Microfluidic chip device for optical force measurements and cell imaging using microfluidic chip configuration and dynamics

Abstract

Provided are methods and devices for assessing biological particles for use in cell immunotherapy. By utilizing a microfluidic chip device together with optical force measurement and cell imaging, the methods enable comprehensive assessment and characterization of biological particles with regard to morphology, motility, binding affinities, and susceptibility to external forces, including but not limited to, chemical, biochemical, biological, physical and temperature influences. The methods enable the selection and production of biological particles, such as engineered T-cells, for use in immunotherapy and biomanufacturing.

1 . A method for assessing biological particles for use in cell immunotherapy, comprising the use of a device wherein the device comprises:
 substrate comprising a plurality of channels configured to transport one or more biological particles, wherein the plurality of channels comprises:
 a first channel disposed vertically within the substrate, 
 a second channel in operable communication with the first channel and disposed horizontally within the substrate, 
 a third channel in operable communication with the second channel and disposed vertically within the substrate, and 
 a fourth channel in operable communication with the third channel and disposed horizontally within the substrate; 
   wherein the first, second, third and fourth channels are disposed in such a manner as to provide a path for movement of the one or more biological particles through the substrate from the first channel to the second channel to the third channel to the fourth channel,   wherein the biological particles may comprise engineered T-cells, including CAR T cells,   wherein assessing the biological particles may comprise the characterization of T-cell receptors, regulatory T-cells, allogeneic T-cells, bionic T-cells,   wherein the assessment may yield information pertaining to morphology, motility, binding affinities, binding profiles, effect on other biological particles, effect on target cells, susceptibility to external forces such as biological, biochemical, chemical, physical, and temperature influences,   and wherein the information yielded by such an assessment is relevant for developing clinically effective immunotherapy through optimized biomanufacturing.