Dr. Peter Hodder, senior scientific director and head of Lead Identification Division at The Scripps Research Institute in Florida talks to Tanuja Koppal, Ph.D., contributing editor to Lab Manager Magazine, about his experiences moving from big pharma to academia to set up a high-throughput screening laboratory from the groundup. He highlights some of the factors that were critical to his decision making when he started designing his labs and ones that are important today for the efficient use and maintenance of the space and equipment.
Q: When did you get involved in designing the cell culture and screening labs at Scripps, Florida?
A: When I joined Scripps, we first started out in a temporary building where everything—the tissue culture, highthroughput screening (HTS), robotics and compound storage—was in one room and that was a mess. When we had to move into a new, permanent facility I got involved with the lab design from the very beginning. Being a screening lab we cannot really discriminate on the type of assay that comes to us, so we work with a variety of cells—mammalian, yeast, insect and microbiology-derived cell lines. For us it’s all about location, location, location. For instance, we designed the mammalian cell culture lab such that it is accessible from both the assay development and robotics labs, but at the same time, since it’s located in one corner of the facility, it does not get much traffic. We also generate a lot of waste, and so we have a vestibule where service personnel can get in and pick up waste without disturbing the environment.
Q: What are some of the key factors to be considered as you design and use a cell culture facility?
A: There are really four things that are very critical—cleanliness, organization and business rules, maintenance and, in terms of the facility itself, there is training, location, and access. When it comes to cleanliness, look into everything, from the air quality to the materials you use for the flooring and furniture. In our particular case, with using HTS, we have to control all the fiber that can get into the equipment and the assay plates. We have to be anal retentive about the air quality in terms of particulates! Our systems are set up to minimize the possibility of dust or particulates causing any airborne infections to the cells and even if they are introduced, they are cleared out rapidly because of the airflow. When it comes to maintenance, all the equipment we use, such as the tissue culture incubators and ultra-sonic vaporizers, are all sophisticated devices that are actively controlled and can self-sterilize. In some ways, this makes them less robust and they need more routine maintenance. Hence, in some cases we use secondary backups to monitor the environment within these incubators to constantly calibrate temperature, carbon dioxide and humidity.
We have received nearly 50 to 60 cell lines in the past few years and we have set up milestonedriven protocols for everything—for quarantine, mycoplasma testing and such and that’s very important. As long as you are well organized and have good business rules set up, it really works well. It is then independent of the equipment we use and is more dependent on the people who use it. That comes down to training and personnel. People must know what to do and they should want to follow the rules. Establishing a routine and protocol-driven facility is very important.
Q: Would you do anything differently if you were to do it today?
A: At the time that we were setting up and designing the lab the trend was to buy large automated robotic systems. So we had all the necessary hook-ups installed and the space dedicated for automation. But then we realized that different cells need different culture conditions and hence, we needed different incubators for different projects. So if you are in a lab like ours that handles different cells and sets up different screens, it’s far more useful to have many multi-layered flasks and incubators. It is much more efficient than spending the time and effort to get the robot to do what you want it to do.
Q: How early did you have to pick your screening format?
A: This applies not only to tissue culture but to every piece of equipment that I buy. Everything we have has wheels on it! For instance, a workhorse incubator becomes quarantined and has to be moved out. If we need more storage, a refrigerator or a cold storage unit moves in. This has been good for us because we did not anticipate the different types of cells we would be handling. Something else that I didn’t anticipate in the lab design was our increased cell culture storage capacity due to the different types of cells we have. With the diversity of cells, serum, media, and storage units, it benefits us to have things on wheels so we can re-structure, re-purpose and move things in and out quickly. If you are looking to set up a new lab or upgrade an existing one, pay attention to technologies that have changed in the last decade. For instance, we do a lot of transfections in our lab and those can now be automated and we don’t have to rely on the older methods. A lot of the technology in terms of cell storage and handling has also improved, so less maintenance is needed. So keep an eye on the new trends.
Dr. Peter Hodder is the senior scientific director and head of Lead Identification Division at the Translational Research Institute and an Associate Professor in Molecular Therapeutics at The Scripps Research Institute in Florida. Scripps Florida is a branch of The Scripps Research Institute (TSRI), based in La Jolla, California. The Institute was designed to link basic research to a focused drug discovery and development platform using new technologies and translational research. Scripps Florida has a set of interdisciplinary academic departments (Cancer Biology, Infectology and Molecular Therapeutics) and a Translational Research Institute (TRI) that supports these efforts. Dr. Hodder directs Scripps Florida’s high-throughput screening (HTS) and compound management operations and has over a decade of drug discovery research experience in the pharmaceutical industry and academia. His 20 member group employs sophisticated technologies to implement and screen novel assays against both Scripps’ proprietary >600,000 member library as well as the NIH’s >300,000 member MLPCN collection. To date, his group has successfully completed more than 70 industrial and academic HTS-related collaborations that have identified and characterized several “lead” compounds with drug-like properties. Dr. Hodder is also an adjunct professor at the Florida Atlantic University, Boca Raton, and is engaged in the discovery of novel anti-bacterials. He received his Ph.D. in chemistry from the University of Washington in 1999 and joined the Merck Research Labs, where he was employed, until he moved to Scripps Florida in 2005.
If you missed the Ask The Expert webinar “What You Should Know When Setting Up a Cell Culture Lab”, originally broadcast on Tuesday December 21, 2010, click here to watch the archived video.