Ph.D. Oral Examination -- Neville Z. Mehenti (Thursday, 12/14)

[Neville Mehenti]

PH.D. ORAL EXAMINATION

"NOVEL INTERFACES FOR BIOMIMETIC RETINAL PROSTHESES"

Neville Z. Mehenti
Department of Chemical Engineering, Stanford University

Date:  Thursday, December 14, 2006
Time:  2:00 pm (Refreshments at 1:45 pm)
Place:  Center for Integrated Systems, CIS-X 101


Abstract

Retinal prostheses, usually in the form of a planar microelectrode array, 
are being developed to restore vision to patients suffering from retinal 
degenerations, such as age-related macular degeneration and retinitis 
pigmentosa.  Both diseases result in the irreversible deterioration of 
photoreceptors in the sensory retina, but cell layers within the neural 
retina remain relatively intact and excitable.  While results are 
encouraging from current prostheses, which electrically stimulate groups of 
these neurons, numerous challenges remain before retinal prosthetic devices 
can produce useful vision.  This thesis work addresses some of the challenges.

The first part of this thesis focuses on applying micropatterning 
technologies to direct neuronal growth to individual electrodes for single 
cell stimulation.  Microcontact printing (µCP) was applied to align and 
pattern laminin across a microelectrode array, over which retinal ganglion 
cells (RGCs) were seeded and extended discrete 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 µCP on cell 
excitability.  The stimulation results quantitatively demonstrate the 
potential benefits of a retinal prosthetic interface based on directed 
neuronal growth.

The second portion of this thesis presents a flexible microfluidic device 
that actuates neurotransmitter release for localized cell stimulation.  The 
device is based on a polymer membrane with an aperture, through which the 
selective release of chemical pulses is controlled by microfluidic 
switching in an underlying channel network.  The chemical release 
properties have been characterized using fluorescence microscopy as a 
function of pulse frequency and duration.  Hippocampal neurons were 
cultured on the microdevices, and it was shown that the glutamate 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.  The results establish the feasibility of a prosthetic 
interface based on localized neurotransmitter delivery to achieve safe and 
repeatable neuron stimulation.

This thesis addresses key limitations of current retinal prostheses by 
engineering interfaces that achieve high-resolution and physiological cell 
stimulation, and thus potentially useful vision.  The development of these 
novel technologies may provide the biomimetic approach that is necessary 
not only to treat retinal degenerations, but a variety of neurological 
disorders as well.