Investigating integrated central nervous system neural circuitry at time scales pertinent to information encoding necessitates chemically specific <i>in vivo</i> neurotransmitter sensors that approach the size of nanometer-sized synapses and respond in milliseconds or less. To tackle this challenge, we employ aptamers as artificial receptors, which have emerged as superior synthetic alternatives to antibodies for molecular recognition. However, to realize their full potential for neurotransmitter biosensing, novel nanotools need to be developed that enable substrate-based high affinity interactions between tethered neurotransmitters and nucleic acid libraries. We have developed “neurochips” by designing and combining advanced surface chemistries, patterning methods, and high-throughput microfluidics, which can be used to screen for neurotransmitter-specific aptamers in an environment optimized for biorecognition. We have tethered dopamine molecules and employed a previously identified dopamine-specific aptamer as a test to show that our devices are functional. Furthermore, using pre-functionalized neurotransmitter-tethered molecules, we fabricated multiplexed substrates having the capacity to capture and to sort different neurotransmitter-specific aptamers while simultaneously measuring <i>in situ</i> binding affinities. This platform to identify aptamers targeting neurotransmitters will not only enable significant steps toward understanding chemical neurotransmission but will serve to identify other biomolecules important in brain disorders and their treatment.

Multiplexed neurochips as screening platforms for neurotransmitter-specific high-affinity aptamers

251st National Meeting (2016)

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