Gentle Mixing, Aeration for Biological Samples
“Shaken, not stirred” was James Bond’s preferred mixing method for martinis. Similarly, biological shakers aerate and mix cells with their media by the action of a moving platform.
“Shaken, not stirred” was James Bond’s preferred mixing method for martinis. Similarly, biological shakers aerate and mix cells with their media by the action of a moving platform. Shaking is often preferred with cell cultures because overhead or magnetic stirrers can induce shear damage in cells and are impractical with multiple culture vessels.
Shakers may be deployed inside or outside incubators, depending on the requirements of the specific cell or organism. They are common equipment in pharmaceutical, biotechnology, and vaccine development, as well as in biological safety and environmental labs.
Shakers lend their name to another category of cell culture product, the shaker flask, a cell culture vessel specially designed for use with shakers. Until the advent of large-scale cell culture, many vaccine manufacturing processes occurred in shaker flasks.
The two main shaker designs are orbital and reciprocating. In the former, the platform rotates around a perpendicular axis, creating a vortex; in the latter, vessels are moved back and forth within the platform’s plane. Of these two basic models, orbitals predominate.
A third type of shaker employs a rocking mechanism. GE Healthcare (Piscataway, NJ) sells several benchtop units that handle sealed, disposable plastic bags laid on their sides, with volumes ranging from 50 to 500 mL. These products are scaled-down versions of the company’s much larger (up to 1,000 liters) bioprocess bags, which also employ rocking to mix and aerate cells.
Despite their maturity as a product category, biological shakers have experienced several technical upgrades over the last three years. User interfaces have improved, as have data acquisition and other advanced features. Thermo Fisher Scientific has introduced stackable shakers to improve capacity in space-strapped labs and Boekel Scientific sells a shaker with multiple speed ranges, while Grant Instruments markets linear shaking baths for highly sensitive microbiology work. Saturated with options
“Orbital designs provide maximum mixing or aeration based on the orbital velocity,” explains Scott Egyed, director of sales and marketing at Boekel Scientific (Feasterville, PA). Boekel manufactures shakers ranging in size from tabletop to high-capacity floor models.
Unlike some instrument types, for which components may be “mixed and matched” to provide custom configurations, shakers are typically sold off-the-shelf with little customization. “The market is saturated with options,” Mr. Egyed says, that include size, footprint, capacity, clamping or hold-down methods, and other features.
Customization may occur when working with unusually shaped vessels or specialized cell cultures. Boekel has also received requests for integrating small orbital shakers with carbon dioxide incubators. This setup is suitable for biological samples that thrive in anaerobic environments and require temperature control as well.
Microtiter plates require some special care when subjected to automated shaking. “You need a system with a good hold-down mechanism,” explains Mr. Egyed. Some systems use clamps or spring-loading to keep plates from slipping on the platform. The other consideration is a means of sealing plates without encouraging condensation or leaching of foreign materials into the wells.
Product manager Kristoff O’Connor at Heidolph USA (Elk Grove, IL) notes that microtiter plate shakers have become more common during the last few years. Shakers enable “reformatting” plates from lower to higher densities. During this operation, a 96-well plate is charged with cells and shaken. After the cell populations expand, they are transferred robotically to a 384- or 1536-well format. From there, cells may be subjected to assays or imaging, according to the experimental protocol.
Despite the wealth of feature possibilities, Eberbach Corp. (Ann Arbor, MI) does “quite a bit of custom manufacturing” of its shaker products, according to company president Ralph “Trip” Boehnke III. “A fair number of our customers want something they cannot find in a catalog.”
Eberbach’s flexible manufacturing approach enables it to quote a custom unit at a price that is “very competitive” with other vendors’ standard models, Mr. Boehnke adds. “Customization is our niche.”
The key to Eberbach’s success may lie in their strong presence in non-lifescience markets. The company sells shakers to the petroleum and biofuels industries, where desirable features include explosion-proofing and motorized controls. Biofuels plants that culture bacteria for pilot production sometimes require a shaker with a capacity of 300 pounds. “Not many off-the-shelf shakers can handle that,” Mr. Boehnke says.
Eberbach has recently introduced a model with a wired remote controller for operation inside cold rooms or fume hoods; the company is contemplating a wireless remote.
What to look for
The feature-richness of biological shakers is a blessing but should also raise red flags for potential buyers. Heidolph’s Kristoff O’Connor says the first consideration should be capacity, specifically how much weight the shaker can handle compared with the weight of flasks plus contents currently run. Purchasers should also consider the possibility of future expansion. “Because shakers are a workhorse product, buyers should strongly consider the length of the warranty.”
The third set of criteria are “reproducibility” features such as digital display, timers, and alarms. Finally, consider the environment in which the shaker will be used—benchtop, fume hood, incubator, or cold room—and how it will be cleaned. “Purchasing a shaker that does not meet the standards of its intended operating environment will shorten its usable life and possibly void its warranty,” Mr. O’Connor says.
“Users want a controllable shaker that will provide the same or better results from one run to the next,” observes Eberbach’s Ralph Boehnke. “Our customers don’t ask for too many exotic features. The main thing they’re interested in is robustness, a shaker that will run continuously without problems.” Nevertheless, customer service “must be top-notch” since units do occasionally break down.