MXPA99008681A - Improvements related to ens devices - Google Patents

Abstract

A test assembly comprising a fragment (10) in which a series of reluctant species immobilize the fragment being located in a storage well (10) having a base (4) and the side walls (

Description

IMPROVEMENTS RELATED TO DEVICES D? TEST DESCRIPTION OF THE INVENTION The invention relates to test devices for immunoassays and the like. Recently to increase the performance of the immunoassays, assay devices have been developed in the form of fragments in which a series of localized reactive sites containing potentially many different reactive species, for example the different antibodies, are deposited. These reactive species react with a respective different analyte in a sample provided to the fragment. Following the extraction of the unbound sample, the fragment can then be examined to determine the presence or absence of the respective analytes. An example of a method for preparing the reaction sites is described in more detail in GB-A-2324866 and a method for analyzing the substrate is described in more detail in EP-A-0902394. Both applications are incorporated herein by reference. The analysis typically involves chemiluminescent radiation seen and mediated at reaction sites that use a slightly low level of CCD camera system or the like. One problem with these substrates is that they are small, they have typical dimensions of 10mm x 10mm x 1mm so they are difficult to handle. This problem is improved by the fact that the fragments carry many small reaction sites that would be damaged if handled incorrectly. A typical fragment will have 100 or more such reaction sites. EP-A-197729, EP-A-745851 and GB-A-2147698 all describe immunoassay devices with inserts, which carry reactive sites, for placement in the respective wells. They are relatively uncomfortable and much less convenient than fragments. In accordance with the present invention, an assay assembly comprises a fragment in which a series of reagent species is immobilized, the fragment being located in a storage well having a base and walls. A removable, protective packing, which can be provided over the storage well to protect the test device in transit. This invention overcomes the aforementioned problems by placing the fragment in a storage well, thus protecting the assay device while it is being operated during an immunoassay process. In addition, to provide a protective, removable packing on the storage well (as is preferred), the complete assembly of the fragment, the storage well, and the packing can be prepared centrally and then easily sent to the terminal user, without risk of damage the fragment and in particular the reactive sites. The shape of the storage well will depend on a number of factors. For example, if the reactive sites are examined using a chemiluminescent technique (or fluorescent or other illumination machine), it is advantageous to make the walls of the dark storage well, preferably black, to reduce the reflections / scattering of light and, where the Storage well joins adjacent storage wells, reducing or eliminating light transmission in adjacent wells. The base and the side wall of the storage well of a black material such as pigmented plastic can therefore be made or they could be covered / painted in a black material. The base is preferably continuous but could have a central opening surrounded by a flange. Another problem that may arise with the use of storage wells is due to the liquid meniscus of the liquid reagent that is used in the storage well during the immunoassay. If this reagent should remain in the well during a final analysis phase, the meniscus will contribute to the distortion and aberration of the image of the reactive sites seen by the camera system. One method is to place the fragment on its edge in the storage well. The well would need to have a transparent side wall to allow to see the reactive sites to be seen. or they could have a top opening large enough to allow the device to be viewed from the top. Conventionally, however, the inner surface of the side wall tapers internally adjacent the base. The use of a tapered side wall allows the transverse sectional area of the open part of a well to be maximized and therefore thus the meniscus which is thus crushed and thus the aberrations are reduced. Also, the fragment can be placed flat on the base to see from the top. In addition, the flattening can be achieved by the selection of the appropriate well material and surface * finished internal. Of course, the material selected for the weand any coating applied to the interior must be chemically non-reactive so as not to affect the immunoassay. Preferred materials comprise PVC and polypropylene. An additional advantage of the use of a taper is that it facilitates simple substrate placement and location. This is particularly important in the case of an automated process for well loading substrates. Although individual storage wecould be provided, preferably a number of such storage weare provided fixed together in a series. This again simplifies the handling of fragments by protecting them within the weand also makes it easier to manage the storage wesince the series will be larger than each individual well. Preferably, the fragment is retained in the storage well by some form of retaining means. The retaining means could be in the form of retaining clips or adhesives for bonding the substrates to the base. None of these is particularly desirable since they could perform the immunoassay. Preferably, the retaining means comprise one or more projections formed hot or cold on the inner surface of the side wall. These could be formed prior to supplying the substrate, which is then pressed adapted into the well, or after the substrate has been provided. Typically, each storage well is square in design since this is adapted to the square format of conventional CCD cameras. However, other forms of design such as rectangular or circular are displayed. To further ease the handling, preferably the assembly comprises a carrier tray for carrying one or more storage wefor use with a test device that processes the instrument. Just as a carrier tray can then be used not only to hold the well or storage weduring delivery to a user but also in an immunoassay machine. An example of a series of storage weaccording to the invention will now be described with reference to the accompanying drawings, in which: - Figure 1 is a perspective view of the previous series; Figure 2 is a section taken on line 2-2 in Figure 1 but showing a biofragment in one of the storage we Figure 3 is a perspective view of the section shown in Figure 2; and, Figure 4 is a perspective view of a carrier tray for the series of storage we Figure 1 illustrates a series of three storage we1-3 formed from a piece of molded plastics of P.V.C. or polypropylene. For the reasons given in the above, the plastic materials incorporate a black pigment. Each storage well 1-3 has a similar shape and as can be seen in Figure 1 it is substantially square in design. For convenience, only storage well 1 will be described in detail. The storage well 1 has a base 4 and a side wall 5 surrounding the base. As can be seen in Figure 2, the side wa5 of each storage well are formed integrally formed at the junctions between the storage we The protrusions 6 are molded at each end of the series to allow handling the series easily. Each side wall 5 has an upper section 7 which is substantially vertical with respect to the base 4 and a lower section 8 which tapers inwardly. The tapered ends just short of the base 4 as well as defines a region 9 that has a width and height corresponding to that of a biofragment 10. The dimensions of the typical series are: 42mm long, 9mm high and 14mm wide at the top. The next construction of the series of storage we1-3, each is supplied with a biochip 10. The biochips 10 can be prepared in any conventional manner to bind ligands at respective reaction sites. For example, the ligands could be immobilized by means of the microfluidic dispersion of the ligand to the substrate, which is chemically activated. Alternative chemical or physical methods could be used. It is important that the method of immobilization, for example, covalent immobilization, is that the ligands are not released during the incubation and washing steps. Each fragment that is 10mm x 10mm in dimensions and is about 1mm thick is then dropped into the respective storage well 1-3 and a biofragment 10 is shown in the well in storage 1 in Figures 2 and 3. Each biofragment 10 is then secured at the base of the storage well by cold or heat forming dents 11 in at least one side section of the side wall 5. These dents can be made by press fit or post formed after the insertion of the biofragment 10. As well as being tapered, the inner surfaces of the side walls 5 are preferably provided with a polished finish to reduce the curvature of the liquid meniscus and minimized optical aberrations. Following these steps, the set of three storage pits can then be pre-packaged in an individual sealed "bubble" in a ribbon that forms a roll by spool dispersion. However, in the preferred method, three sets of storage well series of the type shown in Figure 2 are loaded onto a carrier tray 20 as shown in Figure 4. This carrier tray is made of a molded plastic and has two sets of crosspieces 21, 22 extending respectively between the opposite side walls 23, 24. Nine openings 25 are defined in which the respective storage wells can be located. Each set of three storage wells 1-3 are loaded parallel to the crosspieces 21 with the crosspieces 22 entering corresponding recess 30 between the adjacent storage wells. The loaded carrier tray is then sealed in packaging materials suitable for transport. The user can then remove the storage wells from the carrier tray or, preferably, leave them in place and use the carrier tray to move the storage wells over the immunoassay process, for example as described in more detail in our Application European Copending Patent No. 98307706.6. An additional option is to locate several of the trays shown in Figure 4 with storage wells loaded in the individual compartments of a stack defined by a housing. That accommodation can then be packaged for transport. In this case, the trays could be extracted directly from the housing by a test instrument or, of course, manually extracted as required.

Claims (1)

CLAIMS 1. A test assembly comprising a fragment in which a series of reactive species are immobilized, the fragment being located in a storage well having a base and side walls. The assembly according to claim 1, characterized in that it also comprises a removable, protective packing, provided on the storage well. 3. The assembly according to any of the preceding claims, characterized in that the fragment substantially fills the area of the base. The assembly according to any of the preceding claims, characterized in that the fragment is retained in the storage well by means of retention. The assembly according to claim 4, characterized in that the retaining means comprise one or more projections formed hot or cold on the inner surface of the side wall. The assembly according to any of the preceding claims, characterized in that it further comprises a carrier tray for carrying one or more storage wells for use with a fragment processing instrument. . The assembly according to claim 6, characterized in that it also comprises a plurality of carrier trays placed in a stack. The assembly according to any of the preceding claims, characterized in that the internal surface of the side wall of the storage well tapers internally adjacent the base. The assembly according to any of the preceding claims, characterized in that the base is square. The assembly according to any of the preceding claims, characterized in that the storage well comprises molded plastics. The assembly according to any of the preceding claims, characterized in that the assembly has a plurality of the storage wells fixed together in a series. The assembly according to claim 11, characterized in that the series comprises three storage wells, preferably placed in a line. The assembly according to claim 11 or claim 12, when dependent on claim 10, characterized in that, the storage wells in the series are made of a single molded plastics.

1 . The assembly according to any of the preceding claims, characterized in that it also comprises a removable, protective packaging, on or in each storage well.