U.S. patent number 3,713,780 [Application Number 05/111,360] was granted by the patent office on 1973-01-30 for apparatus for chemical testing.
This patent grant is currently assigned to Becton, Dickinson and Company. Invention is credited to Stephen Shapiro.
United States Patent |
3,713,780 |
Shapiro |
January 30, 1973 |
APPARATUS FOR CHEMICAL TESTING
Abstract
A reagent container having a series of tiered compartments
containing prepackaged reagents for the chemical evaluation of a
test sample. A frangible diaphragm seals each compartment from the
succeeding compartment. A sample is introduced into the top
compartment. After incubation a breaker punctures the seal of the
adjacent compartment, allowing the reagents to mix and react. The
procedure is repeated for each reagent filled compartment.
Inventors: |
Shapiro; Stephen (East
Bridgewater, MA) |
Assignee: |
Becton, Dickinson and Company
(East Rutherford, NJ)
|
Family
ID: |
22338072 |
Appl.
No.: |
05/111,360 |
Filed: |
February 1, 1971 |
Current U.S.
Class: |
422/413; 206/222;
422/430 |
Current CPC
Class: |
B01L
3/502 (20130101) |
Current International
Class: |
B01L
3/00 (20060101); G01n 001/16 (); B65d 079/00 () |
Field of
Search: |
;23/292,253,259,230
;206/47A |
References Cited
[Referenced By]
U.S. Patent Documents
Primary Examiner: Wolk; Morris O.
Assistant Examiner: Serwin; R. E.
Claims
I claim:
1. A unitary tiered reagent container adapted for the chemical
evaluation of a material by the sequential addition of pre-packaged
reagents thereto comprising:
a plurality of tiered cylinders in abutting axial alignment and
having a bottom cylinder of smallest diameter and each succeeding
cylinder having a greater diameter than the preceding cylinder;
each cylinder having a radially disposed annular shoulder means for
sealingly mounting a frangible partition means dividing the
cylinders into individual compartments.
each of said partition means being supported on said shoulder means
and frangible cover means enclosing the cylinder of greatest
diameter and means permanently enclosing the end of the cylinder of
smallest diameter whereby a tiered reagent container is formed
adapted to house sequentially a reagent in each cylinder in tiered
abutting axial alignment.
2. The invention in accordance with claim 1, wherein each
compartment contains a predetermined quantity of a preselected
reagent, whereby a sample may be introduced into the compartment
sealed by the frangible cover means and sequentially exposed to the
balance of the reagents in the container by sequentially puncturing
the succeeding frangible partitions.
3. A unitary tiered container for chemically evaluating a test
sample, having discreet compartments, each compartment having a
predetermined amount of a preselected liquid reagent,
comprising:
a cylindrical hollow base receptacle permanently enclosed at one
end;
a plurality of hollow cylinders in integral, abutting axial
alignment therewith, each successive cylinder having a greater
diameter than the preceding;
a continuously disposed annular shoulder joining the abutting ends
of each successive cylinder;
a plurality of frangible, inert, impermeable diaphragms dividing
the cylinders into individual compartments, each of said diaphragms
supported and adhesively affixed to an annular shoulder and one of
said diaphragms overlying the cylinder of greatest diameter and
forming a cover for the container.
4. The invention in accordance with claim 3, in combination with
puncture means for successively rupturing each of said frangible
partition means, said puncture means comprising an elongated
gripping tube having a needle point and a cylinder fixedly secured
thereto and in axial alignment therewith, spaced adjacent said
needle point, wherein the diameter of the cylinder is less than the
diameter of the base receptacle.
Description
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention is directed to an apparatus and method for
performing a chemical evaluation of a material employing
prepackaged reagents. In particular, it relates to a tiered reagent
cup for storing prepackaged reagents and puncturing and mixing
means for sequentially exposing a material to be tested to the
prepackaged reagents.
2. Description of the Prior Art
In order to perform a chemical evaluation of a serum or other
material in the field, it has proven necessary to employ a series
of reagent containers. Often a conventional pipetting device is
employed to transfer reagents, sequentially, to a reaction chamber
in order to test a serum or other material for various properties.
This procedure has several major defects. With manual pipetting,
reagent volume is always subject to variation. It is also
cumbersome to store and clean a series of reagent containers which
are to be taken into the field. Prior art compartmented devices for
storing reagents have proven, for the most part,
unsatisfactory.
In U.S. Pat. Nos. 2,568,029 029 and 2,753,868, a container having a
series of compartments is provided for storing ingredients suitable
for hypodermic injection. Owing to the narrow-neck compartment
design, it is difficult to load the compartments with reagents.
The odd-shaped necks of the compartments have proven difficult to
seal, as evidenced by the cumbersome "drop" method for providing
septa.
Further, the narrow-necked compartment design prevents adequate
mixing of the reagents. Even more important, it is necessary to
employ a hypodermic syringe for introducing or removing reagents
from the compartments, once the unit is sealed.
Certain prior art devices provide a receptacle for the mixing of
reagents prepackaged therein, but do not permit introduction of a
material to be tested into the compartments. Such a device is
illustrated in U.S. Pat. No. 3,415,360. The non-unitary nature of
the receptacle makes it difficult to assemble. The rigid cap
prohibits addition of a serum or the like to the top,
reagent-containing chamber.
Certain prior art reagent-containing devices are formed wherein a
reagent-containing cylindrical insert is spaced within an outer
receptacle. Such devices provide various problems in fabrication,
since the insert must be correctly positioned and supported by some
external support mechanism. In many cases the inserts are sealed by
a self-supporting membrane. Such a membrane can be difficult to
rupture during mixing of the reagents. Illustrative of such prior
art devices is the insulating device disclosed in U.S. Pat. No.
3,359,361.
SUMMARY OF THE INVENTION
It is, therefore, the primary object of the invention to provide a
reagent-containing device particularly adapted to evaluate a test
sample by the sequential addition of reagents to the test
sample.
It is another object of the invention to provide a
reagent-containing test device which can be accurately prefilled
with reagent and which is of simple design and easily
fabricated.
It is an additional object of the invention to provide a device
having prepackaged reagents and adapted for the sequential addition
of reagents to a test material which also provides enhanced mixing
of each of the reagents with the test sample.
It is a further object of the invention to provide a method for
introducing a test sample into a reaction chamber containing a
prepackaged reagent and thereafter mixing the sample and first
reagent with at least one further reagent for further testing.
The above and other objects are met in a unitary tiered reagent
cup. The tiered cup has a series of hollow cylinders. The bottom
cylinder or base receptacle is closed at one end. The diameter of
each cylindrical tier is progressively greater from the bottom to
the top of the cup. Each stepped tier is hermetically sealed by a
frangible diaphragm which overlies the cylindrical tier and is
supported by the step resulting from the diametrical increase of
the next larger tier. The frangible diaphragm, therefore, serves to
seal the top of one cylindrical tier and becomes the bottom of the
cylindrical tier spaced immediately thereabove. The reagent cup may
be fabricated with as many tiers, as desired. The top of the
reagent cup is hermetically sealed by a frangible diaphragm which
is supported by a final step.
In order to fill the cup with reagents, a manual or automatic
metering device dispenses a pre-selected quantity of reagent into
the base receptacle. The receptacle is then sealed by the frangible
diaphragm. This procedure is repeated for each succeeding
cylindrical tier employing the same or different reagents in each
tier. The top tier is sealed by a frangible diaphragm to complete a
prepackaged reagent cup.
In use, a test sample is introduced into the top compartment
through a hollow needle which is adapted to make a small puncture
in the frangible top cover. After a suitable incubation period a
breaker means ruptures the seal forming the base of the top
compartment, thereby allowing the contents of the top and next
succeeding compartment to mix.
After a suitable time the breaker means is employed to rupture the
seal forming the base of the second compartment from the top,
thereby allowing the contents of the top and next succeeding
compartment to mix with the contents of the compartment immediately
thereinbelow. This procedure is repeated until all the frangible
seals have been broken.
From the above, it is seen that the invention provides a novel
apparatus for prepackaging accurate quantities of various reagents
in a combination shipping container and reaction cup. The unitary
tiered container is readily fabricated by conventional extrusion
techniques or the like and does not require specially fabricated
and mounted inserts. Since the top of the reagent container has a
wide opening, it is possible to employ accurate reagent delivery
means to fill each compartment with a carefully predetermined
quantity of reagent. By his novel design, applicant has eliminated
the necessity of carrying a series of reaction flasks and reagent
containers for subjecting a test sample to a sequential addition of
reagents. Complete mixing of reagents and test sample is
facilitated by the relatively wide openings to the compartments.
Further, the action of the breaker as it punctures each succeeding
compartment seal, promotes further enhanced mixing.
The invention will be more fully understood when considered in
terms of the following description and the accompanying drawing, in
which a preferred embodiment of the invention has been illustrated,
and in which:
BRIEF DESCRIPTION OF THE DRAWING
FIG. 1 is an axial cross-sectional view of a prepackaged reagent
container, constructed in accordance with the invention, showing
the prepackaged reagents in separate compartments;
FIG. 2 is a view similar to FIG. 1, with a thin, hollow tube
puncturing the top seal, illustrating the introduction of a test
sample into the top compartment (as illustrated by the arrows);
FIG. 3 is a view similar to FIG. 1, in which a breaker has
punctured the seals of the top and next succeeding compartment of
the reagent container, and in which the contents of the second
compartment are circulating into the top compartment illustrated by
the upwardly disposed arrows): and
FIG. 4 is a view similar to FIG. 3 in which the breaker has
punctured the seal of the base receptacle.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
The reagent cup, as illustrated in FIG. 1, includes a container 10
having a series of stepped tiers. The container is in the form of a
stepped hollow cylinder. At the base of the container is a
receptacle 12 enclosed by an integral flat bottom plate 14.
A flat annular step or shoulder 16 is continuously disposed about
the periphery of the top of the base receptacle 12. In axial
alignment with the base receptacle is a cylindrical section 18
upwardly disposed from the outer periphery of shoulder 16. The
radius of cylinder 18 is greater than the radius of base receptacle
12. The width of shoulder 16 is equal to the difference between the
radius of cylinder 18 and receptacle 12.
Annular shoulder 20 is continuously disposed outwardly from the
periphery of the top edge of cylinder 18. Hollow cylinder 22 has
upstanding walls continuously disposed about the periphery of
shoulder 20. The radius of cylinder 22 is greater than the radius
of cylinder 18. Shoulder 20 is equal in length to the difference
between the radius of cylinder 22 and the radius of cylinder 18.
Cover seal supporting means 24 is continuously disposed about the
top edge of cylinder 22. As illustrated in FIG. 1, cover supporting
means 24 forms a flat annular shoulder with respect to cylinder
22.
Container 10 may be formed from rigid, semirigid or flexible
materials. Suitable materials include thermosetting and
thermoplastic polymers; including polystyrene, polyethylene and
polypropylene.
In order to provide discrete reagent compartments within container
10 frangible seals are provided. The seals are supported by the
respective annular shoulders of the container. Suitable frangible
materials for the seal include thin metal foils and heat-sealable
materials, including polymeric films, such as cellophane and
laminates. The seals should be inert to the reagents employed and
impermeable to the liquid reagents employed. The thickness of the
seal will, of course, vary to some extent with the diameter of
different sized devices. As a practical matter the seal should
rupture on the application of an axial force of less than about
three pounds. Once ruptured, the seal should tear easily to
accommodate the pointed breaker which is preferably employed to
rupture the seal. To facilitate assembly the seal may have
impregnated at the outer periphery thereof a suitable adhesive
material capable of forming a liquid impermeable bond with the
container. If desired, a heat activatable seal may be employed and
suitable heating means applied to the periphery of the seal to form
a suitable bond with the container.
As illustrated in FIG.1, a thin plastic diaphragm 26 overlies base
receptacle 12 to form a base compartment 28 in the container.
Diaphragm 26 acts as a cover for base compartment 28 and as a base
for the compartment of cylinder 18. Diaphragm 28 overlies cylinder
18 forming compartment 30, a second reagent chamber in the
container.
Shoulder 20 forms a seal supporting means for diaphragm 28.
Shoulder 16 forms a seal supporting means for diaphragm 26.
Cover seal 32 overlies cylinder 22 to form top reagent compartment
34. Container seal 32 is supported by top shoulder 24.
In order to fill the tiered container with suitable reagents, the
container is supported by suitable supporting means. Such
supporting means includes a bracket of complementary configuration
with container 10, test tube holder means, or an apertured test
tube bracket capable of accepting and retaining in a perpendicular
position, the container wherein the container is supported across
an aperture by top shoulder 24. A first reagent is metered into
compartment 28 in base receptacle 12. Conventional manual or
automated reagent delivery means may be employed. Thereafter,
plastic diaphragm 26 is placed on shoulder 16 and adhesively sealed
to the shoulder. Next, a second reagent is introduced into
compartment 30 by suitable delivery means. Thereafter, diaphragm 28
is emplaced on shoulder 20 and adhesively adhered to the shoulder.
Finally, a third reagent is introduced into compartment 34 and
cover diaphragm 32 is bonded to shoulder 24 to form a completed
reagent cup.
Of course, the quantity of reagent in each of the respective
compartments will be dependent, in part, upon the nature of the
material being tested and of the quantity of material added to the
reagent cup. In order to prevent overflow and to provide enhanced
mixing, it is generally preferred that the top and middle reagent
compartments are filled to no greater than about one half their
respective capacity.
The bottom receptacle may be filled to virtually its full capacity,
if necessary. Although the drawings illustrate the use of a reagent
cup with liquid reagents, solid reagents may be employed in one or
more compartments. The quantity of solid reagent which may be added
to the top and middle compartments is dependent, in part, on the
physical properties of the plastic diaphragm forming the base of
these compartments.
Turning now to FIGS. 2-4, there is illustrated a method for the
sequential addition of prepackaged reagents to a sample of material
to be tested, whereby a chemical evaluation of the material may be
performed. Initially, as illustrated in FIG. 2, a liquid test
material is introduced into the top reagent compartment by means of
a thin tube 36. A micropipette or syringe needle may be employed
for this purpose. Turning now to FIG. 3, after an appropriate
incubation or reaction period, a breaker 38 descends and punctures
the diaphragm 28 separating the top and middle reagent
compartments. As the breaker descends, it forces the reagent out of
the second compartment up into the first compartment, thereby
promoting mixing. The breaker then retracts and is washed. The
procedure is repeated for as many reagents as are present. In FIG.
4 washed breaker 38 punctures the diaphragm 26 between the middle
and bottom reagent compartments, thereby effecting mixing of the
entire contents of the container.
It will be obvious to those skilled in the art that various breaker
designs are possible. A preferred breaker design is illustrated in
FIG.3. Breaker 38 includes a thin gripping tube 39 which may be
knurled or scored to facilitate handling. Cylinder 40 is
concentrically disposed about tube 39. For best mixing results, the
diameter of cylinder 40 should be less than the diameter of base
receptacle 12. The diameter of cylinder 40 should be preselected
such that upon introduction into base receptacle 12, the contents
therein are forced upwardly about the outer periphery of cylinder
40 and intimately mixed with the contents of compartments 30 and
34.
Puncture tip 42 in axial alignment with tube 38 is centrally
disposed on the lower face 44 of cylinder 40. The breaker may be
readily fabricated, employing a sharp pointed needle and a cylinder
with a hollow core, wherein the diameter of the core is slightly
smaller than the diameter of the needle. The cylinder is heated,
and while in its expanded state, is slipped over the needle such
that the needle point is exposed below the bottom face of the
cylinder. Thereafter, the cylinder is cooled in order to form a
shrink fit about the needle.
Alternatively, the cylinder may be force-fit over the needle.
Further, a unitary breaker may be formed or extruded from plastic
materials by employing a suitable die or mold. The container may be
fabricated by conventional extrusion processes employing a tiered
die.
The following example is given to further illustrate the novel
method for the sequential addition of reagents which have been
prepackaged within the tiered reagent cup of the invention for the
purpose of performing a chemical evaluation of a test material and
is not limitative of scope.
EXAMPLE I
One drop of pyridine is introduced into the bottom receptacle of
the tiered reagent cup of the invention. The bottom receptacle is
thereafter sealed by an impervious frangible diaphragm. Two drops
of a solution made by dissolving 1 gram of ferric chloride in 100
ml of chloroform is introduced into the compartment immediately
above the bottom receptacle. An impervious frangible plastic
diaphragm is then adhesively sealed above the compartment. One
milliliter of chloroform is introduced into the top compartment.
The compartment is hereafter sealed in the manner described
hereinabove.
One drop of a liquid suspected of containing phenols or enols is
then introduced into a thin hollow glass tube by capillary action.
An opened end of the capillary tube is forced through the top
frangible diaphragm of the reagent container and the unknown liquid
is forced into the top compartment. After about a minute, a pointed
breaker is pushed through the top and next succeeding frangible
seal, thereby mixing the contents of the top and the next
succeeding compartment. The breaker is removed and thoroughly
washed, thereafter the washed breaker is forced through the
frangible seal covering the bottom receptacle, thereby agitating
and mixing the contents of the reagent cup. The breaker is removed
and the contents of the cup are examined for a color change typical
of phenols and/or enols.
It will be obvious that the above test procedure is applicable to
reagent cups having more than one compartment. If desired, the
reagent cup can be fabricated from transparent material so that
precipitates, color changes and other physical properties may be
observed through the walls of the cup. A suitable transparent
material is the polycarbonate identified by the trademark Lexan. In
any event, the cup material must be nonreactive to the reagents
employed therein. Further, the seal material should be inert to and
impervious to the vapors of any liquid reagents employed therein.
It will be obvious to those skilled in the art that serum or other
organic materials may be evaluated employing suitable reagents in a
predetermined sequence of addition, as provided by the
invention.
Having thus described the invention it is not intended to be
limited, except as set forth in the following claims.
* * * * *