A High-Throughput and Flexible System for Integrating Mechanobiology with Drug Development and Toxicity Screening
Life Sciences : Research Tools
Available for licensing
- Aaron Baker, Ph.D. , Biomedical Engineering
- Mitchell Wong , University of Texas at Austin
Creating in vitro screening assays that more closely represent biological conditions could improve the success rate of drug discovery and toxicity screens. Improving the predictive accuracy could save drug developers millions of dollars for each campaign. For example, cardiotoxicity is a major cause for withdrawal of drugs during development and oftentimes not identified until the later stages of development. One way to increase the predictive accuracy of cell culture screens is to more closely mimic the environmental conditions of the body. This is especially true for vascular cells, which are continually exposed to rhythmic variations in pressure, leading to cyclic distension and stretch. While there are small scale culture systems capable of applying dynamic mechanical forces to vascular cells, there are no platforms that can be integrated with the high throughput systems used by drug developers.
A novel device to apply complex mechanical strains to cells in culture in a high throughput format. The device allows the performance of drug activity and toxicity screening in the presence of physiologic loads and can facilitate more biologically relevant predictive screens for therapeutic compounds.
- Higher throughput, provides uniform mechanical strain to 576 wells simultaneously
- Compatible with automated drug screening robotics and plate reading technology
- Increased uniformity and repeatability
- Capable of applying constant strain patterns for long periods of time
- Provides a wider range of forces and more complex waveforms
- Can accurately simulate the biphasic stretch of the cardiac cycle
- Feedback controlled, linear motor can apply any arbitrary temporal strain profile
- Can provide static and dynamic loads with complex wave forms
- Compatible with standard cell culture incubators
- Platform is easily adaptable to many standard formats
- Validated to apply uniform strain profiles across the individual wells
This technology can be applied to several different applications, including:
1) Screening of compounds for cardiotoxicity using cultured myocytes under physiological
2) Screening of compounds for therapeutic activity in cultured cells in the presence of
3) Genetic screening for identification of drug targets.