Microfluidic device for rapid investigation of the deformability of leukocytes in whole blood samples

Abstract

The mechanical properties of cells, such as leukocytes, in a diseased state differ from those of healthy cells, typically due to their microstructure. The deformability of the cells through a constrictive area is analyzed by the applied stress to the cell. This study investigates the relationship between the sample flow speed and distribution of captured leukocytes based on the cell deformability using a microfluidic device. The device comprises of microfilters that serve as the filtration mechanism. The microfilter gap size gradually decreases from 15 to 3 µm to facilitate the deformability-based separation. Leukocytes have various sizes; hence, they can be separated by microfilters directly from whole blood samples without any cell clogging, and they do not require sample pre-processing such as centrifugation or red blood cell lysis. The distribution of leukocytes captured by the microfilters with respect to the sample flow speed can be analyzed; at higher sample flow speeds of 6 µL/min, small leukocytes with a size of 7 µm could not be captured and they passed through the smallest microfilter gap size of 3 µm. For smaller leukocytes, such as lymphocytes, the distributions are mainly at gap sizes of 4 µm to 8 µm, with most of the lymphocytes captured at the 6 µm microfilter gap size. We conclude that the distribution of the cells captured during the filtration varies depending on the microfilter gap sizes, applied sample flow speed, cell sizes, and the ability of the cells to deform. The deformability imaging profiles of the sample could be developed from the images of the cell distribution, which might be useful for preliminary screening in the clinical applications. This work presents the development of a simple device for the study of cell deformability as the results provide a biophysical marker in high throughput and bulk sample analyses.