Monitoring neurotransmitters in vivo necessitates sensors that approach the spatiotemporal resolution of neuronal communication, while differentiating similarly structured neurochemicals with high selectivity. We have developed biosensors based on nucleic-acid aptamers, coupled to ultrathin In2O3(~3-nm) field-effect transistors (FETs). These biosensors show high sensitivity and selectivity for serotonin and dopamine with fM detection limits in vitro. To enable in vivo measurements, we miniaturized our sensor architecture to fabricate neuroprobes with arrays of aptamer-field-effect transistors. The initial prototype for an implantable microprobe is fabricated using micro-electro-mechanical systems (MEMS) technologies on Si (150-μm thick). Each neuroprobe has lithographically patterned interdigitated gold electrodes deposited atop ultrathin, semiconducting In2O3channels, with a shank width and thickness of 150 μm. Functionalization of the exposed semiconducting surfaces with neurotransmitter-specific aptamers facilitated electronic neurotransmitter sensing. Miniaturization of individual FETs leads to increases in the number of independent transistors on a single neuroprobe for multi-site/multi-target detection capabilities. We characterized target sensitivity ranges, detection limits, and sensor stabilities in vitro prior to conducting in vivo measurements. We assessed biofouling of neuroprobes by performing ex vivo measurements in brain tissue homogenates. We also fabricated flexible neuroprobes using polyimide as a substrate instead of rigid Si to reduce immunological responses. Implantable aptamer-field-effect transistor-neuroprobes, including additional designs on flexible substrates, will enable in vivo detection of neurotransmitters in the brain with high spatial resolution and selectivity.

Implantable aptamer field-effect transistor neuroprobes: Towards in vivo neurotransmitter detection

2019 Fall National Meeting

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