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Research Focus:

Microfluidic processing of cryopreserved blood suspensions for infusion into patients

Over the past two years, Professor Ellen Longmire and Professor Allison Hubel (ME), an expert in cell cryopreservation, have been developing methods for processing suspensions of blood cells needed for transplantation after receiving grants from the National Blood Foundation and the National Institutes of Health. The transplantation of blood-derived stem cells has been used for decades to treat a variety of diseases and disorders including leukemia, malignant tumors, and immunodeficiencies, and the list of possible uses for these cells is growing continuously. Historically, the cells have been collected from adult donors, but the use of cells from umbilical cord blood is rapidly increasing. Cord blood is easy to collect (with no risk to the donors), and requires less-strict matching between the donor and recipient. This blood is also rich in stem cells. Adult and cord blood sources are cryopreserved (frozen) and stored until they are needed.
In conventional cryopreservation methods, dimethyl sulfoxide (DMSO) is added to the blood suspension to prevent cell loss from shrinkage during freezing. However, DMSO is a toxic compound that causes significant adverse reactions in patients. Therefore, it must be removed from the cell suspension before patient infusion. DMSO is currently removed from graft suspensions using centrifugation, typically resulting in a 25-30% cell loss. Since the available sample volume is often small at the start, this loss adversely affects the success of transplantations.
The current research focuses on developing a microfluidic device capable of removing DMSO from a cryopreserved cell suspension while minimizing cell losses. The device, an enclosed channel with depth ~500 microns, operates in a laminar regime permitting diffusion-based extraction of the DMSO from the cell suspension into a neighboring, parallel-flowing wash stream. The laminar flow prevents the cells from spreading into the wash stream and also precludes strong shearing and straining forces that occur in centrifuges. At the downstream end of the channel, the wash stream and DMSO-depleted cell stream exit through opposing outlets. Thus far, numerical simulations of model flows have been used to determine scaling effects and design experimental prototypes that are fabricated under the direction of Dave Hultman. The simulations predict that a device incorporating two wash stages in series can match the DMSO-removal performance of centrifugation and that the stages can also be designed with reasonable but sufficient spanwise dimensions to process clinical volumes of cell suspensions in the required time frame. Preliminary experiments on DMSO solutions and DMSO-containing suspensions of Jurkat cells yield concentration results that match closely with those predicted numerically. Also, experiments on prototypes have demonstrated a very high capture rate of viable cells (>90%) at device outlets. Ongoing research is aimed at determining parametric limits related to device performance and the physical causes of these limits, demonstrating device scale-up, and testing device performance on samples of umbilical cord blood. On an applied level, the development of methods to improve cell processing efficiency will directly facilitate the use of blood-related cell-based therapies for the treatment of disease.
Moreover, these studies are enhancing our fundamental understanding of cell flow through microfluidic devices. We expect that this understanding will lead to improved methods for controlling the motion of and processing of additional cell types.