The University of California, Los Angeles (UCLA) School of Public Health is in the programming stages for a new high-speed, high-volume laboratory network capable of quickly analyzing and processing high quantities of biological samples. The network will expedite widespread collection and testing of influenza samples and will enable public health experts to track diseases in near real time, dramatically shortening the time needed to produce effective vaccines.
When completed, the UCLA lab is expected to serve as the basis for the global laboratory network devoted to dealing with the highly pathologic avian influenza, which is labeled as a Select Agent and must be handled under BSL-3 agricultural (BSL-Ag) conditions.
The UCLA School of Public Health will operate the prototype laboratory, direct the laboratory network development, and work in partnership with the Los Alamos National Laboratory to link participating laboratories in a global network.
The UCLA lab, initially funded by a congressionally directed Department of Defense investment, was recently awarded a $9-million grant from the State of California’s Office of Homeland Security.
“This laboratory network is absolutely essential for the United States to effectively handle the likely spread of avian flu,” says Dr. Scott Layne, associate professor of epidemiology at UCLA. “The lab network will provide rapid, accurate, and up-to-date information that is not available today to deal with an outbreak.”
Layne, who has studied high-volume epidemiologic and genetic analyses for nearly 20 years, feels it is imperative for the new lab to be modeled on what he calls “real-time surveillance” of infectious diseases. By this he means that after samples are gathered in the field, the sample should reach a laboratory and be comprehensively analyzed within a matter of days so that real-time information is available to help make monumental public health decisions.
Avian Flu Overview
Avian flu initially emerged in 1997 with an outbreak in Hong Kong. It reemerged again in 2004 in Asia and is now spreading in birds throughout the world, including documented cases in Mongolia, Russia, Europe, Africa, and the Middle East.
In late 2005, avian flu appears to have been carried by wild migratory birds to northern China, Mongolia, Tibet, Kazakhstan, and Siberian Russia. It has also spread to Turkey, Romania, Bulgaria, Greece, Macedonia, and Croatia.
Layne notes that there have been more than 200 known human cases of avian flu in the world, with more than 100 documented deaths. He adds that there is growing concern that a deadly strain of avian flu could potentially turn into a quick-moving human pandemic.
“If the flu continues to have a case fatality rate of 50 percent, a large part of the population could be wiped out by this virus,” says Layne. “There is every reason to believe that avian influenza will spread worldwide and that it will likely be introduced to North America via migrating bird flyways that link Asia and Russia to Alaska and Canada.”
Dealing with an Outbreak
“In an outbreak situation, rapid and accurate information about the geographic location of the avian influenza and the genetic mutations taking place will be essential for infection control and public health interventions,” says Layne.
He explains that the new UCLA lab will be designed so that surveillance teams will go to the source of the outbreak, record epidemiologic observations, and collect samples that can be quickly sent back to the laboratory. The laboratory’s high-throughput automation equipment will then process and sequence the influenza genes within the collected samples 24 hours a day, seven days per week.
The lab, which will be located on the top floor of UCLA’s seven-story California NanoSystems Institute, will include equipment capable of analyzing the phenotypic, genotypic, and epidemiologic features of virus samples. While final space decisions have not been reached, Layne anticipates the new lab to be approximately 5,000 or 6,000 sf depending on final funding.
“To date, such up-to-date surveillance and laboratory firepower have not been combined,” says Layne. “The high-throughput laboratory will provide faster information for vaccine strain selection and assessment, potentially saving one to two months in vaccine delivery.”
Layne adds that each lab within the proposed network could have the capability to analyze up to 10,000 samples per year, a substantial improvement over current capabilities.
“One of the key architectural challenges we are addressing is how to safely operate this kind of facility in the middle of a highly populated, busy university campus,” says Layne. “We are very focused on keeping the lab areas safe and we are taking all of the necessary precautions to prevent the waste stream and effluent from reaching any other area on campus.”
Inside the Lab
Plans call for epidemiologic questionnaires and instructions to arrive at the lab via the Internet, while bar-coded virus samples will arrive in the lab’s shipping and receiving area by air freight in safety boxes. The boxes will be opened in biosafety cabinets before being sent to accessioning or straight through to the lab’s BSL-3Ag area, which will include containment areas, screening rooms, and a manual laboratory.
The lab’s proposed accessioning system will be used to split virus samples and automatically move samples into storage within the archiving system. The system will allow samples to be split into half-ml cryotubes, 0.3 ml cryotubes, or 0.1 cryotubes, which can then be stored in well- racks that use two dimensional bar codes.
Archiving systems would store influenza samples for an extended time. The archiving system would take stocks from the field or from a replication system that verify whether influenza antigens are present in samples and set aside negative ones. The samples would then be placed into modular bar-coded storage containers within approximately 800 sf of freezer space planned for the lab. Every step in the storage and retrieval process would be recorded by scanners and managed by an inventory tracking program.
Plans for UCLA’s new high-throughput lab also include a fumigation room for decontaminating equipment, rooms dedicated specifically to growing virus samples, separate rooms for phenotyping, and two genotyping rooms, one devoted to chemistry, and a second for sequencers.
The new facility will include several different types of alarming systems, including the possibility of a bleach wash system that would release bleach through built-in sprinkler systems in the case of an earthquake or other catastrophic events. An emergency power generator in the building will ensure that samples remain frozen during power outages.
By Amy Cammell