Clinical diagnostics provide new opportunities.

Clinical applications make up a large and growing share of the analytical instrumentation market. Many analytical instruments are found in clinical labs and many companies, including Amersham, Beckman Coulter, Bio-Rad Laboratories and PerkinElmer, participate in both markets. But the growing molecular diagnostics market has brought the two markets even closer as analytical instruments, and companies, pursue new roles in clinical diagnostic applications.

One of the higher profile examples of these markets' synergy is the formation of Celera Diagnostics by Applied Biosystems and Celera Genomics in 2001. Celera Diagnostics plans to commercialize new molecular and protein diagnostics tests. Earlier this month, the company received FDA approval for its first in vitro diagnostic product, the ViroSeq HIV-1 Genotyping system, which the company hopes will become a standard for clinical testing for therapy decisionmaking. Such a market is not new to Applied Biosystems, whose sequencing products and PCR products are used by clinical labs for diagnostic applications such as genotyping and sequence analysis. To enter the market, Celera Diagnostics has partnered with companies familiar with the territory such as Quest Diagnostics, Laboratory Corporation of America and Bristol Myers Squibb. Abbott Diagnostics will develop and market the products, and a number of its new diagnostic tests will run on Applied Biosystems sequencing and real-time PCR systems.

As with Applied Biosystems, a number of other instrument companies have also made a name for themselves in the clinical lab market with their sequencing products for genotyping and sequence analysis, among other applications. Among the clinical applications for Sequenom's MassARRAY system are genotyping, targeted SNP discovery, allele frequency analysis and gene expression profiling. Its customers include Quest Diagnostics and Specialty Laboratories. In the case of DNA sequencing technology company Pyrosequencing, the company has created its own Molecular Diagnostics unit, which is currently developing tests for thyroid cancer with the Mayo Foundation for Education and Research and is working with the Genomics Collaborative to develop cardiovascular diagnostic and therapeutic products. For Amersham, which sells diagnostics through Amersham Health and instruments through Amersham Bioscience, the company may be working on bringing the two sides of its business closer together. When Amersham Bioscience purchased Motorola Life Science's CodeLink pre-arrayed slides business (see IBO 7/31/02), it noted the clinical diagnostic opportunities for the product. With the purchase of Pharmacia's share of Amersham Bioscience (see IBO 3/15/02), the company stated "This will enhance our ability to create value from the emerging possibilities in personalised medicine." In the case of Variagenics, it introduced its Trugene HIV-1 Genotyping Kit and OpenGene DNA Sequencing Systems last year and was acquired by Bayer Diagnostics earlier this year for $61.4 million (see IBO 7/31/02) .

Biochips is another analytical technique that holds promise for diagnostics applications. While Motorola may have sold its CodeLink business, it kept its eSensor DNA Detection System as part of its Motorola Clinical Systems division. Among the applications under development for the eSensor are Cystic Fibrosis assays and tests for cancer. Microarray company Nanogen has focused its business on the molecular diagnostics market. Its NanoChip Molecular Biology Workstation was placed at four clinical reference laboratories during the third quarter. The company seeks to establish the NanoChip System and reagents as the standard platform for genetic mutation detection.

Affymetrix has also been busy in the market. In 1996, it signed an agreement with bioMerieux for the development infectious disease diagnostics system, and in 1998, it entered into an agreement with Roche Molecular Systems for the development of diagnostics kits for HIV drug resistance. In 2001, it announced a collaboration with deCODE genetics to develop DNA-based tests for patient responsiveness to treatment. This year, it established a joint research project with clinical genomics company Ardais that will combine its GeneChip technology with Ardais' BIGR human tissue library and clinical information to study gene expression for the development of new microgenomics array-based diagnostic products. Also this year, Affymetrix announced a collaboration with the Whitehead Institute for Genome Research, which is using GeneChip technology for clinical cancer studies.

With many of the same features that make microarrays attractive for diagnostic testing, other chip-based platform companies have also pursued the market. Caliper Technologies entered the clinical diagnostic market in late 2001 through an agreement with Bacterial BarCodes to distribute clinical diagnostic systems based on Caliper's LabChip technology and Bacterial BarCodes' proprietary rep-PCR bacterial fingerprinting technology for the detection and diagnosis of invasive bacterial infections. In addition, Caliper's partner in the biochip market, Agilent Technologies, is currently researching molecular diagnostic solutions utilizing microfluidics, microarrays and other analytical instrument products. Likewise, protein chip company Ciphergen is exploring application of its SELDI ProteinChip System to diagnostics through the discovery of protein biomarkers. Earlier this year, Harvard researchers identified a potential biomarker for use in early detection of ovarian cancer using Ciphergen's technology, and the National Cancer Institute's Early Detection Research Network has used the systems for cancer identification.

Analytical instrument companies are also participating in the diagnostic market through the automation of diagnostic testing. For companies that also participate in the lab automation market, such as Beckman Coulter and Tecan, the connection is obvious. Tecan recently entered into an agreement with Abbott Laboratories to develop and commercialize an automated sample prep system for molecular diagnostic assays based on its Genesis Freedom workstation. In addition, earlier this year, Tecan agreed to include Chiron's Procleix HIV-1/HCV assay on its high-throughput Genesis platform. Beckman Coulter supplies numerous diagnostic instruments and consumables to clinical diagnostic labs, including its CEQ 8000 Genetic Analysis systems, but the company also has collaborated with Ciphergen, Promega and Orchid Bioscience to automate their technologies for clinical diagnostics applications.

For companies that participate in both the nucleic acid and instrument market, the clinical diagnostic market also provides numerous opportunities. In particular, Qiagen has pursued the diagnostic market. Among recent deals are Qiagen GmbH's collaboration with Roche Diagnostics to create and market the TaqPrep diagnostic system for nucleic acid sample prep, detection and quantification of the Hepatitis B, Hepatitis C and Human Immunodeficiency viruses. In addition, PreAnalytiX GmbH, a subsidiary of Qiagen and Becton, Dickinson, has formed agreements with several companies, including GlaxoSmithKline, for the PreAnalytiX system. The PreAnalytiX system integrates sample collection, sample stabilization and nucleic acid purification for applications such as molecular diagnostics and clinical trial monitoring

Even mass spectroscopy is stepping up its role in clinical labs for diagnostic applications. Earlier this year, Bruker Daltonics partnered with Matritech to create an automated mass spectrometer system to facilitate proteomics-based cancer screening tests in clinical labs. The first screening tests to be automated are the NMP66 blood-based breast cancer test and the NMP48 blood-based prostate cancer test. The new system includes Bruker's MALDI-TOF technology, automated sample handling, reagent kits and bioinformatics. In fact, Bruker Daltonics' MALDI-TOF is also a part of Sequenom's platform. Also, last year, Shimadzu's Kratos Analytical formed a strategic partnership with LumiCyte to use Kratos' AXIMA-CFR mass spec systems with its SELDI Biochip arrays. LumiCyte is developing its Protein BioChips, Readers and informatics technologies for diagnostics based on protein biomarkers.

Instrument makers will find that applications in diagnostics will continue to grow as long as life science technologies, such as sequencers, biochips, nucleic acid techniques and mass spec, can meet the different, and sometimes quite difficult, demands of clinical diagnostic labs.

Point of Care Diagnostics

Point of care diagnostics are also taking advantage of analytical techniques. These new devices allow for almost instantaneous diagnosis of the problem and in many cases, a completely non-invasive procedure.

Approved for sale to emergency rooms by the FDA, Quantech's FasTraQ System and PrePaQ Total hCG systems use surface plasmon resonance. The FasTraQ system is for diagnostic analysis and the PrePaQ Total hCG detects pregnancy through the measurement of chorionic gonadotropin in blood. Otsuka Pharmaceutical in Japan was given 510K clearance for its UbiT-IR300 infrared spectrophotometer. The UbiT-IR300 analyzes the ratio of 12C/13C C[O.sub.2] in a breath sample to diagnose helicobacter pylori infection, which causes peptic ulcer disease. The FDA has also given approval to Hutchinson Technology to market its InSpectra Tissue Spectrometer System, which uses NIR spectroscopy to measure tissue oxygenation. For the measurement of oxygen intake, the FDA recently approved HealtheTech's MedGem indirect calorimeter. Under development by Brunel University is a doctor-on-a-chip kit, allowing for the detection of conditions such as Hepatitis B, HIV and other viruses at one time. Technology using polymer beads to detect chemical reactions in blood, urine or saliva is being developed by 3D Molecular Sciences.