenylalanine accumulates and persists at levels that alter brain development and cause permanent neurological damage and cognitive dysfunction. Recent approaches for treating phenylketonuria focus on injectable medications that efficiently break down phenylalanine but sometimes result in detrimentally low phenylalanine levels. We have identified new DNA aptamers for phenylalanine in two formats, initially as fluorescent sensors and then, incorporated with field-effect transistors (FETs). Aptamer-FET sensors detected phenylalanine over a wide range of concentrations (fM to mM). para-Chlorophenylalanine, which inhibits the enzyme that converts phenylalanine to tyrosine, was used to induce hyperphenylalaninemia during brain development in mice. Aptamer-FET sensors were specific for phenylalanine versus para-chlorophenylalanine and differentiated changes in mouse serum phenylalanine at levels expected in patients. Aptamer-FETs can be used to investigate models of hyperphenylalanemia in the presence of structurally related enzyme inhibitors, as well as naturally occurring amino acids. Nucleic acid-based receptors that discriminate phenylalanine analogs, some that differ by a single substituent, indicate a refined ability to identify aptamers with binding pockets tailored for high affinity and specificity. Aptamers of this type integrated into FETs enable rapid, electronic, label-free phenylalanine sensing.
Project description:Wearable technologies for personalized monitoring require sensors that track biomarkers often present at low levels. Cortisol—a key stress biomarker—is present in sweat at low nanomolar concentrations. Previous wearable sensing systems are limited to analytes in the micromolar-millimolar ranges. To overcome this and other limitations, we developed a flexible field-effect transistor (FET) biosensor array that exploits a previously unreported cortisol aptamer coupled to nanometer-thin-film In2O3 FETs. Cortisol levels were determined via molecular recognition by aptamers where binding was transduced to electrical signals on FETs. The physiological relevance of cortisol as a stress biomarker was demonstrated by tracking salivary cortisol levels in participants in a Trier Social Stress Test and establishing correlations between cortisol in diurnal saliva and sweat samples. These correlations motivated the development and on-body validation of an aptamer-FET array–based smartwatch equipped with a custom, multichannel, self-referencing, and autonomous source measurement unit enabling seamless, real-time cortisol sweat sensing.
Project description:Chemically modified field-effect transistor (FET) nanodevices were shown to be a selective and extremely sensitive detection platform. In FET-based sensors, signal amplification and transduction is based on electrostatic gating of the nanometric semiconductor channel by analyte-receptor interactions, which measurably affect the transconductance of the device. However, chemically modified FETs must overcome several fundamental limitations before they can be effectively deployed as real-time sensors for bioevents occurring on their surface in complex biofluids. Here, we demonstrate the development of amperoFET devices for the real-time continuous monitoring of small molecular metabolites in biofluids. The surface of the nanowires is covalently modified with a redox reversible moiety, which is easily oxidized in the presence of H2O2. The reversible redox transformation of the surface-confined molecules is carried out by a hot electron injection mechanism, conducted simply by the modulation of the source-drain current through the nanoFET sensing device. By this approach, electrons may be injected by the nanowire element into the surface-confined redox moiety and thus maintain a whole-electrically actuated redox system in which the oxidation state is completely controlled by the current applied to the amperoFET system. The modulation of the source-drain current allows the control of the reduced versus oxidized redox moieties population on the nanowire surface, and this, in turn, is applied as the main sensing mechanism. At a given constant source-drain and gate voltage, the chemical perturbation exerted by the presence of chemical oxidants in the tested biofluid will lead to a measurable conductance change. Alteration in the concentration of the specific metabolite will chemically regulate the extent of perturbation applied to the redox system, which can be utilized for the quantification of the molecular metabolite of interest. These 'equilibrium'-type sensors are fully electrically operated and can be further used in implantable sensing applications.
Project description:Aptamer functionalized graphene field effect transistor (apta-GFET) is a versatile bio-sensing platform. However, the chemical inertness of graphene is still an obstacle for its large-scale applications and commercialization. In this work, reduced carboxyl-graphene oxide (rGO-COOH) is studied as a self-activated channel material in the screen-printed apta-GFETs for the first time. Examinations are carefully executed using lead-specific-aptamer as a proof-of-concept to demonstrate its functions in accommodating aptamer bio-probes and promoting the sensing reaction. The graphene-state, few-layer nano-structure, plenty of oxygen-containing groups and enhanced LSA immobilization of the rGO-COOH channel film are evidenced by X-ray photoelectron spectroscopy, Raman spectrum, UV-visible absorbance, atomic force microscopy and scanning electron microscope. Based on these characterizations, as well as a site-binding model based on solution-gated field effect transistor (SgFET) working principle, theoretical deductions for rGO-COOH enhanced apta-GFETs' response are provided. Furthermore, detections for disturbing ions and real samples demonstrate the rGO-COOH channeled apta-GFET has a good specificity, a limit-of-detection of 0.001 ppb, and is in agreement with the conventional inductively coupled plasma mass spectrometry method. In conclusion, the careful examinations demonstrate rGO-COOH is a promising candidate as a self-activated channel material because of its merits of being independent of linking reagents, free from polymer residue and compatible with rapidly developed print-electronic technology.
Project description:The outbreak of the coronavirus disease 2019 (COVID-19) in December 2019 has highlighted the need for a flexible sensing system that can quickly and accurately determine the presence of biomarkers associated with the disease. This sensing system also needs to be easily adaptable to incorporate both novel diseases as well as changes in the existing ones. Here we report the feasibility of using a simple, low-cost silicon field-effect transistor functionalised with aptamers and designed to attach to the spike protein of SARS-CoV2. It is shown that a linear response can be obtained in a concentration range of 100 fM to 10 pM. Furthermore, by using a larger range of source-drain potentials compared with other FET based sensors, it is possible to look at a wider range of device parameters to optimise the response.
Project description:The discharge of oily industrial wastewater containing heavy metal ions with the development of industry severely threatens the environment and human health. Therefore, it is of great significance to monitor the concentration of heavy metal ions in oily wastewater quickly and effectively. Here, an integrated Cd2+ monitoring system consisting of an aptamer-graphene field-effect transistor (A-GFET), oleophobic/hydrophilic surface and monitoring-alarm circuits was presented for monitoring the Cd2+ concentration in oily wastewater. In the system, oil and other impurities in wastewater are isolated by an oleophobic/hydrophilic membrane before detection. The concentration of Cd2+ is then detected by a graphene field-effect transistor with a Cd2+ aptamer modifying the graphene channel. Finally, the detected signal is collected and processed by signal processing circuits to judge whether the Cd2+ concentration exceeds the standard. Experimental results demonstrated that the separation efficiency of the oleophobic/hydrophilic membrane to an oil/water mixture was up to 99.9%, exhibiting a high oil/water separation ability. The A-GFET detecting platform could respond to changes in the Cd2+ concentration within 10 min with a limit of detection (LOD) of 0.125 pM. The sensitivity of this detection platform to Cd2+ near 1 nM was 7.643 × 10-2 nM-1. Compared with control ions (Cr3+, Pb2+, Mg2+, Fe3+), this detection platform exhibited a high specificity to Cd2+. Moreover, the system could send out a photoacoustic alarm signal when the Cd2+ concentration in the monitoring solution exceeds the preset value. Therefore, the system is practical for monitoring the concentration of heavy metal ions in oily wastewater.
Project description:The real-time monitoring of neurochemical release in vivo plays a critical role in understanding the biochemical process of the complex nervous system. Current technologies for such applications, including microdialysis and fast-scan cyclic voltammetry, suffer from limited spatiotemporal resolution or poor selectivity. Here, we report a soft implantable aptamer-graphene microtransistor probe for real-time monitoring of neurochemical release. As a demonstration, we show the monitoring of dopamine with nearly cellular-scale spatial resolution, high selectivity (dopamine sensor >19-fold over norepinephrine), and picomolar sensitivity, simultaneously. Systematic benchtop evaluations, ex vivo experiments, and in vivo studies in mice models highlight the key features and demonstrate the capability of capturing the dopamine release dynamics evoked by pharmacological stimulation, suggesting the potential applications in basic neuroscience studies and studying neurological disease-related processes. The developed system can be easily adapted for monitoring other neurochemicals and drugs by simply replacing the aptamers functionalized on the graphene microtransistors.
Project description:Bioelectronic devices that convert biochemical signals to electronic readout enable biosensing with high spatiotemporal resolution. These technologies have been primarily applied in biomedicine while in plants sensing is mainly based on invasive methods that require tissue sampling, hindering in-vivo detection and having poor spatiotemporal resolution. Here, we developed enzymatic biosensors based on organic electrochemical transistors (OECTs) for in-vivo and real-time monitoring of sugar fluctuations in the vascular tissue of trees. The glucose and sucrose OECT-biosensors were implanted into the vascular tissue of trees and were operated through a low-cost portable unit for 48hr. Our work consists a proof-of-concept study where implantable OECT-biosensors not only allow real-time monitoring of metabolites in plants but also reveal new insights into diurnal sugar homeostasis. We anticipate that this work will contribute to establishing bioelectronic technologies as powerful minimally invasive tools in plant science, agriculture and forestry.
Project description:This paper presents an approach to the real-time, label-free, specific, and sensitive monitoring of insulin using a graphene aptameric nanosensor. The nanosensor is configured as a field-effect transistor, whose graphene-based conducting channel is functionalized with a guanine-rich IGA3 aptamer. The negatively charged aptamer folds into a compact and stable antiparallel or parallel G-quadruplex conformation upon binding with insulin, resulting in a change in the carrier density, and hence the electrical conductance, of the graphene. The change in the electrical conductance is then measured to enable the real-time monitoring of insulin levels. Testing has shown that the nanosensor offers an estimated limit of detection down to 35 pM and is functional in Krebs-Ringer bicarbonate buffer, a standard pancreatic islet perfusion medium. These results demonstrate the potential utility of this approach in label-free monitoring of insulin and in timely prediction of accurate insulin dosage in clinical diagnostics.