A wide variety of devices are now available for detecting analytes present in body fluids, such as whole blood, plasma, serum and urine, to aid in medical diagnosis. The simplest form of such a device performs the in vitro diagnostic test on the surface of a dry porous carrier, such as a sheet or strip of nitrocellulose membrane, which is usually contained within a housing that defines a sample application site and a detection site for viewing the assay result. In the so-called “spot test”, sample is applied as a drop to a carrier having immobilized thereon a reagent capable of binding to the analyte targeted for detection. After washing the carrier, the presence of bound analyte is revealed by incubation with an analyte-specific labeling agent. An alternative one-step approach, the so-called “lateral flow” format, similarly makes use of a reagent that is immobilized on the carrier. In this format, sample is applied to one end of a nitrocellulose strip, and flows by capillary action toward reagent immobilized at the other end. As the sample migrates along the strip, additional mobile reagents become entrained in the sample stream so that, typically, a detectable reagent “sandwich” is developed at the other end, consisting of the immobilized reagent, the analyte of interest, and an analyte-binding detector reagent that is labeled to reveal the analyte's presence.
Diagnostic devices of this type are intended to be disposable after a single use, and must therefore be designed for inexpensive production. Importantly, however, the engineering required to perform the test in a rapid and reproducible fashion, with maximum sensitivity and specificity and with minimum sample volume, is highly demanding. The art is therefore continuously refining the design of such devices in order to improve their price and practicality.
One device, which incorporates numerous improvements over those currently marketed, is described in WO00/08466 published Feb. 17, 2000 in the name of the present assignee. Described therein is a diagnostic device that, like many others, incorporates both a dry porous carrier in the form of a nitrocellulose sheet, and a housing for that carrier that incorporates both a sample inlet and a window for viewing the assay result. The sample inlet of the device is particularly unique, in providing a U-shaped channel from which sample can be deposited across a wide sample deposition zone for capillary flow into a narrowed detection channel in which the analyte is captured for detection. By channeling the flow of sample confocally through the mobile reagents located upstream in the deposition zone, the device concentrates reagents and analyte and retards red blood cell migration, and thereby enhances the sensitivity of the assay for a given volume of sample.
That device utilizes a carrier that most desirably is a uniplanar, single sheet of nitrocellulose, and uses both the housing and repellant border material to drive sample flow from the sample zone to the relatively narrow detection channel. In other devices, a multiplanar construction is incorporated in which the various pads, formed of the carrier material, are coupled in flow communication. In this arrangement, each pad can be used for a different purpose. For instance, and as shown in co-assigned U.S. Pat. No. 5,658,801, each one of a plurality of pads can be impregnated with a different one of the various reagents required to detect a given analyte by the lateral flow method. These pads can then be “stacked” one above the other and in flow communication with a base carrier. Reagents deposited in the pads are picked up by sample that has been applied to the top pad, and any complexes formed with the analyte then are captured by reagent immobilized downstream on the base carrier, where a reading can be taken.
In an alternative multi-pad design, described for instance in U.S. Pat. No. 5,559,041, a sample pad optionally impregnated with reagent is positioned in flow communication with a detection pad bearing immobilized reagent. One or more intervening pads are also incorporated, to function as a filter for particulates contained in the sample.
Despite these advances in diagnostic devices, there remains a need to improve the ease with which they can be used and manufactured, without sacrificing their reliability.
It is an object of the present invention to provide an improved device for detection of analytes in a liquid sample.