SBIR-STTR Award

SF424 - Understanding how the brain generates certain behaviors requires an understanding of the function of individual neurons in dynamical neural circuits. Currently, there are few technologies available however that allow researchers to record both the activity within a brain region, and between brain regions in the brains of awake, behaving animals. Recent advances in microelectrode fabrication are now enabling recordings of recording hundreds to thousands of neurons simultaneously across brain regions that will lead to functional analyses of dynamical neural circuits. To date however, there are no commercially available low-cost solutions for these kinds of revolutionary high-density probes. In addition, currently available high-density probes do not offer customization in design and layout. Neural Dynamics Technologies will develop low-cost, highly customizable, high-density probes for acute and chronic experiments in rodent in close collaboration with MIT. These probes are innovative because they rely on a new fabrication process that allows for both customization in probe design and low-cost fabrication. Furthermore, our probes will be made compatible for integration with existing commercial amplifier systems that are standardly used for both acute and chronic experiments in rodents. The first aim of this proposal is to streamline the design process of high-density probes such that the fabrication process will be ready to produce a wide variety of probe designs at low cost. The second aim will involve streamlining the production methods to enable fabrication of customizable probes with broad compatibility with existing commercial amplifier systems, which will allow neuroscience labs to use the probes with their existing equipment and analysis methods.

Public Health Relevance Statement:
SF424 - Project Narrative Neurological disease is projected to be the second largest cause of chronic disease in coming decades, but to confront this development, we need a better understanding of the neural circuit activity that underlies both healthy as well as diseased brain function. To understand the function of dynamical neural circuits we need technologies with the capability to measure the spiking activity of many individual neurons in vivo, in intact brains. Neural Dynamics Technologies focuses on the development of new neural interfaces that can record the activity of hundreds to thousands to neurons simultaneously within and across brain regions that will be available at low cost and that will offer customizability and compatibility with existing hardware and analysis methods.

Project Terms:
Amplifiers; Animals; Automation; Behavior; Brain; Encephalon; Brain Nervous System; Brain Diseases; Intracranial Central Nervous System Disorders; Intracranial CNS Disorders; Encephalon Diseases; Brain Disorders; Chronic Disease; chronic disorder; Chronic Illness; Communities; Electrophysiology (science); electrophysiological; Neurophysiology / Electrophysiology; Electrophysiology; Engineering; Equipment; Goals; Head; Methods; Microelectrodes; Miniaturized Electrodes; nervous system disorder; neurological disease; Neurological Disorders; Neurologic Disorders; Nervous System Diseases; Neurobiology; neurobiological; Neurons; neuronal; Neurocyte; Neural Cell; Nerve Unit; Nerve Cells; Neurosciences; Production; Research Personnel; Researchers; Investigators; Rodent; Rodents Mammals; Rodentia; Running; Silicon; Si element; Software Design; Designing computer software; Technology; Testing; Work; Measures; Custom; density; improved; Site; Area; Acute; Chronic; Phase; Failure; awake; Individual; Collaborations; tool; System; Location; experience; relating to nervous system; neural; neural circuit; synaptic circuitry; synaptic circuit; neural circuitry; Brain region; Caliber; Diameter; Academia; in vivo; Neurosciences Research; Monitor; trend; Process; developmental; Development; cost; designing; design; nanofabricate; nano fabrication; nano fabricate; nanofabrication; manufacturing process; Population; innovative; innovate; innovation; neurotechnology; prototype; flexible; flexibility; time measurement; temporal resolution; temporal measurement; experimental research; experiment; experimental study

Understanding how the brain controls behavior requires studying the dynamic activity of different types of neurons in distributed neural circuits in awake behaving animals. Currently, there are few technologies available however that allow researchers to record the activity of hundreds to thousands of neurons at arbitrary depth in the brains of awake, behaving animals. While there has been much recent progress in the development of high-density micro-fabricated silicon probes, current commercially available probes offer little to no customizability to the morphology of different brain regions and different cell types within brain regions. Even more importantly, there are no commercially available solutions of high-density probes with integrated stimulation capabilities enabling causal, closed-loop experimentation. In Phase I, we designed and fabricated customizable high-density recording probes for acute head-fixed recordings and streamlined our fabrication strategies. The resulting devices had high yields of functional electrode sites and were successfully used by beta-tester labs to generate data with good signal-to-noise ratios. We furthermore built an online graphical interface where end-users can design their probes and submit their designs for fabrication. In Phase II, Neural Dynamics Technologies LLC will develop customizable, high-density probes with integrated closed-loop capabilities that can be chronically implanted for use in animals that are either head-fixed or able to move around freely. The first aim of our Phase II proposal is to integrate light delivery and electrical stimulation capabilities onto our probes to enable closed-loop experimentation. The locations for light delivery and electrical stimulation will be customizable so that customers can specify their desired location. The second aim will be to develop a packaging approach that involves building an application specific integrated circuit (ASIC) and a head-stage that can control all integrated functionalities. The combined packaged device will be small enough to enable chronic experiments in either head- fixed or freely moving animals. The third aim will be to perform both bench-top testing and in vivo animal testing of devices to establish basic functionality and effectiveness of the devices. In summary, NDT will design innovative closed-loop interfaces that will enable causal studies addressing the functional role of different brain regions and neuron types in the brains of both head-fixed and freely moving animals. These types of closed-loop devices may be further evolved into neural implants to treat neurological diseases such as refractory epilepsy, Parkinson's and other tremor disorders.

Public Health Relevance Statement:
NARRATIVE Neurological disease will be a leading cause of chronic disease in the coming decades and to confront this development with effective therapeutics, we need a better understanding of the neural circuit activity that underlies both healthy and diseased brain function. To study the dynamics of neural circuit activity, technologies are required that can chronically measure the spiking activity of many individual neurons in vivo, in intact brains. Neural Dynamics Technologies develops innovative high-density implantable neural interfaces that can be customized to the morphology of different brain regions, and that offer integrated stimulation capabilities, therefore enabling causal, closed-loop and chronic recording of neural circuit activity.

Project Terms:
Animals; Ursidae Family; Bears; Ursidae; bear; Behavior; Brain; Brain Nervous System; Encephalon; Brain Diseases; Brain Disorders; Encephalon Diseases; Intracranial CNS Disorders; Intracranial Central Nervous System Disorders; Chronic Disease; Chronic Illness; chronic disorder; Disease; Disorder; Electric Stimulation; Electrical Stimulation; electrostimulation; Electrodes; Electrophysiology (science); Electrophysiology; Neurophysiology / Electrophysiology; electrophysiological; Goals; Head; Institutes; Lead; Pb element; heavy metal Pb; heavy metal lead; Learning; Light; Photoradiation; Longevity; Length of Life; life span; lifespan; Memory; Methods; nervous system disorder; Nervous System Diseases; Neurologic Disorders; Neurological Disorders; neurological disease; Neurons; Nerve Cells; Nerve Unit; Neural Cell; Neurocyte; neuronal; Neurosciences; Noise; Parkinson Disease; Paralysis Agitans; Parkinson; Parkinson's disease; Parkinsons disease; Primary Parkinsonism; Research; research and development; Development and Research; R & D; R&D; Research Personnel; Investigators; Researchers; Rodent; Rodentia; Rodents Mammals; Role; social role; Signal Transduction; Cell Communication and Signaling; Cell Signaling; Intracellular Communication and Signaling; Signal Transduction Systems; Signaling; biological signal transduction; Silicon; Si element; Software Design; Designing computer software; Technology; Testing; Tremor; Work; Measures; Custom; Computer-Aided Design; Computer-Assisted Design; density; Site; Acute; Chronic; Specific qualifier value; Specified; Phase; awake; Individual; Databases; Data Bases; data base; Collaborations; Therapeutic; Mule; Equine mule; Morphology; tool; Diagnostic; Behavioral Manipulation; behavioral control; Behavior Control; Investigation; cell type; System; 3-D; 3D; three dimensional; 3-Dimensional; Location; brain control; mind control; Animal Models and Related Studies; model of animal; model organism; Animal Model; neural; relating to nervous system; Devices; neural circuitry; neurocircuitry; synaptic circuit; synaptic circuitry; neural circuit; Refractory epilepsy; drug-resistant epilepsy; Intractable Epilepsy; Brain region; Effectiveness; Causality; causation; disease causation; Etiology; Address; Animal Testing; Data; in vivo; Process; Grouping; groupings; Development; developmental; Image; imaging; cost; virtual; design; designing; manufacturing process; Population; innovation; innovate; innovative; Implant; user-friendly; graphical user interface; Graphical interface; graphic user interface; software user interface; prototype; effective therapy; effective treatment; flexibility; flexible; optogenetics; experimental study; experiment; experimental research; phase 1 designs; phase I designs; neural implant; brain implant; two photon microscopy; 2-photon microscopy; two photon excitation microscopy; therapeutically effective