Highly sensitive biosensor based on organic electrochemical transistors

Abstract

Different biological and chemical sensing methods based on solution gated field-effect transistor have been investigated in recent decades due to their many advantages, including miniaturization without the loss of signal to noise ratio, signal amplification on applied gate voltage and operation in solution environment. However, conventional inorganic field-effect transistors (FET) are usually not bio-compatible. Furthermore, the high temperature processing in device fabrication and the rigid architecture of the devices make it difficult to integrate the devices with biological systems and hinder the applications in biological or chemical sensing. Recently, organic electrochemical transistors (OECTs), a special kind of organic thin film transistor (OTFTs), can operate in various solution or electrolytes at low working voltages with stable performance. The devices can be prepared by solution process such as spin-coating on various substrates at low temperatures. Therefore, OECTs have become promising transducers/sensors for biological and chemical sensing. In this thesis, OECTs with poly(3,4-ethylenedioxythiophene)poly(styrene sulfonic acid) (PEDOT:PSS) channels have been introduced to detect three analytes, including epinephrine, cholesterol and Adenosine triphosphate (ATP), based on different mechanisms and showed high performance in comparison with conventional electrochemical approaches. Epinephrine, as an important neurotransmitter, was successfully detected by OECTs with platinum (Pt) gate electrodes. Epinephrine molecules can undergo direct electro-oxidation on the Pt gate electrode and lead to obvious changes of the channel current of the OECTs. The device performance was optimized by modifying Nafion and carbon-based nanomaterials (graphene, graphene oxide and single-wall carbon nanotubes) on the gate electrodes. It was found that Nafion and singlewalled carbon nanotube co-modified gate electrodes can lead to the lowest detection limit of 0.1nM for epinephrine, which covers the normal range in human body (~0.2nM). Compared to the previously reported sensors based on ion-sensitive field effect transistor (ISFET) and cotton-based OECTs, the detection limit of our OECTs is much lower than the reported results due to the different sensing principle and device architecture. A high cholesterol level in human blood plasma will lead to a high risk in having heart disease and high blood pressure. Therefore, highly sensitive cholesterol biosensors based on different methods have been extensively investigated. In this thesis, OECT-based cholesterol sensors were realized by functionalizing Pt gate electrodes with cholesterol oxidase (ChOx), nanomaterials and the biocompatible polymer Nafion. The sensing mechanism of the cholesterol sensor is as follows. Hydrogen peroxide (H₂O₂) molecules are produced by the reaction of cholesterol molecules catalyzed by ChOx near the functionalized Pt gate electrode and undergo electro-oxidation on the gate surface, which can influence the gate surface potential and thus the effective gate voltage applied on the device. Since the amount of H₂O₂ produced is directly proportion to the concentration of cholesterol, the indirect cholesterol sensing based on the detection of H₂O₂ is thus realized. The cholesterol sensor can show a detection limit down to 10nM, depending on the surface modification of gate electrodes. Besides the above sensing principles based on the direct electro-oxidation of biomolecules or indirect sensing by producing H₂O₂ of decomposed biomolecules, OECT can be operated by testing reduced signal. In ATP sensing, dual enzyme (glucose oxidase (GOx) and hexokinase (HEX)) co-modified gate electrodes were employed. GOx can decompose glucose and produce H₂O₂ while HEX can combine ATP and glucose to generate electrochemically inactive molecules and reduce the glucose concentration and thus the concentration of H₂O₂ that can be detected by the device. So the concentration of ATP can be decided according to the decrease of the signal generated by H₂O₂ at a controlled condition. The ATP sensor can show a detection limit down to 10μM, depending on the surface modification of the gate electrodes. In summary, OECTs are promising transducers for biological and chemical sensing because of high sensitivities and convenient fabrication process. The devices can be prepared on flexible substrate by solution process at low temperature with low cost, making it possible to integrate the devices with various systems, such as wearable electronics and healthcare products. Furthermore, the device performance should be optimized by improving the stability and uniformity of the devices before being considered for commercial applications, which will be the future work of this field.