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3D living neural networks

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R43MH102946-01
Agency Tracking Number: R43MH102946
Amount: $486,995.00
Phase: Phase I
Program: SBIR
Solicitation Topic Code: 101
Solicitation Number: PA11-134
Timeline
Solicitation Year: 2015
Award Year: 2014
Award Start Date (Proposal Award Date): 2014-09-04
Award End Date (Contract End Date): 2016-08-31
Small Business Information
5964 IRIS PKWY
Frederick, CO 80504-6412
United States
DUNS: 109079004
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 ANNA LINNENBERGER
 (303) 833-4333
 anna@meadowlark.com
Business Contact
 GARRY GORSUCH
Phone: (303) 468-5971
Email: ggorsuch@meadowlark.com
Research Institution
N/A
Abstract

DESCRIPTION provided by applicant Mental disease including schizophrenia depression and autism spectrum disorders are still poorly understood although it is clear that they mostly represent cortical disorders The cortex is the primary site of higher mental functions yet despite extensive research there is still no unified theory of how the cortex works This is partly
due to the fact that neuroscientists have limited tools required for precise repeatable studies of neural circuit formation and for studies of the mechanisms that control plasticity and repair Most
research completed to date relies on D cell cultures or studies of live brains Some ability to control cellular distribution within D cultures has been demonstrated by patterning an extra cellular protein for example polylysine to direct neuronal cell attachment However cells are subsequently washed onto the substrate While cells generally adhere to the patterned surfaces there is no mechanism for controlling cellular distribution with single cell resolution Other techniques have investigated use of grids of planar electrode arrays with andquot cagesandquot that only allow a single cell to be deposited in each cage This improved the ability to unambiguously map detected signals to specific neurons and to confine stimulation to single cells However this approach is not easily scalable to D environments and metallic substrates do not accurately mimic a cells natural environment which can alter cell behavior Alternatively studies of brain slices using photostimulation and calcium imaging circumvent many of these problems However this approach presents a daunting level of complexity making it challenging for neuroscientists to unravel function of the brain Our approach offers several key benefits to neuroscience research By taking advantage of recent advances in calcium imaging and photostimulation we remove the need for electrodes throughout our neural network to stimulate and probe connectivity As a result a purely hydrogel scaffold can be used as the supporting structure and as the source of channels to direct neural growth Stereolithography enables the user to rapidly define the shape of the polymer network step and repeat methods enable structures of arbitrary dimensions in x and y and additive layering enables large scale axial dimensions Furthermore by merging stereolithography with optical trapping micron scale control of the position of cells within the polymer structure is realized Our commercially available optical trapping system is capable of manipulating hundreds of objects simultaneously at high speed and with sub cellular resolution When the optical trapping system is combined with stereolithography the complete solution will allow scientists to study biological processes with unprecedented speed resolution and repeatability Boulder Nonlinear Systems and the University of Colorado propose to combine their expertise in building SLMs and in SLM microscopy in a two phase project with the ultimate goal of making dynamic D tissue scaffold fabrication a practical reality in neuroscience and clinical research In the first phase we plan t build a compact inexpensive user friendly inverted microscope with modules for optical trapping and stereolithography The device will be self aligning and integrated with appropriate software so that it can be used out of the box for applications in several neurobiological projects including studies of mechanisms for plasticity and repair drug and toxin screening chemical and biological sensing biocompatibility tests at the interface between a prosthetic device and human body and research into regeneration of nerve connections for spinal cord injuries In Phase II we will increase the throughput of the fabrication system and extend the automation of the system The ultimate goal is to design a tool capable of fabricating large scale neural networks and tissue scaffolds with micron resolution free of user control Additionally in the Phase II BNS will collaborate with Olympus to design andquot bolt onandquot optical trapping and stereolithography modules for existing Olympus microscopes This will provide an established distribution channel for the proposed research and will allow users to utilize existing imaging modalities specialized to their individual studies PUBLIC HEALTH RELEVANCE Boulder Nonlinear Systems BNS and the University of Colorado CU propose to combine an inverted microscope platform with optical manipulation of live cells and micro stereolithography of D polymer tissue scaffolds to create a revolutionary commercial tool for neuroscience research The tool will enable rapid fabrication of D polymer tissue scaffolds of arbitrary dimensions with programmable and precise distributions of cells The device will find widespread use in neuroscience research addressing a range of applications including but not limited to studies of neural circuit formation aimed at unlocking the mechanisms of neural growth and communication fabrication of neural networks for sensing and transducing minute environmental perturbations for drug and toxin screening for studies of biocompatibility at the interface between a prosthetic device and human body and for research of nerve connections for spinal cord injury repair

* Information listed above is at the time of submission. *

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