The Artificial Synapse Chip: A Flexible Retinal Interface Based on Directed Retinal Cell Growth and Neurotransmitter Stimulation

Abstract

The Artificial Synapse Chip is an evolving design for a flexible retinal interface that aims to improve visual resolution of an electronic retinal prosthesis by addressing cells individually and mimicking the physiological stimulation achieved in synaptic transmission. We describe three novel approaches employed in the development of the Artificial Synapse Chip: (i) micropatterned substrates to direct retinal cell neurite growth to individual stimulation sites; (ii) a prototype retinal interface based on localized neurotransmitter delivery; and (iii) the use of soft materials to fabricate these devices. By patterning the growth of cells to individual stimulation sites, we can improve the selectivity of stimulation and decrease the associated power requirements. Moreover, we have microfabricated a neurotransmitter delivery system based on a 5- micro m aperture in a 500-nm-thick silicon nitride membrane overlying a microfluidic channel. This device can release neurotransmitter volumes as small as 2 pL, demonstrating the possibility of chemical-based prostheses. Finally, we have fabricated and implanted an equivalent device using soft flexible materials that conform to the retinal tissue more effectively. As many of the current retinal prosthesis devices use hard materials and electrical excitation at a lower resolution, our approach may provide more physiologic retinal stimulation.

Fabrication of Flexible Binary Amplitude Masks for Patterning on Highly Curved Surfaces

“…For phase shift lithography, it would be quite difficult to engineer the phase mask to correct for the mechanical deformations, and thus elimination of the distortions would likely require manipulation of the exposure conditions. [22] Advances in microfabrication, namely in the area of nonplanar electronic devices, such as curved photodiode arrays for solar cell applications and synthetic retinal implants, [36][37][38][39][40] demand the ability to pattern metals, and other materials with electrical functionality, on geometrically diverse surfaces. The aforementioned fabrication methods are intended to replace traditional contact lithography by finding novel ways to use PDMS as a patterning element.…”

Characterization of a patch-clamp microchannel array towards neuronal networks analysis

“…An improved etching process is under investigation in order to achieve smoother surfaces and thus better seals. Nevertheless, our present sealing quality can still allow signal transmission analysis as in an MEA (action potentials recording), since it does not injure the cell membrane, and it offers a platform where a wider range of different experimental techniques can be exploited: for example electroporation, stimulation and detection through artificial synapses (Peterman et al 2003), and perforated patch clamping. Furthermore, it is likely to be good enough for patch clamp experiments once the cells adhere and start growing on the microchip, due to cytoskeleton rearrangements and membrane adhesion effects: there is, however, to date no evidence in the literature of exploiting such an approach and it is thus the novel and challenging aspect of future study.…”

“…The dimensions of the cell-patch sites (*2 lm diameter, *30 lm depth) were defined to obtain electrical characteristics comparable to glass pipettes and the high resistance seal of traditional patch-clamping (Fertig et al 2002). The pitch of the microholes (400 lm) is a compromise to guarantee an easier fabrication, better electrical independence between the microholes and finally to allow neurite development and potential synapses establishment (Taylor et al 2005;Oliva et al 2003;Peterman et al 2003). The microchip is disposable and can be inserted in a polymer-based system containing advanced fluidic structures for perfusion and suction and a set of Ag/AgCl wire electrodes, as well as a chamber for cell injection and Fig.…”

A model retinal interface based on directed neuronal growth for single cell stimulation

“…While many groups have micropatterned neurons on MEAs and have performed detailed electrical recordings of the cells for such applications as neural networks (Maher et al, 1999;Nam and Wheeler, 2004;Zeck and Fromherz, 2001), using the electrodes in such an array for selective stimulation of neurons, as opposed to electrical recording, has not yet been investigated in detail. The potential for these micropatterning technologies to achieve direct stimulation of individual neurons has important implications for prosthetic applications, as described previously (Peterman et al, 2003). In addition, such a well-controlled platform allows a fundamental study to be carried out on the effectiveness of stimulation parameters.…”