Metrology and characterization of SU-8 microstructures using autofluorescence emission.

Sophisticated three-dimensional microstructures fabricated using the negative tone SU-8 photoresist are used in many biomedical and microfluidic applications. Scanning electron microscopy (SEM) and profilometry are commonly used metrological techniques for the dimensional characterization of fabricated SU-8 microstructures but are not viable for non-destructive measurements and characterization of subsurface features like hidden microchannels. In this study, we report a unique methodology for the non-destructive dimensional characterization of SU-8 microstructures using the emitted autofluorescence radiation from fabricated SU-8 microstructures to generate depth profiles.

Neuromodulation using electroosmosis.

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 previousstudies using pneumatic actuation indicate that chemical retinal stimulation is achievable, an actuation technology that is amenable to microfabrication, as needed for animplantable 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.

Novel imaging technique for non-destructive metrology and characterization of ultraviolet-sensitive polymeric microstructures.

The negative photoresist SU-8 has attracted much research interest as a structural material for creating complex three-dimensional (3D) microstructures incorporating hidden features such as microchannels and microwells for a variety of lab-on-a-chip and biomedical applications. Achieving desired topological and dimensional accuracy in such SU-8 microstructures is crucial for most applications, but existing methods for their metrology, such as scanning electron microscopy (SEM) and optical profilometry, are not practical for non-destructive measurement of hidden features. This paper introduces an alternative imaging modality for non-destructively characterizing the features and dimensions of SU-8 microstructures by measuring their transmittance of 365 nm ultraviolet (UV) light.

Correlation between retinal ganglion cell loss and nerve crush force-impulse established with instrumented tweezers in mice.

: Rodent models of optic nerve crush (ONC) have often been used to study degeneration and regeneration of retinal ganglion cells (RGCs) and their axons as well as the underlying molecular mechanisms. However, ONC results from different laboratories exhibit a range of RGC injury with varying degree of axonal damage. We developed instrumented tweezers to measure optic nerve (ON) crush forces in real time and studied the correlation between RGC axon loss and force-impulse, the product of force and duration, applied through the instrumented tweezers in mice.

Investigation of Injection Depth for Subretinal Delivery of Exogenous Glutamate to Restore Vision via Biomimetic Chemical Neuromodulation.

Chemical neuromodulation of the retina using native neurotransmitters to biomimetically activate target retinal neurons through chemical synapses is a promising biomimetic alternative to electrical stimulation for restoring vision in blindness caused by photoreceptor degenerative diseases. Recent research has shown that subretinal chemical stimulation could be advantageous for treating photoreceptor degenerative diseases but many of the parameters for achieving efficacious chemical neuromodulation are yet to be explored. In this paper, we investigated how the depth at which neurotransmitter is injected subretinally affects the success rate, spike rate characteristics (i.

Mechanical Stimulation of the Retina: Therapeutic Feasibility and Cellular Mechanism.

Retinal prostheses that seek to restore vision by artificially stimulating retinal neurons with electrical current are an emerging treatment for photoreceptor degenerative diseases but face difficulties achieving naturalistic vision with high spatial resolution. Here, we report the unexpected discovery of a technique for mechanically stimulating retinal neurons with the potential to bypass the limitations of electrical stimulation. We found that pulsatile injections of standard Ames medium solution into explanted retinas of wild type rats under certain injection conditions (pulse-width > 50ms at 0.

Microfluidics-Based Subretinal Chemical Neuromodulation of Photoreceptor Degenerated Retinas.

Purpose: Retinal prostheses can restore rudimentary vision in cases of photoreceptor degeneration through electrical stimulation, but face difficulties achieving high spatial resolution because electrical current is an inherently unnatural stimulus. We investigated the therapeutic feasibility of using patterned delivery of the glutamate neurotransmitter, a primary agent of natural synaptic communication of the retina, as a biomimetic chemical alternative to electrical current for neuromodulation of photoreceptor degenerate retina.

Methods: We injected small quantities of the neurotransmitter glutamate into the subretina of 20 explanted photoreceptor degenerated S334ter-3 rat retinas using glass micropipettes and a prototype multiport microfluidic device to accomplish single- and multisite stimulation in vitro.

Methodology for Biomimetic Chemical Neuromodulation of Rat Retinas with the Neurotransmitter Glutamate In Vitro.

Photoreceptor degenerative diseases cause irreparable blindness through the progressive loss of photoreceptor cells in the retina. Retinal prostheses are an emerging treatment for photoreceptor degenerative diseases that seek to restore vision by artificially stimulating the surviving retinal neurons in the hope of eliciting comprehensible visual perception in patients. Current retinal prostheses have demonstrated success in restoring limited vision to patients using an array of electrodes to electrically stimulate the retina but face substantial physical barriers in restoring high acuity, natural vision to patients.

Prototype chemical synapse chip for spatially patterned neurotransmitter stimulation of the retina .

Biomimetic stimulation of the retina with neurotransmitters, the natural agents of communication at chemical synapses, could be more effective than electrical stimulation for treating blindness from photoreceptor degenerative diseases. Recent studies have demonstrated the feasibility of neurotransmitter stimulation by injecting glutamate, a primary retinal neurotransmitter, into the retina at isolated single sites. Here, we demonstrate spatially patterned multisite stimulation of the retina with glutamate, offering the first experimental evidence for applicability of this strategy for translating visual patterns into afferent neural signals.

Differential stimulation of the retina with subretinally injected exogenous neurotransmitter: A biomimetic alternative to electrical stimulation.

Subretinal stimulation of the retina with neurotransmitters, the normal means of conveying visual information, is a potentially better alternative to electrical stimulation widely used in current retinal prostheses for treating blindness from photoreceptor degenerative diseases. Yet, no subretinal electrical or chemical stimulation study has stimulated the OFF and ON pathways differentially through inner retinal activation. Here, we demonstrate the feasibility of differentially stimulating retinal ganglion cells (RGCs) through the inner nuclear layer of the retina with glutamate, a primary neurotransmitter chemical, in a biomimetic way.

Biomimetic stimulation of rat retinal ganglion cells with the neurotransmitter glutamate.

Millions of people worldwide face partial or total vision loss due to inherited photoreceptor degenerative diseases, which currently have no cure. Retinal prostheses have been developed to restore vision by electrically stimulating surviving retinal neurons, but have low spatial resolution and nonselectively stimulate retinal ganglion cell (RGC) axons along with somata. We propose a biomimetic solution: using the neurotransmitter glutamate to chemically stimulate RGCs to avoid the disadvantages of electrical stimulation.

Chemical stimulation of rat retinal neurons: feasibility of an epiretinal neurotransmitter-based prosthesis.

Objective: No cure currently exists for photoreceptor degenerative diseases, which cause partial or total blindness in millions of people worldwide. Electrical retinal prostheses have been developed by several groups with the goal of restoring vision lost to these diseases, but electrical stimulation has limitations. It excites both somas and axons, activating retinal pathways nonphysiologically, and limits spatial resolution because of current spread.

Development of a chemical retinal prosthesis: stimulation of rat retina with glutamate.

Retinal degenerative diseases cause partial or total blindness and affect millions of people worldwide, yet currently have no treatment. Retinal prostheses using electrical stimulation are being developed but face significant problems moving forward. Here we propose using chemical stimulation, via the neurotransmitter glutamate, to modulate retinal ganglion cell (RGC) spike rates.

A benchtop system to assess cortical neural interface micromechanics.

A benchtop brain tissue-microelectrode insertion model system was developed to aid in improving the design of cortical neural interfaces. The model partially mimics the in vivo environment via the use of human cadaver brain specimens (nspecimen = 6), or agar gel exposed to physiologically relevant mechanical oscillations. 150 lpm diameter stainless-steel microelectrode wires (TS = 600 MPa) implanted 3.