Microfluidic assay in idealized microvascular network for characterization of leukocyte adhesion cascade

A method for identifying one or more agents that modulate leukocyte rolling, adhesion, and/or migration, the method comprising:

• providing an optically transparent microfluidic chip comprising:
• one or more idealized flow channels having one or more inlets and one or more outlets and a first cross-sectional dimension;
• and
• one or more tissue spaces bordering and fluidly coupled with the one or more idealized flow channels and having a second cross-sectional dimension, wherein the one or more idealized flow channels define a perimeter of the one or more tissue spaces,
• wherein a first wall separating a first idealized flow channel from a first tissue space includes a plurality of apertures that fluidly couple the first idealized flow channel with the first tissue space, the plurality of apertures having a third cross-sectional dimension;
• flowing a suspension of leukocytes through the one or more idealized flow channels;
• flowing a solution containing one or more agents through the one or more idealized flow channels before, during, or after flowing the suspension of leukocytes;
• locating and counting leukocytes in the microfluidic chip;
• and
• based upon the locations and numbers of leukocytes, determining whether the one or more agents modulate leukocyte rolling, adhesion, and/or migration.

A method for identifying one or more agents that modulate leukocyte rolling, adhesion, and/or migration, the method comprising:

• providing an optically transparent microfluidic chip comprising:
• one or more idealized flow channels having one or more inlets and one or more outlets and a first cross-sectional dimension;
• and
• one or more tissue spaces bordering and fluidly coupled with the one or more idealized flow channels and having a second cross-sectional dimension, wherein the one or more idealized flow channels and the one or more tissue spaces are planar,
• wherein a first wall separating a first idealized flow channel from a first tissue space includes a plurality of apertures that fluidly couple the first idealized flow channel with the first tissue space, the plurality of apertures having a third cross-sectional dimension;
• flowing a suspension of leukocytes through the one or more idealized flow channels;
• flowing a solution containing one or more agents through the one or more idealized flow channels before, during, or after flowing the suspension of leukocytes;
• locating and counting leukocytes in the microfluidic chip;
• and
• based upon the locations and numbers of leukocytes, determining whether the one or more agents modulate leukocyte rolling, adhesion, and/or migration.

A method for identifying one or more agents that modulate leukocyte rolling, adhesion, and/or migration, the method comprising:

• providing an optically transparent microfluidic chip comprising:
• one or more idealized flow channels having one or more inlets and one or more outlets and a first cross-sectional dimension;
• and
• one or more tissue spaces bordering and fluidly coupled with the one or more idealized flow channels and having a second cross-sectional dimension, wherein luminal surfaces of the one or more idealized flow channels are coated with a first cell type and the one or more tissue spaces are either devoid of cells or include a different second type of cell,
• wherein a first wall separating a first idealized flow channel from a first tissue space includes a plurality of apertures that fluidly couple the first idealized flow channel with the first tissue space, the plurality of apertures having a third cross-sectional dimension;
• flowing a suspension of leukocytes through the one or more idealized flow channels;
• flowing a solution containing one or more agents through the one or more idealized flow channels before, during, or after flowing the suspension of leukocytes;
• locating and counting leukocytes in the microfluidic chip;
• and
• based upon the locations and numbers of leukocytes, determining whether the one or more agents modulate leukocyte rolling, adhesion, and/or migration.