Detection of Various Biomolecules and Targets in a Novel Electrochemical Biosensing Platform Essence

ESSENCE is a flow-through electrochemical sensor that utilizes a nanoporous and capacitive electrode architecture based on a nonplanar interdigitated microelectrode array (NP-IDμE). It consists of three layers: a top and bottom IDμE and a middle layer of adsorptive capture probes (see Figure 1). The integration of our novel electrode technology with this innovative microfluidic design allows us to decouple the device’s sensitivity and selectivity. The frequency of the electric field generated by the NP-IDμE around the microfluidic channel enables us to fine-tune the device’s sensitivity, whereas our device’s selectivity is tunable by using appropriate flow velocities. Further, flow-through the electrode enhances the generated shear force, allowing us to mitigate fouling and prevent non-specific binding. As a result of the device’s improved sensitivity and selectivity, our device has a high signal-to-noise ratio. Also, in our device, the microfluidic chip and the capture molecule can be stored separately to preserve the capture molecule from degradation and then integrated at the point of use or care. Ultimately, this allows the device to be applied to the detection of other biomolecules and targets simply by changing the capture molecule. As a proof-of-concept, we have demonstrated the unparalleled sensitivity of our device for the detection of oligonucleotides (short stranded DNA) at 1 fM^[1] and perfluorooctane sulfonate (PFOS) at a limit of 0.5 ng/L.^[2] Further, we have demonstrated our device has limit of detection (LOD) of 5×10 ^-16 M for the breast cancer biomarker p53 with a limit of quantification of 3.63 ×10 ^-16 M. Moreover, when HER2 (another breast cancer biomarker) was flowed through the biosensor with CNT functionalized with p53 capture antibodies, no changes in the EIS signal were observed, indicating its high specificity. Next, we will work on translating our device into a multiplexed sensing platform capable of simultaneous detecting different biomolecules by testing our device against a three-biomarker panel in serum for detection of breast cancer.

This work is supported by Sagnik Basuray’s National Science Foundation (NSF) CAREER Award No. 1751759 (“ASSURED” electrochemical platform for multiplexed detection of Cancer Biomarker Panel using Shear-Enhanced Nanoporous-Capacitive Electrodes) and New Jersey Health Foundation (NJHF) Grant No. PC 54-20 (ESSENCE - A Selective and Sensitive Electrochemical POC Platform for Liquid Biopsy).

[1] Cheng, Y.-H., Moura, P. A. R., Zhenglong, L., Feng, L., Arokiam, S., Yang, J., ... Basuray, S. (2019). Effect of electrode configuration on the sensitivity of nucleic acid detection in a non-planar, flow-through, porous interdigitated electrode. Biomicrofluidics, 13(6), 064118. doi: 10.1063/1.5126452

[2] Cheng, Y. H., Barpaga, D., Soltis, J. A., Shutthanandan, V., Kargupta, R., Han, K. S., ... Chatterjee, S. (2020). Metal–Organic Framework-Based Microfluidic Impedance Sensor Platform for Ultrasensitive Detection of Perfluorooctanesulfonate. ACS Applied Materials & Interfaces. doi: 10.1021/acsami.9b22445