Experimental study of diffusion-based extraction from a cell suspension

Abstract

A recently proposed application of microfluidics is the post-thaw processing of biological cells. Numerical simulations suggest that diffusion-based extraction of the cryoprotective agent dimethyl sulfoxide (DMSO) from blood cells is viable and more efficient than centrifugation, the conventional method of DMSO removal. In order to validate the theoretical model used in these simulations, a prototype was built and the flow of two parallel streams, a suspension of Jurkat cells containing DMSO and a wash stream that contained neither cells nor DMSO, was characterized experimentally. DMSO transport in a rectangular channel (depth 500 lm, width 25 mm and overall length 125 mm) was studied as a function of three dimensionless parameters: depth ratio of the streams, cell volume fraction in the cell solution, and the Peclet number (Pe) based on channel depth, average flow rate and the diffusion coefficient for DMSO in water. In our studies, values of Pe ranged from O(10 3 ) to O(10 4 ). Laminar flow was ensured by keeping the Reynolds number between O(1) and O(10). Experimental results based on visual and quantitative data demonstrate conclusively that a microfluidic device can effectively remove DMSO from liquid and cell laden streams without compromising cell recovery. Also, flow conditions in the microfluidic device appear to have no adverse effect on cell viability at the outlet. Further, the results demonstrate that we can predict the amount of DMSO removed from a given device with the theoretical model mentioned previously.

Selectively modified microfluidic chip for solvent extraction of Radix Salvia Miltiorrhiza using three-phase laminar flow to provide double liquid–liquid interface area

“…Laminar flow is a well-known phenomenon in microfluidic chips and has extensive applications (Sia and Whitesides 2003;Mu et al 2009a). Laminar flow extraction usually depends on the diffusion and repartitioning of specific molecule between two immiscible and parallel streams (Tokeshi et al 2000;Hisamoto et al 2001;Hibara et al 2002;Maruyama et al 2004;Aota et al 2007;Aota et al 2009;Mata et al 2008). In micrometer dimension, interface area between water and organic streams is relatively large, and diffusion distance is rather short.…”

A numerical study on distributions during cryoprotectant loading caused by laminar flow in a microchannel

“…Modeling discrete cells using Lagrangian particle tracking could be of use in device design as well, where cell separation and recovery is dependent on channel geometry and operating conditions. [30][31][32]36 The simulations presented herein also include the effect of a parabolic velocity profile in three dimensions that the cells are initially evenly distributed across. Ramifications of this inclusion are two-fold: (1) all cells do not have the same residence time, and (2) all cells do not experience the same external CPA concentration throughout their residence time.…”

Assessment of Cryoprotectant Concentration by Electrical Conductivity Measurement and Its Applications in Cryopreservation

“…These problems prevent dialysis method from being an effective and reliable approach for CPA removal. Recently, Hubel et al developed a method based on mass diffusion in microfluidic flows for CPA removal [21,22]. However, therein the mass transfer rate is low since passive diffusion due to concentration gradient is the driving force for mass transfer.…”