Integration of Organic Electrochemical Transistor with Electrochemical Aptamer-Based Sensor for Transforming Growth Factor Beta 1 Sensing

Organic electrochemical transistors (OECTs) have been widely used as biosensors to sense biomarkers such as pH, ions, small molecules (glucose, lactate), nucleic acids, and even proteins and cells in last few decades. Various bio-recognition elements like ion-selective membranes (ISM), enzymes, aptamers, and antibodies have been integrated with OECTs for sensing. Among those bio-recognition elements, aptamers have drawn a lot of attention owing to their ease of chemical synthesis, wider applicability of different targets, good thermal/environment stability and low-cost. Electrochemical aptamer-based sensors based on a single modified electrode has been used as a standard structure in the aptamer-based biosensor research community. The sensing ability is achieved by monitoring the change of electron transfer rate in redox reporter/electrode interface that is altered by the structural rearrangements of aptamers induced by target binding. However, the current change in this sensor is usually very small especially when the area of sensing electrode is reduced for miniaturization purposes, which limit its sensitivity. In this work, we use the OECT as an on-site amplifier to enhance this small current change in the surface of an individual electrode. A new device structure is proposed that can be used to perform OECT testing and traditional electrochemical measurements like cyclic voltammetry (CV) and square-wave voltammetry (SWV) at the same time. Au working electrode functionalized by methylene-blue modified aptamer, PEDOT:PSS counter electrode and on-chip Ag/AgCl reference electrode are monolithically integrated in a same substrate. During the traditional electrochemical measurement with three-electrode setup, the change of in-plane conductivity at the counter electrode (PEDOT:PSS) can be monitored at the same time and can be regarded as the output of an OECT device. By using this approach, direct amplification of the current in the working electrode (gate) to the in-plane current in the counter electrode (channel) can be achieved. The device can be used to sense transforming growth factor beta 1 (TGF-β₁), which is an important cytokine of interest in wound healing. A sensitivity enhancement around 3000-fold can be observed in our device (294 μA/dec) compared to the sensing results from a single electrode-based sensor (85 nA/dec), with similar detection limit (~1ng/mL). This new approach is likely to be generalizable to a wide range of electrochemical aptamer-based sensors to enhance the sensitivity, which can help to ease the burden in the backend signal amplification.