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New high-speed cell sorter shows promise in genetic engineering and cell transplants

EDITORS: Color slides and black-and-white photomicrographs of particles used in U-M fluidized beds are available on request.

ANAHEIM, Calif.—University of Michigan chemical engineers are merging two existing technologies to develop a new high-speed cell sorter and filtration system for biological materials.

When perfected, the new system could provide an efficient, cost-effective way to maintain pure strains of genetically-engineered bacteria used to produce insulin and other drugs, according to Mark A. Burns, U-M assistant professor of chemical engineering. It also could filter out cells that can trigger dangerous immune system reactions in patients receiving bone marrow transplants, and provide high-speed, economical cell sorters for research laboratories.

In a poster session at the American Chemical Society meeting held here April 2-6, U-M graduate student David D.Putnam displayed results of his initial experiments using the system to separate Type B and Type O red blood cells from a mixed solution.

"This experiment is an interim step toward our long- term goal, which is to combine the speed and efficiency of magnetically stabilized fluidized beds with the specificity of cell-affinity chromatography," according to Putnam.

Scientists use cell affinity chromatography (CAC) to " identify and grab one type of cell from a large, mixed population of cells, which often have very similar characteristics," Burns explained. CAC works by binding to cells with specific chemical receptor molecules on their surface membranes.

CAC is accurate, but very slow and labor-intensive, according to Putnam, so its use is limited to small-scale analytical separations. To adapt CAC for high-volume use with large cell populations, Putnam and Burns are trying to combine it with another type of technology called magnetically stabilized fluidized beds (MSFB).

MSFBs are columns of tiny spherical magnetically susceptible particles suspended in fluid. When the magnetic field is off, the particles and fluid mix freely, but when the field is turned on, the particles instantly freeze in position—lining up along the lines of the magnetic field.

"The magnetic bonds that hold the particles together are sort of like the bonds that hold Jello together when it is cooled," Burns said.

When the magnetic field is on, the particles turn into little magnets which stick to each other, according to Burns. When a cell suspension is fed into the fluidized bed, the cells are attracted to and stick to the surfaces of the particles.

As particles near the bottom of the column become saturated with cellular material, they are removed and fresh particles are added at the top to take their place.

"The big advantage of an MSFB is speed," Burns explained. " You can separate a billion cells from solution per minute. The disadvantage is that the system is not selective enough. We are trying to find a way to reduce non-specific binding or the number of unwanted cells that stick to the particles. "

To test the selectivity of the U-M system, Putnam coated the nickel particles he used in his experiment with a protein that binds to a molecule found only on the surface of Type B red blood cells. When he ran a mixture of Type B and Type O cells through the device, he removed 80 percent of the Type B cells, but also picked up 30 percent of the Type O.

While not perfect, Putnam and Burns believe the initial results are promising and demonstrate the potential of the new merged technology. Future research will focus on improving the system's specificity and developing a continuous flow, high-volume prototype.

The research is funded by the National Science Foundation, the Cellular Biotechnology Training Program of the National Institutes of Health and the Petroleum Research Fund, which is administered by the American Chemical Society.