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Nanoparticle diffusion in sheared cellular blood flow

Published online by Cambridge University Press:  24 May 2019

Zixiang Liu
Affiliation:
George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA
Jonathan R. Clausen
Affiliation:
Sandia National Laboratories, Albuquerque, NM 87185, USA
Rekha R. Rao
Affiliation:
Sandia National Laboratories, Albuquerque, NM 87185, USA
Cyrus K. Aidun*
Affiliation:
George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USAParker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332, USA
*
†Email address for correspondence: cyrus.aidun@me.gatech.edu

Abstract

Using a multiscale blood flow solver, the complete diffusion tensor of nanoparticles (NPs) in sheared cellular blood flow is calculated over a wide range of shear rate and haematocrit. In the short-time regime, NPs exhibit anomalous dispersive behaviors under high shear and high haematocrit due to the transient elongation and alignment of the red blood cells (RBCs). In the long-time regime, the NP diffusion tensor features high anisotropy. Particularly, there exists a critical shear rate (${\sim}100~\text{s}^{-1}$) around which the shear-rate dependence of the diffusivity tensor changes from linear to nonlinear scale. Above the critical shear rate, the cross-stream diffusivity terms vary sublinearly with shear rate, while the longitudinal term varies superlinearly. The dependence on haematocrit is linear in general except at high shear rates, where a sublinear scale is found for the vorticity term and a quadratic scale for the longitudinal term. Through analysis of the suspension microstructure and numerical experiments, the nonlinear haemorheological dependence of the NP diffusion tensor is attributed to the streamwise elongation and cross-stream contraction of RBCs under high shear, quantified by a capillary number. The RBC size is shown to be the characteristic length scale affecting the RBC-enhanced shear-induced diffusion (RESID), while the NP submicrometre size exhibits negligible influence on the RESID. Based on the observed scaling behaviours, empirical correlations are proposed to bridge the NP diffusion tensor to specific shear rate and haematocrit. The characterized NP diffusion tensor provides a constitutive relation that can lead to more effective continuum models to tackle large-scale NP biotransport applications.

Information

Type
JFM Papers
Copyright
© 2019 Cambridge University Press 
Figure 0

Figure 1.(a) The RBC–NP bidisperse suspension in a triply periodic domain at shear rate $\dot{\unicode[STIX]{x1D6FE}}=1000~\text{s}^{-1}$ and haematocrit $\unicode[STIX]{x1D719}=40\,\%$. (b) The RBC membrane immersed in the LB lattice domain. The RBC membrane dynamics and deformation are captured by the course-grained spectrin-link method (Pivkin & Karniadakis 2008; Fedosov et al.2010; Reasor et al.2012). (c) The NP suspension dynamics is captured by the LB-LD method (Liu et al.2018, 2019), which captures the NP Brownian motion and long-range HI in an off-lattice fashion.

Figure 1

Table 1.Simulation data. Each case is simulated independently in an LB domain of size $128\times 128\times 80$ at specified $Pe$, $Ca_{G}$ and $\unicode[STIX]{x1D719}$. NP long-time diffusivities, $\unicode[STIX]{x1D60B}_{xx}^{\infty }$, $\unicode[STIX]{x1D60B}_{yy}^{\infty }$, $\unicode[STIX]{x1D60B}_{zz}^{\infty }$ and $\unicode[STIX]{x1D60B}_{xy}^{\infty }$, normalized by the theoretical Brownian diffusivity, $\unicode[STIX]{x1D60B}^{B}$, are listed for all cases. The unlisted off-diagonal diffusivities, $\unicode[STIX]{x1D60B}_{xz}^{\infty }$ and $\unicode[STIX]{x1D60B}_{yz}^{\infty }$, are found to be negligible. The measured diffusivities have a standard deviation less than 5$\,\%$. RBCs have an effective radius of $a_{2}=2.9~\unicode[STIX]{x03BC}\text{m}$. Brownian diffusivity is calculated by $\unicode[STIX]{x1D60B}^{B}=k_{B}T/6\unicode[STIX]{x1D707}\unicode[STIX]{x03C0}a_{1}$ at temperature $T=310$ K.

Figure 2

Figure 2.(a) The RBC–NP complex configuration at $t\dot{\unicode[STIX]{x1D6FE}}=0$. NPs and RBCs are randomly and uniformly mixed in an unbounded shear flow. RBCs are shown partially in the domain to visualize the NP phase. The athermal system is determined by shear rate $\dot{\unicode[STIX]{x1D6FE}}$, haematocrit $\unicode[STIX]{x1D719}$ and NP radius $a_{1}$. (b–f) The RBC–NP complex configuration in the long-time scale regime under a shear rate of (b) $\dot{\unicode[STIX]{x1D6FE}}=10$, (c) 100, (d) 1000, (e) 2000 and (f) $10\,000~\text{s}^{-1}$ with $\unicode[STIX]{x1D719}=0.4$.

Figure 3

Figure 3.Normalized MSDs plotted against relative shear strains in logarithmic scale at various haematocrits for different shear rates. Panels (a)–(d) are concerned with evolutions of $\langle y(t)y(t)\rangle /a_{1}^{2}$; (e) and (f) depict evolutions of $\langle x(t)x(t)\rangle /a_{1}^{2}$ and $|\langle x(t)y(t)\rangle |/a_{1}^{2}$, respectively; (g) and (h) depict evolutions of $\langle z(t)z(t)\rangle /a_{1}^{2}$. The imposed shear rate is denoted on each plot. Inset of (b) shows the RBC–NP distribution at $t\dot{\unicode[STIX]{x1D6FE}}\sim 1$ under $\dot{\unicode[STIX]{x1D6FE}}=100~\text{s}^{-1}$. Insets of (c) show the RBC–NP distribution at $t\dot{\unicode[STIX]{x1D6FE}}\sim 1$ (upper) and $t\dot{\unicode[STIX]{x1D6FE}}\sim 100$ (lower) under $\dot{\unicode[STIX]{x1D6FE}}=2000~\text{s}^{-1}$ and $\unicode[STIX]{x1D719}=0.4$. An NP radius of $a_{1}=50$  nm is used for normalization. Cross-stream MSDs (a–d) and (g,h) are sampled starting from $t\dot{\unicode[STIX]{x1D6FE}}=0$ to capture the transient NP dispersive behaviour; streamwise and off-diagonal MSDs are sampled starting from $t\dot{\unicode[STIX]{x1D6FE}}=400$ to avoid the initial extra affine displacement induced by RBC elongation and orientation.

Figure 4

Figure 4.RBC–NP partial pair distribution function, $g_{21}(\boldsymbol{r})$, projected on the $xy$ plane under various haemorheological conditions and averaged in the strain range of $t\dot{\unicode[STIX]{x1D6FE}}=1{-}3$.

Figure 5

Figure 5.Normalized particle long-time RESID in (a) $xx$, (b) $yy$, (c) $zz$ and (d) $xy$ directions against normalized shear rate ($Pe$ or $Ca_{G}$) in a log–log scale. Each curve at specific $\unicode[STIX]{x1D719}$ forms by connecting $\hat{\unicode[STIX]{x1D60B}}_{ij}^{R}$ data at shear rate $\dot{\unicode[STIX]{x1D6FE}}=10$, 30, 100, 300, 1000, 2000 and $10\,000~\text{s}^{-1}$, from left to right; $\hat{\unicode[STIX]{x1D60B}}_{xy}^{R}$ at $\dot{\unicode[STIX]{x1D6FE}}=10~\text{s}^{-1}$ is not shown for scaling purpose due to its small magnitude. Experimental results for RBC enhanced solute (Diller, Mikic & Drinker 1980; Wang & Keller 1985) and platelet (Grabowski, Friedman & Leonard 1972; Antonini et al.1978) diffusivity in the velocity-gradient ($yy$) direction are plotted for comparison. NPs of size $2a_{1}=100~\text{nm}$ yield $\unicode[STIX]{x1D60B}^{B}=3.78~\unicode[STIX]{x03BC}\text{m}^{2}~\text{s}^{-1}$.

Figure 6

Figure 6.Normalized particle long-time RESID in (a) $xx$, (b) $yy$, (c) $zz$ and (d) $xy$ directions against haematocrit under different shear rate in logarithm scale. Lines are the best power-law fits to the data points at specific $\dot{\unicode[STIX]{x1D6FE}}$. The $\hat{\unicode[STIX]{x1D60B}}_{xy}^{R}$ value at $\dot{\unicode[STIX]{x1D6FE}}=10~\text{s}^{-1}$ (not shown) is positive with negligible magnitude compared to other diffusion terms. NPs of size $2a_{1}=100~\text{nm}$ yield $\unicode[STIX]{x1D60B}^{B}=3.78~\unicode[STIX]{x03BC}\text{m}^{2}~\text{s}^{-1}$.

Figure 7

Figure 7.RBC–NP partial pair distribution function, $g_{21}(\boldsymbol{r})$, projected onto the $xy$, $xz$ and $yz$ planes in the long-time regime under various haemorheological conditions, where the PPDF contour has the horizontal edge aligned with the first axis (e.g. $xy$ PPDF contour has the horizontal edge aligned with the $x$ axis). The edge length of the sampling box for computing $g_{21}(\boldsymbol{r})$ is three times the maximum diameter of the undeformed RBC.

Figure 8

Figure 8.The $Pe$ dependence of the (a) diagonal and (b) off-diagonal RESID terms at fixed capillary number (by rescaling $G$) with $\unicode[STIX]{x1D719}=0.4$. Two RBC capillary numbers, $Ca_{G}=0.55$ and $0.055$, are considered to see the isolated effect of changing RBC deformability ($Ca_{G}$) or adjusting the inertial effect ($Pe$).

Figure 9

Table 2.Simulation data for numerical experiments concerning the isolated RBC deformation effect in NP–RBC suspensions. The RBC membrane shear modulus, $G$, is rescaled to numerically match specific $Ca_{G}$ while changing shear rate. Here, the NP size is fixed to $2a_{1}=100~\text{nm}$; RBC has an effective radius of $a_{2}=2.9~\unicode[STIX]{x03BC}\text{m}$. Brownian diffusivity is calculated by $\unicode[STIX]{x1D60B}^{B}=k_{B}T/6\unicode[STIX]{x1D707}\unicode[STIX]{x03C0}a_{1}$ at a temperature of $T=310$  K.

Figure 10

Figure 9.RESID plotted against (a) Péclet number $Pe$ and (b) the rescaled Péclet number $\widetilde{Pe}$, at $\dot{\unicode[STIX]{x1D6FE}}=1000~\text{s}^{-1}$ and $\unicode[STIX]{x1D719}=0.2$ in logarithmic scales. Both $Pe$ and $\widetilde{Pe}$ are adjusted with NP size in the range of $2a_{1}=50{-}800~\text{nm}$. (c) Linear dependence of RESID on $\widetilde{Pe}$ at fixed $Ca_{G}=0.55$ and $\unicode[STIX]{x1D719}=0.2$; $\widetilde{Pe}$ is adjusted by shear rate (with $2a_{1}=100~\text{nm}$) or NP size (with $\dot{\unicode[STIX]{x1D6FE}}=1000~\text{s}^{-1}$). The diffusion tensor in monodisperse colloidal suspensions (Foss & Brady 1999) is also plotted for comparison, where $\widetilde{Pe}$ degrades to $Pe$.

Figure 11

Table 3.Simulation data for numerical experiments concerning the relevant length scale in NP–RBC suspensions. NP size is varied in the range of $2a_{1}=50{-}800~\text{nm}$. RBC has an effective radius of $a_{2}=2.9~\unicode[STIX]{x03BC}\text{m}$. Brownian diffusivity is calculated by $\unicode[STIX]{x1D60B}^{B}=k_{B}T/6\unicode[STIX]{x1D707}\unicode[STIX]{x03C0}a_{1}$ at temperature $T=310$  K. For the $800~\text{nm}$ case, the number of NPs is set to 500 to satisfy the dilute condition for the NP volume fraction. The last three cases are performed with adjusted $G$ to fix $Ca_{G}$.

Figure 12

Figure 10.RBC and NP distributions and morphology in the cross-stream plane ($y$–$z$) with (a) $Ca_{G}=0.055$, (b) $Ca_{G}=0.55$ and (c) $Ca_{G}=1.1$ at $Pe=0.066$ and $\unicode[STIX]{x1D719}=0.4$. Large non-circular disks are RBC cross-sectional contours. Small circles are NP cross-sectional contours. The $\bar{a}_{2,yz}$ value can be estimated from the PPDF analysis.

Figure 13

Figure 11.Measured NP RESID, $\unicode[STIX]{x1D60B}_{ij}^{(R,m)}=\unicode[STIX]{x1D60B}_{ij}^{\infty }-\unicode[STIX]{x1D60B}^{B}\unicode[STIX]{x1D6FF}_{ij}$, as a function of the theoretical RESID, $\unicode[STIX]{x1D60B}_{ij}^{(R,th)}=\unicode[STIX]{x1D719}\dot{\unicode[STIX]{x1D6FE}}a_{2}^{2}\unicode[STIX]{x1D614}_{ij}^{q}$, based on the empirical correlations presented in equations (3.6a) and (3.6b). For cases with $\dot{\unicode[STIX]{x1D6FE}}\leqslant 100~\text{s}^{-1}$ (filled symbols), $\unicode[STIX]{x1D614}_{ij}^{l}$ is applied to calculate $\unicode[STIX]{x1D60B}_{ij}^{(R,th)}$. For cases with $\dot{\unicode[STIX]{x1D6FE}}>100~\text{s}^{-1}$ (open symbols), $\unicode[STIX]{x1D614}_{ij}^{h}$ is applied to calculate $\unicode[STIX]{x1D60B}_{ij}^{(R,th)}$.

Figure 14

Table 4.Correlation constants for the empirical correlations of NP diffusion tensor in sheared cellular blood flow.

Figure 15

Figure 12.(a) NP long-time diffusivities in the cross-stream directions plotted against the relative variation of the Morse potential well depth (a) and equilibrium distance (b).

Liu Supplementary Movie 1

Instantaneous NP-RBC distribution under unbounded simple shear flow at 100 s-1 shear rate and 40% RBC concentration. Views on the left column show all the NPs and RBCs. Views on the right column show only a few RBCs so as to visualize the NP phase and the single RBC morphology.

Download Liu Supplementary Movie 1(Video)
Video 10.4 MB

Liu Supplementary Movie 2

Instantaneous NP-RBC distribution under unbounded simple shear flow at 2000 s-1 shear rate and 40% RBC concentration. Views on the left column show all the NPs and RBCs. Views on the right column show only a few RBCs so as to visualize the NP phase and the single RBC morphology.

Download Liu Supplementary Movie 2(Video)
Video 10.6 MB