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:Cortisol is a hormone released in response to stress and is a major glucocorticoid produced by adrenal glands. Here, we report a wearable sensory electronic chip using label-free detection, based on a platinum/graphene aptamer extended gate field effect transistor (EG-FET) for the recognition of cortisol in biological buffers within the Debye screening length. The device shows promising experimental features for real-time monitoring of the circadian rhythm of cortisol in human sweat. We report a hysteresis-free EG-FET with a voltage sensitivity of the order of 14 mV/decade and current sensitivity up to 80% over the four decades of cortisol concentration. The detection limit is 0.2 nM over a wide range, between 1 nM and 10 µM, of cortisol concentrations in physiological fluid, with negligible drift over time and high selectivity. The dynamic range fully covers those in human sweat. We propose a comprehensive analysis and a unified, predictive analytical mapping of current sensitivity in all regimes of operation.
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:Wearable biosensors have emerged as an alternative evolutionary development in the field of healthcare technology due to their potential to change conventional medical diagnostics and health monitoring. However, a number of critical technological challenges including selectivity, stability of (bio)recognition, efficient sample handling, invasiveness, and mechanical compliance to increase user comfort must still be overcome to successfully bring devices closer to commercial applications. We introduce the integration of an electrochemical transistor and a tailor-made synthetic and biomimetic polymeric membrane, which acts as a molecular memory layer facilitating the stable and selective molecular recognition of the human stress hormone cortisol. The sensor and a laser-patterned microcapillary channel array are integrated in a wearable sweat diagnostics platform, providing accurate sweat acquisition and precise sample delivery to the sensor interface. The integrated devices were successfully used with both ex situ methods using skin-like microfluidics and on human subjects with on-body real-sample analysis using a wearable sensor assembly.
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:In this paper, we demonstrate the possibility of direct protein sensing beyond the Debye length limit using a molecular-charge-contact (MCC)-based ion-sensitive field-effect transistor (ISFET) sensor combined with a microfluidic device. Different from the MCC method previously reported, biotin-coated magnetic beads are set on the gate insulator of an ISFET using a button magnet before the injection of target molecules such as streptavidin. Then, the streptavidin-a biotin interaction, used as a model of antigen-antibody reaction is expected at the magnetic beads/gate insulator nanogap interface, changing the pH at the solution/dielectric interface owing to the weak acidity of streptavidin. In addition, the effect of the pH or ionic strength of the measurement solutions on the electrical signals of the MCC-based ISFET sensor is investigated. Furthermore, bound/free (B/F) molecule separation with a microfluidic device is very important to obtain an actual electrical signal based on the streptavidin-biotin interaction. Platforms based on the MCC method are suitable for exploiting the advantages of ISFETs as pH sensors, that is, direct monitoring systems for antigen-antibody reactions in the field of in vitro diagnostics.
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:A field-effect transistor-based cortisol sensor was demonstrated in physiological conditions. An antibody-embedded polymer on the remote gate was proposed to overcome the Debye length issue (?D). The sensing membrane was made by linking poly(styrene- co-methacrylic acid) (PSMA) with anticortisol before coating the modified polymer on the remote gate. The embedded receptor in the polymer showed sensitivity from 10 fg/mL to 10 ng/mL for cortisol and a limit of detection (LOD) of 1 pg/mL in 1× PBS where ?D is 0.2 nm. A LOD of 1 ng/mL was shown in lightly buffered artificial sweat. Finally, a sandwich ELISA confirmed the antibody binding activity of antibody-embedded PSMA.