A Universal Surface for Label-Free Electrical and Optical Sensing of Disease Markers
Authors: Tsai Meng-Yen , Tarasov Alexey , Gray Darren W , Shields Niall , Creedon Niamh , Montrose Armelle , Flynn Erin M , Joiner Corey A , Taylor Robert , Lovera Pierre , O' Riordan Alan , Mooney Mark H , Vogel Eric M 
Published: February 2020

Quantitative point-of-care (POC) diagnostic tools are crucial for next-generation human (and animal) health monitoring and disease diagnosis to rapidly infer effective treatment decisions. ELISA based disease diagnostics is often performed off-site in centralized labs, requiring long turnaround times (>72hrs), reducing the effective period for disease intervention. In this study, a gold sensing surface is shown to provide ELISA-equivalent results across multiple label-free and rapid biosensing platforms including potentiometric field-effect transistor (FET) biosensors, electrochemical impedance spectroscopy (EIS) biosensors and surface plasmon resonance (SPR) devices. Using the model pathogen Bovine Herpes Virus 1 (BHV-1) (a major source of economic loss in the agri-food industry globally 1), BHV-1 glycoprotein E (gE) was attached to sensor surfaces to detect the immunological interaction against anti-BHV-1 antibodies. The use of a gold sensing surface offers access to the well-established thiol surface functionalization and protein immobilization via amine coupling. This functionalized gold sensing surface is used to compare the response of ELISA in four different sensing platforms: (1) as the gate electrode for graphene ion-sensitive field-effect transistor (ISFET), (2) as the gate electrode for extended-gate field-effect transistor (EGFET) sensors (3) as the working electrode (WE) for EIS sensors, and (4) as the sensing surface for SPR.
The results show that the sensitivity of the EGFET biosensors is equivalent to the ISFETs.2 Moreover, EGFET biosensors provide many advantages including improved reliability by separating the sensor and transducer components, low-cost and easy fabrication, disposable chip design and high compatibility with state-of-art semiconductor technologies.3-5 While the mechanism for EIS is quite different than potentiometric FET-based sensing, the dynamic response is found to be equivalent. Similarly, the same Au surface can be used in optical SPR biosensors using the same surface chemistry. The universality of a Au sensing surface allows detection using multi-platforms but with a single chip and, therefore, simplifies the sample preparation and reduces the required sample volumes for diagnostics. All three electrical sensors demonstrate performance equivalent to SPR and ELISA, with dynamic range approaching the limit of detection for sera dilutions < 10-3of anti-BHV-1 antiserum. However, the potentiometric and EIS sensors provide results much faster (~10 min.) than SPR (~2 hr.) and ELISA (> 20 hr.) Additionally, the electronic biosensors are compact in size and are promising for POC devices.
In conclusion, a gold surface is shown to provide universal and equivalent sensing across multiple platforms using well-established surface chemistry. Furthermore, the use of one surface to facilitate integration of multiple sensing mechanisms can potentially improve specificity. Among all of the available biosensor technologies, electrical biosensors provide rapid, label-free and cost-efficient sensing capability in a compact size, which is promising for quantitative point-of-care devices.

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