A nanocoaxial-based electrochemical sensor for the detection of cholera toxin

Abstract

Sensitive, real-time detection of biomarkers is of critical importance for rapid and accurate diagnosis of disease for point of care (POC) technologies. Current methods do not allow for POC applications due to several limitations, including sophisticated instrumentation, high reagent consumption, limited multiplexing capability, and cost. Here, we report a nanocoaxial-based electrochemical sensor for the detection of bacterial toxins using an electrochemical enzyme-linked immunosorbent assay (ELISA) and differential pulse voltammetry (DPV) or square wave voltammetry (SQV). The device architecture is composed of vertically-oriented, nanoscale coaxial electrodes in array format (~106 coaxes per square millimeter). The coax cores and outer shields serve as integrated working and counter electrodes, respectively, exhibiting a nanoscale separation gap corresponding to ~100 nm. Proof-of-concept was demonstrated for the detection of cholera toxin (CT). The linear dynamic range of detection was 10 ng/ml – 1 μg/ml, and the limit of detection (LOD) was found to be 2 ng/ml. This level of sensitivity is comparable to the standard optical ELISA used widely in clinical applications, which exhibited a linear dynamic range of 10 ng/ml – 1 μg/ml and a LOD of 1 ng/ml. In addition to matching the detection profile of the standard ELISA, the nanocoaxial array provides a simple electrochemical readout and a miniaturized platform with multiplexing capabilities for the simultaneous detection of multiple biomarkers, giving the nanocoax a desirable advantage over the standard method towards POC applications.

Detection of cholera toxin with surface plasmon field‐enhanced fluorescent spectroscopy

“…Different design strategies using different transducers have yielded in 0.1 pM to 10 nM LOD values 61–67 . When CTX‐B was used as model analyte, 0.2–12 ng/ml LOD values were achieved by different groups, 68–74 which is the range of our LOD (10 ng/ml). Detection limits lower than 1 ng/ml were obtained either by complex detection protocols involving several steps 69 or by the use of home‐made apparatus via magnetic frequency mixing detection 71 .…”

“…Reproducibility of the biosensor was tested for 0. In the literature, CTX detection was done by several research groups using different detection techniques, [59][60][61][62][63][64][65][66][67][68][69][70][71][72][73][74][75][76][77] and either whole toxin (CTX, AB 5 form) or its truncated form (CTX-B) were used (Table S1). The commonly used capture molecules are anti-CTX-B antibodies and GM1 (binding target of CTX).…”

Recent advances and challenges in electrochemical biosensors for emerging and re-emerging infectious diseases

“…Though a good number of researches are going on in the field of voltammetric biosensors, the platform for miniaturization to a portable device is necessary for POC applications. In an approach to develop an immuno based voltammetric sensor device for the detection of cholera toxin, Archibald et al in 2015 designed a vertically oriented, nanocoaxial electrodes in array format [ 54 ]. The linear range was obtained as 10 ng/mL - 1 μg/mL and the limit of detection was found to be 2 ng/mL, which is comparable to the optical ELISA approach.…”

On-Chip Electrochemical Detection of Cholera Using a Polypyrrole-Functionalized Dendritic Gold Sensor

“…Electrochemical ELISA. ELISAs were performed as previously described 21 with the following modifications to allow for on-chip detection on a gold electrode. PCEPy-modified surfaces were incubated for 48 h at 4 °C with ELISA primary antibody (anti-CTXantibody) diluted to 1 mg mL −1 in 10 mM HEPES.…”