For the past twenty-five years, Applied Biosystems (www.appliedbiosystems.com) has been recognized as a leading manufacturer of laboratory instruments for biotechnology and pharmaceutical researchers. In 1982, it developed the first protein sequencer, followed by the first successful DNA sequencer a year later, and then real-time PCR instruments in 1995.
Now these tools are branching out to help experts working in law enforcement, clinical diagnostic laboratories, and biosecurity. “We’ve been pulled by our customers to enter these areas and we’ve evolved tools and products for these applications,” says Mark Stevenson, president of the molecular and cell biology division at Applied Biosystems, headquartered in Foster City, CA.
Applied Biosystems has supplied kits for DNA testing to law-enforcement agencies since the 1990s. “It’s hard to imagine a criminal justice system these days without the use of DNA typing,” says Leonard Klevan, president of Applied Biosystems’ applied markets division. Today the company is a leading supplier of DNA-typing reagents, instruments, and software for law-enforcement laboratories.
“We have a forensic system that consists of a DNA-sequencing instrument and reagents that have been validated through extensive testing,” Klevan says. Experts at Applied Biosystems work closely with the FBI to develop forensic kits based on genetic loci that are incorporated into the Combined DNA Index System (CODIS), a database that allows crime labs to exchange DNA profiles electronically.
The FBI system requires the identification of 13 gene loci, and at least 10 of these loci are needed to make a valid CODIS match. Applied Biosystems also works with crime labs around the world to develop and improve forensic products.
In January 2007, Applied Biosystems will launch a new line of reagents and kits for DNA testing called the MiniFiler. This latest technology will allow forensic scientists to retrieve data from degraded DNA, making it possible to solve cold cases or find missing persons. The underlying technology was pioneered at the National Institute of Standards and Testing, where researchers discovered a way to use miniature short tandem repeats to reduce the amount of DNA needed.
“We improved the methods to perform the analysis and incorporated it into our system,” says Klevan. The methods developed to examine low copy number DNA samples also could be used to analyze DNA from fingerprints or to develop portable DNA typing systems to scan crime scenes in the near future.
Applied Biosystems observed that other customers were adapting its sequencing technologies to develop home-brewed molecular tests to find markers for human disease. Celera Genomics(www.celera.com), a sister company of Applied Biosystems, manufactures and markets diagnostic products used for hepatitis C virus and HIV viral load and genotype determination through Abbott Laboratories(www.abbott.com).
As researchers discover new biomarkers and SNPs, many more diagnostic tests are expected to reach the marketplace. To meet the future needs of personalized medicine, the molecular and cell biology division at Applied Biosystems is developing instruments for clinical laboratories that technicians will find easier to operate.
After customers identify and validate new biomarkers and the tests are approved, large numbers of patient samples will be analyzed on real time-PCR or DNA-sequencing instruments. In the past, research scientists were the end users of these complex types of equipment. However, as molecular diagnostic tools advance personalized medicine, more straightforward instruments will be needed to speed throughput at clinical laboratories. “We’re experiencing strong demand from our customer base to produce open platforms that can be used to develop and run clinical tests,” says Stevenson.
Applied Biosystems also offers assays and software to speed the search for molecular biomarkers. These include the VariantSEQr™ Resequencing System with pre-designed primers for resequencing human genes; more than two million TaqMan SNP Genotyping Assays for gene and disease association studies; and the TargetSEQ™ Resequencing System, a software module that doubles the throughput of the 3730 DNA Analyzer for medical sequencing. The long-term goal is to detect disease early in its molecular evolution and tailor treatments to patients based on their genetic characteristics.
Technology platforms developed at Applied Biosystems also support the detection of microorganisms that contaminate food, water, and air. Ever since the deadly anthrax powder contaminated U.S. mail in 2001, the Postal Service now screens mail sorting machines at large distribution centers.
The detecting device, marketed by Cepheid (www.cepheid.com), samples the air and feeds the samples into a DNA detector that scans for a unique genetic signature. Applied Biosystems provides the reagents to test for the presence of anthrax spores, and the underlying technology is based on real-time PCR technology developed at Applied Biosystems. “It’s another example of the adoption of our core real-time PCR technology for a different application,” says Stevenson.
The assays used to detect anthrax are robust and highly accurate because of oligonucleotides and proprietary dyes manufactured at Applied Biosystems’ large-scale, ISO-accredited facility in Pleasanton, CA, according to Stevenson. The same core technologies and manufacturing processes are being explored to develop similar tests for other pathogens that could trigger bioterrorism events.
In collaboration with the Centers for Disease Control and Prevention, Applied Biosystems developed mass spectrometry protocols to assist laboratories to screen for 150 water pollutants that could cause disease outbreaks. The company reports that its ABI 4000Q Trap mass spectrometer detects water contaminants at part-per-trillion levels in less than 15 minutes with no sample preparation required. The system also can detect environmental toxins, such as pesticides in farm runoff water, or evaluate water quality after natural disasters like Hurricane Katrina.
At the International Association of Food Protection meeting held in Calgary, Alberta in August, DuPont Qualicon rolled out the BAX® PCR Assay for the quantitative detection of Camplyobacter jejuni on chicken carcasses. This test identifies and quantitates Campylobacter, which causes food poisoning from eating contaminated chicken.
“This will lead to a revolution in testing and set a new standard in the market,” says Klevan. Innovative real-time PCR technology from Applied Biosystems was incorporated into the design of the BAX system, which Klevan says can detect concentrations as low as 10 cells per 30 milliliter samples in wash water from chicken carcasses.