Wearing a long white lab coat and sterile gloves, a technician, working diligently at his bench top, reaches for his samples. As a member of a rodent diagnostic lab, this technician is part of a team responsible for screening mice and rats for potential infections. Just arrived, is a shipment of samples from an outside company contracting their services. They are vials of fecal pellets and fur swabs collected from mice, which could be infected with a virus, bacterium or parasite. From these samples, the technician will extract and pool the DNA and apply it to a PCR Rodent Infectious Agent (PRIA®) Panel on the OpenArray® technology–a tool which may change the way the biomedical industry conducts health monitoring forever.
This tool–a chip the size of a microscope slide–has over 3,000 wells, each of which contains a single assay. When filled with an astonishingly small 33 nanoliters of reaction cocktail, each assay can detect as few as 1-10 copies of DNA from bacteria, viruses or parasites in any of the shipment’s feces or fur swabs.
But let’s back up. How, and why, did our technician get these samples? Well, when working with research animals, the saying goes: “A compromised animal is compromised research.” That is, infection of a study animal with a virus, bacterium, parasite, or fungus can increase variability in, or even invalidate, research results. Therefore, before animals are used for research purposes, they must be tested for a spectrum of infectious diseases. This is especially true with regard to special models, such as genetically engineered mice whose health status is oftentimes uncertain.
The traditional method of such testing involves putting test mice or rats in contact with research animals’ bedding material. Once these control animals, referred to as “sentinels,” have had enough time to potentially produce an immune response to any pathogens (usually 4-8 weeks), they are sent to a rodent diagnostic lab. Lab workers, like our trusty technician, test these sentinels for a specific list of agents to determine if they are free of infection. About two weeks later, a company gets their results and knows if their animals are “dirty.” The problem with this whole process is that it’s slow (up to 10 weeks or more), expensive and not all that sensitive.
But a new technology is changing all that and may transform how the entire process of health monitoring is viewed and implemented. It’s called OpenArray®–a PCR platform in chip form, the size of a standard microscope slide, containing individual PCR assays in a high-density format. Instead of requiring entire sentinel animals, diagnostic laboratories using PCR-based testing only need representative fecal pellets or fur swabs, thus eliminating the need to ship live animals. And because shipping costs can be as much, or more than, the actual testing costs, it represents a huge cost savings. Additionally, because this PCR-based method directly tests the animals in question, sentinels are not required, which reduces the amount of animals needed. This also shortens the entire process to two weeks as opposed to 6-10, allowing researchers to make critical health-based decisions earlier and potentially save money on per diem costs. And, because PCR assays performed on the OpenArray® platform uses TaqMan® technology, it is much more sensitive and specific than sentinel-based detection schemes, or even PCR using traditional gel-based PCR assays.
And this type of PCR-based health testing may be evolving at just the right time as well. In the past 10 years, there has been an explosion in the use of genetically modified mice and rats in biomedical research. Development of these critical resources however, can be derailed by any one of a 100 different “uncontrolled” variables–such as the health status of animals from universities or other companies which lack strict quality control measures to ensure “clean animals” (which could obscure or distort valuable genetic traits). The proliferation of genetically engineered strains across so many research institutions has created a great need for more rapid and precise health screening. This need could ultimately be filled through the use of PCR panels–often complemented by modern bead-based fluorometric serology panels.
The continued expansion and refinement of PCR and serology panels may come close to replacing the need for sentinel animals, as well as the need to ship live animals for complete health assessments. With the sensitivity of this new innovation, laboratories can more definitively determine not only whether a population is infected, but also which individuals carry a given pathogen. This new paradigm of testing, pioneered at Charles River, is not just more sensitive and faster than traditional methods, it’s also more practical, more cost-effective and more humane, and the biomedical community will likely see its widespread adoption in the coming years.