A High-Throughput Flow System to Probe Biomechanics of Pathophysiology Recent advances in cell culture modalities and high-throughput screening technology have vastly expanded our potential for biological discovery, and have opened the door toward therapeutic advances in the development of new compounds and cell-based therapies for treatment of a wide range of diseases. Nevertheless, current systems do not have the capability to probe cellular function in the context of the complex biomechanical environments that dictate the fate and functional phenotype of multiple cell types comprising diverse tissue milieus in vivo. Here we propose to develop and implement a dynamic high-throughput flow system that delivers programmable, time- varying fluid dynamic waveforms to cultured cells grown in individual wells of a commercially available 96-well plate. This platform should allow the systematic investigation of signaling pathways in biological systems whose function and dysfunction critically depends on the fluid mechanical environment. Development of this instrument will enable better understanding of human pathophysiology and lead to the discovery of new therapeutic targets or modalities for clinical interventions for a broad range of diseases and clinical and research applications.

Public Health Relevance

Narrative A High-Throughput Flow System to Probe Biomechanics of Pathophysiology This project aims to develop, for the first time, a high-throughput instrument capable of culturing cells in a conventional 96-well plate and applying precise mechanical forces to them. This capability will enable new and more efficient methods to investigate cardiovascular diseases, blood disorders, cancer and other conditions using more realistic laboratory models, and will accelerate the development of safer and more efficacious therapeutic treatments for these diseases.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21RR031253-02
Application #
8116992
Study Section
Special Emphasis Panel (ZRR1-BT-7 (01))
Program Officer
Friedman, Fred K
Project Start
2010-08-01
Project End
2013-04-30
Budget Start
2011-05-01
Budget End
2012-04-30
Support Year
2
Fiscal Year
2011
Total Cost
$216,818
Indirect Cost
Name
Charles Stark Draper Laboratory
Department
Type
DUNS #
066587478
City
Cambridge
State
MA
Country
United States
Zip Code
02139
Borenstein, Jeffrey T; Vunjak-Novakovic, Gordana (2011) Engineering tissue with BioMEMS. IEEE Pulse 2:28-34