Smartphone-powered, ultrasensitive, and selective, portable and stable multi-analyte chemiresistive immunosensing platform with PPY/COOH-MWCNT as bioelectrical transducer: Towards point-of-care TBI diagnosis.

Traumatic Brain Injury, one of the significant causes of mortality and morbidity, affects worldwide and continues to be a diagnostic challenge. The most desirable and partially met clinical need is to simultaneously detect the disease-specific-biomarkers in a broad range of readily available body fluids on a single platform with a rapid, low-cost, ultrasensitive and selective device. Towards this, an array of interdigitated microelectrodes was fabricated on commercially existing low-cost single-side copper cladded printed-circuit-board substrate followed by the bioelectrodes preparation through covalent immobilization of brain injury specific biomarkers on carboxylic functionalized multi-walled carbon nanotubes embedded polypyrrole nanocomposite modified interdigitated microelectrodes. Subsequently, the immunological binding events were transduced as the normalized change in bioelectrode resistance with and without the target analyte via current-voltage analysis. As proof of concept, current-voltage responses were primarily recorded using a conventional probe station, and later, a portable handheld-electronic-readout was developed for the point-of-care application. The data compilation and analysis were carried out using the in-house developed android-based mobile app. Notably, the smartphone powered the readout through a PL-2303 serial connector, avoiding integrating power sources with the readout. Further, this technology can be adapted to other point-of-care biosensing applications.

Label-free, ultrasensitive and rapid detection of FDA-approved TBI specific UCHL1 biomarker in plasma using MWCNT-PPY nanocomposite as bio-electrical transducer: A step closer to point-of-care diagnosis of TBI.

Traumatic Brain Injury (TBI), a major cause of mortality and neurological disability affecting people of all ages worldwide, remains a diagnostic and therapeutic challenge to date. Rapid, ultra-sensitive, selective, and wide-range detection of TBI biomarkers in easily accessible body fluids is an unmet clinical need. Considering this, in this work, we report the design and development of a facile, label-free, highly stable and sensitive, chemi-impedance-based sensing platform for rapid and wide range detection of Ubiquitin-carboxy terminal hydrolase L1 (UCHL1: FDA-approved TBI specific plasma biomarker), using carboxylic functionalized MWCNTs embedded polypyrrole (PPY) nanocomposites (PPY/f-MWCNT). The said nanocomposites were synthesized using chemical oxidative polymerization method. Herein, the functionalized MWCNTs are used as conducting fillers so as to increase the polymer's dielectric constant according to the micro-capacitor model, thereby augmenting both DC electrical conductivity and AC dielectric property of the nanocomposite. The proposed immunosensing platform comprises of PPY/f-MWCNT modified interdigitated microelectrode (IDµEs) array, on which anti-UCHL1-antibodies are immobilized using suitable covalent chemistry. The AC electrical characterization of the nanocomposite modified IDµEs, with and without the antibodies, was performed through generic capacitance vs. frequency (C-F, 1 KHz - 1 MHz) and capacitance vs. applied bias (C-V, 0.1 V-1 V) measurements, using an Agilent B1500A parametric analyzer. The binding event of UCHL1 peptides to anti-UCHL1-antibodies was transduced in terms of normalised changes in parallel capacitance, via the C-F analysis. Further, we have tested the detection efficiency of the said immunoassay against UCHL1 spiked human plasma samples in the concentration range 10 fg/mL - 1 µg/mL. The proposed sensing platform detected UCHL1 in spiked-plasma samples linearly in the range of 10 fg/mL - 1 ng/mL with a sensitivity and LoD of 4.22 ((ΔC/C0)/ng.mL-1)/cm2 and 0.363 fg/mL, respectively. Further, it showed excellent stability (30 weeks), repeatability, reproducibility, selectivity and interference-resistance. The proposed approach is label-free, and if desired, can be used in conjunction with DC measurements, for biosensing applications.

Artificial Intelligence-Based Portable Bioelectronics Platform for SARS-CoV-2 Diagnosis with Multi-nucleotide Probe Assay for Clinical Decisions.

In the context of the recent pandemic, the necessity of inexpensive and easily accessible rapid-test kits is well understood and need not be stressed further. In light of this, we report a multi-nucleotide probe-based diagnosis of SARS-CoV-2 using a bioelectronics platform, comprising low-cost chemiresistive biochips, a portable electronic readout, and an Android application for data acquisition with machine-learning-based decision making. The platform performs the desired diagnosis from standard nasopharyngeal and/or oral swabs (both on extracted and non-extracted RNA samples) without amplifying the viral load. Being a reverse transcription polymerase chain reaction-free hybridization assay, the proposed approach offers inexpensive, fast (time-to-result: ≤ 30 min), and early diagnosis, as opposed to most of the existing SARS-CoV-2 diagnosis protocols recommended by the WHO. For the extracted RNA samples, the assay accounts for 87 and 95.2% test accuracies, using a heuristic approach and a machine-learning-based classification method, respectively. In case of the non-extracted RNA samples, 95.6% decision accuracy is achieved using the heuristic approach, with the machine-learning-based best-fit model producing 100% accuracy. Furthermore, the availability of the handheld readout and the Android application-based simple user interface facilitates easy accessibility and portable applications. Besides, by eliminating viral RNA extraction from samples as a pre-requisite for specific detection, the proposed approach presents itself as an ideal candidate for point-of-care SARS-CoV-2 diagnosis.

Towards point-of-care diagnosis of Alzheimer's disease: Multi-analyte based portable chemiresistive platform for simultaneous detection of ß-amyloid (1-40) and (1-42) in plasma.

Label-free simultaneous detection of Alzheimer's disease (AD) specific biomarkers Aß40 and Aß42 peptides on a single platform using polypyrrole nanoparticle-based chemiresistive biosensors is reported here. The proposed interdigitated-microelectrode based inexpensive multisensor-platform can concurrently detect Aß40 and Aß42 in spiked-plasma in the range of 10-14 - 10-6 g/mL (with LoDs being 5.71 and 9.09 fg/mL, respectively), enabling the estimation of diagnostically significant Aß42/Aß40 ratio. A detailed study has been undertaken here to record the individual sensor responses against spiked-plasma samples with varying amounts and proportions of the two target peptides, towards enabling disease-progression monitoring using the Aß-ratio. As compared to the existing cost-ineffective brain-imaging techniques such as PET and MRI, and the high-risk CSF based invasive AD biomarkers detecting procedures, the proposed approach offers a viable alternative for affordable point-of-care AD diagnostics, with possible usage in performance evaluation of therapeutic drugs. Towards point-of-care applications, the portable readout used in this work was conjugated with an android-based mobile app for data-acquisition and analysis.

Electrospun CNT embedded ZnO nanofiber based biosensor for electrochemical detection of Atrazine: a step closure to single molecule detection.

In this study we have reported the design and development of a facile, sensitive, selective, and label-free electrochemical sensing platform for the detection of atrazine based on MWCNT-embedded ZnO nanofibers. Electrospun nanofibers were characterized using scanning electron microscope (SEM), transmission electron microscope (TEM), X-ray diffraction (XRD), X-ray photoelectron spectroscope (XPS), UV-Visible spectroscope (UV-VIS), and Fourier-transform infrared spectroscope (FTIR). Electrochemical properties of MWCNT-ZnO nanofiber-modified electrodes were assessed using electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV). Binding event of atrazine to anti-atrazine antibody, which immobilized on nanofiber-modified electrode via EDC and NHS chemistry, was transduced with EIS. Due to high conductivity, surface area, and low bandgap of MWCNT-ZnO nanofibers, we have achieved the sensitivity and limit of detection (LoD) of sensor as 21.61 (KΩ µg-1 mL-1) cm-2 and 5.368 zM for a wide detection range of 10 zM-1 µM. The proposed immunosensing platform has good stability, selectivity, repeatability, and reproducibility, and are less prone to interference.

Electrospun tin (IV) oxide nanofiber based electrochemical sensor for ultra-sensitive and selective detection of atrazine in water at trace levels.

Atrazine, a class 3a carcinogen, is a pesticide of chloro triazine family and is known to severely affect the human endocrine system upon consumption. The toxic effects of atrazine cause damage not only to the humans but also to animals and plants. In lieu of the detrimental effects of atrazine on environment, it is essential to develop a sensor platform capable of its detection in water. Here, we propose ultrasensitive electrochemical detection of atrazine using electrospun SnO2 nanofibers. In this study, the nanofibers have been characterized using Field Emission Spectroscopy, X-ray diffraction analysis (XRD), X-ray photoelectron spectroscopy (XPS), UV-Vis-NIR spectroscopy and Fourier transform infrared spectroscopy (FTIR). Using a label-free transduction, we have detected atrazine in fairly low concentrations, with the limit of detection being 0.9 zM and the sensitivity being 4.11 (µA/µM)/cm2, in a wide dynamic detection range varying from 1 zM to 1 µM. Furthermore, we have reported atrazine detection in trace levels in spiked real time water samples, which is an essential step in ensuring that the sensing platform can be deployed for practical applications. In addition to this, the sensor exhibits excellent selectivity, reasonable stability (when stored at 4 °C), and good interference-resistance.