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Publication numberUS3582283 A
Publication typeGrant
Publication dateJun 1, 1971
Filing dateMar 25, 1970
Priority dateMar 25, 1970
Publication numberUS 3582283 A, US 3582283A, US-A-3582283, US3582283 A, US3582283A
InventorsSalustiano S Mirasol Jr
Original AssigneeXerox Corp
Export CitationBiBTeX, EndNote, RefMan
External Links: USPTO, USPTO Assignment, Espacenet
Chemical package
US 3582283 A
Images(1)
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Description  (OCR text may contain errors)

S. s. MIRASOL, JR

CHEMICAL PACKAGE June` l',` 1971 Filed March 25, 1970 f fJ Azasf/m/a 5.' ,41m/1501., da,

Jy Wm /QrYaAQ/rfy United States Patent O U.S. Cl. 23-253 23 Claims ABSTRACT F THE DISCLOSURE A storage section, suitable for use as a component of a disposable test package, comprising a plate having a thickness on the order of the thickness of the reagent tablets to be stored therein, said plate having at least one reagent storage cavity extending therethrough, one or more holes or channels adjacent each cavity to guide a plunger through the storage cavity during reagent dispensing, and top and bottom membranes adapted to hold one or more reagent tablets in position within the reagent storage cavities. The storage section can be an assembled part of the disposable test package or it can be a separate component positioned adjacent thereto during reagent dispensing.

The top and bottom membranes have particular barrier properties to ensure the proper environmental control for prolonged storage life of the prepackaged reagents. The bottom :membrane is also of low tear resistance so that, during dispensing, a reagent tablet can be easily and reliably dispensed from its storage cavity.

BACKGROUND OF THE INVENTION This invention relates to automated chemical analysis and, more particularly, to the automated chemical analysis of body fluids, such as blood, urine, etc.

In copending application Ser. No. 602,025, led Dec. 15, 1966, and now U.S. Pat. No. 3,504,376, there is disclosed an automated chemical analytical system including a plurality of different disposable reaction containers, a magazine for the storage of the plurality of different reaction containers, a station for the addition of sample material to the reaction container, a mixing and incubation station wherein the reaction mixture is maintained in the disposable container for a period of time sufficient to culminate the chemical reaction, a detection station wherein the analytical data is obtained by monitoring one or more of the physical properties of the reaction mixture, a disposal station wherein the disposable reaction container is eliminated from the system, and means to transport the disposable reaction container from its storage area in the magazine through the system to the disposal station. The heart of the system is the disposable reaction container which, in its broad aspects, has at least one lower compartment for the admixing and reaction of reagents and sample, and an upper section having a plurality of reagent storage chambers in communication with each reaction compartment. At least one wall or end portion of the reaction compartment may be optically transparent so that upon completion of the desired chemical reaction the compartment can be utilized as a cuvette for optical analysis. Optionally, none of the walls need be optically transparent as a probe photometer such as the one disclosed in Gale 3,164,663 may be inserted into the reaction mixture and electromagnetic radiation from a source passed through a radiation conductor, the reaction mixture and back through the radiation conductor to a detection means, without the necessity of passing through the compartment Walls.

In US. No. 3,497,320 there is disclosed a similar, though conceptually and structurally different, analytical apparatus and system. The disposable reaction container "ice in this application has a flexible lower compartment, i.e., one having at least one flexible wall, so that during analysis a radiation source and a detection means can cooperate with the flexible wall or walls of the cuvette to define a -iixed optical path length between the radiation source and the detection means through the reaction mixture. The automatic analytical apparatus including monitoring means having a radiation source and means responsive to the variations in light transmittance or absorbance caused by different concentrations of a tested-for constituent in the reaction mixture. In one embodiment, the light source and the responsive means are pressed against opposite sides of the reaction compartment or cuvette during analysis to define the fixed optical path length through the reaction mixture.

As previously indicated, the heart of each analytical system described above is the disposable reaction container which, in accordance with the disclosures of the aforementioned patents, comprises a test vessel having at least one lower compartment for the admixing and reaction of reagents and samples, and a storage section having a plurality of reagent storage chambers of generally cylindrical configuration which can be placed in communication with each reaction compartment. Means are provided to hold the analytical reagents, preferably in tablet form, in their respective reagent storage chambers until such time as they are to be dispensed, in accordance with the particular analytical procedure prepackaged therein, into the adjacent reaction compartment. In the most signi-iicant embodiment described in the aforementioned patents, a shearable, thin plastic layer is positioned between the reaction compartment section and the reagent storage section. Reagent tablets, predispensed into the reagent storage chambers, are prevented from premature dispensing into the adjacent reaction compartment by this restraining means. During dispensing, force is applied to the top wall of the reagent storage chamber. This force, transmitted to the shearable layer through the reagent tablet stored within the storage chamber, causes the shearable layer to rupture, below the reagent tablet, with the concomitant dispensing of the tablet into the adjacent reaction compartment. With such a design, however, the exacting reagent dispensing goals established for this system by the assignee of the present invention were not obtainable either through failure of the shearable layer to properly rupture or because the reagent tablet was crushed and not totally dispensed from its storage chamber.

Alternate designs, for example as shown by Hamilton in U.S. Nos. 3,477,812; 3,477,822; and 3,480,398; were formulated and tested. Though such packages, as described therein, were more than adequate for those tests which required dispensing of one or two reagent tablets early in the analytical procedure, the extreme hygroscopic nature of the reagent tablets either caused premature dispensing or a failure to dispense for those tablets which would be adjacent a zone of high relative humidity (i.e., the reaction mixture in the adjacent reaction compartment) for any lengthy period of time. It thus appears that if a single test package design is to be utilized for all types of tests conducted in an automated chemical analyzer of the type herein described and offered an extensive test repertoire, some type of barrier, such as the membrane described above, should be provided between the reaction compartments and the adjacent reagent storage chambers to protect the hygroscopic tablets until such time as they are dispensed into the reaction compartment in accordance with the particular analytical procedure prepackaged into the disposable test package. It would be desirable, therefore, to have a disposable test package wherein each reaction compartment is separated by a membrane from the adjacent reagent storage chambers, the test package not being susceptible to the dispensing problems identified above which plagued similar, though structurally dilerent, designs.

OBJECTS OF 'THE INVENTION It is, therefore, an object of this invention to provide a. novel disposable test package of improved design.

It is a further object of the present invention to provide a novel dispos-able test package suitable for use in an automated analytical system.

It is a further object of the present invention to provide a novel storage section for a disposable test package, said storage section being of such configuration that prepackaged reagents can be reliably dispensed therefrom into an adjacent reaction compartment.

Yet a still further object of the present invention is to provide a novel storage section for a disposable test package having a barrier membrane between the reagent storage chambers and underlying reaction compartments, said storage section being of such configuration that the prepackaged reagents can be reliably dispensed through said barrier membrane into an underlying reaction cornpartment.

These and still further objects, features, and advantages of the present invention will become apparent upon consideration of the following detailed disclosure.

BRIEF SUMMARY OF THE INVENTION These and still further objects of the present invention are achieved, in accordance therewith, by providing an improved storage section suitable for use as a component of a disposable test package, said improved storage section comprising a plate having a thickness on the order of the thickness of the reagent tablets to be stored therein, said plate having at least one reagent storage cavity extending therethrough, one or more holes or channels adjacent each cavity to guide a plunger through the storage cavity during reagent dispensing, and top and bottom membranes adapted to hold one or more reagent tablets in position within the reagent storage cavities. This storage section is positioned adjacent a lower reaction compartment section having one or more reaction compartments associated therewith. In a presently preferred embodiment of the invention, the lower reaction compartment section has a plurality of distinct reaction compartments associated therewith, and each storage section has a plurality of reagent storage cavities associated with each reaction compartment.

The storage section of the present invention can be an assembled part of a disposable test package as by bonding or heat sealing to the upper portion of the reaction compartment section thereof.

Alternatively, the storage section can be stored as a separate component, in a suitable magazine, until the time for analysis at which time it is transported into position above the reaction compartment portion of the test package. When in proper position, each prepackaged reagent can be dispensed therefrom into the underlying reaction compartment after which the storage section can be removed and discarded. If found desirable, the storage section can be kept in position until the analysis is complete and then discarded along with the reaction compartment portion of the test package.

The top membrane since it represents the top wall of the disposable test package should be impermeable, or relatively impermeable, to gases, moisture and light. These characteristics serve to prolong the storage life of reagents prepackaged into the reagent storage cavities. Additionally, to assist in maintaining as much of the reaction mixture Within the disposable test package during analysis, such as during mixing, it is desirable that the top membrane be of high tear resistance such that, during dispensing, it is not completely ruptured. This serves to eliminate extremely large holes above each reagent storage cavity and thus minimize the loss, or addition,

of various materials from and to the disposable test package. Additionally, it prevents direct contact between the plunger and the reagent tablet, and other materials Within the reagent storage cavity thereby eliminating one possibility for cross-contamination between dilerent test packages.

The bottom membrane, as opposed to the top membrane, should have 10W tear' resistance so that when force is applied thereto, from the dispensing plunger via the reagent tablet, it will rupture whereby the reagent tablet will be dispensed from its storage cavity. Desirably, the bottom membrane should have good gas, moisture, and light impermeable characteristics, especially where the storage section of the present invention is stored as a separate component in its own supply magazine. Where, however, the storage section of the present invention is physically bonded to the reaction compartment section of a disposable test package, the gas, moisture and light barrier properties of the bottom membrane can be somewhat less severe than when the storage section is stored as a separate component, since the lower portion of the reaction compartment section is, in fact, the bottom and side walls of the disposable test package per se and, accordingly, performs, along that surface, the primary function of maintaining the necessary environment within the disposable test package for prolonged storage life. It is still desirable, however, that the bottom membrane, in this configuration, have some desirable barrier properties to additionally ensure that the prepackaged reagents are not adversely affected during prolonged storage.

In use, when the storage section is properly positioned over an underlying reaction compartment section, either by being attached thereto or by being properly positioned either manually or by an automated analytical system, a reagent dispensing plunger, of specific design, is reciprocated vertically whereby the prepackaged tablets stored within the reagent storage cavity are dispensed into the underlying reaction compartment. Specically, the reagent dispenser comprises a plunger, adapted to contact the top membrane adjacent the reagent tablet and, as it continues in its downward path, force the reagent tablet through the bottom membrane. Mounted on the plunger, or on means adjacent thereto, is pointed probe means extending to a level below the bottom level of the plunger and adapted to pass through the guide holes or channels prior to contact of the plunger with the upper surface of the top membrane. The probes serve to puncture the bottom membrane whereby less force will be required to rupture the bottom membrane when the reagent tablet is pushed thereagainst as it is dispensed from its storage cavity into the underlying reaction compartment. Due to the stresses induced by the probe-caused punctures in the bottom membrane, in combination with the low tear resistance of the bottom membrane, less force will be required to dispense the reagent tablet from its storage cavity with the result that crushing of the reagent tablet should be avoided with an increase in dispensing reliability expected to be attendant thereto.

BRIEF DESCRIPTION OF THE DRAWINGS The nature of the invention will be more easily understood when it is considered in conjunction with the accompanying drawings wherein:

FIG. 1A is a top view of a disposable reaction container incorporating an exemplary reagent storage section ofthe present invention;

FIG. 1B is a side view of the disposable reaction container of FIG. l;

FIG. 2 is an enlarged side-sectional view of the reagent storage section of FIG. 1, showing a multi-pronged reagent dispensing mechanism and the cooperationV thereof with the reagent storage section and a reagent tablet therein; and

FIG. 3 is a top view of an alternate reagent storage section with the top and bottom membranes removed.

Referring to FIGS. 1 and 2, there is seen a disposable test package having an upper reagent storage section 12 and a lower reaction compartment section 14. Reagent storage section 12 comprises a storage plate 1S having a plurality of reagent storage cavities 16 therein. Within each storage cavity 16 there is stored a reagent tablet T held in place by a top membrane 18 and a bottom membrane 20. On opposite sides of each cavity 16 (i.e., 180 apart) are channels 22 through which the dispensing mechanism is guided during reagent dispensing. Guide channels 22 on each side of the cavity are of such dimension that the reagent tablet, or any portion thereof, cannot be situated within the guide channel. This eliminates the possibility of the reagent tablet being in an improper position during reagent dispensing, such that the pointed end of the probe on the reagent dispensing means will not crush or otherwise destroy the reagent tablet. As can best be seen in FIG. 1, the reaction compartment section 14 has two reaction compartments 24 and 26 associated therewith, with reagent storage section 12 having a plurality of reagent storage cavities 16 associated with each reaction compartment. Four such reagent storage cavities are shown associated with each reaction compartment in the embodiment described herein, but it should be understood that more or less storage cavities can be provided if desired. It has been found, however, that four such cavities, either with or without predispensing of analytical reagents into an underlying reaction compartment, are generally sufficient for the storage of the reagents to be utilized in the majority of analytical procedures preprogrammed into an automated chemical analyzer of the type herein contemplated. Accordingly, a single test package design can be utilized for all such procedures even though, in certain procedures, some of the storage cavities may not be filled with reagents. As can best be seen in FIG. 1B, the thickness of plate 15 is on the order of the thickness of reagent tablets T so as to minimize the possibility, during storage, of crushing the stored tablets by contact with items external to the package. In the center of each grouping of reagent storage cavities, there is provided a hole 28 through which access to an underlying reaction compartment can be had, prior to actual dispensing of a reagent tablet from one or more of the reagent storage cavities.

The reagent storage plate can be made, for example, from high density polyethylene sheet on the order of about 60 mils thick. As shown, there are four reagent storage cavities and an aliquoter hole in each of two groups, one group each above each of the two reaction compartments. The reagent storage cavity can be, for example as shown in FIG. 3, a circle with a 5/2 inch diameter with two 3/32 inch diameter circles substantially tangential thereto on opposite sides of the larger circle. The smaller circles from the holes through which the dispensing probes will be guided during reagent dispensing. Such a storage plate would be suitable for storing Ms inch diameter tablets therein.

As indicated above, the top membrane should have high tear resistance and must be impermeable to gases, moisture and light. It can be formed from a single material, if such a material has the combined properties desired, or from a laminate of various materials necessary to give the desired properties. An exemplary top membrane comprises a lower layer of high, medium or low density polyethylene; an intermediate layer of nylon, Surlyn (an ionomeric product of E. I. du Pont de Nemours & Co.), or polypropylene; and a top layer of aluminum foil. The polyethylene layer is sufficiently similar to the high density o-f the storage plate that a strong heat seal can be obtained between these two adjacent materials. During fabrication, the top membrane should be sealed to the reagent storage plate such that the membrane above the reagent storage cavities is in a condition -where it is bowed outwardly. This sealing technique will leave that portion of the membrane above each cavity in a relatively flexible condition such that, during reagent dispensing, it can be inverted (i.e., bowed inwardly of the reagent storage cavity) without actual tearing of the membrane. The only holes, therefore, above each reagent storage cavity will be caused by the reagent dispensing probes as they pass therethrough. The high tear resistance of the top membrane will prevent those holes from becoming larger and will minimize the possibility of inadvertent loss of material from the underlying reaction compartment through the reagent storage cavity.

The bottom membrane can also be formed from a single material, if such a material has the combined properties desired, or a laminate of materials. As indicated above, the bottom membrane should have good gas and water barrier properties, low tear resistance, and should be heat sealable to the adjacent surface of the reagent storage plate. An exemplary membrane is an upper layer of high, medium or low density polyethylene, preferably low density, bonded to a lower layer of aluminum foil. Once again, the polyethylene is sufficiently similar to the high density polyethylene of the storage plate to permit strong bonding thereto. Optionally, a protective coating, such as overprint varnish, can be provided on the lower surface of the aluminum foil at least for those procedures where the reaction mixture will attack the aluminum foil. During fabrication, the bottom membrane is bonded flush with the surface of the storage plate, such that those portions thereof below the reagent storage cavities are in a relatively planar, stressed condition. Thus, during dispensing, there will be no excess material (as compared to the top membrane) to add flexibility to those portions of the membrane below the storage cavities. Accordingly, less force will have to be applied to the membrane, and the dispensing mechanism will traverse a shorter path, to rupture the bottom membrane with the resulting dispensing of the reagent tablet from its storage cavity.

By providing the top and -bottom membranes with the barrier properties described above, sufficient environmental control will be achieved with these components of the disposable test package to ensure prolonged storage life of the prepackaged reagents therein. If desired, the disposable test package, or a plurality of disposable test packages can be packaged in an outer envelope which has the function of preventing the access of deleterious factors to the prepackaged reagents. However, careful selection of the top and bottom membranes should eliminate the need for such an outer envelope.

Since the dispensing force is transmitted from the dispensing plunger through the reagent tablet to the bottom membrane, it is preferred to have a convex tablet configuration. The convex surface will concentrate the force applied by the plunger to a single location on the bottom membrane whereby the membrane will be more readily ruptured. The convex surface also helps to minimize tablet hang-up since the reduced diameter of the upper portion of the tablet eliminates the possibility of the tablet hanging up in the bottom membrane during dispensing and, after the tablet has been dispensed from the storage cavity, it will have essentially point contact, as opposed to surface contact, with the adjacent surfaces of the reaction compartment whereby undesirable sticking iS avoided.

Reaction compartment section 14 has two reaction compartments 24 and 26 associated therewith. Adjacent the upper portion of the reaction compartments is a flange 30 which holds the unit together as a unitary member and further acts to prevent the inadvertent mixing of materials added to the adjacent compartments. As can best be seen in FIG. 1A, flange 30, reagent storage plate 14, and, optionally, bottom and top membranes 18 and 20 are wider along one portion 32 thereof which is adapted for the storage of information thereon. Any suitable type of information coding can be placed on this code area to indicate or record any information which desirably should be known during a chemical analysis, such as the actual test which has been pre-stored in the particulad disposable test package, the patient number, instructions for the associated automated analytical apparatus and system, analytical results, etc. Typical codes include binary coding in the form of light and dark areas, magnetic coding, etc. which can either be in. machineand/or human-readable form.

.As shown, each reaction compartment has a. small Hat portion 36 at the bottom thereof which is adapted to couple ultrasonic energy from an adjacent ultrasonic generating means to the materials previously added to the reaction compartment. From the edges of each flat portion 36 the Walls defining the lower portion of each reaction compartment are slightly rounded and/or substantially flat surfaces diverging upwardly towards the adjacent side walls. Substantially vertical side wall portions 32, on opposite sides of the reaction compartment, are connected to flat portion 36 by substantially flat portions 38. The actual connections between substantially flat portions 38 and substantially vertical side wall portions 32 are slightly rounded connections naturally caused by the process by which this unitary member is formed. Rounded wall portions 40 connect bottom wall portions 38 and 36y with curved side walls 42 and 44. Thus, iiat wall portion 36 is defined as the lowest part of each compartment such that when it is properly positioned over an adjacent ultrasonic generating means, the ultrasonic energy produced by such means is effectively coupled with the materials previously dispensed into the reaction compartment. This is particularly.advantageous where reagent tablets are pre-stored in the disposable test package. Curved side walls 42 and 44 prevent the tablet or reagents from finding a static ultrasonic energy zone of limited magnitude in which it can reside and thus avoid agitation and subsequent dissolution. Since the reagent no longer remains trapped in such a low energy zone, its movement through the reaction mixture is continuous and the agitation caused by the ultrasonic generating means is suicient to bring the reagent formulation into solution.

The reaction compartment section shown in FIG. 1B has been previously described in application Ser. No. 860,140, tiled Aug. 14, 1969, and assigned to the assignee of the present invention. However, other reaction cornpartment designs are also described therein and are suitable for use in conjunction with the reagent storage section of the present invention. Reference should be made to the aforementioned application for a specific description of other suitable reaction compartment designs and, to the extent necessary to complete the disclosure, or understanding, of the present invention, the aforesaid application is incorporated herein by reference.

Vertical side wall portions 32, and rounded side wall portions 42 and 44 terminate at a point intermediate the bottommost portion of the reaction compartment (i.e., bottom wall 36) and the uppermost portion (i.e., flange 30). The uppermost edges of side walls 32, 42 and 44 are connected to ange 30 by curved and rounded upper side wall portions 46 which terminate in legs 48 just prior to the intersection thereof with liange 30'. Since legs 48 are substantially perpendicular to flange 30, they dene positive aligning surfaces which can be utilized, for example, to position the disposable test package during reagent pre-storage and/or to manipulate the disposable test package during transportation thereof through an automated analytical system. Though vit is preferred to have such positive aligning surfaces, they can be omitted, if desired, whereby the side walls, whether curved or straight, defining each reaction compartment will diverge upwardly and outwardly until they intersect with the encircling ange. It is essential, however, that upper side wall portions of each reaction compartment be so positioned as not to adversely affect the addition of material to the reaction compartment or to cause the formation of low energy zones which might adversely affect tablet dissolution.

8 As shown, the side walls partially defining each reaction compartment define a substantially rectangular opening 50 through which materials are added thereto. The shape of the opening is not critical so long as it does not interfere with the introduction of sample material and reagents to the reaction compartment. The sloping Walls in the upper portion of each compartment assist in channeling dovvnwardly al1 materials toward the bottom of the compartment. A portion 52 of flange 30 acts as a distinct barrier between adjacent compartments such that material added to one compartment cannot be admixed with materials from the adjacent compartment.

Vertically extending side wall portions 32, on the opposite sides of each reaction compartment, define an optical window through which appropriate optical analysis can be made. Light of appropriate wavelength is passed from a light source through walls 32 and the reaction mixture therebetween to detection means situated on the opposite side of the reaction mixture from the light source. The amount of light transmitted (or conversely, the amount of light absorbed) by the reaction mixture at the testing wavelength will be indicative of the concentration of the constituent under analysis in the sample aliquot.

Referring to FIG. 3, there is seen an alternate rea'gent storage plate also having a plurality of reagent storage cavities 16 therein. Substantially tangential to each reagent storage cavity 16, and on opposed sides thereof, are a pair of holes 82 through which the probes on the reagent dispensing mechanism 60 are guided during reagent dispensing. Once again, at the center of each grouping of reagent storage cavities, there is provided an aliquoting hole 28 through which access may be had to the underlying reaction compartment. Plate 80 is also wider along one portion thereof, as at 32, which gives support to a top membrane to be supported thereby and, additionally, provides a code area for the storage of information thereon.

In the embodiments described in this application, the guide channels or holes have been shown on opposite sides of the reagent storage cavity. This is the presently preferred embodiment wherein the tear resistance of the bottom membrane is suti'iciently reduced by the opposedv punctures to permit relatively easy and reliable reagent dispensing. It should be understood, however, that other singleor multiple-puncture orientations can be utilized if they are sufficient to reduce the tear resistance of the bottom membrane and do not cause a flap to be severed from the bottom membrane or a flap to extend from the bottom membrane into a position where it interferes with mixing, photometric analysis, etc. Additionally, the configuration of the roles, channels, etc. should be such that they do not permit access of the reagent tablet thereto or to a position where there is a possibility that the reagent tablet will be contacted by the pointed probes during the dispensing operation.

An exemplary reagent dispensing means is shown in FIG. 2. Reagent dispensing means 60 generally comprises a cylindrical plunger 62 terminating in a bottom wall 64. Mounted on plunger 62 are two probes 66, the pointed ends 68 of which extend well below bottom` wall 64.

In use during reagent dispensing, reagent dispensing means 60 is moved downwardly over a particular reagent storage cavity 16. Initially, the ends 68 of pointed probes 66 puncture top membrane 18, pass through and are guided by guide channels 22, and puncture membrane 20 prior to contact of bottom wall 64 with the upper surface of top membrane 18. Continue downward movement of the reagent dispensing means causes the bottom Wall 64 to come into contact with the upper surface of top membrane 18 which, in turn, is tlexed into contact with the upper surface of tablet T. Due to the stresses created in the bottom membrane 20 by virtue of the punctures therethrough, in combination with the general low tear resistance of the `bottom membrane, continued movement of the reagent tablet T will cause the rupturing of the bottom membrane below cavity 16, with the concomitant dispensing of the reagent tablet into the underlying reaction compartment. In this manner, the resistance to reagent dispensing, normally associated with prior membrane-oriented designs, is significantly reduced with the result that reagent dispensing can be more reliably achieved.

The reagent dispensing mechanism can be provided with one or more dispensing plungers, for example as shown in FIG. 2. In a multi-plunger embodiment, it should be understood that each plunger can be designed to operate independently of the operation of other plungers. By providing a plurality of independently operated dispensing plungers, the effective through-put of the automated analytical system Will not be impeded while a plurality of dispensing operations, at any one station, must be accomplished by a single dispensing mechanism.

In such a system as contemplated for use with the disposable test package of the present invention, where the reagent dispensing mechanism is repeatedly caused to enter into a plurality of different reaction compartments, cross contamination is a problem which must be considered. If it is found that the probes become contaminated with liquid material previously added thereto, adequate flushing means should be provided between reagent additions to thoroughly cleanse at least those portions of the dispensing mechanism which enter into the reaction compartments. For example, a cleansing flush between the package dispensing operations can be made into an appropriate waste receptacle, to thoroughly protect against inadvertent cross-contamination.

In operation, disposable test package is taken from a supply magazine and passed to a prepunch station where access holes are made through the membranes above and below aliquoting hole 28. The test package is then passed to a sample addition station where the proper amount of sample is aliquoted into at least one of the reaction compartments. This addition is accomplished, for example, by injecting the sample aliquot through a needle which has been inserted through aliquoting hole 28. Preferably, a diluent fiush through the aliquoting needle follows the injection of the concentrated sample solution into one or more of the reaction compartments. It is also contemplated that an aliquot of distilled Water can be added to the reaction compartment prior to sample addition, if such distilled water addition is found desirable. The sample-holding test package is then passed to one or more reagent addition stations where the tabletted reagents are dispensed, in accordance with the procedure described above, into the adjacent and underlying reaction compartments. Reagent addition can be done in one operation, or it can be done sequentially as dictated by the particular analytical procedure being conducted. If done sequentially, the addition can be done before, during, or after incubation. In essence, reagents can be added any time prior to final detection as determined by the particular analytical procedure utilized. After each reagent addition, it has generally been found desirable to mix the reaction mixture, and the tabletted reagents therein, to bring each reagent tablet into solution. The disposable test package next passes to an incubation station where appropriate reaction conditions are imposed upon the materials within the reaction compartments for a time sufficient to complete the desired reaction or, at least, to bring it to the desired state for analysis. It is not necessary that the mixing and incubation stations be separate and distinct as it is contemplated that these operations may be performed in a single station. The test package is passed to a detection station where light of appropriate Wavelength is passed from a light source through the reaction mixture to detection means situated on the opposite side of the reaction mixture from the light source. The amount of light transmitted (or, conversely, the amount of light absorbed) at 10 the testing wavelength will be representative of the amount of the constituent undergoing analysis in the sample aliquot.

Although the disposable test package of the present invention can have but a single reaction compartment, providing a plurality of distinct reaction compartments, the test package can be utilized for conducting a primary test and, concomitantly therewith, at least one secondary analysis. Normally, the secondary analyses are in the form of a blank, either a sample blank, a reagent blank, and/ or a sample plus reagent blank, under additional conditions which cause a difference in a particular physical property to result from that obtained with the primary test. Appropriate correlation of the data obtained with the primary test and each secondary test yield analytical data of greater clinical value. As indicated above, the difference in the physical properties of the reaction mixtures within the reaction compartments, is usually determined by passing a light of appropriate wavelength through the various reaction mixtures. In one embodiment, the optical path through the reaction mixture is defined by the distance between the substantially vertical side walls through which optical analysis is made. In a separate embodiment, light from the light source and light which is passed through the reaction mixture can be conducted to, and from, the substantially vertical side walls of the reaction compartment through light conduits which cooperate with the relatively flexible walls of the reaction compartment to define a fixed optical path-length therebetween. Either embodiment is suitable for use in the practice of the present invention.

The multi-compartmented test package can be utilized in conjunction with a plural-beam detection mechanism, such as a double-beam detection mechanism, or with a Photometer which is rapidly indexed to bring each reaction compartment, with the reaction mixture therein, into the optical path between the light source and the detection means.

The manner of producing the disposable test packages of the present invention is not considered part of this invention. In general, however, any suitable method can be used which will produce the individual components 0f the test package having the desired characteristics. For example, thermoforming operations, such as pressure forming or vacuum forming, can be used to produce the reaction compartment portion of the test package which has a relatively intricate design. Pressure forming, however, is preferred because it is possible by using high pressure air to get the plastic material into areas 'Where it cannot be drawn by vacuum.

Polyethylene, polyvinylchloride, polystyrene, fluorocarbons, and cellulose propionate are suitable materials for use in the fabrication of the reaction compartment portion of the test package.

While the invention has been described with reference to preferred embodiments thereof, it will be understood by those skilled in the art that various changes in form and detail may be made without departing from the true spirit and scope of the invention. Accordingly, all modi- -fications to which the present invention is readily susceptible, without departing from the spirit and scope of this disclosure, are considered part of the present invention.

What is claimed is:

1. A reagent storage section suitable for use as a component of a disposable test package comprising a plate having a thickness on the order of the thickness of the reagent tablets to be stored therein, said plate having at least one reagent storage cavity extending therethrough, at least one channel adjacent each cavity to guide reagent dispensing means through said storage cavity during reagent dispensing, each of said guide channels being of such configuration and so positioned as to prevent a reagent tablet adjacent thereto from being contacted by the reagent dispensing means during dispensing; a top membrane bonded to the upper surface of said plate,

said top membrane having suicient barrier properties to prevent the access of deleterious factors to the reagent tablets prepackaged in said reagent storage cavities; a bottom membrane bonded to the bottom surface of said plate, said bottom membrane having low tear resistance so that when force is communicated thereto from the reagent dispensing means via a reagent tablet said membrane will rupture adjacent the point of contact thereof with the reagent tablet; and at least one reagent tablet stored within a reagent storage cavity between said top and bottom membranes.

2. The reagent storage section of claim 1 wherein there are a plurality of reagent storage cavities extending through said plate.

3. The reagent storage section of claim 1 'wherein there are a pair of guide channels adjacent each reagent storage cavity, said guide channels being on opposite sides of the adjacent cavity.

4. The reagent storage section of claim 1 further including at least one hole extending through said plate for passing materials through said plate and said top and bottom membranes prior to the dispensing of a reagent tablet therefrom.

5. The reagent storage section of claim 1 wherein the barrier properties of said top membrane cause said top membrane to be at least substantially impermeable to gases, moisture and light.

6. The reagent storage section of claim 1 wherein said top membrane has high tear resistance.

7. The reagent storage section of claim 1 wherein said top membrane is bonded to the upper surface of said plate in such a manner as to leave those portions of said membrane material above each of said reagent storage cavities in a condition where they are bowed outwardly thereby adding flexibility to said portions whereby the tear resistance of said portions is effectively increased.

8. The reagent storage section of claim 1 wherein said top membrane comprises a laminate of materials.

` 9. The reagent storage section of claim 1 wherein said bottom membrane is bonded flush with the bottom surface of said plate, whereby the membrane material below said reagent storage cavities is of such limited ilexibility that its resistance to tear is reduced.

10. The reagent storage section of claim 1 wherein said bottom membrane has sufiicient barrier properties to at least assist in prolonging the storage life of reagent tablets prepackaged in said reagent storage cavities.

11. The reagent storage section of claim wherein said barrier properties cause said bottom membrane to be at least substantially impermeable to gases, moisture and light.

12. The reagent storage section of claim 1 wherein said bottom membrane comprises a laminate of material.

13. The reagent storage section of claim 1 wherein each of said reagent tablets has a convex lower surface in contact with said bottom membrane.

14. A disposable test package comprising a reagent storage section comprising a plate having a thickness on the order of the thickness of the reagent tablets to be stored therein, said plate having at least one reagent storage cavity extending therethrough, at least one channel adjacent each cavity to guide reagent dispensing means through said storage cavity during reagent dispensing, each of said guide channels being of such configuration and so positioned as to prevent the reagent tablet adjacent thereto from being contacted by the reagent dispensing means during reagent dispensing, a top membrane bonded to the upper surface of said plate, said top membrane having sufcient barrier properties to prevent the access of deleterious factors to the reagent tablets prepackaged in said reagent storage cavities whereby the storage life of the prepackaged reagents is prolonged, a bottom membrane bonded to the bottom surface of said plate, said bottom membrane having low tear resistance so that when force is communicated thereto from the reagent dispensing means via a reagent tablet said bottom membrane will rupture adjacent the point of contact thereof with the reagent tablet, and at least one reagent tablet stored within a reagent storage cavity between said top and bottom membranes; and a reaction compartment section adjacent the lower surface of said bottom membrane, said reaction compartment section having at least one compartment for the admixing and reaction of materials added thereto, the reagent storage cavities in said reagent storage section being positioned over an underlying reaction compartment whereby prepackaged reagents can be dispensed therefrom into the adjacent reaction compartment.

15. The disposable test package of claim 14 wherein there are a plurality of reaction compartments and a plurality of reagent storage cavities associated with each of said reaction compartments.

16. The reagent storage section of claim 14 wherein said top membrane has high tear resistance.

17. The disposable test package of claim 14 wherein said top membrane is bonded to the upper surface of said plate in such a manner as to leave those portions of said membrane material above each of said reagent storage cavities in a condition where it is bowed outwardly thereby adding flexibility to said portions whereby the tear resistance of said portions is effectively increased.

18. The disposable test package of claim 14 wherein said bottom membrane is bonded flush with the bottom surface of said plate, whereby the membrane material below said reagent storage cavities is of such limited flexibility that its resistance to tear is reduced.

19. The disposable test package of claim 14 wherein said top and bottom membranes are substantially irnpermeable to gases, moisture and light.

20. The disposable test package of claim 14 further including at least one hole extending through said plate for passing materials through said plate and said top and bottom membranes prior to the dispensing of a reagent tablet from a reagent storage cavity.

Z1. An automated analytical system including the disposable test package of claim 14, a station for the addition of a sample aliquot from a sample storage site to at least one of said reaction compartments; at least one station for the addition of at least one reagent tablet stored within said reagent storage section to at least one reaction compartment, each reagent addition station including reagent dispensing means having a plunger, pointed probe means -mounted adjacent said plunger and extending below the bottom surface of said plunger, means to position said reagent dispensing means over a storage cavity having a tabletted reagent therein, and means to cause said reagent dispensing means to be moved downwardly whereby said pointed probe means will puncture the top and bottom membranes of said disposable test package, the bottom surface of said plunger will contact that portion of the top membrane above the reagent tablet, and the downward force communicated to said bottom membrane from said plunger via the reagent tablet will cause said bottom membrane to rupture adjacent the point of contact thereof with the reagent tablet whereby the reagent tablet will be dispensed into the underlying reaction compartment; a detection station for monitoring at least one of the physical properties of each reaction mixture within each reaction compartment and for deriving a final analytical result based upon the information obtained therefrom; and means to transport said disposable test package through each of said stations to said detection station.

22. The automated analytical system of claim 21 wherein each of said reaction compartments is sufficiently optically transparent so that it can be utilized as a cuvette for optical analysis, said detection station including means for passing a beam of electromagnetic radiation through each of said reaction compartments along 13 an optical path passing through the reaction mixture therein, means to measure the absorbance of the reaction mixture within each reaction compartment and means to derive a nal analytical result therefrom.

23. The automated analytical system of claim 21 wherein there are a plurality of reaction compartments, and the additions to each of said reaction compartments are such that a diierence in the absorbance results and said detection station includes means for measuring the absorbance of the reaction mixture within each reaction compartment and means to derive a nal analytical result based upon the measured absorbance differences.

14 References Cited UNITED STATES PATENTS 3,476,515 11/1969 Johnson et al. 23--253X 3,480,398 1-1/1969 Hamilton 23-253 5 3,497,320 2/1970 Blackburn et a1. 23-292x MORRIS O. WOLK, Primary Examiner R, E. SERWIN, Assistant Examiner U.S. Cl. X.R.

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Classifications
U.S. Classification422/417, 422/942, 206/219, 422/430
International ClassificationB01L3/00
Cooperative ClassificationB01L3/5085
European ClassificationB01L3/5085