Thursday, December 10, 2009
Featured Article
Cell culture is a very labor-intensive and repetitive task. In many cases, it's carried out by highly -qualified scientists who could be spending their time on other things. Cells need care and feeding regularly, even if it's a holiday, even if it's or the middle of the night. Neglect of growing cell lines will kill them as surely as anything. So for many scientists, cell cultures are somewhere between drudgery and slavery.
Enter the automated cell culture system. A robot can be programmed to perform all of the tasks of cell culture—pipetting the media, plating cells. And the robot can handle many hundreds of plates at a time. Cell culture is an ideal candidate for automation.
Currently, there are relatively few systems on the market for automated cell culture. They fall into two basic categories, basically. One is the automated system that has been modified for cell culture. This sort of system may be a good choice for a laboratory that does not have the resources or the space for multiple dedicated automated systems. They need a flexible, all-around robot that can culture their cells, do high throughput assays on 384-well plates, and wash the windows. The other choice is the customized, dedicated system. The advantage of this option is in having something a system designed and purpose-built for cell culture. This type of system will be more “plug-and-play” for the user, with features and interface that make intuitive sense for cell culture procedures.
The MACCS Automated Cell Culture System from Matrical Biosciences (Spokane, WA) is an example of a purpose-built, dedicated system. Looking vaguely like a trailer home for cyborgs, the basic chassis is a self-contained liquid handling and compound storage system. The MACCS allows the user to bring cells up from -80 frozen storage and expand them, or grow them up and freeze them in cryovials for future use.
Kevin Oldenburg, PhD, is President of Matrical, and one of the original founders. The company was based on injection molding technology licensed from DuPont pharmaceuticals, and has grown to include not only plastic consumables, but an array of instruments and automated systems to go with them. Matrical's early history makes the company unusually savvy about plasticware. Says Oldenburg:, “We can store up to 3200 flasks, and maintain all of those flasks, which is almost ten times higher than any of our competitors. . . we're the only group that can grow cells in shaker flasks. . . we can grow things in robo flasks, T-flasks, one liter shaker flasks. All that different plasticware in the same system.”
The newer MACCS DS product line allows for even more specialization. DS stands for “dedicated services,” and it is a physically smaller unit than the regular MACCS. For example, the MS model is designed to “maintain and split” cell cultures. The PS model does everything the MS does, with the addition of a plating capability. Says Oldenburg, “I would have killed to have an automated system to maintain and split cells. There was nothing I hated more than coming in on Sunday to maintain cells, because it had to be done.”
On the other end of the spectrum is Tecan's Cellerity, an automated cell culture solution for their robotic liquid handling platform. Cellerity integrates modifications to software and hardware tools on the Freedom EVO robot to allow maintenance and expansion of cell lines. Physically, it is a compact laboratory bench size. CellGEM (cell growth expansion and maintenance) software controls the operation of the instrument. The flexibility and accessibility of Cellerity has made it a tinkerer's dream. Says Roland Durner, Director of Market and Application for Tecan (Mannedorf, Switzerland):, “What has happened in the last two years is that customers have used this machine for all kinds of crazy things. They have used this machine without changes to grow virus on the cells for infectious disease research.” Common applications for Cellerity include production of cells for high throughput screening, maintenance and preparation of cells for therapeutic groups within an organization, and transient protein expression from DNA.
Cellerity's main attraction is not the instrument so much as the CellGEM software. The robot is quite comparable to robots from other companies. Says Durner, “What people really like is the software. The cell biologists recognize it's speaking in their language. It speaks in terms like passaging, double times—all those terms that cell biologists like. It's purpose-built software.”
One reason that CellGEM is so user-friendly for cell biologists is because Tecan has involved its users in the software development process. The users suggest applications that they would like to perform with the Cellerity instrument, and the programmers do their best to accommodate them. Although Cellerity is very nimble and flexible for small- scale applications, it's not designed to make extremely large quantities of a single cell type. Says Durner, “It's good at doing a lot of different things, not specifically one thing in very high throughput. Our customers maybe want to make ten or twenty different cell lines on the same machine with a few plates each, for screening, and not one cell line at a hundred plates,.” explains Durner.
Until recently, cell culture was much like dairy farming, in that care of the cells was an unavoidable recurrent task, much like milking cows. However, automation offers an additional perk beyond freedom from the cell culture lab. It takes human error and user variability out of the equation. Many researchers become superstitious about specific tools and techniques in the lab that give them better or worse results when handling their sensitive cultures. Automation to a great extent smooths out the element of human variability, allowing scientists to relax and do things that a robot can't do better than a human. Yet.