Subcellular probes for neurochemical recording from multiple brain sites

Abstract

Dysregulation of neurochemicals, in particular, dopamine, is epitomized in numerous debilitating disorders that impair normal movement and mood aspects of our everyday behavior. Neurochemical transmission is a neuron-specific process, and further exhibits region-specific signaling in the brain. Tools are needed to monitor the heterogeneous spatiotemporal dynamics of dopamine neurotransmission without compromising the physiological processes of the neuronal environment. We developed neurochemical probes that are ten times smaller than any existing dopamine sensor, based on the size of the entire implanted shaft and its sensing tip. The microfabricated probe occupies a spatial footprint (9 μm) coordinate with the average size of individual neuronal cells (~10 μm). These cellular-scale probes were shown to reduce inflammatory response of the implanted brain tissue environment. The probes are further configured in the form of a microarray to permit electrochemical sampling of dopamine and other neurotransmitters at unprecedented spatial densities and distributions. Dopamine recording was performed concurrently from up to 16 sites in the striatum of rats, revealing a remarkable spatiotemporal contrast in dopamine transmission as well as site-specific pharmacological modulation. Collectively, the reported platform endeavors to enable high density mapping of the chemical messengers fundamentally involved in neuronal communication through the use of minimally invasive probes that help preserve neuronal viability of the implant environment.

Steerable Microinvasive Probes for Localized Drug Delivery to Deep Tissue

“…Our group has previously demonstrated reduced glial scarring in response to smaller implant diameters, down to 150 µm . Implants that incorporate highly flexible, low‐diameter materials to reduce associated inflammation are thus termed “microinvasive.” Microinvasive implants are capable of targeting deep‐brain structures with increased spatial resolution and minimal scarring . These studies reinforce the necessity for further reducing implant diameter to improve chronic viability and spatial resolution.…”

3D‐Printed Carbon Electrodes for Neurotransmitter Detection

“…For mechanical stability for implantation, polyethyleneglycol (PEG) coatings have been used to stiffen carbon fibers for implantation, with the PEG coating then dissolving in the brain. [40] A similar strategy could work to provide mechanical stability for these printed wire electrodes. Thus, these electrodes should be amenable to mass fabrication strategies in the future and are useful for producing custom surface designs down to the sub-micron scale.…”

Microfabricated Probes for Studying Brain Chemistry: A Review

“…C) Polyimide probe for glutamate recording . D) Subcellular probe for dopamine detection made by combination of assembly of carbon fiber and microfabrication of parylene insulator …”

“…However, the total sizes of microfabricated probes are still larger than a single carbon fiber electrode. Alternatively, one interesting approach was to combine processes of carbon fiber assembly and microfabrication . This approach used a glass microgroove mold for manually aligning 8 carbon fibers to a printed‐circuit board before applying photoresists to protect the fiber tips.…”