Laxman Saggere

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 mum diameter stainless-steel microelectrode wires (TS=600 MPa) implanted 3.0 cm within fixed human primary auditory cortex (ntrial>10) experienced 133plusmn8 and 64plusmn4 mN of peak and steady axial forces. When subjected to a 3 Hz, 3-mm vertical oscillation, dynamic force amplitudes (ntrial>10) of 148plusmn10 mN were measured. The model system allows the study and comparison of static and dynamic forces and their mechanical influences on proposed implanted microelectrode structures

Modeling and Design of an Optically Powered Microactuator for a Microfluidic Dispenser

This paper presents systematic modeling and design of an optically powered piezoelectric microactuator for driving a microfluidic dispenser that could find a potential application in a retinal prosthesis. The first part of the paper treats a microactuator system comprised of a micron-scale piezoelectric unimorph integrated with a miniaturized solid-state solar cell. The microactuator design is tailored for driving a microfluidic dispenser to dispense a stored liquid chemical through its micron-sized outlet ports at a rate of about 1 pl/s when the integrated solar cell is irradiated by light at a power density of 3 W/m 2 , corresponding to the requirements of the potential application. The microactuator system design is accomplished by first obtaining analytical models for the solar cell characteristic behavior and the microactuator displacements and then combining them to obtain the key dimensions of the microactuator through a design optimization. An analysis of the performance characteristics of the microactuator and a finite element analysis validating the analytical model for the microactuators displacements and the peak stresses under the operating loads are presented. The latter part of the paper presents a design of a microfluidic dispenser utilizing the optically powered microactuator and satisfying the desired input/output requirements. An analytical model integrating various energy domains involved in the system, viz. opto-electrical, piezoelectric, mechanical and hydraulic, is derived for the liquid flow through the dispensers micron-sized outlet ports. Finally, the energetic feasibility of the microactuator design obtained for the specified input and output criteria is also discussed.

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. Chemical stimulation of retinal ganglion cells (RGCs) using the neurotransmitter glutamate has been suggested as an alternative to electrical stimulation with some significant advantages. However, sufficient scientific data to support developing a chemical-based retinal prosthesis is lacking. The goal of this study was to investigate the feasibility of a neurotransmitter-based retinal prosthesis and determine therapeutic stimulation parameters. APPROACH We injected controlled amounts of glutamate into rat retinas from the epiretinal side ex vivo via micropipettes using a pressure injection system and recorded RGC responses with a multielectrode array. Responsive units were identified using a spike rate threshold of 3 Hz. MAIN RESULTS We recorded both somal and axonal units and demonstrated successful glutamatergic stimulation across different RGC subtypes. Analyses show that exogenous glutamate acts on RGC synapses similar to endogenous glutamate and, unlike electrical prostheses, stimulates only RGC somata. The spatial spread of glutamate stimulation was ≈ 290 μm from the injection site, comparable to current electrical prostheses. Further, the glutamate injections produced spatially differential responses in OFF, ON, and ON-OFF RGC subtypes, suggesting that differential stimulation of the OFF and ON systems may be possible. A temporal resolution of 3.2 Hz was obtained, which is a rate suitable for spatial vision. SIGNIFICANCE We provide strong support for the feasibility of an epiretinal neurotransmitter-based retinal prosthesis. Our findings suggest that chemical stimulation of RGCs is a viable alternative to electrical stimulation and could offer distinct advantages such as the selective stimulation of RGC somata.

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. We show that controlled pulsatile delivery of glutamate into the subsurface of explanted wild-type rat retinas elicits highly localized simultaneous inhibitory and excitatory spike rate responses in OFF and ON RGCs. We also present the spatiotemporal characteristics of RGC responses to subretinally injected glutamate and the therapeutic stimulation parameters. Our findings could pave the way for future development of a neurotransmitter-based subretinal prosthesis offering more naturalistic vision and better visual acuity than electrical prostheses.

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. Our results demonstrate that it is feasible to stimulate RGCs in an explanted retina using focal ejections of glutamate from either subretinal or epiretinal sides. Preliminary evidence suggests we are primarily activating RGCs as opposed to bipolar cells. This is an important first step in the development of a chemical retinal prosthesis based on microelectromechanical systems (MEMS) technology.

A thin-film piezoelectric microactuator optically powered via an integrated micro-solar cell

A novel optically powered microactuator is developed via the integration of a thin film piezoelectric microactuator with a micro-solar cell on the same chip. The integrated microactuator has an overall area of 2×2 mm2 and is less than 0.25 mm in thickness. The paper presents the details of fabrication and preliminary experimental results confirming the optical actuation. The solar cell is fabricated by doping a n-type dopant in a p-type silicon wafer. The thin film piezoelectric microactuator is fabricated alongside the solar cell via the solgel method. The microactuator prototypes are tested for optical actuation under low light intensities in the range 0.1-1.26 W/m2 , and corresponding center point displacements of the actuators and the photovoltages output by the solar cells are measured. An unpoled microactuator prototype produced a maximum displacement of 31 nm corresponding to an input light intensity 1.26 W/m2 .Copyright

Light-driven actuation of fluids at microscale

This paper discusses the prospects of light-driven actuation particularly for actuating fluids at micro-scale for potential use in a novel retinal prosthesis and other drug delivery applications. The prosthesis is conceived to be comprised of an array of light-driven microfluidic-dispenser units, devices that eject very small amounts of fluids on the order of 1 picoliter per second in response to incident light energy in the range of 0.1-1 mW/cm2. A light-driven actuator, whose size will ideally be smaller than about 100 micrometers in diameter, independently powers each dispenser unit. Towards this application, various approaches for transducing light energy for actuation of fluids are explored. These approaches encompass both direct transduction of light energy to mechanical actuation of fluid and indirect transduction through an intermediary form of energy, for instance, light energy to thermal or electrical energy followed by mechanical actuation of fluid. Various existing schemes for such transduction are reviewed comprehensively and discussed from the standpoint of the application requirements. Direct transduction schemes exploiting recent developments in optically sensitive materials that exhibit direct strain upon illumination, particularly the photostrictive PLZT (Lanthanum modified Lead Zirconate Titanate), are studied for the current application, and results of some preliminary experiments involving measurement of photovoltage, photocurrent, and photo-induced strain in the meso-scale samples of the PLZT material are presented.

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

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. To accomplish pattern stimulation, we fabricated a special microfluidic device comprising an array of independently addressable microports connected to tiny on-chip glutamate reservoirs via microchannels. The device prefilled with glutamate was interfaced with explanted rat retinas placed over a multielectrode array (MEA) with the retinal ganglion cells (RGC) contacting the electrodes and photoreceptor surface contacting the microports. By independently and simultaneously activating a subset of the microports with modulated pressure pulses, small boluses of glutamate were convectively injected at multiple sites in alphabet patterns over the photoreceptor surface. We found that the glutamate-driven RGC responses recorded through the MEA system were robust and spatially laid out in patterns strongly resembling the injection patterns. The stimulations were also highly localized with spatial resolutions comparable to or better than electrical retinal prostheses. Our findings suggest that surface stimulation of the retina with neurotransmitters in pixelated patterns of visual images is feasible and an artificial chemical synapse chip based on this approach could potentially circumvent the limitations of electrical retinal prostheses.

Design of a Compliant Micro-Clasp Mechanism for Micromanipulation Tasks

This paper introduces the concept of a novel compliant micromanipulator that is capable of manipulating irregularly shaped micro-scale objects by positively clasping the object. The controlled clasp capability of the micromanipulator can be useful to accomplish the manipulation of a wide range of micro-scale objects and biological specimens, especially those with irregular shapes and/or floating in a liquid medium where traditional tweezers or grippers are cumbersome or unsuitable. The monolithic structure of the micromanipulator comprises of two distinct parts: a body and a clasp. The body has a topology that magnifies a single rectilinear input actuation into two larger displacements at the input points to the clasp mechanism. The clasp mechanism comprises of rigid links connected by rotary joints in the form of low-resistance serpentine flexures. The mechanism “clasps” the target object by enveloping the object with a continuous mechanical boundary that eventually closes inwards and “locks” the object within the boundary. The paper presents a systematic design of the compliant micromanipulator and the analytical model governing the behavior of the clasp using topology optimization techniques and energy methods.© 2007 ASME

Development of a Light-Driven Thin-Film Piezoelectric Microactuator

This paper presents the design, fabrication and experimental characterization of a self-contained light-driven microactuator that could find a potential application in a novel retinal prosthesis. The conceived actuator system comprises of a miniaturized solid-state solar cell connected in series with a thin-film piezoelectric microactuator, both fabricated and integrated on a single chip through conventional microfabrication processes. When irradiated with light, the solar cell generates voltage across the thin-film microactuator, which bends and produces mechanical actuation. The novelty of the actuator system lies in its unique integrated design to meet its unique application requirements of producing the output mechanical actuation for input light energy at low illumination levels in the range of 0.1–3 W/m2 . The work demonstrates the fabrication feasibility of the miniaturized solar cell and the PZT thin-film microactuator, and characterizes their performance separately. The solar cell is fabricated by creating a p-n junction over a small area on a single crystal p-type silicon substrate. The microactuator is fabricated as a 600 nm sol-gel derived 52/48 PZT thin-film on a silicon diaphragm. The voltage output characteristics of the solar cell, experimentally studied as a function of the incident irradiance, shows an open circuit voltage of 250–300 mV under 0.6–1.6 W/m2 irradiance. The PZT thin-film microactuator, actuated under low voltages of 0–700 mV, showed deflections in the range of 0–16 nm. Finally, the light-driven actuation is demonstrated by connecting the miniaturized solar cell with the PZT thin-film microactuator and measuring deflections of 5–7 nm under low illumination levels of 0.6–1.6 W/m2 .Copyright