Abstract
A miniature device enabling parallel in vivo detection of the neurotransmitter choline in multiple brain regions of freely behaving rodents is presented. This is achieved by combining a biosensor microprobe array with a custom-developed CMOS chip. Each silicon microprobe comprises multiple platinum electrodes that are coated with an enzymatic membrane and a permselective layer for selective detection of choline. The biosensors, based on the principle of amperometric detection, exhibit a sensitivity of 157±35 µA mM-1 cm-2, a limit of detection of below 1 µM, and a response time in the range of 1 s. With on-chip digitalization and multiplexing, parallel recordings can be performed at a high signal-to-noise ratio with minimal space requirements and with substantial reduction of external signal interference. The layout of the integrated circuitry allows for versatile configuration of the current range and can, therefore, also be used for functionalization of the electrodes before use. The result is a compact, highly integrated system, very convenient for on-site measurements.
Acknowledgments
The biosensor microprobe development was supported by the European integrated project NeuroProbes (EU IP IST-027017). The authors are grateful to the staff at the Microsystems Technology Division of the Centre Suisse d’Electronique et de Microtechnique (CSEM SA), Neuchâtel, Switzerland, for support during the fabrication process. Alexander Stettler of the Cleanroom Facility at D-BSSE is acknowledged for CMOS post-processing.
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