Blood-Cell Separation in DLD Devices

Virtual testing of microfluidic deterministic-lateral-displacement designs for cell separation

Deterministic Lateral Displacement (DLD) Devices

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DLD is a continuous-flow passive particle separation technique relying on fluid motion on the micrometer scale, in which particles encounter an array of obstacles arranged in a specific geometry.

deterministic lateral displacement geometry
DLD Unit cell and description of free parameters

They have been applied with great efficiency in the separation of blood cells based on their size or on their shape and deformability [1,2], e.g. for platelets and WBC, or malaria RBCs. However, there is no silver bullet yet and each category of microdevices has to be designed and tested specifically for a specific purpose. The number of free parameters is large, ranging from the size and the shape of the obstacles to the flow-rate and the volume fractions used.

a) deterministic lateral displacement theta0 dp12
b) deterministic lateral displacement theta20 dp12
c) deterministic lateral displacement theta30 dp12
d) deterministic lateral displacement theta30 dp8
Snapshots and results from DLD simulations with respect to varying inclination angle $\theta$ and obstacle size $D_p$. Red particles represent RBCs and yellow platelets. Hematocrit $h=30%$. (a) $\theta=0$ and $D_p=12\mu\mathrm{m}$ (b) $\theta=20$ and $D_p=12\mu\mathrm{m}$ (c) $\theta=30$ and $D_p=12\mu\mathrm{m}$ (d) $\theta=30$ and $D_p=8\mu\mathrm{m}$. Figures on the right show the migration along the Y and Z directions against the average displacement in the X direction. Individual trajectories and mean migrations are plotted. Black guide-line has a slope of 1.0 and signifies that the migration along Y or Z is equal to the displacement along X.
deterministic lateral displacement cell migration efficiencey
Migration efficiency (defined as Ymig/Xmig) versus inclination angle $\theta$ for RBCs and platelets. There is no significant difference in efficiency for the obstacle sizes, as well as between RBCs and platelets. Angle $\theta=30$ is more effective in cell-separation from plasma. For the separation of RBCs and platelets a different technique should be employed, preferably exploiting platelet margination.

Platelet Margination

Platelet margination is the tendency of platelets to migrate towards the walls of an artery, due to their interactions with RBCs. Platelets aid in wound-healing and their enriched concentration close to the vessel walls increases their efficiency.

a) platelet margination b)
Snapshot of blood flow in a channel with $r=32\mu\mathrm{m}$ and $h=30%$. RBCs are transparent to make platelets more visible. View (a) from the side and (b) the front. RBCs migrate towards the center of the vessel while platelets are pushed towards the walls. The rate of platelet margination depends on a great number of parameters, like the hematocrit, the rigidity of RBCs, the flow rate and the size of the vessel.

Advanced filters

Advanced filters have been developed by Sarioglu et al. [3] to capture circulating tumor cell (CTC) clusters.

circulating tumor cells trap filter
Velocity flow field and particles representing CTCs. Triangle edge is $d=48\mu\mathrm{m}$ and maximum velocity $v_\mathrm{max}=120\mu\mathrm{ms}^{-1}$. The filtering principle is different than, e.g. slit-filters: CTCs are isolated exploiting their orientation in the flow and their binding strength when passing through the bifurcating traps under low shear-stresses. However, they are not blocking the plasma flux through the gaps.

Conclusions

Computer-aided design is a well grounded strategy for draft prototyping microfluidic devices. The use of validated blood models, fully resolving cell mechanics and interactions with blood plasma and other cells is of paramount importance in the prediction of blood cell separation processes. Traversing the parameter space and reaching a set of favorable solutions faster saves time and expenses.

References

  • [1] McGrath, J., Jimenez, M., Bridle, H., 2014. Deterministic lateral displacement for particle separation: a review. Lab Chip 14 (21), 4139-4158.
  • [2] Krüger, T., Holmes, D., Coveney, P. V., Sep. 2014. Deformability-based red blood cell separation in deterministic lateral displacement devices—A simulation study. Biomicrofluidics 8 (5), 054114+.
  • [3] Sarioglu, A. F. et al., Jul. 2015, A microfluidic device for label-free, physical capture of circulating tumor cell clusters. Nat Meth 12 (7), 685-691.
  • [4] L. Mountrakis, Transport of blood cells studied with fully resolved models, Ph.D. thesis, University of Amsterdam (2015)
  • [5] Lei, H., Karniadakis, G. E., 2012. Predicting the morphology of sickle red blood cells using coarse-grained models of intracellular aligned hemoglobin polymers. Soft Matter 8 (16), 4507-4516.