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A novel physiologically realistic microfluidic in-vitro blood-brain barrier…

Award Information

Agency:
Department of Health and Human Services
Branch:
N/A
Award ID:
Program Year/Program:
2012 / SBIR
Agency Tracking Number:
R44GM087129
Solicitation Year:
2012
Solicitation Topic Code:
NIGMS
Solicitation Number:
PA10-050
Small Business Information
CFD Research Corporation
215 Wynn Dr., 5th Floor Suite D Huntsville, AL 35805-
View profile »
Woman-Owned: Yes
Minority-Owned: No
HUBZone-Owned: No
 
Phase 2
Fiscal Year: 2012
Title: A novel physiologically realistic microfluidic in-vitro blood-brain barrier model
Agency: HHS
Contract: 2R44GM087129-02
Award Amount: $1,302,528.00
 

Abstract:

DESCRIPTION (provided by applicant): The overall objective of this study is to develop a novel in vitro microfluidic platform to test a drug or delivery vehicle's ability to permeate the Blood-Brain Barrier (BBB). In contrast to current in-vitro models, our proposed device, SIM-BBB, comprises of a microfluidic two-compartment chamber. The chamber is designed in such a way as to permit visualization-friendly evaluation of transport/permeation under appropriate microcirculatory size and flow conditions, while simultaneously simplifying device fabrication. The apical side is seeded with endothelial cells and the basolateral side supports glial cell co-cultures. The increased physiological realism substantially improves BBB characteristics including formation of tight junctions and expression of relevant transporters. The new platform offers greater throughput, increased library coverage, lower cost, rapid turnaround times and increased mechanistic knowledge benefiting drug discovery efforts. In Phase I, thefirst generation microfluidic SIM-BBB device was designed and fabricated using soft lithography. Brain endothelial cells were cultured in the microfluidic constructs with a perfusate of astrocyte conditioned media. Biochemical analysis showed upregulationof tight junction molecules while optical analysis showed intactness of the BBB in the microfluidic device. Finally, transporters assay was successfully demonstrated in the device. Phase II efforts will focus on optimization of the microfluidic device forenhanced physiological fidelity. Electrodes will be integrated for non-visual monitoring of the endothelial cell layers and tight junction formation via trans-endothelial electrical resistance (TEER) measurements. Finally, the developed technology will bedemonstrated for diverse applications including drug penetration studies and leukocyte migration under inflammatory conditions. A multi-disciplinary partnership with expertise in engineering and biology has been assembled for successful completion of the project. PUBLIC HEALTH RELEVANCE: The project seeks to develop an in vitro screening model for screening the potential of drug candidates to cross the BBB and subsequently cause therapeutic or toxic effects. By providing accurate and predictive data, the model will reduce the need for animal models and promises to both reduce late stage drug candidate failures and accelerate central nervous system (CNS) therapeutic development. The product will be commercialized to pharmaceutical firms, drug research labs and universities/non-profit centers engaged in novel neurological therapeutics research and CNS toxicity. Equally important, it is also expected to spur basic research, where it can be used to study the biological mechanisms of BBB (dys) function.

Principal Investigator:

Balabhaskar Prabhakarpandian
256-726-4942
bxp@cfdrc.com

Business Contact:

Melissa A. Evans
256-726-4897
mae@cfdrc.com
Small Business Information at Submission:

CFD RESEARCH CORPORATION
215 WYNN DR, 5TH FL HUNTSVILLE, AL -

EIN/Tax ID: 163094438
DUNS: N/A
Number of Employees: N/A
Woman-Owned: Yes
Minority-Owned: No
HUBZone-Owned: No