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Published on: May 1, 2018
Numerical characterization of diffusion-based extraction in cell-laden flow through a microfluidic channel
K K Fleming1, E K Longmire, A Hubel
1Department of Mechanical Engineering, University of Minnesota, 1100 Mechanical Engineering, 111 Church Street, Minneapolis, Minnesota 55455, USA.
Abstract:
Cells are routinely cryopreserved in dimethyl sulfoxide (DMSO), a cryoprotective agent, for medical applications. Infusion of a DMSO-laden cell suspension results in adverse patient reactions, but current DMSO extraction processes result in significant cell losses. A diffusion-based numerical model was employed to characterize DMSO extraction in fully developed channel flow containing a wash stream flowing parallel to a DMSO-laden cell suspension. DMSO was allowed to diffuse across cell membranes as well as across the channel depth. A variety of cases were considered with the ultimate goal of characterizing the optimal geometry and flow conditions to process clinical volumes of cell suspension in a reasonable time (2-3 ml/min). The results were dependent on four dimensionless parameters: depth fraction of the DMSO-laden stream, Peclet number, cell volume fraction in the DMSO-laden stream, and cell membrane permeability parameter. Smaller depth fractions led to faster DMSO extraction but channel widths that were not practical. Higher Peclet numbers led to longer channels but smaller widths. For the Peclet values and channel depths considered (>or=500 microm) and appropriate permeability values, diffusion across cell membranes was significantly faster than diffusion across the channel depth. Cell volume fraction influenced the cross-stream diffusion of DMSO by limiting the fluid volume fraction available in the contaminant stream but did not play a significant role in channel geometry or operating requirements. The model was validated against preliminary experiments in which DMSO was extracted from suspensions of B-lymphoblast cells. The model results suggest that a channel device with practical dimensions can remove a sufficient level of contaminant within a mesoscale volume of cells in the required time.
Insights
Dimethyl sulfoxide (DMSO) removal from cell suspensions is crucial for medical applications. This study developed a numerical model to optimize DMSO extraction, ensuring patient safety and minimizing cell loss during cryopreservation processes.
Area of Science:
- Biomedical Engineering
- Cell Biology
- Chemical Engineering
Background:
- Cryopreservation of cells for medical use relies on dimethyl sulfoxide (DMSO).
- Infusing DMSO-laden cell suspensions causes adverse patient reactions.
- Existing DMSO extraction methods lead to substantial cell loss.
Purpose of the Study:
- To develop and validate a numerical model for characterizing DMSO extraction from cell suspensions.
- To identify optimal channel geometry and flow conditions for efficient DMSO removal.
- To enable processing of clinical cell volumes at rates of 2-3 ml/min.
Main Methods:
- A diffusion-based numerical model was employed to simulate DMSO extraction.
- The model considered DMSO diffusion across cell membranes and channel depth.
- Simulations analyzed various dimensionless parameters including Peclet number and cell membrane permeability.
Main Results:
- DMSO extraction efficiency is dependent on channel depth fraction, Peclet number, cell volume fraction, and membrane permeability.
- Diffusion across cell membranes was faster than across channel depth for relevant parameters.
- A channel device with practical dimensions can effectively remove DMSO from mesoscale cell volumes.
Conclusions:
- The numerical model provides a framework for optimizing DMSO extraction devices.
- Practical channel dimensions and flow conditions can achieve efficient contaminant removal.
- This research supports safer medical applications of cryopreserved cells by addressing DMSO toxicity concerns.
