SBIR-STTR Award

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.

Public Health Relevance Statement:


Project narrative:
Relevance – Age related cognitive decline creates substantial emotional and financial burden as well as reduced quality of life for patients and their families. Better tools are needed for study of these conditions in preclinical models. Implanted devices generate a chronic inflammatory state caused by vascular perforation and crushing of brain tissue which leads to encapsulation of the implanted device by scar tissue and loss of neural density. This SBIR project develops the Optical Neuroscience Insertion Tool (ONIT) for reduced insertion force and tissue damage during placement of optical imaging systems (fiber optic cannula, GRIN lenses) in preclinical studies.

Project Terms:
Aging; AD dementia; Alzheimer Type Dementia; Alzheimer disease dementia; Alzheimer sclerosis; Alzheimer syndrome; Alzheimer's; Alzheimers Dementia; Primary Senile Degenerative Dementia; primary degenerative dementia; senile dementia of the Alzheimer type; Alzheimer's Disease; Award; Axon; Blood Vessels; vascular; Certification; Cicatrix; Scars; Computers; Demyelinations; demyelinate; Disease; Disorder; Electrodes; Family; Fiber Optics; Freezing; Glial Fibrillary Acidic Protein; Astroprotein; GFA-Protein; GFAP; Glial Fibrillary Acid Protein; Glial Intermediate Filament Protein; Goals; Head; Human; Modern Man; implantable device; biomedical implant; implant device; indwelling device; Industrialization; Inflammation; Investments; Light; Photoradiation; Marketing; Medical Device; Mentors; Methods; Methodology; Motion; United States National Institutes of Health; NIH; National Institutes of Health; Needles; Nerve Degeneration; Neuron Degeneration; neural degeneration; neurodegeneration; neurodegenerative; neurological degeneration; neuronal degeneration; Neurons; Nerve Cells; Nerve Unit; Neural Cell; Neurocyte; neuronal; Neurosciences; Noise; Optics; optical; Legal patent; Patents; Patients; Photometry; pressure; Public Health; Puncture procedure; Punctures; Quality of life; QOL; Research; research and development; Development and Research; R & D; R&D; Research Personnel; Investigators; Researchers; Resources; Research Resources; Rodent; Rodentia; Rodents Mammals; Sales; Signal Transduction; Cell Communication and Signaling; Cell Signaling; Intracellular Communication and Signaling; Signal Transduction Systems; Signaling; biological signal transduction; Silicon; Si element; Technology; Testing; Thinness; Leanness; Tissues; Body Tissues; Translating; Vacuum; Work; Measures; Medical Research; Businesses; density; Microscope; Ultrasound transducer; Ultrasonic Transducer; improved; Peripheral; Area; Surface; Acute; Chronic; Encapsulated; Penetration; Phase; Histologically; Histologic; Medical; Grips; grasp; Fiber; light weight; lightweight; Morphology; Inflammatory; tool; Impaired cognition; Cognitive Disturbance; Cognitive Impairment; Cognitive decline; Cognitive function abnormal; Disturbance in cognition; cognitive dysfunction; cognitive loss; Age-associated memory impairment; Age-associated cognitive decline; Age-related cognitive decline; Benign senescent forgetfulness; age associated memory decline; age related cognitive deficit; age related cognitive impairment; age related memory dysfunction; aspirate; programs; Mechanics; mechanic; mechanical; Investigation; System; brain tissue; Dementia; Amentia; Cannulas; Neurodegenerative Disorders; Degenerative Neurologic Diseases; Degenerative Neurologic Disorders; Nervous System Degenerative Diseases; Neural Degenerative Diseases; Neural degenerative Disorders; Neurodegenerative Diseases; Neurologic Degenerative Conditions; degenerative diseases of motor and sensory neurons; degenerative neurological diseases; neurodegenerative illness; Operative Surgical Procedures; Operative Procedures; Surgical; Surgical Interventions; Surgical Procedure; surgery; Perforation; Postdoctoral Fellow; Postdoc; Research Associate; post-doc; post-doctoral; post-doctoral trainee; research associates; experience; neural; attenuation; Speed; neuroimaging; neural imaging; neuro-imaging; neurological imaging; Devices; Emotional; Central Nervous System; CNS Nervous System; Neuraxis; Ultrasonics; Ultrasonic; Device or Instrument Development; device development; instrument development; Doctor of Philosophy; Ph.D.; PhD; Imaging Device; Imaging Instrument; Imaging Tool; Motor; Pre-Clinical Model; Preclinical Models; in vivo; Patient-Focused Outcomes; Patient outcome; Patient-Centered Outcomes; patient oriented outcomes; Rodent Model; Small Business Innovation Research Grant; SBIR; Small Business Innovation Research; Tissue Model; Monitor; Development; developmental; Image; imaging; pre-clinical; preclinical; preclinical study; pre-clinical study; age dependent; age related; optic imaging; optical imaging; designing; design; neuronal excitability; Cognitive aging; Coupled; innovate; innovative; innovation; clinical relevance; clinically relevant; Implant; implantation; optical fiber; commercialization; lenses; lens; safety testing; verification and validation; operations; operation; Geometry; imaging system; Academic skills; improved outcome; clinically translatable; clinical translation; care costs; brain implant; neural implant; AD related dementia; ADRD; Alzheimer's and related dementias; Alzheimer's disease and related dementia; Alzheimer's disease and related disorders; Alzheimer's disease or a related dementia; Alzheimer's disease or a related disorder; Alzheimer's disease or related dementia; Alzheimer's disease related dementia; multiphoton excitation microscopy; multiphoton microscopy; financial burden; financial distress; financial strain; financial stress; Financial Hardship; Immersion; Alzheimer's care; Alzheimer's disease care; Diameter; comparison control; compare to control