View source for Acoustic and Inertial Flow Cytometry: Pathways to point-of-care and high-speed parallel cellular diagnostics

Flow cytometry is widely used to detect the levels of specific blood cell types to diagnose and monitor many critical diseases ranging from leukemia to AIDS. Furthermore, there is a growing desire to use flow cytometry to detect and monitor truly rare cell populations such as Circulating Tumor Cells (CTCs) for clinical applications. Despite these important uses for flow cytometers in the clinic, they have not been widely used in resource poor areas of the world or for clinical analysis or very rare cell populations due in part to the size, expense, operational requirements, and analytical rate of an individual flow cytometer. Here we will present our work to develop synergistic technologies that dramatically reduce the cost, size, and operational requirements of an individual flow cytometer, while simultaneously enabling highly parallel flow cytometry analysis of multiple flow streams to dramatically increase analytical throughput. Specifically, we will present the development of both acoustic and inertial focusing flow chambers that both concentrate and precisely position cells and particles for analysis, which enables high particle analysis rates at reduced linear velocities. Building on this, we will present data on several prototype flow cytometers that use these flow cells in combination with laser-pointer grade lasers, simple microcontroller data systems, and inexpensive photodiode detectors to perform sheathless analysis of cellular immunophenotyping assays with nearly identical performance as a typical cytometer but at a fraction of the cost. Additionally, as both acoustic and inertial focusing can be implemented in highly parallel fashion, we will demonstrate the development of flow channels that use highly parallel flow streams that will enable parallel application of our inexpensive light sources, detectors, and data systems to increase the analytical rate of a single affordable integrated flow cytometer into the millions of cells per second regime.  Finally, the clear implications of these technical developments will be discussed in regards to both point of care diagnostics in resource poor areas of the world and the application of flow cytometry for rare cell diagnostics.