This Small Business Innovation Research (SBIR) Phase I project addresses the current barrier to performing extensive drug screening on primary cells. Pharmaceutical researchers have long desired to screen drugs on primary cells because they are freshly obtained from human or animal tissue and are considered to have drug responses similar to cells in the human body. However, primary cell samples are highly limited in cell number, and conventional assay technology (based on microtiter plates) does not have the degree of miniaturization needed to reduce cell usage to levels that enable extensive drug screening. This project?s objective is to develop novel ultraminiaturized assays using microfluidics that will allow high throughput drug screening on primary cells and traditional cell lines.
The broader/commercial impacts of this research are both immediate and long-term. Because primary cells are more biologically relevant than currently used cell lines, adoption of the technology by the pharmaceutical industry will improve their ability to identify drug candidates that are more likely to be effective in humans and hence successful in clinical trials. This can reduce the cost and risk associated with new drug development. Academic researchers can also benefit greatly from using the technology to characterize precious or difficult to culture cells, thus helping advance our scientific understanding of biology in the long term. Finally, the miniaturization will result in significant cost savings for academic and industrial clients stemming from reduced usage of expensive biochemical reagents.
This Small Business Innovation Research Phase I project aimed to address the current barrier to performing extensive drug screening on primary cells. Pharmaceutical researchers have long desired to screen drugs on primary cells because they are freshly obtained from human or animal tissue and are considered to have drug responses similar to that of cells in the human body. However, primary cell samples are highly limited in cell number, and conventional assay technology (based on microtiter plates) does not have the degree of miniaturization needed to reduce cell usage to levels that enable extensive drug screening. We set out to demonstrate that a novel microfluidic device can reduce assay volume by a factor of ~100 as compared to the best available conventional technology. We successfully tested and refined the principles underlying the design, resulting in a microfluidic device prototype with the fluid flow properties needed to enable high-throughput parallel experimentation. We determined the operating conditions needed to support cell viability within the device, and we ran pilot experiments to show that the device can be used for cell culture, stimulation, staining and visualization. We also demonstrated its compatibility with existing imaging equipment used in drug screening and academic research applications. This research has a broad commercial and research impact. The use of biologically primary cells can result in drug screening hits that will have the potential for a better chance of success in clinical trials and in real patients, thus increasing the rate of pharmaceutical drug discovery. Academic labs will be able to use this technology to perform cell-based assays with precious cells, leading to biological insights. Additionally, the miniaturization of the technology would lead to reduced usage of costly biochemicals, leading to cost savings for both academic and commercial customers. The technology can also have a future impact in a clinical diagnostic setting, wherein assays can be performed using a patient’s cell samples, in order to determine an optimal individualized drug treatment. Such a treatment would improve patient health outcomes and save treatment costs.
