Abstract
An important step in diagnostics is the isolation of specific cells and microorganisms of interest from blood. Since such bioparticles are often present at very low concentrations, throughput needs to be as high as possible. In addition, to ensure simplicity, a minimum of sample preparation is important. Therefore, sorting schemes that function for whole blood are highly desirable. Deterministic lateral displacement (DLD) has proven to be very precise and versatile in terms of a wide range of sorting parameters. To better understand how DLD performs for blood as the hematocrit increases, we have performed measurements and simulations for spherical particles in the micrometer range moving through DLD arrays for different flow velocities and hematocrits ranging from pure buffer to whole blood. We find that the separation function of the DLD array is sustained, even though blood cells introduce a shift in the trajectories and a significant dispersion for particles that are close to the critical size in the device. Simulations qualitatively replicate our experimental observations and help us identify fundamental mechanisms for the effect of hematocrit on the performance of the DLD device.
Highlights
Blood analysis is an important procedure in biomedicine
We find that the separation function of the Deterministic lateral displacement (DLD) array is sustained even though the blood cells introduce a shift in the trajectories and a significant dispersion for particles whose diameters are close to the critical size in the device
Our results show that particles within an red blood cell (RBC) suspension encounter numerous collisions with the crowding RBCs, which can be roughly divided into two classes on the basis of the corresponding effect on the particle’s movement
Summary
Blood analysis is an important procedure in biomedicine. As the blood sample drawn from a patient usually contains a plethora of biological markers, ranging from electrolytes, signaling molecules, proteins, and nucleic acids to viruses, cells, and microorganisms, an efficient sorting must be accomplished to minimize the confounding effects of irrelevant cells or to enrich the bioparticles of interest for early and accurate blood diagnosis. Successful and reliable separation of particles from whole blood has only been achieved for large cells, such as WBCs [34,35] and circulating tumor cells (CTCs) [36,37,38,39] This is possible because the targeted cells are significantly larger than RBCs, which do not appear to strongly disturb the trajectories of WBCs and CTCs. for smaller cells and microorganisms (e.g., bacteria) in blood, the concern remains that nondeterministic interactions between them and RBCs will affect their trajectories and have deleterious effects on sorting. We perform a combined experimental and simulation study to elucidate the physical mechanisms of particle behavior in concentrated erythrocyte suspensions and the effect of hematocrit on the sorting efficiency of DLD devices. This study provides an understanding of the mechanisms, which govern the dispersion effect of hematocrit on particle sorting, and quantifies the performance of DLD devices for particle isolation from concentrated RBC suspensions
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