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NRL Patents Laser-Based Technology for Autonomous Separation and Characterization of Cells

Dept. of Defense

Inspired by the need for sensitive, selective, automated and cost-effective clinical and research instruments that can sort cell streams for the detection of pathogens and disease, the U.S. Naval Research Laboratory (NRL) has patented a laser-based microfluidic device to help researchers characterize and sort individual cells by measuring their optical force.

The device uses a fluid flow to drive particulate samples through a network of flowing channels. Laser light is then introduced to interact with the particles and reveal optical force by way of radiation pressure.

“This force, when balanced against the fluidic ‘drag’ on the particles, results in changes to the particle’s velocity,” said Dr. Greg Collins, head of the Chemical Dynamics and Diagnostics Branch. “This can be used to identify differing particles or changes within populations of particles based on intrinsic differences in cell biochemistry, morphology and deformability.”

According to Collins, laser separation is achieved when particles transported by laminar flow within a micron-sized channel encounter a highly focused laser beam directed in the opposite direction. These particles are exposed to optical pressure near the beam focal point, i.e., the region of highest photon density, which is intense enough to impart momentum sufficient to overcome the fluid drag force. The result is that particles become trapped, or have their velocities altered, within the fluid flow until the beam diverges and the photon density decreases.

“Using this laser technique, scientists are able to exploit the inherent differences in optical pressure, which arise from variations in particle size, shape, refractive index, or morphology as a means of separating and characterizing particles,” said Collins. “When samples are optically retained within the system, squeezed between the fluid flow and the retaining laser force, the extent to which they are retained, deformed, or ‘squished,’ by the force of the laser and the fluid flow is related to their composition and biomechanical structure.”

Biological cells are affected by diseases, such as cancer, with potential changes in the fibrous proteins (cytoskeleton) that govern the shape and movement of a biological cell. Red blood cells (erythrocytes) undergo age-dependent stretching and compression, with older erythrocytes being less flexible. The potential for the analysis of disease states in biological systems, including cells and small tissue samples, is substantial and wide-ranging.

Under license #NRL-LIC-13-5-284, LumaCyte, LLC, has commercialized the technology to launch its revolutionary apparatus Radiance™, which allows users to identify new or changed cell phenotypes in the absence of antibody based labeling—a costly, time-consuming process that requires prior sample knowledge and may activate cells, which can lead to erroneous conclusions.

Radiance can, for example, detect and measure viral infection in mammalian cells quickly and effectively for diagnostic purposes and vaccine manufacturing, making this LumaCyte’s initial target market. The gold standard viral plaque assay and component-based methods generally take between 5 to 15 days. Radiance can typically accomplish this measurement in 1 to 2 days or less with high quality data and reduced variability, while simultaneously reducing labor and cost.

The technology is not limited to virology and can be applied in many R&D areas, including cancer, induced pluripotent stem cells, cell clearance, and drug development.

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