SEALING FOIL BREAKER PARTICULARLY FOR ANALYZER TEST CUPS

Abstract: An apparatus for breaking a seal which closes an otherwise open top of a cup comprises a reciprocable vertical shaft (21) having a pyramid shaped lower tip for piercing a sealing foil (8d) secured across the top of the cup, which may be an analyzer test cup containing an active substance. The edges (21b) of the pyramid divide the foil into triangular segments which are pressed against the inner wall of the cup by the cylindrical root portion (21c) of the shaft such that they do not engage any of the active substance or interfere with subsequent injections into or withdrawals from the cup.

Description: This invention relates to a sealing foil breaker particularly for test cups used in an analyzer, which may be for detecting and determining a very small quantity of a physiologically active substance in a sample liquid, especially in an enzyme immunoassay (EIA). Enzyme immunoassays in which an enzyme is used as a label of a combined product of a reaction of an antigen or an antibody have recently been studied and energetically developed as immunological methods of detecting and determining very small quantities of a physiologically active substance. Enzyme immunoassays include various methods, such as the sandwich method or competitive method, as disclosed in, for example, "Clinical Chemistry", Vol. 22, No. 8, 1243-1255 (1976). In a regularly used method, a competitive method, a conjugate with which an enzyme is combined as a label is brought into contact with an antigen or an antibody fixed to an insoluble carrier to generate a reaction of the antigen or antibody and form a complex. A substrate, which receives an active enzyme and causes an optically detectable change (in, for example, the fluorescent strength) to occur, is then brought into contact with this complex. An optical change occurs and the quantity of the antibody or antigen in a test liquid sample can thereby be measured. Since these operations are usually carried out for a plurality of samples, a device having a plurality of cells, such as a multi-titre plate has been provided and used in practice. The method described above, in which such a multi-titre plate is used, is suitable for conducting measurements on the same inspection item or a certain number of a predetermined kind of inspection items. However, this method requires intensively laborious preparations prior to the stage in which the practical measurements are conducted, particularly where the inspection items for each sample are varied when occasion calls. Under these circumstances, the present inventors have proposed the following system to improve the practical operability and operation efficiency of the enzyme immunoassay. In this system, a special antibody (or antigen) corresponding to predetermined inspection items is bound to the surfaces of beads serving as insoluble carriers, and the carriers are placed in a cup type vessel whose upper opening is sealed. A plurality of groups of such test cups are prepared in advance for a plurality of inspection items. When a practical analysis is carried out, a test cup that corresponds to an inspection item necessary for an object sample is selected from the groups of test cups, and it is supported on a carrier and sent to an analyzer. Such a system can be used very effectively, especially in an analyzer in which automated measurement is conducted. The present invention has been developed to provide a seal breaker which can be suitably applied to a system in which the test cups described above are used. An object of the present invention is thus to provide a sealing foil breaker for conveniently breaking the sealing foil of a test cup of the above-mentioned type in a stage prior to the stage(s) in which the measurements are conducted. Another object of the invention is to provide a sealing foil breaker wherein the possibility of the broken foil adversely affecting a measurement operation carried out in the test cup in subsequent steps can be reduced or eliminated, so that no error occurs in an operation for determining a very small quantity of a substance. Referring now to the prior art in GB 1113468 the tip 5 passes right the way through the can, both top and bottom openings. In US 1962415 the tip does not go through the bottom of the container, but the specification gives no teaching that the tip 10 should not contact the contents of the container. French 2427958 is not concerned with apparatus having a shaft but merely is a closure cap for a container, the interior surface of which is provided with a seal penetrating protrusion. This specification is concerned with a closure for a food containing tube, e.g. a tube of mayonnaise, and the invention is the provision of a cap which seals the end of the tube in one orientation but pierces it when placed on the tube in a reverse orientation. According to the present invention, there is provided a combination comprising one or more cups having a seal closing an otherwise open top, and an apparatus for breaking the said seal which closes the otherwise open top of the cup, said cup containing a reaction generating substance, the apparatus comprising a shaft having a pointed tip defined by less than seven flat pyramidally converging sides, a region of the shaft next to the pointed tip being so sized and shaped as to fit closely within the top of the cup, and an actuator means for causing relative movement between the shaft and the cup to cause the tip of the shaft to pierce the seal and to cause the shaft to urge portions of the pierced seal towards the cup wall or walls, the actuator means causing the said relative movement to stop with a clearance between the tip of the shaft and material in the cup. The apparatus preferably comprises transport means for moving the shaft and/or the cup to and from a position in which the shaft is aligned with the cup. Each of the top of the cup and the said region of the shaft next to the pointed tip preferably has a circular section. The apparatus preferably comprises a plurality of shafts, each for breaking the seal of a respective cup. In preferred aspects of the combination the apparatus is characterized in that it comprises stationary mounting means, and in that the transport means retain and convey the said sealed cup past and below the said mounting means, and in that the downwardly depending, vertically oriented, cylindrical, reciprocable shaft is secured to the mounting means and in that the actuator means is secured to the mounting means and is disposed in engagement with said shaft for selectively driving the said shaft downwardly. In another preferred form the combination is characterized in that a plurality of the shafts are arranged in a row downwardly depending and vertically oriented and fixed to a stopper plate, and in that the actuator means are disposed in engagement with the said stopper plate for driving the said shafts downwardly. The four sided pyramid shaped lower end of the wedge member divides the foil into four equal tongues and presses them against the inner surface of the test cup, thus avoiding any irregular segments. The sealing foil tends to be broken irregularly when the lower end of the breaker has a simple conical configuration or more than six flat side surfaces converging at their lower ends. In the previously mentioned analysis, a substance placed in a test cup and contributing to, for example, an immunological reaction comprises a special antibody (or an antigen) fixed to the surfaces of synthetic resin beads and a labelled antibody (or an antigen as a conjugate). These beads may contain magnetic bodies so that they may be vibrated in the test cup by a varying external magnetic field. The test cup usually has a small capacity of not more than several millilitres, and is made of a transparent or opaque synthetic resin; the latter is more preferable for shielding the stray light. The sealing foil preferably has a sufficiently high sealability and such fragility that it may be easily broken by a sharp jig. The foil may be a metal foil such as aluminium, or an aluminium coated plastics film, but the material or the foil is not limited to these. The foil is generally heat sealed or bonded to the outer edge of the upper lip of the test cup. The foil breaking wedge member may be made of metal, a ceramic material, or a hard synthetic resin. For a better understanding of the present invention and to show how it may be put into effect, reference will now be made by way of example to the accompanying drawings, in which: FIGURE 1 shows a schematic example of an enzyme immunity analyzer in which a sealing foil breaker according to the present invention is installed; FIGURE 2 is a perspective view of a test plate on which test cups are supported, and a transfer mechanism therefor; FIGURE 3 is a perspective view showing the construction of the sealing foil breaker; and FIGURES 4(a), 4(b) and 4(c) sequentially illustrate the breaking of a sealing foil by a wedge type member. FIGURE 5 is a perspective view showing the construction of a multiple-shaft type sealing foil breaker according to the present invention. The present invention will now be described taking as an example an enzyme immunity analyzer in which the sealing foil breaker shown in the drawings is installed. Referring to Figure 1, reference numeral 1 denotes a transfer passage along which a test plate 7 with test cups, which will be described later, arranged in order and supported thereon is conveyed in the direction of the arrow. Above the transfer passage a sealing foil breaker 2, a sample liquid injector 3, a B/F separator 4, a substrate injector 5 and a photometer 6 are arranged in the mentioned order from the upstream side of the passage to the downstream side thereof. The sample liquid injector 3, B/F separator 4, substrate injector 5 and photometer 6 are respectively used to inject a predetermined quantity of a sample liquid into an opened reaction cell in a test cup, thereafter wash the interior of the reaction cell, i.e., remove a free antibody reaction complex which is not bound to the surfaces of the beads in the reaction cell from the interior thereof or subject the interior of the cell to B/F separation, inject into the B/F separated reaction cell a substrate which receives an active enzyme used as a sign on the antibody reaction complex to cause a detectable change to occur therein, and determine the change occurring in the substrate. The test cup 8 referred to above, as shown in Figures 3 and 4, comprises an open cup type vessel body 8a containing a plurality of beads 8b, and a sealing foil 8d sealing an upper opening 8c of the vessel body. A special antibody (or antigen) is bound to the beads 8b in advance. The test tray or plate 7 is provided with a plurality of holes to accommodate a plurality of selected test cups 8 as shown in Figure 2. The test plate is adapted to be conveyed along the transfer passage between its side plates 9, 9 by an intermittent drive mechanism shown in Figure 2, wherein reference numeral 10 denotes an eccentric cam, 11 is a transfer bar, 12 is a ratchet pawl attached to the transfer bar, and 13 are ratchet teeth formed in a side wall of the test plate 7 and adapted to be engaged by the ratchet pawl. With such a drive mechanism the test plate 7 is conveyed step-by-step or intermittently to positions below the devices shown in Figure 1, in succession. The sealing foil breaker 2 comprises a shaft 21 supported on a lower member 20b of a fixed frame 20 for vertical reciprocation, an air cylinder 22 having a downwardly extending plunger 23 engaging a flanged upper head 21a of the shaft, and a return spring 24 urging the shaft in the upward direction to maintain engagement between the head 21a and plunger 23. When air is supplied from a source (not shown) into the cylinder 22, the plunger 23 and shaft 21 are driven downwardly such that the sealing foil 8d of a test cup positioned below the shaft is pierced by its sharp lower tip 21b. Reference numeral 22a denotes an air supply line extending to the cylinder 22, and 22b is a bracket for mounting the cylinder to an upper frame member 20a. The lower tip 21b of the shaft has four flat side surfaces converging at their lower ends in a pyramid shape. the length of the tip is sufficiently less than the height of the test cup 8 as shown in Figure 4c, so that, even when the shaft 21 is moved down to a maximum extent into the test cup, the sharp piercing point 21e of the tip does not contact the beads 8b in the cup. The diameter of the base or root section 21c of the shaft is slightly smaller than that of the upper opening 8c of the test cup. For example, the diameter of the section 21c is 9.3mm while the diameter of the outer opening 8c is 10mm. When a sealing foil is broken by the apparatus described above, it is centrally pierced by the downward movement of the shaft 21 as shown in Figure 4 and divided into four triangular tongue-like segments which are bent downwardly and pressed against the inner surface of the test cup (Figure 4c). This maintains the upper opening of the test cup unobstructed after the shaft is withdrawn, and the retention of the segments on the upper lip of the cup prevents them from absorbing any injected samples or otherwise adversely affecting the accuracy of any measurement made. Although only a single foil breaker is shown in Figures 1 and 3, a transverse row of, for example, five such breakers could be combined as shown in Figure 5 to simultaneously pierce a plurality of sealing foils of the test cups in the conveyor tray of Figure 2. In Figure 5 spring-urged five breaker shafts 121 are fixed to a stopper plate 121a which is moved up and down by the plunger 123 connected to a double-acting air cylinder 122. The air cylinder is controlled by a speed controller 122a comprising a pair of air pressure tubes connected to an electromagnetic valve (not shown). The springs 124 may be omitted totally or partially.

Claims: A combination comprising one or more cups having a seal (8d) closing an otherwise open top (8c), and an apparatus for breaking the said seal which closes the otherwise open top of the cup (8), said cup containing a reaction generating substance, the apparatus comprising a shaft (21) having a pointed tip defined by less than seven flat pyramidally converging sides, a region of the shaft next to the pointed tip being so sized and shaped as to fit closely within the top of the cup, and an actuator means (22) for causing relative movement between the shaft and the cup to cause the tip of the shaft to pierce the seal and to cause the shaft to urge portions of the pierced seal towards the cup wall or walls, the actuator means causing the said relative movement to stop with a clearance between the tip of the shaft and material in the cup. A combination as claimed in claim 1 characterised in that the apparatus includes transport means (1,7) for moving the shaft and/or the cup to and from a position in which the shaft is aligned with the cup. A combination as claimed in claim 1 or Claim 2 characterised in that each of the top of the cup and the said region of the shaft next to the pointed tip has a circular section. A combination as claimed in any one of claims 1 to 3, characterised in that the apparatus comprises a plurality of shafts, each for breaking the seal of a respective cup. A combination as claimed in Claim 1, 2, 3 or 4 characterised in that the apparatus comprises stationary mounting means (20), and in that the transport means (1, 7) retain and convey the said sealed cup past and below the said mounting means, and in that the downwardly depending, vertically oriented, cylindrical, reciprocable shaft (21) is secured to the mounting means, and in that the actuator means (22) is secured to the mounting means and is disposed in engagement with said shaft for selectively driving the said shaft downwardly. A combination as claimed in Claim 5, characterised in that a plurality of the shafts (21) are arranged in a row downwardly depending and vertically oriented and fixed to a stopper plate, and in that the actuator means are disposed in engagement with the said stopper plate for driving the said shafts.

Inventors: HAYASHI, HIDECHIKA, HIGO, YUJI
Applicants: TOSOH CORPORATION
Application year: 1987
Main classification: B67B7
IPC codes: B26F3, G01N33, B67B7, B26F1, G01N35