Neuromodulation using electroosmosis

Abstract

Objective. Our laboratory has proposed chemical stimulation of retinal neurons using exogenous glutamate as a biomimetic strategy for treating vision loss caused by photoreceptor (PR) degenerative diseases. Although our previous in-vitro studies using pneumatic actuation indicate that chemical retinal stimulation is achievable, an actuation technology that is amenable to microfabrication, as needed for an in-vivo implantable device, has yet to be realized. In this study, we sought to evaluate electroosmotic flow (EOF) as a mechanism for delivering small quantities of glutamate to the retina. EOF has great potential for miniaturization. Approach. An EOF device to dispense small quantities of glutamate was constructed and its ability to drive retinal output tested in an in-vitro preparation of PR degenerate rat retina. Main results. We built and tested an EOF microfluidic system, with 3D printed and off-the-shelf components, capable of injecting small volumes of glutamate in a pulsatile fashion when a low voltage control signal was applied. With this device, we produced excitatory and inhibitory spike rate responses in PR degenerate rat retinae. Glutamate evoked spike rate responses were also observed to be voltage-dependent and localized to the site of injection. Significance. The EOF device performed similarly to a previously tested conventional pneumatic microinjector as a means of chemically stimulating the retina while eliminating the moving plunger of the pneumatic microinjector that would be difficult to miniaturize and parallelize. Although not implantable, the prototype device presented here as a proof of concept indicates that a retinal prosthetic based on EOF-driven chemical stimulation is a viable and worthwhile goal. EOF should have similar advantages for controlled dispensing of charged neurochemicals at any neural interface.

Progress on Designing a Chemical Retinal Prosthesis

“…While most demonstrations of glutamate activation of retinal ganglion cells from the epiretinal ( Finlayson and Iezzi, 2010 ; Inayat et al, 2015 ) or from the subretinal side ( Rountree et al, 2016 , 2018 , 2020 ) have relied on pneumatic injection ( Rountree et al, 2017b ), it was recognized by Peterman et al (2004) that electroosmotic flow might be better suited as a neurotransmitter release mechanism in a microfabricated device. Kare et al (2021) have shown recently that electroosmosis can be used effectively to dispense glutamate to rat retinas and evoke responses from its ganglion cells with properties similar to those evoked through pneumatic actuation.…”

Spatiotemporally Controllable Chemical Delivery Utilizing Electroosmotic Flow Generated in Combination of Anionic and Cationic Hydrogels

“…EOF is the convective movement of solvent generated by the preferential electrophoretic movement of mobile counter cations (or anions) through negatively (or positively) charged microchannels, such as glass capillaries, [19,20] nanotubule membranes [21,22] and porous oxide materials. [23,24] Therefore, EOF can even transport solute chemicals in the opposite direction of their electrophoresis [20,25] (Figure S1, Supporting Information). In addition to the charged microchannels, hydrogels are also attractive materials for generating EOF when they possess fixed charges along with their soft and hydrophilic nature.…”

“…The absence of external current flow is a unique property of the developed system; many conventional electroosmotic pumps have an external electrode, and therefore chemical delivery with such a system might be accompanied by unwanted electrical stimulation of target cells and tissues. A few previous works of EOF pump [23,24] prevented the current from flowing to outside by utilizing a porous material sandwiched between electrodes; however, in this structure, one of the electrodes is close to the target, which raises concerns about the effects of electrolysis. On the other hand, the electrodes of the present system can be placed away from the delivery target.…”

Connected Droplet Shape Analysis for Nanoflow Quantification in Thin Electroosmotic Micropumps and a Tunable Convex Lens Application

“…Since EOF velocity and pressure are controlled by the applied voltage, EOF provides a wide range of tunability with high resolution. Response latency between voltage application and observable fluid flow is on the order of a few milliseconds . EOF micropumps can be very thin, − making them suitable for applications such as lab-on-a-chip and drug delivery devices.…”

“…Response latency between voltage application and observable fluid flow is on the order of a few milliseconds. 6 EOF micropumps can be very thin, 7−11 making them suitable for applications such as lab-on-achip and drug delivery devices. These applications demand precise quantification of the relationship between the applied voltage and flow rate and/or pressure.…”