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Publication numberUS3545935 A
Publication typeGrant
Publication dateDec 8, 1970
Filing dateNov 22, 1968
Priority dateNov 22, 1968
Also published asCA933494A1, DE1957735A1, DE1957735B2, DE1957735C3
Publication numberUS 3545935 A, US 3545935A, US-A-3545935, US3545935 A, US3545935A
InventorsWilliam J Kearns
Original AssigneeXerox Corp
Export CitationBiBTeX, EndNote, RefMan
External Links: USPTO, USPTO Assignment, Espacenet
Disposable reaction container for an automatic chemical analyzer
US 3545935 A
Abstract  available in
Images(5)
Previous page
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Claims  available in
Description  (OCR text may contain errors)

1970 w. J. KEARNS 3,54

DISPOSABLE REACTION CONTAINER FOR AN AUTOMATIC CHEMICAL ANALYZER Filed Nov. 22, 1968 5 Sheets-Sheet 1 HG 3 lNVENTOR WILLIAM J. KEARNS BY 9 5,4 MS ATTORNEY Dec. 8, 1970 w. J. KEARNS I 3,545,935

. DISPOSABLE REACTION CONTAINER FOR AN AUTOMATIC I CHEMICAL ANALYZER Filed Nov. 22, 1968 5 Sheets-Sheet 2 Dec. 8, w. J. KEARNS DISPOSABLE REACT CONTAINE OR AN AUTOMA CH AL ANALY Filed NOV. 22, 1968 5 Sheets-Sheet 5 3,545,935 TIC Dec. 8, 1970 w. J. KEARNS 3,545,935 DISPOSABLE REAC N CONTAINER FOR AN'AU'IOMATIC 4 C ICAL ANALYZER Filed Nov. 22, 1968 s Sheets-Sheet FIG9 Dec. 8, 1970 w. J. KEARNS 73,545,935 DISPOSABLE REACTION CONTAINER FOR AN AUTOMATIC CHEMICAL ANALYZER Filed Nov 22,- 1968 v 5 Sheets-Sheet 5 102\ P\ v w 44 /1oo s2A 60 2o 22 FIG 10 FIG 11 United States Patent Office 3,545,935 Patented Dec. 8, 1970 York Filed Nov. 22, 1968, Ser. No. 778,185 Int. Cl. B01] 3/00; G01n 33/16 US. Cl. 23-253 47 Claims ABSTRACT OF THE DISCLOSURE Disposable reaction container comprising a lower section having at least one compartment for the admixing of materials added thereto; an upper storage section having at least one separate, rigid cylindrical reagent storage chamber associated with each reaction compartment, each of said storage chambers having a piston therein for dispensing tableted reagents therefrom; and restraining means to prevent the premature movement of prepackaged reagents from the plurality of storage chambers. Each piston has a cavity in the lower portion thereof suitable for surrounding a tableted reagent within the storage chamber during the downward stroke of the piston, whereby the force necessary to break the restraining means, normally in the form of a thin plastic layer, is not transmitted to the restraining means through the tableted reagent.

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

In copending application Ser. No. 602,025 filed Dec. 15, 1966, now US. No. 3,504,376, there is disclosed an automated chemical analytical system including a plurality of diiferent 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 copending application Ser. No. 602,018 (also filed Dec. 15, 1966) now US. No. 3,497,320 there is disclosed a similar, through conceptually and structurally different, analytical apparatus and system. The disposable reaction container in this application has a flexible lower compartment, i.e., one having at least one flexible wall, so that during analysis a light source and a detection means pressed against the flexible wall or walls defining the lower cuvette(s) will cause the wall(s) to yield a distance sufiicient to define a fixed optical path between the light source and the detection means through the reaction mixture. The automatic analytical apparatus includes monitoring means having a light source and a means responsive to the variations in light transmittance caused by different concentrations of a constituent under analysis in the reaction mixture. The light source and the responsive means are pressed against opposite sides of the reaction compartment or cuvette during analysis to define a fixed optical path through the reaction mixture. Thus, there is provided an automatic analytical apparatus having the optical path defining means built into the detection station.

In the practice of the analytical methods disclosed in either of the aforementioned co-pending applications, the reaction container can be mass produced and disposed of after use without significant additional cost.

In co-pending application Ser. No. 645,665, filed June 13, 1967, and now abandoned, there is disclosed a disposable reaction container of improved design. Specifically, the lower section of the disposable reaction container comprises positioned walls adapted to channel the material added thereto to a portion of the lower compartment defined by a substantially rectangular volume. It is through this rectangular volume that optical analysis is made. Optionally, a still lower compartment can be provided for the storage therein of a magnetic stirring bar so that thorough mixing of added materials could be achieved through use of external urging means magnetically coupled to the magnetic stirring bar.

The disposable container shown in Ser. No. 645,665, now abandoned is considered typical of containers most easily adapted for use in an automated analytical system. In its most salient features, the container has two reaction compartments, a plurality of reagent storage chambers associated with each reaction compartment, and restraining means adapted to prevent the premature movement of prepackaged reagents from their respective storage chambers. In the disclosed embodiment the restraining means is in the form of a thin layer heat sealed between the lower reaction compartment section and the upper reagent storage section.

For numerous reasons, it was found desirable to store the necessary reagents in tablet form. Liquid storage is not as desirable because there is a greater propensity towards chemical reaction, either with the storage wall or with material permeating therethrough. Additionally, liquid materials are generally known to be more sensitive to light and other portions of the electromagnetic spectrum and, therefore, degrade faster unless adequate filters are provided to eliminate deleterious radiation.

Tableting, on the other hand, is less subject to these disadvantages so that increased storage times can be attained. When stored in tablet form, the reagents can be tableted either singly or in combination with other compatible reagents. This is preferred to storing two or more powdered reagents together since powder storage inherently provides an extreme amount of surface area available for chemical reaction. Thus, each reagent which is chemically incompatible with other reagents can be prepackaged in its own tableted composition suitable for storage in its own, separate storage chamber. Finally, severe dust, cross-contamination, and electrostatic problems exist when a plurality of different powdered chemicals are being deposited into reagent storage chambers which are but a fraction of an inch apart. When a tablet form of reagent addition is utilized, these problems are, at least, eliminated from the packaging line and placed in their own environment where they can be dealt with separately.

And, in package quality control, it is easier to determine if the reagent tablet has been placed in a storage chamber as opposed to determining whether the proper amount of powdered material has been added.

In general, however, the tableted reagents are extremely hygroscopic and, therefore, must be prepared, packaged and maintained under dry, non-humid conditions. In use, where different tablets are added to the reaction chamber at different times in the analytical sequence, it has been found necessary to provide some means to prevent the liquid material in the reaction compartment from contacting tableted reagents not yet dispensed. The most convenient means for achieving this was the restraining means, also called the restraining layer, already provided in the disposable package. This layer effectively prevented deleterious liquid already added to the reaction compartment from contacting the tableted reagent. However, it was found that acceptable and reproducible dispensing of the tableted reagents through this layer could not be achieved. While mere inversion of the storage chamber generally dispensed the tableted reagent stored therein into the reaction compartment, this dispensing did not always take place. Obviously, nothing less than 100% accurate and reliable dispensing is acceptable if one wishes to achieve the maximum use from the analytical system through which this container will pass. Attempts to use thinner and thinner layers did not overcome this deficiency even though layers of the minimum thickness available under the present state of technology were utilized. It has now been found that the aforementioned deficiency can be overcome, that is, that tableted reagents can be stored above a thin layer protected from adjacent liquid in a reaction compartment yet reliably dispensed from its storage site by the proper design of the upper reagent storage chamber section of the disposable test container, as hereinafter set forth.

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

It is a further object of the present invention to provide a novel disposable reaction container suitable for use in an automated analytical system.

It is a further object of the present invention to provide a novel upper storage section of a disposable reaction container.

Yet a still further object of the present invention is to provide a novel, injection molded upper storage section of a disposable reaction container having a plurality of storage cylinders, each cylinder having a piston therein for shearing the restraining layer provided between the storage cylinders and a reaction compartment section adjacent thereto.

Yet a still further object of the present invention is to provide novel pistons for use in conjunction with the novel upper storage section of the present invention.

SUMMARY OF THE INVENTION Now in accordance with the present invention, there is provided a further improved disposable reaction container for use with the aforementioned analytical apparatus and systems. The improved disposable reaction container has a uniquely configurated upper section for the storage of reagents, preferably tableted reagents, added thereto. The storage section of the present invention comprises a rigid member having at least one reagent storage chamber formed therein, and a lower layer or flange surrounding the opening(s) therethrough at the bottom of the substantially vertically extending rigid storage cylinder(s). Restraining means are provided adjacent the openings at the bottom of the storage cylinders to prevent the premature movement of stored reagents therefrom. Normally, the restraining means comprises a thin plastic layer securely bonded to the lower portion of the flange encircling the lower openings of the storage cylinders. A piston is positioned within each storage chamber so that upon downward movement thereof, the restraining means will be broken whereby material stored within the storage chamber will be dispensed therefrom. The storage section of the present invention is utilized in combination with a lower reaction compartment, for example, the lower reaction compartment described in application Ser. No. 764,850, filed Oct. 3, 1968, to provide a complete disposable testing unit suitable for conducting a complete chemical analysis therein.

In one embodiment, there is at least one rigid storage cylinder associated with a single lower reaction compartment therebeneath.

In a further embodiment, there is provided a plurality of lower reaction compartments and an upper storage section having at least one storage cylinder associated with each reaction compartment. In the presently preferred embodiment, there are a plurality of storage cylinders associated with each reaction compartment, for example, four storage cylinders as shown in FIGS. l-3.

The storage cylinders can have individual walls, such as shown in FIGS. 1-3, or a plurality of the storage cylinders can be enclosed in a block of material as shown, for example, in FIGS. 4 and 5. In either design, a hole or channel can be provided through the upper storage section for the addition therethrough of material, such as sample, water, etc., to the lower reaction compartment associated therewith.

Restraining means are provided between the upper storage section and the lower reaction compartment to prevent the premature movement of the stored materials from their respective storage cylinders. Normally, and preferably, the restraining means comprises a thin plastic layer, of equal dimension to the flange surrounding the opening(s) in the bottom of the storage cylinder(s), to which both the upper storage section and the lower reaction compartment section are firmly bonded on opposite sides thereof. Downward movement of the piston in the storage cylinder destroys the restraining means thereby permitting dispensing of the stored material. Since the upper storage section of the present invention differs from previous storage section configurations in that the upper portion of the storage cylinder is not closed to the atmosphere, means must be provided to prevent the admission of deleterious components, such as water vapor, etc., which might adversely affect the chemical stability and activity of the stored material. After the pistons have been inserted in the storage cylinder(s), this can be achieved, for example, by bonding a separate barrier layer or membrane across the upper portion of the storage section [i.e., over the top openings of the storage cylinder(s)], or by adding a hot melt coating to the top of each storage chamber, etc.

The piston placed in the storage cylinder can take on many shapes and forms. However, the essential feature which is common to all forms of the piston is that it have a cavity in the lower portion thereof which will enclosed the stored reagent, preferably in tablet form, as the piston is moved downwardly in the cylinder. The outer circumference of the lower portion of the piston will thereby cut through the restraining means prior to the time when the portion of the piston at the top of the cavity contacts the tableted reagent. The tablet is not crushed during the dispensing operation and, as such, is termed a passive tablet since it is not utilized to break the restraining means. In previously disclosed embodiments, force was always applied on the top of the storage chamber for inversion thereof during the dispensing operation. This inherently caused force to be applied to the tablet for transmittal therethrough to the restraining means (termed an active tablet) in an effort to break the restraining means. Unfortunately, many times the tablet was crushed and/ or the restraining means not properly broken whereby reliable dispensing of the stored product was not achieved. This defect has been cured by the present invention, wherein the force to break the restraining means applied to the piston is not transmitted through the tablet, by providing a piston having a cavity in the lower portion thereof. During dispensing, the beveled cutting edge of the piston severs the restraining means as the tableted reagent is positioned within the cavity. Direct transmittal of the breaking force through the tablet is hereby avoided. To prevent ejection of the piston, a step or shoulder is provided in the cylinder wall which coacts with a corresponding step on the outer piston wall to limit the downward movement of the piston.

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. 1 is a top view of the reagent storage section of the present invention;

FIG. 2 is a side sectional view of the reagent storage section of FIG. 1 taken along lines 2-2 thereof;

FIG. 3 is a bottom view of the reagent storage section of FIG. 1;

FIG. 4 is a top view of an alternate embodiment of the reagent storage section of the present invention;

FIG. 5 is a side sectional view of the reagent storage section of FIG. 4 taken along lines 5-5 thereof;

FIGS. 6-9 are side sectional views of pistons suitable for use within the storage cylinders of the reagent storage sections; and

FIGS. 10 and 11 are side sectional views of a single storge cylinder showing the two primary piston positions during reagent storage and dispensing.

Referring to FIGS. 1-3, there is shown a disposable reaction container upper section 10 having a pluarlity of storage cylinders 12 for the storage of prepackaged reagent therein. Storage section 10, including the plurality of storage chambers 12 is formed as a rigid unitary member having the configuration to be described hereinafter. As shown, each storage chamber is cylindrical in form having a cylindrical sidewall 14 open both at the top 16 and at the bottom 18. Around the inner circumference of wall 14 adjacent opening 18 is a step or shoulder 20 adapted to prevent a piston inserted therein from being dispensed through opening 18 during the reagent addition operation. In this embodiment, the reagent storage cylinders are paired into two groups of four cylinders each, each group being positioned over a lower reaction compartment (not shown) in the manner as shown in copending application Ser. No. 645,665, now abandoned. Surrounding the lower perimeter of upper section 10 is a flange 22 holding the reagent storage chambers together as an over-all unit and providing space 24 for the recording or storing of informational data thereon. A small hole 26, centered between each group of four reagents storage cylinders 12, is provided in flange 22 through which sample material, or diluents such as water, etc. are added to the reaction compartment positioned therebeneath. Polystyrene and polyvinyl chloride are two suitable materials from which the aforementioned storage sections can be mass produced by well-known injection molding techniques.

Referring to FIGS. 4 and 5, there is shown an alternate embodiment upper storage section of the present invention. Like numerals as found in FIGS. 1-3 indicate elements of the upper storage section common to embodiments. The embodiment shown in FIGS. 4 and 5 differ from the embodiment shown in FIGS. 1-3 in three primary features. Initially, the plurality of storage cylinders are formed in a block of rigid material as opposed to having individual walls. This provides sufiicient surface area for the bonding of a barrier-membrane to the upper surface thereof. As shown, the side walls of the block are slightly tapered, such as at 32, so the storage section can more easily be removed from its assembly mold. Obviously, since a block of material surrounds the storage cylinders, hole 26 is now in the form of a channel extending from the upper surface of the block 30 to the channels opening at the bottom of flange 24. Finally, step 20 is angled to the side walls of the storage cylinder rather than being perpendicular thereto. This reduces the possibility of a cutting edge of the piston inadvertently being forced or locked into the right angle corner such that effective piston introduction and/or reagent dispensing cannot be achieved.

Optionally, ribs (not shown) can be provided encircling the lower perimeter of each storage cylinder to thereby clearly define that portion of the restraining layer which is to be severed by the piston during its downward stroke. Shearing of the restraining layer is confined to the appropriate area within the encircling rib and does not spread to other portions of the layer below other storage cylinders. A rib can also be provided substantially midway between adjacent reaction compartments to assist in maintaining the separate integrity of each reaction compartment and its associated plurality of reagent storage chambers.

Referring to FIGS. 6-9, there are shown pistons suitable for use within the reagent storage cylinders. As shown in FIG. 4, piston has a substantially cylindrical side wall 42 which is stepped inwardly to provide a ledge 44 adapted to seat against step 20 within the reagent storage chamber. This inward step should be positioned such that when the piston is in its lowermost position (i.e., resting on step 20 in the storage cylinder), that portion of the piston extending into the reaction compartment does not interfere with optical analysis therethrough. The upper portion of the piston is hollowed out to define a cavity 46 having an interior side wall 48 and bottom wall 50. Side wall 48 is inclined slightly to the vertical, for example at an angle of about 10, so that when a plunger is inserted into the cavity it will be guided by side wall 48 to the lowest portion of the cavity, i.e., to bottom wall 50. The bottom portion of the piston is also hollowed out to define a second cavity 52 having interior wall 54 and top wall 56. Bottom Wall of cavity 46 and top wall 56 of cavity 52 are substantially parallel to thereby define a circular rib 58 connecting the opposite sides of substantially cylindrical wall 42. Rib 58 should be of sufiicient strength so that application of force thereto, in a downward direction, will cause the desired piston movement. From the point of intersection of side wall 54 with top wall 56, side wall 54 angles downwardly and outwardly, for example at an angle of about 2", so that the opening at the bottom of the cavity defines a circle of larger diameter than the circle defined by top wall 56. This slight outward taper insures that the lower leg 59 of side wall 42 contacts a reagent tablet in such a manner as not to crush the tablet before it is ejected from the storage chamber. A tablet contacted by interior wall 54 will be guided further up into the cavity as the piston is lowered during the reagent addition operation. The lower end of leg 59 is beveled upwardly and outwardly from its lowest point to define a cutting edge 60 for shearing through the restraining layer as the piston is lowered in the storage cylinder. The angle formed by an extension of outer wall 64 and beveled wall 62 can be, for example, 30. Beveled wall 62 is adapted to prevent seating of leg 59 against stop 20 within the reagent storage chamber. That is, as the piston is lowered, the slanted wall 62 will inherently cause the downwardly moving piston to be guided through opening 18 as opposed to having it seat against stop 20. Perfect alignment of the piston with opening 18 is thereby achieved.

An alternate piston embodiment is shown in FIG. 7. Piston 70, as shown therein, also has a substantially cylindrical side wall 42 stepped inwardly at 44 to provide a stop to seat against shoulder 20 within the reagent storage cylinder for limiting the downward movement of the reagent dispensing piston. As with the piston of FIG. 6, the upper and lower portions of the piston are hollowed out to define cavities 46 and 52 having therebetween rib 58. The exterior upper portion of side wall 42 is, however, flared outwardly at 72 to provide a better seal with the cylinder wall to prevent the admission of both air and ambient moisture. In a similar manner, though to a greater extent, the upper portion of wall 48 is flared outwardly to clearly define a much greater circular opening at the top of cavity 46 than either at the plane 76 where the flared portion 74 begins or at the bottom wall 50 of cavity 46. This greatly emphasized flaring of interior wall 48 more positively assures that the piston actuating means (not shown) will be directed against rib 58 during reagent dispensing.

The lower portion of the piston is similar to that described in FIG. 6 in that it has a lower leg 59 beveled upwardly and outwardly to define a similar cutting edge 60. The wall portion 62 also defined thereby functions to inherently guide the piston through opening 18. The lower portion differs from that shown in FIG. 6, however, by

the provision of a notch 80 cut out of a portion of leg 59. The vertical dimension of notch 80 is such that the portion of the restraining layer therebeneath is not severed during the dispensing operation. As shown, the notch extends substantially for the total height of cavity 52. The vertical distance between the top edge 82 of notch 80 and step 44 and piston wall 42 is less than the vertical distance between stop on the storage cylinder wall and the lowermost surface of flange 22 encircling the lower perimeter of the storage chamber. Thus, when the piston is in its lowermost position (i.e., step 44 is resting on stop 20) top edge 82 of notch 80 will not have reached that portion of the restraining layer therebelow. A flap will result whereby the small portion of the restraining layer below the storage cylinder will not be completely severed from the remainder thereof. Providing notch 80 is sufficiently wide and/or the dimensions of the disposable container are properly selected, the dangling flap will not interfere with either mixing of the materials added to the reaction compartment (including reagent tablets to be dissolved) or optical analysis therethrough. As indicated above, the essential feature of the notch is that it prevents complete severance of the restraining layer below the storage cylinders.

Cavities 46 in the pistons of FIGS. 6 and 7 can be utilized for the addition of material, such as hot melt wax, thereto for providing a barrier to the admission of substance(s) which would have a deleterious effect on the activity, etc. of the reagent stored within the storage cylinder. Accordingly, such a material can be added to the cavity and overlap the interface between the piston wall and the cylinder wall to provide an effective seal.

Referring to FIG. 8, piston 86, as shown therein, has a substantially cylindrical side wall 42 slanted inwardly at 44 to provide a stop adapted to seat against shoulder 20 within the reagent storage cylinder. As with the piston of FIGS. 6 and 7, the lower portion of piston 86 is hollowed out to define cavity 52; however, there is no cavity in the upper portion of the piston. The length of the piston is such that when cutting edge 60 is resting on the restraining means, the top surface 88 of the piston is substantially coplanar with the top surface of the reagent storage section. Thus, when a hot melt wax is utilized as the barrier material, less wax is necessary to completely seal the upper portion of the piston-cylinder against the admission of deleterious components. On the other hand, when this piston is used in conjunction with the storage section of FIGS. 4 and 5, it provides additional surface area for the bonding of a barrier-membrane across the upper surface of block 30.

Stop 44 is angled upwardly and outwardly, for example at an angle of 45, from leg 59 to side wall 42 and is most suitable for use in conjunction with a similarly angled stop 20 in the cylinder wall. Additionally, the lower portion of leg 59 is beveled upwardly and inwardly (as opposed to outwardly) from its lowermost point to define cutting edge for shearing through the restraining layer as the piston is lowered in the storage cylinder. The angle formed by the wall portions defining cutting edge 60 can be, for example, 30. Beveled wall 90 is adapted to assist in the positioning of a reagent table within cavity 52 during the downward stroke of piston 86. Additionally, by providing cutting edge 60 at the outermost point of leg 59, the restraining layer is severed or broken closer to the point where it is sealed to the bottom surface of flange 22.

Referring to FIG. 9, the piston shown therein is similar to the piston of FIG. 8 with two exceptions. Initially, cutting edge 60 is formed by beveling portions of leg 59 upwardly and outwardly from its lowermost point. Thus, along one side of the piston, cutting edge 60 is defined by leg 59 and slanted wall 92. From that cutting edge, however, the lowermost portion of the piston is tapered at a slight angle, say on the order of 4 or 5, so that, at the side of the piston directly opposite therefrom, leg 59 terminates in a blunt wall 94 unsuitable for severing that portion of the restraining layer therebeneath. During the downward stroke of the piston, the restraing layer is initially cut by cutting edge 60 substantially, but not completely, around the circle circumscribed by the piston. Since surface 94 is incapable of cutting through the restraining layer, that portion of the restraining layer beneath the piston is not completely severed from that portion of the restraining layer which remains bonded to flange 22. Accordingly, the restraining layer so severed does not interfere with the subsequent optical analysis. This particular modification eliminates the need for the notch as shown in FIG. 7.

As previously indicated, the essential structural characteristic of the piston is that it have a cavity in the lower portion thereof suitable for surrounding, and not adversely contacting, the tableted reagent during the downward stroke of the piston. Other disclosed features such as the upper cavity vs. the flat top, the right angle step vs. the slanted step, the inward bevel vs. the outward bevel, the tapered cutting edge vs. the notch, and other equivalent design features, etc. can be interrelated to define a piston not exactly described herein but which would be suitable for use in the present invention. All such design variations not specifically covered in the drawings are intended to be covered by the present invention.

In operation, a complete disposable container is taken from a supply magazine and passed to a sample addition station where the proper amount of sample diluted with distilled water is aliquoted into the reaction compartment, for example through hole 26. The sample-holding container is then passed to a reagent addition station wherein reagents stored in the storage chambers are emptied into the appropriate compartments. Reagent addition can be done in one operation or it can be done sequentially as it is necessary to complete the analytical procedure. If done sequentially, the addition can be done during or after incubation. In essence, reagents can be added any time prior to final detection as determined by the particular analytical procedure utilized. The container is passed to a mixing station where it is maintained for a time sufiicient to ensure the dissolution of all solid materials in the liquid contained in the lower compartments. The container next passes to an incubation station where appropriate reaction conditions are imposed upon the materials within the container for a time suflicient to complete the desired reaction which is then measured at a detection station. If necessary the package passes to further reagent addition, mixing and incubation stations as dictated by the analytical procedure. 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.

At a detection station, 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 the testing wavelength will be representative of the amount of the constituent under analysis in the test solution.

Preferably, the disposable container as shown in the drawings is used in conjunction with a double-beam detection mechanism. In one compartment there is provided a solution of the material being tested with all the reagents which will bring the reaction mixture to the desired point for analysis. The other compartment contains a solution of the material being tested in the absence of reagents. In certain instances, one or more reagents can be added to this latter solution, provided the reagents do not carry the reaction to completion or do not adversely atlect, in any other way, the optical analysis. This latter solution is called a critically incomplete blank and will enable the analytical system to compensate for the efifects of the sample and the reagents added thereto. To maintain the detection mechanism in calibration, standard solutions are passed through the detection mechanism at intervals so that the latter can adjust for deviations which occur during operation.

To dispense with the necessity of passing standard solutions through the detection mechanism at regular intervals, a disposable container having three compartments, and the plurality of storage chambers associated with each compartment where reagents need be added, is provided for use with a triple-beam detection mechanism. The standard solution can be injected into the disposable container at any point in the system prior to optical analysis and will obviate the need for passing distinct disposable container holding standards through the system. Alternatively, standard solution-producing materials can be stored in the upper section, dispensed into the lower compartment and diluted to give the desired concentration. The detection mechanism will analyze the standard and adjust for deviations from the known value. The analysis of the materials in the other two compartments is conducted in accordance with the teachings above. If one wishes to conduct an extremely precise analysis and take into consideration every possible influencing factor, additional lower compartments can be built into the disposable container for the introduction of such factors and the analysis thereof. Thus, adjustments can be made which will compensate for the efiect which these materials have upon the particular analysis.

Optionally, light from the light source and light which has passed through the reaction mixture can be conducted to the disposable container and the detection means, re-

spectively, through light conduits which can be caused a to contact an opposite pair of rigid walls which comprise a portion of the lower compartment. Preferably, these con duits contact the substantially vertical walls of each reaction compartment. In this embodiment, the optical path is defined by the distance between the opposite walls of the lower compartment against which the light conduits, or the equivalent thereof, are in contact. This optional form of optical analysis is shown in FIG. of Ser. No. 645,665. Alternatively, higher than atmospheric pressure means can be positioned over the upper storage section so that a relatively inert gas can be admitted to the reaction compartment through the hole made in the upper section during sample addition. The flexible walls will be bowed outwardly and can be made to contact accurately positioned optical path-defining means.

Since it is preferred to maintain the optical path constant for all like analytical procedures, to aid in assuring reproducibility of results, less strict production requirements must be met in the production of disposable containers having semi-rigid lower compartment walls than in the production of disposable containers having rigid lower compartment walls Where the walls cannot be deformed by external means. That is, by providing a fixed optical path in this manner, it is easier to mass produce the disposable container as a critical production feature, the optical path, has been eliminated as a strict production standard. The optical path defining means is now built into the detection station and, as would be expected, significantly less detection stations should be produced than disposable containers. Since a fixed optical path is defined by the detection station and will be the same for each container passing therethrough, highly accurate and reliable data can be obtained with this system.

It is also contemplated that this form of optical analy sis can be used in a doubleor triple-beam detection mode, as described above.

The number of reagent tablets necessary will depend upon the particular analysis being prepackaged into the disposable container as well as the compatibility of the different reagents. In certain instances, it is possible to tablet more than one reagent in a single tablet. However, where it is contemplated that the disposable containers will be prepared long before their actual use, the compatibility of the reagents over this long period of time must clearly be established. If this cannot be done, then it is desirable to tablet the reagents separately. In turn, the number of storage chambers will depend upon the number of reagent tablets utilized.

The cooperation of the piston and the reagent storage section is more clearly set forth in FIGS. 10 and 11 where the dispensing of a tableted reagent is shown. Referring to FIG. 10, single storage cylinder 100 has a piston P positioned therein. Beneath storage cylinder 100, and flange 22 surrounding the cylinder, is a thin restraining layer 92 adapted to hold reagent tablet T Within the storage cylinder. A barrier membrane 106 is bonded to the top surfaces of piston P and the walls of storage cylinder 100. The piston is shown in its uppermost position in the storage cylinder whereby lower cavity 52 partially surrounds and encloses reagent tablet T with the cutting edge 60 at the lower portion of the piston only in slight contact with restraining layer 92. When piston driving mean (not shown) strikes top surface 102, the piston will be driven downward to the position shown in FIG. 11. That is, the piston will be driven downwards until it is stopped by stop 20 as it comes into contact with slanted piston wall portion 44. When the piston is in the FIG. 11 position, reagent tablet T has been dispensed from the storage cylinder through opening 18 and the hole in restraining layer 92 which has been cut therein by cutting edge 60 into lower reaction compartment section 104 having flange 108 upon which layer 92 and the storage section is mounted. Because of notch in cutting edge 60, that portion of the restraining layer below opening 18 is not completely severed from the remainder of the layer and does not fall into the reaction compartment. Mixing and dissolution of the tablet now takes place, followed by incubation, further reagent addition, optical analysis, etc. as dictated by the particular analytical technique being conducted.

The present preferred form of the lower reaction compartment section is as shown in co-pending application Ser. No. 764,850, filed Oct. 3, 1968, assigned to the assignee of the present invention, and incorporated herein by reference. A side view of such a reaction compartment section (showing only a single reaction compartment) is as shown at 104 in FIGS. 10 and 11. The reaction compartment has a unique configuration adapted to promote coupling of the ultrasonic energy from an ultrasonic generating means adjacent thereto with materials held within the reaction compartment. The unique design includes a fiat portion at the bottom of each reaction compartment, and upwardly extending bottom wall portions connecting said fiat portion to the four side walls of the reaction compartment whereby said flat portion is positioned as the lowest point within the reaction compartment. Solid materials, especially in tablet form, added to the reaction compartment will be preferentially positioned over the fiat portion such that highly effective coupling is attained when the flat portion is properly aligned over the adjacent ultrasonic generating means. A more complete discussion of that design is given in the aforementioned co-pending application and to the extent necessary to complete the disclosure of this application is incorporated herein by reference. Other lower reaction compartment sections can be utilized in conjunction with the reagent storage section of the present invention; for example, another suitable lower reaction compartment section is disclosed in Ser. No. 645,665 now abandoned; which is also incorporated herein by reference.

As previously indicated, the upper section of the present invention has a flange extending about the lower perimeter of the plurality of reagent storage chambers. One side of this flange which extends the length of the disposable reaction container is slightly wider than the border that encircles the remainder of the upper storage section. The flange which encircles the adjacent lower sec tion also has such a wider portion of similar dimensions. Thus, the rectangles with slightly rounded edges formed by the flange encircling the upper perimeter of the lower section, the flange encircling the lower perimeter of the upper section, and, optionally, the restraining layer as shown in aforementioned co-pending application Ser. No. 645,665 now abandoned, are of equal size and dimension so that the members can be suitably joined to provide a unitary disposable container. Preferably, each member is formed out of a plastic material which can be heat sealed to the adjacent member to provide an exceptionally strong bond which cannot be broken under normal use. The wider portion of the flange encircling the perimeter of the upper storage section is sufficiently wide so that a suitable code can be provided thereon. Any suitable type of coding can be placed on the 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 particular disposable reaction container, patient number, instructions for the associated automatic analytical apparatus and system, analytic results, etc. Typical codes include binary coding in the form of light and dark areas, magnetic coding, etc.

While the invention has been described with reference to its preferred embodiments, it will be understood by those skilled in the art that various changes may be made and equivalents may be substituted for elements thereof without departing from the true spirit and scope of the invention. For example, other methods can be utilized to bond the upper storage section of the present invention to the lower reaction compartment or the restraining means. Adhesive bonding, such as with an 87% polyvinyl chloride-l3% polyvinylacetate copolymer, identified as VMCH obtainable from Union Carbide, when solvent coated from a methyl ethyl ketone solution has been found suitable. The aforementioned thermally activated adhesive suitably bonds the various elements or sections together such that they will not come apart under normal use. In addition, many modifications may be made to adapt a particular situation or material to the teaching of the present invention without departing from its essential teachings.

What is claimed is:

1. A storage section comprising a rigid member having at least one substantially vertical, cylindrical storage chamber formed therein, each of said storage chambers having a shoulder on the interior wall thereof for limiting the downward movement of a piston positioned therein, and a flange encircling the bottom opening of each of said storage chambers; restraining means securely bonded to the lower surface of said flange for preventing the premature movement of prepackaged reagents from each of said storage chambers; and a piston positioned in each of said storage chambers and freely movable within said storage chamber along the longitudinal axis thereof, each of said pistons having a cavity in the lower portion thereof which is adapted to enclose a reagent tablet therein as said piston is moved downwardly within said storage chamber, said cavity being of such vertical dimension that the reagent tablet therein is not contacted by the upper portion of said piston prior to the time when the lower portion of said piston creates an opening in that portion of said restraining means underlying said storage chamber.

2. The storage section of claim 1 further including a dry tabletted reagent stored in at least one of said storage chambers.

3. The storage section of claim 2 further including barrier means disposed over the upper portion of said storage cylinders for preventing the admission of deleterious materials thereto.

4. A storage section comprising a rigid member having a plurality of cylindrical storage chambers formed therein, each of said storage chambers having top and bottom openings and a shoulder on the interior wall thereof for limiting the downward movement of a movable piston positioned therein, a flange encircling said bottom openings of said storage cylinders; restraining means firmly bonded to the lower surface of said flange; and a piston positioned in each of said storage cylinders and freely movable within said storage cylinder along the longitudinal axis thereof, each of said pistons having a cavity in the lower portion thereof which is adapted to enclose a reagent tablet therein as said piston is moved downwardly within said storage cylinder, said cavity being of such vertical dimension that the reagent tablet therein is not contacted by the upper portion of said piston prior to the time when the lower portion of said piston creates an opening in that portion of said restraining means underlying said storage cylinder.

5. The storage section of claim 4 wherein said plurality of storage cylinders are sectioned into two groups of four cylinders each, the centers of said four cylinders in each of said groups being at the corners of a rectangle.

6. The storage section of claim 5 further including an aperture in said flange for each group of cylinders, each of said apertures being positioned between said cylinders within the rectangle defined thereby.

7. The storage section of claim 4 further including a dry tabletted reagent stored in at least one of said storage cylinders.

8. The storage section of claim 4 further including barrier means positioned over the upper surface of said storage cylinders for preventing the admission of deleterious materials thereto.

9. The storage section of claim 8 wherein said barrier means comprises a shearable layer.

10. The storage section of claim 8 wherein said barrier means comprises a hot melt sealant.

11. The storage section of claim 5 wherein each group of four storage cylinders are formed within a block of material such that individual exterior wall portions of said cylindrical storage chambers are not formed.

12. The storage section of claim 11 further including a shearable layer firmly bonded to the upper surface of said block of material.

13. The storage section of claim 12 wherein said shearable layer is bonded to the coplanar surface defined by the upper surfaces of said pistons and said block of material. i

14. The storage section of claim 4 wherein said shoulder is at a right angle to said interior wall.

15. The storage section of claim 4 wherein said shoulder is angled to said interior wall.

16. The storage section of claim 4 wherein said shoulder is more closely adjacent said bottom opening than said top opening.

17. A storage section comprising a rigid member having a plurality of cylindrical storage chambers formed therein, said plurality of storage cylinders being sectioned into two groups of four cylinders each, the centers of said four cylinders in each of said groups being at the corners of a rectangle, each of said storage cylinders having top and bottom openings and a shoulder on the interior wall thereof for limiting the downward movement of: a piston positioned therein, a flange encircling said bottom openings of said storage cylinders, an aperture in said flange for each group of cylinders, each of said apertures being positioned between said cylinders within the rectangle defined thereby; restraining means firmly bonded to the lower surface of said flange; a piston positioned in each of said storage cylinders and freely movable within said storage cylinder along the longitudinal axis thereof, each of said pistons having a cavity in the lower portion thereof which is adapted to enclose a reagent tablet therein as said piston is moved downwardly within said storage cylinder, said cavity being of such vertical dimension that the reagent tablet therein is not contacted by the upper portion of said piston prior to the time when the lower portion of said piston creates an opening in that portion of said restraining means underlying said storage cylinder; and barrier means positioned over the upper surface of said storage cylinders for preventing the addition of deleterious materials thereto.

18. The storage section of claim 17 further including dry tabletted reagent stored in at least a portion of said storage cylinders.

19. A disposable reaction container comprising an admixing compartment section having at least one compartment for the admixing of materials added thereto, said lower section having a flange adjacent the upper perimeter thereof and encircling the opening at the top of each admixing compartment; a substantially rigid storage section securely mounted on said admixing compartment section, said storage section having a plurality of separate, substantially rigid cylindrical reagent storage chambers adjacent said opening at the top of each of said compartment, each of said storage cylinders having top and bottom openings and a shoulder on the interior wall thereof for limiting the downward movement of a piston positioned therein, and a flange encircling said bottom openings of said storage cylinders; restraining means to prevent the premature movement of prepackaged reagents from said plurality of storage cylinders; and a piston positioned in each of said storage cylinders and freely movable within said storage cylinder along the longitudinal axis thereof, each of said pistons having a cavity in the lower portion thereof which is adapted to enclose a reagent tablet therein as said piston is moved downwardly within said storage cylinder, said cavity being of such vertical dimension that the reagent tablet therein is not contacted by the upper portion of said piston prior to the time when the lower portion of said piston creates an opening in that portion of said restraining means underlying said storage cylinder.

20. The disposable reaction container of claim 19 wherein said admixing compartment section has a plurality of separate admixing compartments.

21. The disposable reaction container of claim 19 wherein at least one set of opposite walls of each admixing compartment is optically transparent so that upon completion of the desired chemical reaction, each compartment can be utilized as a cuvette for optical analysis.

22. The disposable reaction container of claim 19 wherein said restraining means comprises a shearable layer sandwiched between said storage section and said admixing compartment section, said shearable layer being sufficiently strong so that it will shear only below a particular storage chamber when a prepackaged reagent is dispensed therefrom.

23. The disposable reaction container of claim 19 wherein said restraining means comprises a shearable thin plastic layer sandwiched between said storage section and said admixing compartment section.

24. The disposable reaction container of claim 19 wherein said storage section, said restraining means, and said admixing compartment section are bonded together.

25. The disposable reaction container of claim 19 wherein said piston has a smaller diameter in the lower portion thereof than the upper portion thereof to define a stop which coacts with said shoulder in each of said storage cylinders to limit the downward movement of said piston.

26. The disposable reaction container of claim 19 wherein each of said pistons has a beveled cutting edge at the lower extremity thereof.

27. The disposable reaction container of claim 19 wherein said beveled cutting edge of each piston does not completely encircle the lower diameter thereof, where- -by a portion of the lower edge of said piston prevents the complete severance of said restraining means during the dispensing action of said piston.

28. A piston comprising a unitary member having a cylindrical side wall and a cavity in the lower portion thereof, said cavity being defined by interior wall portions and an opening in the bottom wall of said piston, said opening having suflicient diameter and said cavity extending for a suflicient vertical distance to permit a tabletted material to be enclosed within said cavity during the downward stroke of said piston.

29. A piston comprising a cylindrical member, the diameter of the upper portion of said member being greater than the diameter of the lower portion thereof to thereby define upper and lower cylindrical wall portions and an intermediate wall portion adapted to limit the downward movement of the piston, a cavity in the lower portion of said piston, said cavity being defined by interior wall portions and an opening in the bottom wall of said piston, said opening having a diameter slightly less than the diameter of said lower portion, said cavity extending for a vertical distance sufficient to permit a tableted material to be enclosed within said cavity during the downward stroke of said piston, and said cylindrical lower wall portion being beveled at the bottom of said piston to define a distinct cutting edge about said opening.

30. The piston of claim 29 further including a cavity in the upper portion of said piston, said upper cavity and said lower cavity defining a substantially horizontal rib therebetween.

31. The piston of claim 29 wherein the upper portion of said piston terminates in a flat upper wall.

32. The piston of claim 29 wherein said intermediate wall portion is at a right angle to said upper and lower cylindrical wall portions.

33. The piston of claim 29 wherein said intermediate wall portion is angled to said upper and lower cylindrical wall portions.

34. The piston of claim 29 wherein said cutting edge is beveled inwardly.

35. The piston of claim 29 wherein said cutting edge is beveled outwardly.

36. The piston of claim 29 wherein the upper cylindrical wall portion is flared slightly outwardly to define a compression-type seal about the upper portion of said piston.

37. The piston of claim 29 wherein said cutting edge has a notch removed therefrom to limit the cutting action of said edge during the downward movement of said piston.

38. The piston of claim 37 wherein said notch subtends an are less than 39. The piston of claim 29 wherein the cutting edge is uniformly tapered at a slight angle from one side thereof through the opposite side to thereby define a blunt bottom wall portion at said opposite side.

40. A disposable reaction container comprising an admixing compartment section having at least one compartment for the admixing of materials added thereto, said admixing compartment section having a flange adjacent the upper perimeter thereof and encircling the opening at the top of each admixing compartment; a substantially rigid storage section securely mounted on said admixing compartment section, said storage section having at least one separate, substantially rigid reagent storage chamber adjacent said opening at the top of each of said compartments, each of said storage chambers having a bottom opening and a shoulder on the interior wall thereof for limiting the downward movement of a movable piston positioned therein, and a flange encircling said bottom openings of said storage chambers; restraining means to prevent the premature movement of prepackaged reagents from each of said storage chambers; and a piston positioned in each of said storage chambers and freely movable within said storage chamber along the longitudinal axis thereof, each of said pistons having a cavity in the lower portion thereof which is adapted to enclose a reagent tablet therein as said piston is moved downwardly within said storage chamber, said cavity being of such vertical dimension that the reagent tablet therein is not contacted by the upper portion of said piston prior to the time when the lower portion of said piston creates an opening in that portion of said restraining means underlying said storage chamber.

41. The disposable reaction container of claim 40 wherein said admixing compartment section has a plurality of separate admixing compartments.

42. The disposable reaction container of claim 41 wherein there are a plurality of storage chambers associated with each of said admixing compartments.

43. The disposable reaction container of claim 40 wherein at least one set of opposite walls of each admixing compartment is optically transparent so that upon completion of the desired chemical reaction, each compartment can be utilized as a cuvette for optical analysis.

44. The disposable reaction container of claim 41 wherein those walls of each reaction compartment parallel to the longitudinal axis of said reaction container are optically transparent so that upon completion of the desired chemical reaction each compartment can be utilized as a cuvette for optical analysis.

45. The disposable reaction container of claim 40 wherein said restraining means comprises a shearable thin plastic layer sandwiched between said storage section and said admixing compartment section.

46. The disposable reaction container of claim 40 wherein said storage section, said restraining means and said admixing compartment section are bonded together.

47. The disposable reaction container of claim 40 wherein each of said storage chambers has a top opening and barrier means positioned over the upper surface of each of said storage chambers for preventing the admission of deleterious materials thereto.

References Cited UNITED STATES PATENTS 3,476,515 11/1969 Johnson 23-230 3,480,398 11/ 1969 Hamilton 23-230X MORRIS O. WOLK, Primary Examiner R. E. SERWIN, Assistant Examiner U.S. Cl. X.R.

Patent Citations
Cited PatentFiling datePublication dateApplicantTitle
US3476515 *Apr 26, 1966Nov 4, 1969Du PontAnalytical test pack and process for analysis
US3480398 *Dec 26, 1967Nov 25, 1969Xerox CorpChemical package
Referenced by
Citing PatentFiling datePublication dateApplicantTitle
US3715189 *Jun 15, 1970Feb 6, 1973Secretary Of The TreasuryQualitative analysis device
US4215092 *Jul 11, 1978Jul 29, 1980Osmo A. SuovaniemiApparatus for liquid portioning and liquid transferring
US4720374 *Jul 22, 1985Jan 19, 1988E. I. Du Pont De Nemours And CompanyContainer having a sonication compartment
US4863693 *Dec 23, 1987Sep 5, 1989E. I. Du Pont De Nemours And CompanyAnalysis instrument having a blow molded reaction chamber
Classifications
U.S. Classification422/417, 422/942, 206/222, 220/23.8, 220/522, 422/430
International ClassificationB01L3/00
Cooperative ClassificationB01L3/5085
European ClassificationB01L3/5085