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: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: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: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.
Project description:Real-time, high resolution, simultaneous measurement of multiple ionic species is challenging with existing chromatographic, spectrophotometric and potentiometric techniques. Potentiometric ion sensors exhibit limitations in both resolution and selectivity. Herein, we develop wafer scale graphene transistor technology for overcoming these limitations. Large area graphene is an ideal material for high resolution ion sensitive field effect transistors (ISFETs), while simultaneously enabling facile fabrication as compared to conventional semiconductors. We develop the ISFETs into an array and apply Nikolskii-Eisenman analysis to account for cross-sensitivity and thereby achieve high selectivity. We experimentally demonstrate real-time, simultaneous concentration measurement of K+, Na+, [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text] and Cl- with a resolution of [Formula: see text] concentration units. The array achieves an accuracy of ±0.05 log concentration. Finally, we demonstrate real-time ion concentration measurement in an aquarium with lemnoideae lemna over three weeks, where mineral uptake by aquatic organisms can be observed during their growth.
Project description:Painless, needle-free, and continuous glucose monitoring sensors are needed to enhance the life quality of diabetic patients. To that extent, we propose a first-of-its-kind, highly sensitive, noninvasive continuous glycemic monitoring wearable multisensor system. The proposed sensors are validated on serum, animal tissues, and animal models of diabetes and in a clinical setting. The noninvasive measurement results during human trials reported high correlation (>0.9) between the system's physical parameters and blood glucose levels, without any time lag. The accurate real-time responses of the sensors are attributed to their unique vasculature anatomy-inspired tunable electromagnetic topologies. These wearable apparels wirelessly sense hypo- to hyperglycemic variations with high fidelity. These components are designed to simultaneously target multiple body locations, which opens the door for the development of a closed-loop artificial pancreas.
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.