Investigating brain chemistries in real time at the spatiotemporal level of neural circuits and across diverse signaling molecules necessitates neurochemical biosensors that approach these critical attributes. We couple the molecular recognition properties of rationally designed, chemically synthesized DNA sequences, termed aptamers, with direct signal detection via field-effect transistors. Aptamers can be designed for a range of target detection, signal transduction, response speed, and in vivo stability. Changes in neurotransmitter concentrations can be monitored via optimized binding-induced aptamer conformation changes that are transduced into electrical signals. Reversible binding of target neurotransmitters such as serotonin and dopamine by specific aptamers are hypothesized to shift electric potentials in close proximity to FET surfaces, resulting in conductance changes. Serotonin- and dopamine-specific aptamer field-effect transistors have high sensitivity with a limit of detection of 10 fM, approximately six orders of magnitude lower than the dissociation constant of the artificial recognition elements. These devices retain their functionality in full ionic strength biological fluids including artificial cerebrospinal fluid. We are now conducting measurements ex vivo in brain tissue homogenates of Tph2 knockout mice that lack serotonin to test device response upon controlled addition of serotonin while assessing biofouling of devices. We envision unprecedented capacity to measure neurochemical signaling directly, in vivo, and in real time, which will impact our understanding of brain function in relation to complex behaviors.

Aptamer field-effect transistors as neurochemical sensors to monitor neurotransmitters in vivo

253rd National Meeting (2017)

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