Our Research

BioCor offers service, research, and education resources described below. Ask the BioCoR expert if you have questions about preservation. Check out BioCoR's online library for resources related to preservation.

Research Project 1:
A Window into the Frozen Cell

Advancing our understanding of cell damage during freezing involves observing and quantifying the response of a cell to freezing. Early studies used low temperature light microscopy to characterize biophysical changes during freezing to characterize freezing response.  Raman spectroscopy is a powerful imaging technique that has become very instrumental in our understanding of the response of the cell to freezing environment. The spatial resolution of Raman (~300 nm) permits us to image single cells during freezing and even subcellular structures in side the cell (nucleus, mitochondria, etc.). Raman Spectroscopy of cells in in the frozen state demonstrated distinct differences in cell response when cells are frozen in different solutions. These studies help us understand the specific changes that happen when a cell is frozen in the specialized solutions used for cell preservation. 6 We continue to expand the power of Raman spectroscopy for imaging cells during freezing.

Publications from BioCoR faculty in this area:
Dong JP, Malsam J, Bischof JC, Hubel A and Aksan A. “Spatial distribution of the state of water in frozen mammalian cells,” Biophys. J, 99: 2453-2459, 2010.

Dong JP, Hubel A, Bischof JC and Aksan A. “Freeze-Induced phase separation and spatial microheterogeneity in protein solutions,” J. Phys Chem B, 113(30): 10081-10087, 2009.

Research Project 2:
Preservation of stem cells for clinical use

Published on: Tuesday 12, August 2014
Author: BioCoR

Mesenchymal stem cells (MSCs) are currently in use in over 200 clinical trials worldwide (www.clinicaltrials.gov).  Recent studies suggest that poor post thaw function of MSCs was the source of failure for a recent clinical trial.  We are actively involved with the development of new methods of preserving MSCs with a focus on improving post thaw function and eliminating dimethylsulfoxide.

Induced pluripotent stem cells (iPS cells): There is tremendous interest in taking cells from a patient, reprogramming those cells and then developing treatments from those cells or testing drugs or other therapies on those cells.  As with embryonic stem cells, iPS cells are typically cultured (and cryopreserved) in colonies.  We are developing new methods of preserving iPS cells without DMSO and in a manner that preserves cell-to-cell contact that is critical for normal function of the cells.

Publications from BioCoR faculty in this area:
Pollock K, Sumstad D, Kadidlo D, McKenna DH, “Clinical mesenchymal stromal cell products undergo functional changes in response to freezing”, Cytotherapy, 17(1): 38-45, 2014.

Pollock K, Budenske JW, McKenna DH, Dosa PI, Hubel A, “Algorithm-driven optimization of cryopreservation protocols”, J Tissue Engr Regen Med, in press.

Research Project 3:
Development of a Microfluidic Device for DMSO Removal

Published on: Monday 11, August 2014
Author: BioCoR

research-proj-3The vast majority of umbilical cord blood (UCB) units are cryopreserved using a 10% DMSO solution.  Despite its clinical use, DMSO is not approved for systemic administration and the infusion of cryopreserved cells containing DMSO into humans has been associated with various adverse events.  Current methods of removing of DMSO are time consuming, labor intensive and result in cell losses of 25-30%.

The objective of this project is to develop a clinical-scale microfluidic device that removes DMSO from frozen-and-thawed UCB.  The device would reduce both cell losses and processing time for DMSO removal from UCB (process a standard 30 ml unit of UCB in 15 minutes with high cell recovery and 95% DMSO removal).

Cryopreservation of cells requires the use of specialized solutions that must be introduced and removed.  Therefore, the development of microfluidic devices to perform these tasks could improve biopsecimen quality by reducing time, cell losses and sample to sample variability.

We are in the process of commercializing this device and expanding its use beyond cord blood to other cell types.

Publications from BioCoR faculty in this area:
Fleming KK, Longmire EA and Hubel A. “Numerical characterization of diffusion-based extraction in cell-laden flow through a microfludic channel”, J Biomech Engr, 129: 703-711, 2007.

Mata C, Longmire EK, McKenna DH, Glass KK and Hubel A. “Experimental study of diffusion based extraction from a cell suspension,” Microfluid Nanofluid, 4: 529-540, 2008.

Glass KK, Longmire EK and Hubel, A. “Optimization of a microfluidic device for diffusion based extraction of DMSO from a cell suspension,” Int. J. Heat Mass Transfer, 51: 5749-5757, 2009.

Mata C, Longmire EA, McKenna DH and Hubel A. “Cell motion and recovery in a two-stream microfluidic device,” Microfluid & Nanofluid, 8: 457-465, 2010.

Hanna J, Hubel A, Lemke E. “Diffusion-based extraction of DMSO from a cell suspension in a three stream, vertical microchannel, Biotech. & Bioengr, 109: 2316-2324, 2012.

Bala Chandaran R, Reinhart J, Lemke E, Hubel A. “Influence of buoyancy-driven flow on mass transfer in a two-stream microfluidic channel: Introduction of cryoprotective agents into cell suspensions”, Biomicrofluidics, 6: 044110, 2012.