Current automated laboratory instruments for the analysis of immunoassays are relatively complex, difficult to use, have lower reliability than their general chemistry counterparts, and have high production costs due to the many mechanisms that are typically required for assay processing. These assay processing mechanisms include those involving wet reagent storage with strict storage conditions, those that perform precise incubation, mechanisms to wash unbound materials effectively, as well as mechanisms for precise metering of assay and signal reagents and precise measurement of very low levels of signal.
To that end, many high volume immunoassay systems utilize micro-plates, individual wells or cuvettes either with solid phase coatings that capture antibody reactions to the walls of the vessel or with coated magnetic particles that capture antigens in solution and then are pulled to the walls by magnetic force. These systems must store wet reagents for long periods of time and under well controlled environmental conditions. Current technology is usually limited to single test measurements or are used with a test “cocktail” in which the measurement of multi-analytes is measured in total. No real multiplexing capability presently exists for assay specific measurement. The large liquid volume of expensive rare reagents used in standard immunoassay tests has significant impact to the cost of testing. Immunochemistry is also procedurally complex requiring frequent calibration, an understanding of the complex operations, and tight control of reagent storage conditions.
There has been significant evolution in terms of eliminating certain hardware from automated “wet” chemistry analytical systems. For example, U.S. Pat. No. 7,250,303 to Jakubowicz et al., describes a combinational analyzer in which pluralities of disposable metering tips are used in order to eliminate wash modules and on board fluidic systems that were previously required. This elimination of hardware enabled integration of the above noted wet chemistry hardware with additional systems for permitting the testing of so-called dry slide or thin film analytical test elements within the same apparatus. These latter analytical test elements, as generally described by U.S. Pat. No. 3,992,158 to Przbylowicz et al., are generally defined by an integral multi-layered support structure onto which sample fluid can be added and in which results can be obtained to detect various changes in the condition of the sample to yield analytical results. The above noted test elements are relatively compact and therefore a plurality of these elements can be stored for use on board an automated analyzer, such as the above-noted version. In this analyzer, a predetermined volume of sample fluid is added from a sample supply using a metering mechanism having a proboscis wherein the sample is dispensed onto the slide test element at a dispensing station of the analyzer. Upon dispensing, the sample is affected by a porous spreading layer relative to a reagent layer of the slide element in which an analyte of interest can react. The slide element includes the reagent layer as well as a reflective intermediate layer, wherein reaction results can be detected through a change in electromagnetic radiation or through a colorimetric change, by way of example.
According to the above reference and following the addition of a predetermined volume of patient sample, the slide elements are incrementally shuttled into an incubator that is defined by a set of concentric rings, the rings being independently rotatable about a center axis. The slide elements are caused to pass through an ion selective electrode station and/or a colorimetric station provided on separate rings of the incubator. A wash module can also be optionally included in the center of the incubator or elsewhere within the automated clinical analyzer, as needed.
Following incubation/test, the slide elements can be disposed of by shuttling them into an exit chute or other similar waste port. Significant throughput has been achieved using dry slide test element technology in regard to certain analyte tests that are amenable to this format. The addition of immunoassays expands the overall menu of tests that can be handled, including those requiring a plurality of tests to be performed on a single sample as performed in a test cuvette or similar form of assay supporting structure.
As noted, the use of so-called “wet” chemistry technology for the conduction and detection of immunoassays, though providing good throughput and satisfactory test results, is relatively limited given the overall expense and complexity involved. As a result, there is a general need in the field to provide additional assay measurement/analysis techniques that reduce overall complexity while further enabling the capability of performing multiple tests on a single element.