Diversity Supplement for Development of an Oscillated Insertion tool to Eliminate Surgically Induced Neurodegeneration for Optical Neuroimaging of Cognitive Aging and Dementia - This Phase I SBIR develops a system for gentle and accurate insertion of large optical neuroscience probes
(e.g., GRIN lenses) to improve outcomes in aging research. Additionally, the project supports Qingguang
Zhang. Ph.D. through the NIA Research and Entrepreneurial Development Immersion (REDI) program at a
small business. Entrepreneurial development activities for his project will include project factors such as
reaching Design Freeze in an ISO-13485 system, Verification and Validation, Patent Development, FDA-
Regulatory interactions and MedTech business operations. Dr. Zhang will interact with AMI mentors that have
experience in translating their academic skillsets to commercial and R&D activities at a small company.
Public Health Problem: Aging and neurodegenerative disorders are associated with loss of dendritic
complexity, demyelination of axons and reduced neuronal excitability. Optical imaging tools such as fiber
photometry, and implantable GRIN lenses coupled to head mounted microscopes, can be used to image
neuron morphology and activity beyond the depths accessible through multiphoton microscopy. However,
tissue damage caused by their surgical implantation methods can result in similar changes in neural activity
and morphology as seen in aging and cognitive decline, confounding experimental results. Previous studies of
oscillated insertion of needles into the peripheral tissue and electrodes in the central nervous system have
reduced insertion force and tissue damage.
A tool is needed to reliably reduce tissue damage and strain associated with implantation of large diameter
(>100µm) imaging lenses used in optical neuroscience to eliminate the experimental confound and improve
studies of age-related changes in neuron morphology and function.
Value Proposition: This project develops the Optical Neuroscience Insertion Tool (ONIT) to improve insertion
dynamics of GRIN lenses and other optical neuroscience systems. Later work will expand ONIT to insert large
devices, like DBS probes, with less tissue damage, for treatment of neurodegenerative diseases in humans.
Aim 1- Optimize, build, and test lightweight ONIT system. (AMI: Months 1-9).
Acceptance Criteria: Construction of a computer controlled ultrasonic actuator capable of 1) grasping and
releasing fiber optic cannula and GRIN lenses with vacuum pressure, 2) Advancing the implant at speeds less
than 100µm/sec, 3) reducing the puncture force of fiber optic cannula (200µm diameter) >60% in an ex vivo
rodent brain tissue model, and 4) monitoring force applied to actuator during insertion.
Aim 2 - Demonstrate improved signal to noise of in vivo measures of neural activity and histological
markers of neuron complexity for six weeks following oscillated insertion of large diameter GRIN
lenses in a rodent model. (Months 9-12; AMI/ PSU).
Acceptance Criteria: Ability to insert large diameter GRIN lenses without the need for tissue aspiration,
reduced attenuation (>50%) of baseline and evoked GCaMP7f signal intensity 6wks following implant.
Reduced histological indicators of neurodegeneration (>50% greater neuron complexity using Sholl analysis)
and scar formation (<50% compared to control GFAP+ area) within 500µm of GRIN lenses implanted with
oscillated insertion.
Commercialization & Marketing: Early sales via third party distributors will be reinvested to continue
development towards a clinically relevant system to insert similarly large DBS electrodes, a market expected to
reach $4.3B by 2030.
