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.

Using muCP to pattern surfaces with growth factors, individual neuronal processes from pure RGC culture and whole retinal explants can be directed to discrete sites on a microelectronic chip surface. By directing RGC neurite processes to specific sites, single cell stimulation becomes possible. This may allow discrete populations of retinal neurons to be addressed so that physiologic retinal processing of visual information can be achieved.

Reverse microemulsion-mediated synthesis of various inorganic and organic nanoparticles is of interest for a variety of applications. Mixtures of commercially available polyethoxylated alcohols and linear alcohols can be employed to stabilize reverse microemulsions suitable for such use. The phase behavior, electrical conductivity, and stability of the water/isooctane and water/cyclohexane microemulsion systems stabilized by a mixture of Neodol 91-6 nonionic surfactants and 1-pentanol are presented in this paper. Quasi-elastic light scattering and small-angle neutron scattering were employed to characterize the aggregation state and morphology of the aqueous and oil phases in these reverse microemulsions. Barium hexaaluminate, a complex oxide of interest for catalytic applications, was successfully synthesized via sol-gel processing in the resulting reverse microemulsion media. The recovered inorganic nanoparticles exhibited morphologies characteristic of the aqueous phase in the reverse microemulsion systems.

While functional electrical stimulation has been applied to treat a variety of neurological disorders, it cannot mimic function that is primarily achieved using neurochemical means. In this work, we present a neurotransmitter-based prosthetic interface in the form of a flexible microdevice that selectively releases chemical pulses through an aperture in a polymer membrane. The release profiles through the aperture are controlled by microfluidic switching in an underlying channel network. The profiles have been characterized using fluorescence microscopy as a function of pulse duration and frequency. Hippocampal neurons were cultured on the microdevices and cell stimulation via glutamate delivery was detected using calcium imaging. The release properties could be tuned to repeatedly elicit discrete action potentials in cells seeded proximate to the aperture, including single cell stimulation at 2 Hz. This model neural interface based on functional chemical stimulation may provide the biomimetic platform necessary to restore physiological pathways and function that electrical stimulation cannot fundamentally address.

In this work, we use cell micropatterning technologies to direct neuronal growth to individual electrodes, and demonstrate that such an approach can achieve selective stimulation and lower stimulation thresholds than current field-effect based retinal prostheses. Rat retinal ganglion cells (RGCs) were purified through immunopanning techniques, and microcontact printing (microCP) was applied to align and pattern laminin on a microelectrode array, on which the RGCs were seeded and extended neurites along the pattern to individual electrodes. The stimulation threshold currents of RGCs micropatterned to electrodes were found to be significantly less than those of non-patterned RGCs over a wide range of electrode-soma distances, as determined with calcium imaging techniques. Moreover, the stimulation threshold for micropatterned cells was found to be independent of electrode-soma distance, and there was no significant effect of microCP on cell excitability. The effects of additional stimulation parameters, such as electrode size and pulse duration, on threshold currents were determined. The stimulation results quantitatively demonstrate the potential benefits of a retinal prosthetic interface based on directed neuronal growth.