Several factors have been converging that present the laboratory with significant challenges with regard to diagnostic testing. This was highlighted, for example, during the 2009 influenza pandemic, which required the prompt development and implementation of patient management strategies needed to quell the growing anxiety of the public over the new flu outbreak. The outbreak caused large numbers of patients to demand treatment and most were often unaware that testing was available. Consequently, many facilities deployed rapid point-of-care (POC) influenza tests to support the testing demand to quickly identify H1N1pdm09 positive patients, only to find out that many of these tests were simply inadequate. This was later validated in several post-pandemic studies, which found some POC flu tests gave less than 50% sensitivity. Additionally, these studies determined that most, if not all, POC flu tests performed well below their respective package insert claims for this virus.
Defining next generation
The following criteria can be used by laboratories to define next-generation technology and screen the many technological possibilities:
- Platforms must offer significantly improved performance over current rapid tests.
- The total time from sample collection to reporting the test result is to be within the time frame of a typical patient visit.
- Results must be objective and not include operator interpretation.
- The platform should be simple (CLIA-waived) and small enough to use in most settings.
- The platform's total cost of ownership should be much lower than that of other existing technologies.
- The platform must offer LIMS and EMR capabilities.
To meet the above criteria, some diagnostic companies are moving to fluorescence-based chemistries combined with small, simple, and yet sophisticated analyzers. Their development teams are using several innovative approaches to couple fluorophores with monoclonal antibodies to yield substantial improvements in avidity while amplifying the test signal. Using a fluorophore instead of a visual latex bead has many advantages, including the potential for dyes that have a sufficiently large Stokes shift to prevent fluorescent material, that may be in biological samples, from giving a false signal in the assay. The placement of a large number of fluorescent molecules inside individual microbeads, perhaps as many as 1 x 106 molecules per bead, has the advantage of yielding a highly amplified signal in the assay. Further, some manufacturers have made strides by working with fluorophores that are resistant to bleaching under ambient light, obviating the need to protect from room light.
From the point of view of instrumentation, highly experienced device manufacturers are offering analyzers with assay analysis software that further improves assay performance. These newer analyzers also ensure ease of use for the end user.
Benefits of next generation assays and systems
When new and emerging POC analyzers are coupled with the latest science in assay chemistry, the following benefits can be expected:
- Improved patient care and physician services, resulting from fast and accurate test results.
- Reduced operator variability, resulting from objective test results.
- Greater flexibility. Newer systems offer multiple work modes to meet the demand of varying test volumes, including single and batch-mode testing capabilities.
- Improvements in quality control result from applying barcode technology, user lock-out, with on-board QC, and automatic calibration, along with the ability to print specific test records. These features help to ensure the lab supervisor has the data to monitor both users and results. Additionally, many supervisor-controllable features provide the ability to search for and retrieve previous test results as performed by specific operators. External barcode units can be used to support data entry prior to a test run (e.g. user, patient, and assay QC information). Some assay cartridges even come with 2D barcodes imprinted on them to provide the analyzer with information from each test cassette including test type, expiration dating, and related information, all of which ensure the correct analysis algorithm is applied to each test.
- Finally, LIMS connectivity is a basic requirement.
Right-sizing your lab's capabilities
Given the several challenges that labs are facing today, including financial constraints, increasing demands, and personnel shortages, labs can greatly benefit from adopting next-generation POC immunoassay analyzers. The greatly improved performance, objectivity, LIMS compatibility and ease of use means the lab can complement its existing instruments and platforms with a faster, simpler to use, cost-effective solution. The incumbent technologies still have their place, but they can be better allocated when coupled with a new generation analyzer.
For example, molecular methods for infectious diseases provide superb performance but at the expense of speed and cost. When these same tests are offered on a next-generation POC analyzer format, offering high sensitivity and negative predictive value, the reliance on more expensive and slower methods can be reserved for multiplexing and reflexing, when needed.
Next-generation POC assay systems are now available that give medical professionals, including lab managers, options that did not exist even only two or three years ago. These options include improved assay performance, reduced reliance on less skilled lab workers to properly interpret and record test results, and the ability to directly transmit the results to lab information systems.
Richard L. Egan, PhD, is Director, Research and Development, Quidel Corporation. He managed the development of the recently FDA-cleared and CLIA-waived Sofia® Fluorescent Immunoassay system with the associated Influenza A+B FIA and is currently managing the development of a series of follow-on assays for the Sofia system. Rhys de Callier, MBA, is Business Unit Leader for the Fluorescent Immunoassay platform for Quidel. He has served in various roles in marketing, business development and strategic planning with a primary focus on the evaluation, development and commercialization of new products and technologies.
