SBIR-STTR Award

Diseases of the central and peripheral nervous systems affect the quality of life of millions of people worldwide. Progress in understanding the function of neural networks and in developing associated insights into the underlying causes of these diseases can be accelerated by advances in techniques and methodologies for neuroscience research. Collaborative efforts between the Rogers and Bruchas groups recently yielded a wireless, battery-powered system for fluid delivery and optogenetics in a single, head-mounted platform. These probes operate without physical connection to external light or fluid sources or power supply systems, thereby greatly simplifying the equipment requirements and user interfaces for the investigator. The complex, multi-part construction and the required batteries limit the manufacturability and the size/weight/operating time of the system, respectively. The proposed program focuses on the development of a wireless, battery-free platform with similar functionality but in a low-cost, manufacturable design that is fully compatible with a commercially available wireless electronic platform and control software from the company NeuroLux. This technology represents an important advance in tools for neuroscience research, with many application possibilities and unique advantages over any other research or commercial alternative. The Specific Aims of the proposed work are to (1) develop a wireless, battery-free electrochemical micropump, (2) integrate electrochemical micropumps with ultrathin, soft microfluidic and microscale inorganic light emitting diode (?-ILED) probes, and associated wireless, battery-free electronics and (3) evaluate the efficacy and robustness of optofluidic devices in awake, behaving animals in behavioral tests.

Public Health Relevance Statement:
Project Narrative The proposed program focuses on the development of a wireless, battery-free optofluidic device for programmable pharmacological delivery and optogenetics in a low-cost, manufacturable system that is fully compatible with the NeuroLux HF wireless electronic platform and control software. Here, lightweight, implantable electrochemical micropumps and microscale light emitting diodes operate in a centralized system to enable externally and independently triggered delivery of drugs and light to specific neuronal populations in freely moving animals for diverse studies in neuroscience research.

Project Terms:
Affect; Animals; aqueous; Area; awake; base; behavior test; Benchmarking; Biological Neural Networks; Brain; brain tissue; Caliber; Color; Complex; Computer software; cost; Data; Dependovirus; design; Development; Devices; Diffusion; digital; Disease; Drug Delivery Systems; Dyes; Electrodes; Electronics; Equipment; experimental study; Extravasation; flexibility; Foundations; Gel; Genetic Recombination; Geometry; Gold; Head; Imagery; Implant; In Vitro; in vitro testing; in vivo; Infusion procedures; Injectable; Injection of therapeutic agent; insight; Light; light weight; Liquid substance; Methodology; Microfluidics; minimally invasive; Needles; Neurons; Neurophysiology - biologic function; Neurosciences; Neurosciences Research; operation; optogenetics; Performance; Peripheral Nervous System; Pharmaceutical Preparations; Pharmacology; Population; Power Sources; programs; Pump; Quality of life; Reproducibility; Research; Research Personnel; Sepharose; Side; Source; System; targeted delivery; Techniques; Technology; Testing; Time; Tissues; tool; uptake; Weight; Wireless Technology; Work

Neuroscience research over the last decade has been revolutionized by many technological advancements. Pharmacology and optogenetics represent two distinct, and sometimes complementary tools used in neuroscience research to study the central and peripheral nervous systems in the context of the BRAIN initiative. Advanced interrogations of underlying neural circuits and biology are often frustrated, however, by technological limitations that prevent the use of these approaches to study natural behaviors of untethered, freely moving animals. Traditional fiber-optic cable for optogenetics and bulky metal cannulas connected with external mechanical pumps for pharmacology impart significant damage to fragile neural tissue, limit the natural behavior of freely moving animals, affect social interactions and movements in complex, naturalistic 3D environment, and lead to persistent irritation at the biotic/abiotic interface due to mechanical mismatch and micromotions. These drawbacks, together with the costly setup, of current technologies motivate the development of innovative engineering designs to improve fidelity, operational ease, versatility and range of advanced brain research studies with live animal models. Our work during Phase I developed an integrated, wireless platform that combines capabilities in programmable pharmacology via soft ?-fluidic channels and optogenetics through an implantable ?-scale inorganic light emitting diodes (?-ILEDs). The proposed work for Phase II focuses on translational engineering research to refine the device designs and to develop a low-cost, mass-manufacturing process. Specifically, the proposed work will (1) establish device designs, and manufacturing process for low-cost, outsourced production, (2) expand the functionality for directly interfacing with peripheral nerve and spinal cord, and (3) develop advanced capabilities in power harvesting, modulation, and control, and broaden the impact on neuroscience research. This work will yield a broadly useful, low-cost, wireless platforms for programmable pharmacology and optogenetics in various contexts of essential relevance to the BRAIN initiative.

Public Health Relevance Statement:
Project Narrative The goal of this project is to advance novel classes of soft, flexible device technologies that will allow for the delivery of pharmacological agents to precisely targeted regions of the deep brain. It will also advance capabilities in advanced, wireless, optoelectronic systems for optogenetics, and combined with the pharmacological platforms listed above, will extend experimental possibilities in neuroscience research beyond the brain, and to the spinal cord and peripheral nervous system. Over the course of this project, we will develop and deploy novel manufacturing schemes that will allow for low-cost production of these platforms, to effectively distribute them to the neuroscience community.

NIH Spending Category:
Basic Behavioral and Social Science; Behavioral and Social Science; Bioengineering; Biotechnology; Mental Health; Networking and Information Technology R&D (NITRD); Neurosciences

Project Terms:
3-Dimensional; Affect; Animal Model; Animals; base; Behavior; behavioral study; Biology; body system; Brain; BRAIN initiative; brain research; Bypass; Cannulas; Cicatrix; Communities; Complex; cost; design; Development; Device Designs; Device or Instrument Development; Devices; Disease; Drug Delivery Systems; Drug Targeting; Electrolytes; Electronics; Engineering; engineering design; Environment; Equipment; experimental study; Fiber Optics; flexibility; free behavior; Frequencies; frontier; Goals; Harvest; improved; in vivo; innovation; irritation; Lasers; Lead; Light; Liquid substance; manufacturing process; Mechanics; Metals; Microfabrication; Microfluidics; Motion; Movement; Nature; nervous system disorder; Nervous system structure; neural circuit; Neurophysiology - biologic function; Neurosciences; Neurosciences Research; neurotechnology; novel; operation; Optics; optogenetics; Performance; Peripheral Nerves; Peripheral Nervous System; Pharmacology; Phase; prevent; Process; Production; programs; Pump; relating to nervous system; Research; Research Design; research study; Scheme; Small Business Technology Transfer Research; Social Interaction; social movement; Spinal Cord; Structure; System; targeted delivery; Techniques; Technology; Tissues; tool; Tube; Validation; Vendor; Wireless Technology; Work