Three-Dimensional Polymeric Biointerface for Ultra-Sensitive and Selective Detection of Low-Molecular-Weight Biomarker Using Semiconductor-Based Biosensor
Authors: Nishitani Shoichi , Sakata Toshiya 
Published: February 2020

Selective molecular sensing is of great importance in clinical applications. Due to the background noises caused by impurities in physiological samples, realization of selective detection of biomarkers, especially of small biomolecules, remains a great challenge. Herein, we propose a novel biosensing platform based on the extended-gate field-effect transistor (EG-FET) biosensors, particularly targeting glucose in physiological samples.

Glucose is one of the most well-known and important biomolecules as a relation to various diseases and the index of health conditions. Moreover, further sensitive and selective detection enables non-invasive monitoring in biological fluids such as tears.

FET biosensors can directly detect small biomolecules when they have intrinsic molecular charges, which are recognized inside the Debye length around a gate/solution interface. In particular, the extended-Au gate enables an ultra-sensitive detection of various biomolecules such as glucose, based on the electrochemical and catalytic reactions of glucose with the Au gate surface. If a chromatographic effect is supplied with polymeric membranes on the Au gate surface, only a small biomolecule as target reaches the sensing surface through the polymeric membrane, while the polymeric membrane as a filter captures various impurities outside the Debye length. In a case of glucose, uric acid (UA) and albumin will be the major impurities in tears or serum samples. In this study, we would like to show the impact of filtering effect by particularly utilizing dopamine as a model sample of small molecules, a well-known neurotransmitter, and phenylboronic acid (PBA) as a receptor.

To investigate the filtering effect, we prepared the FET sensors, of which surface was modified by the polymeric membrane with or without PBA. Polymerization was carried out using visible light mediated atom transfer radical polymerization (ATRP). After the modification of a Au electrode with ATRP initiator using diazonium salt chemistry, co-polymerization of methacrylic acid, 2-hydroxyethyl methacrylate, and N,N’-methylenebisacrylamide was carried out. Finally, PBA was introduced into the polymeric structure through carboxyl-amino chemical reaction between methacrylic acid and m-aminophenylboronic acid.

　The gate surface potential was monitored using the FET real-time monitoring system while continuously adding dopamine in it. While the detection limit of the polymer-coated FET sensor without PBA was as low as in nM order, the detection sensitivity of the sensor with PBA polymer decreased significantly to a µM order. This result indicated that dopamine was captured by the PBA-based polymer membrane. Thus, the possibility of both an ultra-sensitive detection of small biomolecules and a filtering effect was clearly verified in this study. The sensor is further applied to the glucose sensor by designing an UA-capturing polymeric membrane above the Au sensing surface. The results will be discussed in the talk.