Defining the Need
Until recently, the concept of molecular testing has been associated with images of high-throughput instrumentation housed in centralized, high-complexity facilities and operated by skilled technicians. The multistep procedures required for nucleic acid purification and amplification demand precision, reproducibility, and controlled environmental conditions that are difficult to achieve with manual operations and problematic to export to point-of-care testing sites.
With existing molecular testing technologies, trained operators are needed to manage the protocols, minimize the risk of sample contamination, and interpret the results. Other limitations including processing times of many hours on high-throughput instrumentation, the need for frozen reagents, and a restricted menu of approved assays have confined the use of molecular testing methods to centralized diagnostic laboratory settings.
Yet the need for accurate point-of-care diagnostics is reaching a critical level, particularly for infectious agents. At present, in a typical microbiology laboratory the sample-analysis workflow based on traditional cell culture requires as long as three to four days to deliver a result to the clinician. In the event of a false positive or false negative result, the test may need to be repeated, adding further delays. Technician training and experience in cell culture techniques are essential for reliable results.
A new generation of PCR-based molecular testing platforms offers real-time diagnostic solutions with on-site results delivery to enable a single-visit test-and-treat paradigm. Consider a scenario in which high-risk patients brought into the emergency department could be tested on-site for methicillin-resistant Staphylococcus aureus (MRSA). This would dramatically improve efforts to treat and contain the infection. In the biodefense sector, localized testing would allow for implementation of rapid response and control measures in the event that a biological threat agent was detected.
Infectious diseases such as MRSA, Clostridium difficile, pandemic influenza, and SARS represent a real public health threat. Pandemic human influenza in particular has been given high political priority. In 2007, for example, the Ranger consortium received funding from the European Union Seventh Framework Programme to develop diagnostic and surveillance tools for seasonal and pandemic influenza.
Currently, molecular testing is confined to the high-complexity, centralized CLIA laboratories representing only about 10% of diagnostic laboratories. Next-generation molecular testing systems could be placed in a wide range of decentralized laboratories as well as many near patient settings including hospital and outreach clinics, pharmacies, prisons, universities, and pandemic testing sites.
The value of being able to put rapid molecular diagnostic capabilities directly into the hands of community-based clinicians, first responders, military personnel in the battlefield, and relief workers in developing regions and at the site of natural disasters or acts of terrorism is incalculable.
Furthermore, as pharmaceutical companies shift away from a strategy of delivering widely prescribed blockbuster drugs and toward a stratified drug development ideology and the production of targeted therapeutic agents, they are increasingly relying on molecular tests and companion diagnostics to guide drug development and treatment decisions. This paradigm shift will enable progress toward realizing the vision of personalized medicine.
The genetic testing market represents another opportunity for penetration by point-of-care diagnostics, allowing for earlier diagnoses, rapid adjustment of therapeutic protocols, and discontinuation of ineffective treatments. The ability to screen and quantify biomarkers associated with disease prognosis and predictive therapeutic response would aid in treatment selection and support the trend toward stratified medicine.
Beyond the human healthcare markets, the food industry would benefit from rapid at-plant pathogen testing to ensure the early and safe release of perishable foods and raw materials. At present in the food industry, the majority of pathogen tests are performed by culture, which takes days to return a result. Opportunities exist to provide automated molecular tests to the 40,000 worldwide food plants. In the veterinary sector, point-of-care diagnostics would facilitate in-field testing for early identification of animal pandemics and monitoring the spread of disease, allowing for rapid implementation of appropriate control and containment measures.
Combining sample preparation, amplification, and results calling into a single portable instrument has proven a significant technical challenge. This is especially true for infectious disease testing, which often requires preparation of a large sample to capture sparse concentrations of the target agent.