Localized neurotransmitter release for use in a prototype retinal interface.
OBJECTIVE
Current neural prostheses use electricity as the mode of stimulation, yet information transfer in neural circuitry is primarily through chemical transmitters. To address this disparity, this study was conducted to devise a prototype interface for a retinal prosthetic based on localized chemical delivery. The goal was to determine whether fluidic delivery through microfabricated apertures could be used to stimulate at single-cell dimensions.


METHODS
A drug delivery system was microfabricated based on a 5- or 10- microm aperture in a 500-nm thick silicon nitride membrane to localize and limit transmitter release. The aperture overlies a microfluidic delivery channel in a silicone elastomer. To demonstrate the effectiveness of this transmitter-based prosthesis, rat pheochromocytoma cells (PC12 cell line) were grown on the surface of the device to test the precision of stimulation, using bradykinin as a stimulant and measuring fluorescence from the calcium indicator, fluo-4.


RESULTS
The extent of stimulation could be controlled accurately by varying the concentration of stimulant, from a single cell adjacent to the aperture to a broad area of cells. The stimulation radius was as small as 10 microm, corresponding to stimulation volumes as small as 2 pL. The relationship between the extent of stimulation and concentration was linear.


CONCLUSIONS
The demonstration of localized chemical stimulation of excitable cells illustrates the potential of this technology for retinal prostheses. Although this is only a proof of concept of neurotransmitter stimulation for a retinal prosthesis, it is a significant first step toward mimicking neurotransmitter release during synaptic transmission.
Peterman
Mark C
MC
Department of Applied Physics, E. L. Ginzton Laboratory, Stanford University School of Medicine, Stanford, California 94305, USA.
Bloom
David M
DM
Lee
Christina
C
Bent
Stacey F
SF
Marmor
Michael F
MF
Blumenkranz
Mark S
MS
Fishman
Harvey A
HA
D000814:Aniline Compounds; D000818:Animals; D001920:Bradykinin / Q000008:administration & dosage*; D002118:Calcium / Q000378:metabolism; D016503:Drug Delivery Systems / Q000295:instrumentation*; D005456:Fluorescent Dyes; D008954:Models, Biological; D009885:Ophthalmology / Q000295:instrumentation; D016716:PC12 Cells / Q000187:drug effects* / Q000378:metabolism; D019736:Prostheses and Implants; D051381:Rats; D012160:Retina / Q000601:surgery; D012162:Retinal Degeneration / Q000601:surgery; D014966:Xanthenes
D000814:Aniline Compounds; C409648:Fluo 4; D005456:Fluorescent Dyes; D014966:Xanthenes; D001920:Bradykinin; D002118:Calcium