Essence - A New Electrochemical Platform

Abstract

There is a great demand for a fast, on-site screening test, especially during the COVID-19 pandemic. However, most point-of-care (POC) sensors usually suffer from insufficient sensitivity and selectivity. Often these devices have a very high rate of false positives and false negatives. The incorrect data could result in low customer usage (both the patient and the doctor) due to decreased confidence in the results. Portable ELISA-based kits can have low rates of false-positive and false negatives. However, ELISA is inherently complicated and often requires a specialist on-site to ensure the success of each sample's high costs and time.Here we show a new electrochemical platform called ESSENCE. ESSENCE is an Electrochemical Sensor that uses a Shear-Enhanced, flow-through Nanoporous Capacitive Electrode. ESSENCE can overcome current electrochemical sensors' selectivity and sensitivity limitations. The ESSENCE sensor architecture is a microfluidic channel sandwiched between two gold micro-electrode glass slides, formed a non-planar interdigitated porous electrode that improved electric field penetration compared with the traditional planar interdigitated electrode. The porous electrode structure used in this research has a high Zeta potential compared to the bare glass surface. This results in a significantly smaller Debye double-layer (EDL) length than in a clear channel. Due to a smaller EDL length, the relaxation frequency increases, which shifts the EIS signal to a higher frequency range (1kHz to 100MHz) and results in a fast response with a higher signal-to-noise ratio in Electrochemical Impedance Spectroscopy(EIS) measurements.Further, the modular fabrication of the ESSENCE chip allows ESSENCE to target different biomolecules from DNAs to protein cancer biomarkers by simply changing the packed transducer material. However, the packing material’s conductivity represents a significant challenge to the electrochemical response of ESSENCE. The high conductivity of the transducer material shorts the system leading to a pure resistive response. Impedance spectroscopy (EIS) response of ESSENCE cannot be distinguished enough to determine if the sensor is working. ESSENCE has a switchable electrode system for usage in multiple configurations like a material electrode, clear electrode, and working electrode to overcome these limitations. For carbon nanotube (CNT) transducers with functionalized oligos on the CNT, a 20-fold jump in the signal is noticed from the working electrode configuration compared to the other configurations. It is worthwhile to note that depending on the biomolecule (DNA or Protein), the surface charge transfer resistance (Rct) in the EIS signal of ESSENCE can either show a decrease (DNA) or increase (protein) on the binding of the target bio-molecule (target DNA to DNA or target protein to protein). The change in the Rct depends on the charge of the molecule. It has been seen that on the binding of a target protein, the active area of the electrode surface decreased, leading to a reduction in current and a concomitant increase in Rct. On binding of the target DNA, the capture-target DNA pair essentially becomes a part of the electrode due to its charge. This increase in charge is more significant than any reduction in the surface area due to the DNA's binding. This leads to an increase in current to the packed electrode, leading to a concomitant decrease in Rct.The fluid flow through the porous electrode increases mixing, minimizes diffusion, and generates a significantly enhanced fluidic shear force. This force e can unbind most of the false-positive signals generated by non-specific binding, such as physical adhesive or biofouling. The porous electrode also provides a high surface area to volume ratio to capture the target analyte leading to increased sensitivity. We have an automatic fluidic control system in ESSENCE that minimized any errors in the operation of ESSENCE. Our system has high selectivity and sensitivity for DNA (fM sensitivity, selective against non-target DNA), breast cancer biomarker proteins (p53, pg/L sensitivity, selective against non-target HER2). Figure 1