How Closed, Automated Cell Separation Systems Reduce Cell Culture Contamination Risk

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Cancer immunotherapies continue to show great promise across disease states. But as uptake soars, so does the risk of cell culture contamination in the lab.

Traditional cell separation techniques such as manual filtration and open centrifugation can either introduce external microbial contaminants (such as bacteria or viruses) or not fully remove unwanted populations or protectants inherent in the cells, such as when lysing red blood cells or washing off dimethyl sulfoxide (DMSO).

Managing contamination risks is critical. And yet researchers too often rely too heavily on equipment like biosafety cabinets without weighing such factors as ventilation and pressure regulation, which can elevate the bioburden, says Ben Josey, Ph.D., a field application scientist at Corning Life Sciences.

"Some scientists may overestimate the extent to which their facility and equipment controls are effective in reducing their contamination," Josey said. "For example, a biosafety cabinet is only effective if it's used properly and operated in a rated clean room. While you may be pretty knowledgeable about your own independent aseptic techniques, that's not always good enough if you're managing an open system in a highly contaminated, high-bioburden environment."

Closing the Platform

Cell contamination concerns have led many researchers to switch from open systems with manual workflows to closed platforms, which offer all-in-one automation. Switching systems helps maintain sterility, even on an open bench, says Alejandro Montoya, M.S., a senior product manager of advanced cell culture at Corning Life Sciences.

"Open systems require more manipulation to add density gradient media and other manual steps inherent in open centrifugation, which can make them more prone to microbial contamination," Montoya said. "In a closed system, you can greatly reduce the number of processing steps, which, in turn, minimizes contamination risk."

Closed systems may protect against outside contaminants, and certain platforms can remove undesired components from samples more effectively than manual processes can. For example, Corning's X-SERIES Cell Separation Platform includes X-LAB® and X-WASH®, which support sensor-guided cell isolation and cell washing, respectively.

In the X-LAB System, samples get transferred into a single-use, sterile cartridge, either through tube welding or aseptically via Luer lock connectors or syringes. From there, samples flow into a preprogrammed centrifuge, where the accelerometer and sensors in the Control Module track G-force and cell layering. Once the cells are stratified, the cartridge's valves automatically open and close to move samples into their respective compartments.

"Using a combination of an accelerometer, intelligent sensors and a multichamber device cartridge, the X-LAB System is very effective at separating out populations such as red blood cells, which are a common source of inherent cellular contaminant when you're isolating immune cell populations," said Josey, who spoke about the technology for a BioProcess International webinar. "It can reduce red blood cell levels down to below 1 percent without the need for the lysis step, compared to the 3 percent achieved with lysis."

The ability to eliminate introduction of density gradient media and skip lysis can help prevent contamination, as these reagents are fraught with inherent risks through required manipulation and extended exposure.

"The amount of time that you expose your cells to the lysis buffer can have a contamination impact and affect cell viability," Josey said. "Alternatively, not needing to add an additional reagent is one less processing step that you have to do, and every step comes with added risk. So if you're looking at sources of external contamination, not having to do lysis is certainly beneficial."

Washing Cryoprotectants From Samples

Inherent contaminants in cryopreserved cells like DMSO and other cryoprotectants can also affect cell viability, making automated washing platforms even more valuable. Corning's X-WASH System operates similarly to X-LAB® in that intelligent sensors within the Control Module monitor washed cells for more precise and sensitive harvesting.

In one study, Montoya said, X-WASH removed 90 percent of DMSO after one wash and 99 percent after two washes.

"Those benefits are achieved with minimal manipulation," he said. " Compared to other technologies used for these processes, these are quite desirable outcomes."

Controlling Contamination

Whether their systems are open or closed, researchers will want to keep facility and equipment control top of mind for cellular separation techniques. Countless contaminants and other obstacles await any experiment; all it takes is one to knock a project off track. With research as precious as cancer immunotherapy, contamination control matters — perhaps more than ever.