SBIR-STTR Award

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) project is to improve the efficiency of discovering new drugs by introducing a new type of instrument for fluorescent imaging of cells at high throughput. This innovation will allow pharmaceutical researchers to image individual cells at speeds more than an order of magnitude faster than the state-of-the-art instrumentation, which will improve the rate at which scientists run drug screening experiments. By taking high-resolution images of individual cells during these screening experiments, far more detailed information can be gleaned than using conventional high throughput methods, leading to a deeper scientific understanding of drug-cell interactions. This instrument will address the growing $15 billion drug discovery instrumentation market by providing a new type of high throughput readout capability for the drug discovery industry. Further, the ability to perform multiplexed multi-color fluorescent imaging of cells will reduce the number of experiments required to identify new pharmaceutical compounds, thereby improving the efficiency and reducing the cost of drug discovery, ultimately reducing the time-to-market of new drugs.

This SBIR Phase I project proposes to develop an imaging flow cytometer instrument to improve the speed of single-cell analysis in the field of drug discovery. While multi-parameter single-cell phenotypic analysis provides great information about the cellular interactions of a pharmaceutical compound, this type of experimental readout is too slow to perform on the large numbers of samples common in a drug discovery laboratory. By performing parallel fluorescent image analysis of cells in flow, this process can be accelerated such that more than 100,000 compounds can be screened each day in an automated laboratory setting. This project aims to develop an instrument capable of such high throughput image analysis using fluorescence, combining techniques and technologies adapted from the fields of flow cytometry and high-speed fluorescence microscopy to accomplish this throughput goal. The successful outcome of this project will yield an instrument capable of imaging cells flowing at meter per second flow rates with diffraction-limited spatial resolution using multiple fluorescent colors.

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase II project will be to develop an imaging flow cytometer to enable high-throughput, precision analysis of biological cells for the drug discovery and biotechnology industries. The goal for this project is to provide order-of-magnitude throughput improvements versus other high content cell analysis technologies, which will ultimately lead to an increase in the efficiency of drug discovery. A high throughput imaging flow cytometer is an ideal solution for the pharmaceutical and biotechnology industries, as well as flow cytometry core facilities, because of the demand for higher throughput cellular analysis. In addition to drug discovery, the imaging capability of this flow cytometer will enable researchers to perform rare cell detection with higher precision than is currently available, and ultimately, in vitro hematology and oncology diagnostics using imaging flow cytometry. Finally, a high throughput flow cytometer with an order of magnitude greater throughput will dramatically reduce the time researchers spend in flow cytometry core facilities, ultimately enabling a general increase in biomedical research productivity.This SBIR Phase II project proposes to improve the efficiency of drug discovery by introducing a higher throughput, high content screening (HCS) instrument. HCS investigates the effects and associated mechanisms of action of therapeutic compounds by measuring multiple parameters from individual cells, typically using imaging. Although HCS has been highly effective in discovery new drugs, it, unfortunately, has significant throughput limitations. Namely, HCS requires data to be collected at the single cell level versus the population level. Typically, low-throughput readout techniques, such as flow cytometry and fluorescence imaging, are used to collect this data. This project aims to alleviate the speed limitations associated with imaging in drug discovery by introducing a high-throughput imaging flow cytometer capable of performing sub-cellular imaging at the speeds of traditional high throughput screening. The project leverages a high-speed fluorescence imaging modality based on frequency domain multiplexing, which was developed and demonstrated in Phase I, to provide market-leading imaging performance. Expanding this technology into a full flow cytometer by the end of Phase II, the goal is to have a 3-laser, 10-color imaging flow cytometer ready for researchers performing HCS as well as the general biomedical research community.