Neural probes with multi-drug delivery capability

Abstract

Multi-functional neural probes are promising platforms to conduct efficient and effective in-depth studies of brain by recording neural signals as well as modulating the signals with various stimuli. Here we present a neural probe with an embedded microfluidic channel (chemtrode) with multi-drug delivery capability suitable for small animal experiments. We integrated a staggered herringbone mixer (SHM) in a 3-inlet microfluidic chip directly into our chemtrode. This chip, which also serves as a compact interface for the chemtrode, allows for efficient delivery of small volumes of multiple or concentration-modulated drugs via chaotic mixing. We demonstrated the successful infusion of combinatorial inputs of three chemicals with a low flow rate (170 nl min(-1)). By sequentially delivering red, green, and blue inks from each inlet and conducting visual inspections at the tip of the chemtrode, we measured a short residence time of 14 s which corresponds to a small swept volume of 66 nl. Finally, we demonstrated the potential of our proposed chemtrode as an enabling tool through extensive in vivo mice experiments. Through simultaneous infusions of a chemical (pilocarpine or tetrodotoxin (TTX) at inlet 1), a buffer solution (saline at inlet 2), and 4',6-diamidino-2-phenylindole (DAPI at inlet 3) locally into a mouse brain, we not only modulated the neural activities by varying the concentration of the chemical but also locally stained the cells at our target region (CA1 in hippocampus). More specifically, infusion of pilocarpine with a higher concentration resulted in an increase in neural activities while infusion of TTX with a higher concentration resulted in a distinctive reduction. For each chemical, we acquired multiple sets of data using only one mouse through a single implantation of the chemtrode. Our proposed chemtrode offers 1) multiplexed delivery of three drugs through a compact packaging with a small swept volume and 2) simultaneous recording to monitor near real-time effects on neural signals, which allows for more versatile in vivo experiments with a minimum number of animals to be sacrificed.

Micro-drive and headgear for chronic implant and recovery of optoelectronic probes

“…Hence, using an external light-source is still designated for achieving a strong illumination power with minimally invasive light guides. Last, it is noteworthy that our OEP option might not only be useful for OEPs but also for other types of hybrid electrodes, such as silicon probes with integrated micro-fluidic channels 29 .…”

“…Second, the recording sites are precisely arranged into geometric patterns that can span over hundreds of microns, allowing one to infer the spatial organization of cells and structures 19–22 . Finally, silicon probes have been the foundation for several lines of hybrid electrodes, such as silicon probes with integrated light guides (‘optoelectronic probe’ [OEP]) or light sources used for optogenetic stimulations 23–28 and silicon probes with integrated micro-fluidic channels for local drug delivery 29 .…”

Microfabricated Probes for Studying Brain Chemistry: A Review

“…Microfabrication has been employed to embed microfluidic channels into neural probes . Small channels with different shapes and material types can be constructed by a variety of techniques, such as surface micromachining using sacrificial layer, and bulk micromachining using buried channel technology or wafer bonding.…”

“…Microfabrication has been employed to embed microfluidic channels into neural probes. [143][144][145] Small channels with different shapes and materialt ypes can be constructed by av ariety of techniques, such as surfacem icromachining using sacrificial layer,and bulk micromachining using buried channeltechnology [146,147] or wafer bonding. Using microfabrication technologies, various microfluidic neural probes have been developed for neurological studies and treatments.…”

Combined in vivo recording of neural signals and iontophoretic injection of pathway tracers using a hollow silicon microelectrode

“…For convection enhanced drug delivery purposes, a variety of microdevices has been successfully tested in vivo [15][16][17][18][19]. In our work, we propose an in vivo method of using neural microelectrode with monolithically integrated microfluidic channel to control tracer delivery in the close vicinity of the recording sites by iontophoresis.…”