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Automated Screening System for Modifiers of Cardiac Output in Zebrafish

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 2R44HL086809-03
Agency Tracking Number: HL086809
Amount: $967,900.00
Phase: Phase II
Program: SBIR
Solicitation Topic Code: N/A
Solicitation Number: PHS2007-2
Timeline
Solicitation Year: 2008
Award Year: 2008
Award Start Date (Proposal Award Date): N/A
Award End Date (Contract End Date): N/A
Small Business Information
PHYSICAL SCIENCES INC 20 NEW ENGLAND BUSINESS CENTER
ANDOVER, MA 01810
United States
DUNS: 073800062
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 () -
Business Contact
Phone: (978) 689-0003
Email: sasso@psicorp.com
Research Institution
N/A
Abstract

DESCRIPTION (provided by applicant): The zebrafish, Danio rerio, has become widely accepted as a model for human disease. Small molecule screens have been performed to identify both modifiers of normal cardiovascular processes and modifiers of cardiovascul
ar disease. High-throughput systems under development aim to measure heart rate but do not address other critical parameters of cardiovascular function such as blood velocity, stroke volume and ejection fraction. We propose to develop a high-throughput sys
tem that would simultaneously: 1) measure heart rate; 2) generate a velocity profile of the ventral aorta; and 3) measure end diastolic and end systolic ventricular volume. The microscope-based system will utilize spectral domain optical coherence tomograp
hy with Doppler to generate, within a matter of seconds, a three dimensional structural image of zebrafish embryos and larvae and measure blood flow. In Phase I we developed a breadboard system that enabled collection of images from both the dorsal and ven
tral views of the animals. In the breadboard system the animals were located and the scan angle was adjusted manually. In Phase II a complete, automated screening system will be developed that includes: 1) software algorithms to rapidly locate the animals
for imaging and adjust the scan angle along their axial length; 2) automated image collection; and 3) automated image processing. Phase II testing will include a pilot screen to detect animals with decreased cardiac output. PUBLIC HEALTH RELEVANCE: This re
search will develop technologies that will enable the use of zebrafish models of human disease in high-throughput screens for active pharmaceutical compounds. In particular, such screens are expected to accelerate discovery of new pharmaceuticals to treat
cardiovascular diseases. These technologies will also enable high-throughput assays of cardiotoxicity.

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

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