Generalized plasma skimming model for cells and drug carriers in the microvasculature

Abstract

In microvascular transport, where both blood and drug carriers are involved, plasma skimming has a key role on changing hematocrit level and drug carrier concentration in capillary beds after continuous vessel bifurcation in the microvasculature. While there have been numerous studies on modeling the plasma skimming of blood, previous works lacked in consideration of its interaction with drug carriers. In this paper, a generalized plasma skimming model is suggested to predict the redistributions of both the cells and drug carriers at each bifurcation. In order to examine its applicability, this new model was applied on a single bifurcation system to predict the redistribution of red blood cells and drug carriers. Furthermore, this model was tested at microvascular network level under different plasma skimming conditions for predicting the concentration of drug carriers. Based on these results, the applicability of this generalized plasma skimming model is fully discussed and future works along with the model's limitations are summarized.

Influence of feeding hematocrit and perfusion pressure on hematocrit reduction (Fåhræus effect) in an artificial microvascular network

“…The difference in V RBC between the two capillary microchannels of equivalent dimensions may be explained, in part, by the difference in branching order (see Figure ): Capillary 2 is a seventh‐order branch after the “arteriolar” inlet (7 divisions), and Capillary 3 is a fourth‐order branch (2 divisions and 2 confluences). Because of plasma skimming, the branch with the higher flow rate receives a disproportionately larger number of RBCs at every bifurcation in a capillary network . The effect of plasma skimming on vessel Hct accumulates with branching order, producing the network Fåhræus effect .…”

“…As plasma is creeping along vessel walls, capillary vessel branching leads to plasma skimming and alters the ratio of plasma to RBCs in the daughter vessels (phase separation effect), thus changing local Hct, which is sometimes called network Fåhræus effect . The degree of plasma skimming and subsequent Hct alteration depends on the angle of the bifurcation and the difference between the diameters of the daughter vessels …”

Effect of fractional blood flow on plasma skimming in the microvasculature

“…Interestingly, the plasma skimming is recently revisited to develop new microchannels for detecting specific DNAs, proteins and cells by efficiently separating plasma from whole blood [9][10][11]. Also, it has been highlighted to accurately predict drug carrier distribution in the microvasculature [12][13][14][15][16][17][18]. For utilizing the plasma skimming to new applications in vitro and in vivo, it is crucial to quantitatively predict the redistribution of RBCs and plasma at bifurcations.…”

“…Recently, for improving extensibility of plasma skimming model to various conditions in microvascular networks, Gould and Linninger [26] suggested a new model that can quantify the plasma skimming with a single parameter, M . Also, Lee et al [16] introduced a generalized version of plasma skimming model for cells and drug carriers.…”

“…A microvascular network model is computationally generated based on mathematical algorithms by choosing vessel diameter (d i ), vessel length (l i ), and bifurcation angles (θ i and φ i ) [16,31]. Diameters of daughter vessels at each bifurcation are governed by…”