Biochemical piezoresistive sensors based on hydrogels for biotechnology and medical applications

Abstract

Many conventional analysis techniques achieve a high-detection sensitivity; however, they are equipment or time expensive due to a multi-step procedure. Sensor concepts, introduced in this work, using piezoresistive pressure sensor chips with integrated analyte-sensitive hydrogels enable inexpensive and robust biochemical sensors, which are miniaturized and in-line capable. For these sensor setups, it is important to optimize current established analyte-sensitive, reversible and biocompatible hydrogels for pH and glucose monitoring of chemical and biochemical processes. Therefore, low-viscous monomer mixtures based on hydroxypropyl methacrylate (HPMA), 2-(dimethylamino)ethyl methacrylate (DMAEMA), tetraethylene glycol dimethacrylate (TEGDMA) and ethylene glycol (EG) were prepared in molar ratios of 70∕30∕01∕20, 60∕40∕01∕20 and 60∕40∕02∕20, respectively. Redox-polymerization of these pre-gel solutions were realized with N,N,N′,N′-tetramethylethylenediamine and ammonium persulfate. The reversible pH-sensitive swelling behavior of hydrogels with compositions were compared. By using the photoinitiator 2-hydroxy-4′-(2-hydroxyethoxy)-2-methylpropiophenone, the free radical photopolymerization could be implemented leading to an increase of the swelling degree (SG). Glucose-sensitive hydrogels were prepared via immobilization of glucose oxidase in HPMA–DMAEMA–TEGDMA–EG hydrogel discs. These showed increasing swelling degrees with higher glucose concentrations in aqueous media and a reversible swelling behavior. The synthesized hydrogels were integrated in different piezoresistive sensors of different designs. The pH-depending course of the output voltage of a dip sensor with photopolymerized 60∕40∕02∕20 hydrogel was studied in detail. Besides the usage of a dip sensor, two implantable, parylene C-coated setups are presented. The implantable sensor with long isolated gold bond wires was proved to be functional even after storage in aqueous media for several days.