After applications and processes, workflow optimization is the primary consideration when setting up a cell culture lab. Workflow relates to how samples and cultures move through the lab, the number of operations going on simultaneously, and chain of custody. “Particularly with cell culture, having a tight understanding of where and how things move through the facility protects you against cross-contamination and enables troubleshooting for unusual or unexpected occurrences,” says Bryan Monroe, principal at Primus Consulting (Kingston, WA). Primus advises on cell culture facility design, process scaleup, and technology transfer. “Lacking that understanding makes it difficult to see how and why things are not going right with equipment, reagents, and everything affecting your process.” Companies that overlook these issues will regret it later, Monroe adds. “A solid chain of custody is a top priority.” Cell culture workflows break down into approximately five areas:
- Cell isolation and preparation, beginning with either tissue from a vial or from a cell bank
- Growth and passaging, when cell populations increase to reach levels that allow routine experimentation
- Harvest – removing cells from the dish for re-culturing or expansion
- Storage under freezing or refrigeration in convenient aliquots
Optimizing cell culture workflows is an “inside out” exercise, involving three concentric workflow factors: facilities, large equipment, and operations (including personal equipment and consumables). “The point of cell culture is to mimic a cell’s native physiologic environment,” says Mary Kay Bates, global cell culture specialist at Thermo Fisher Scientific (Milford, MA)., “So that a culture represents what occurs inside the organism. Everything you use in the lab must contribute to that goal.”
Some layout concepts are common sense. Electrical outlets should be sufficient in number, and of adequate voltage, to power standard equipment. Designers should consider installing several circuits to avoid overloading, and providing extra outlets near benchtops, where a lot of equipment is used simultaneously. David Craig, national sales manager for BINDER (Bohemia, NY) says that lines, or tanks, should be located close enough to incubators (or other equipment requiring specialty gases) so that plumbing is minimized. “You’d be surprised how often incubators are located on one side of the room and CO2 tanks on the other,” Craig says. This layout requires the use of reinforced tubing to prevent pinching and crimping.
Others ideas must be learned, sometimes through experience. Craig also warns against installing incubators near heating or cooling vents. “During our seminars on contamination control we ask people to walk up to their incubator, take one or two steps back, and look up. The last thing you want to see is an air diffuser for heating or air-conditioning above your incubator. Every time you open the door the diffuser is blowing spores and bacteria into your work space.” Craig dismisses the contention by some facility managers that air is filtered at intake. “Take some quilting fabric and leave it inside the vent for a couple of weeks, and it will emerge covered in black gunk.”
When incubators are stacked, the bottom unit is significantly more likely to experience contamination than the upper boxes. According to Craig, that is because dirt and grime (read: microorganisms) accumulate in difficult-to-reach parts of the lab. He suggests placing stacked incubators on locking casters to facilitate cleaning below the units and to provide access for service. The cost of casters, about $350, is easily justified if they prevent just one contamination.
Insight into design and layout comes from a variety of sources. Sometimes managers don’t have much choice. Academic groups tend to move into generically designed labs with legacy layouts and locations of utilities and fume hoods. Many companies do this as well.
Well-heeled new facilities tend to hire engineering and design firms experienced in the demands of their particular workflows. Yet a surprising amount of information is available from equipment vendors, scientific meetings, colleagues’ laboratories, trade publications, and regulators.
Vendors can provide invaluable information at the very earliest stages of lab setup, particularly if they talk to the designers and assist in planning with equipment dimensions, power requirements, and noise levels. Nothing short of a reciprocating saw will save the day when the designers have specified and built a 40-inch-wide space for a 48-inch-wide incubator.
Meetings, conferences, colleagues’ facilities, and trade publications can provide valuable insight in the same way that garden magazines inspire doit- yourselfers. The trick is to understand the differences and similarities between the pretty picture in the magazine or PowerPoint slide and your facility’s actual requirements. And, like many amateur landscapers, many labs lack the will and resources to execute a do-it-yourself cell culture design project.
Regulated (FDA, EPA, OSHA) labs face an additional dimension of design complexity. While agencies do not specify how to conduct work, they set standards that must be met to remain in business. All the usual scientific standards apply, alongside the requirements of traceability, documentation, quality, and the potential for legal or regulatory repercussions.
Monroe cautions against laboratory “creep” or what he calls “organic facility growth,” common in academic labs or companies inexperienced with cell culture. “They decide they need to do cell culture work, and the facility grows out organically as they assume more and more work.” These labs add equipment and take on new processes, and eventually one group or process begins to overlap others next to it. “Labs designed or expanding on an ad hoc basis often crash due to contamination or instrument failure, requiring rework or redesign because they have not controlled the workspace or designed it to accommodate the workflows optimally. They’re in the forest, but they can only see one or two trees at a time. Lab design must be approached with an overarching perspective.”
Large, more experienced organizations tend to be more deliberate, Monroe says. They ask who will be using the facility, for what purposes, and conducting what processes, and then fit those factors in with the facility’s existing footprint or within the newly designed workspace. “And by doing this they achieve not only higher quality and functionality, but the flexibility to accommodate different processes. Unfortunately, these labs are in the minority.”
Regardless of the source of lab layout ideas, remember that all labs are different. “Forget about the cookiecutter approach,” Monroe warns. “The sheer variety of equipment and operations comprising a cell culture lab make one-size-fits-all approaches unworkable."