U.S. patent number RE45,194 [Application Number 14/076,031] was granted by the patent office on 2014-10-14 for penetrable cap.
This patent grant is currently assigned to Gen-Probe Incorporated. The grantee listed for this patent is Gen-Probe Incorporated. Invention is credited to Nick M. Carter, Daniel L. Kacian, Mark R. Kennedy.
United States Patent |
RE45,194 |
Kacian , et al. |
October 14, 2014 |
Penetrable cap
Abstract
A cap having a core structure dimensioned to receive a pipette
therethrough. The cap includes two axially aligned frangible seals
that are affixed to the core structure in a spaced-apart
relationship. The frangible seals are constructed so that air
passageways are formed between the frangible seals and a pipette
tip when the pipette tip penetrates the frangible seals. The cap
optionally includes a filter interposed between the first and
second frangible seals.
Inventors: |
Kacian; Daniel L. (San Diego,
CA), Kennedy; Mark R. (Madison, CT), Carter; Nick M.
(Hove, BE) |
Applicant: |
Name |
City |
State |
Country |
Type |
Gen-Probe Incorporated |
San Diego |
CA |
US |
|
|
Assignee: |
Gen-Probe Incorporated (San
Diego, CA)
|
Family
ID: |
23048419 |
Appl.
No.: |
14/076,031 |
Filed: |
November 8, 2013 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
Issue Date |
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12753010 |
Nov 8, 2011 |
8052944 |
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11869233 |
Apr 6, 2010 |
7691332 |
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10954578 |
Nov 13, 2007 |
7294308 |
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10093511 |
May 17, 2005 |
6893612 |
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60274493 |
Mar 9, 2001 |
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Reissue of: |
12959016 |
Dec 2, 2010 |
8057762 |
Nov 15, 2011 |
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Current U.S.
Class: |
422/570; 436/180;
215/249; 215/247; 422/547; 422/513; 422/500; 422/568; 422/550;
215/250; 215/248; 422/534; 436/177; 422/512 |
Current CPC
Class: |
B65D
41/0414 (20130101); H01L 21/67784 (20130101); B65D
51/002 (20130101); B01L 3/565 (20130101); B01L
3/50825 (20130101); B65D 51/1616 (20130101); B01L
2300/047 (20130101); B01L 2300/0887 (20130101); B01L
2300/069 (20130101); Y10T 436/25375 (20150115); B01L
2200/026 (20130101); B01L 2300/0681 (20130101); B01L
2300/044 (20130101); B65G 2203/044 (20130101); Y10T
436/2575 (20150115) |
Current International
Class: |
B65D
41/20 (20060101); B01L 3/02 (20060101) |
Field of
Search: |
;422/500,501,512,513,527,534,535,547,549,550,558,568,570
;436/174,177,180 ;215/247-250,258,232 ;73/864.74 ;435/6.1 |
References Cited
[Referenced By]
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1 209 004 |
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CA |
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37 33 696 |
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DE |
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199 38 078 |
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Feb 2001 |
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DE |
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0 081 976 |
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Jun 1983 |
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EP |
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0 115 480 |
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Aug 1984 |
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EP |
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0 330 883 |
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Sep 1989 |
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EP |
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0454493 |
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Oct 1991 |
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EP |
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0513901 |
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Nov 1992 |
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EP |
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1 468 801 |
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Mar 1977 |
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GB |
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2 048 836 |
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Dec 1980 |
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GB |
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7051253 |
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JP |
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2594337 |
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JP |
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8103433 |
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JP |
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9945360 |
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WO |
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00/69389 |
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Nov 2000 |
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WO |
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WO00/69389 |
|
Nov 2000 |
|
WO |
|
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|
Primary Examiner: Wallenhorst; Maureen
Attorney, Agent or Firm: Cappellari; Charles B.
Parent Case Text
CROSS-REFERENCE TO RELATED APPLICATIONS
This application is .Iadd.a reissue of U.S. Pat. No. 8,057,762,
which is .Iaddend.a continuation of U.S. application Ser. No.
12/753,010, filed Apr. 1, 2010, now .[.pending.]. .Iadd.U.S. Pat.
No. 8,052,944.Iaddend., which is a continuation of U.S. application
Ser. No. 11/869,233, filed Oct. 9, 2007, now U.S. Pat. No.
7,691,332, which is a continuation of U.S. application Ser. No.
10/954,578, filed Sep. 29, 2004, now U.S. Pat. No. 7,294,308, which
is a divisional of U.S. application Ser. No. 10/093,511, filed Mar.
8, 2002, now U.S. Pat. No. 6,893,612, which claims the benefit of
U.S. Provisional Application No. 60/274,493, filed Mar. 9, 2001,
each of which applications is hereby incorporated by reference
herein in its entirety.
Claims
What we claim is:
1. A penetrable .[.screw.]. cap comprising: a generally cylindrical
core structure configured to be screwed onto an open-ended vessel,
the core structure being a molded plastic formed to have an opening
extending therethrough; and first and second disk-shaped, frangible
seals affixed to the core structure, .[.wherein.]. the second seal
.[.is.]. .Iadd.being .Iaddend.axially aligned with and positioned
below the first seal .[.in a spaced-apart relationship,
and.]..Iadd.,.Iaddend. wherein the second seal is constructed and
arranged to provide a barrier to the passage of a fluid through the
opening formed in the core structure, wherein the cap is capable of
being penetrated by a plastic pipette tip, and wherein the first
and second seals are constructed and arranged so that air
passageways are formed between a plastic pipette tip and the first
and second seals when the pipette tip penetrates the first and
second seals.Iadd., thereby permitting air to be vented through the
cap.Iaddend..
2. The cap of claim 1, wherein the core structure comprises an
inwardly extending ledge, and wherein the second seal is affixed to
a surface of the ledge.
3. The cap of claim 2, wherein the ledge comprises a depending
skirt.
4. The cap of claim 3, wherein the second seal is affixed to a
bottom surface of the skirt.
5. The cap of claim 2, wherein the first seal is affixed to a top
surface of the core structure.
6. The cap of claim 1, wherein the first seal is modified to
facilitate penetration of the first seal by a plastic pipette tip,
and wherein the modification reduces the tensile strength of the
first seal.
7. The cap of claim 6, wherein the first seal is modified to
include perforations that facilitate penetration of the first seal
by a plastic pipette tip.
8. The cap of claim 1 further comprising a filter interposed
between the first and second seals.
9. The cap of claim 8, wherein the filter is comprised of a
resilient material.
10. The cap of claim 8, wherein the filter is gas permeable.
11. The cap of claim 10, wherein the filter is constructed and
arranged to trap an aerosol and/or bubbles.
12. The cap of claim 1, wherein the cap does not include a filter
interposed between the first and second seals.
13. The cap of claim 1, wherein the first and second seals tear
when penetrated by a plastic pipette tip, thereby forming air
passageways between the pipette tip and the first and second
seals.
14. A .[.collection device.]. .Iadd.closed system
.Iaddend.comprising the cap of claim 1 screwed onto an open end of
a fluid-holding vessel, thereby providing a substantially
leak-proof seal between the cap and the vessel.
15. A method for removing a fluid substance from the .[.collection
device.]. .Iadd.closed system .Iaddend.of claim 14, the method
comprising the steps of: (a) penetrating the first and second seals
.Iadd.of the cap .Iaddend.with a plastic pipette tip, thereby
forming air passageways between the pipette tip and the first and
second seals; .Iadd.(b) venting air from the vessel through the air
passageways;.Iaddend. .[.(b).]. .Iadd.(c) .Iaddend.drawing a fluid
substance contained in the vessel into the pipette tip; and
.[.(c).]. .Iadd.(d) .Iaddend.removing the pipette tip from the
.[.collection device.]. .Iadd.cap.Iaddend..
16. The method of claim 15, wherein the core structure comprises an
inwardly extending ledge, and wherein the second seal is affixed to
a surface of the ledge.
17. The method of claim 16, wherein the ledge comprises a depending
skirt.
18. The method of claim 17, wherein the second seal is affixed to a
bottom surface of the skirt.
19. The method of claim 16, wherein the first seal is affixed to a
top surface of the core structure.
20. The method of claim 15 further comprising a filter interposed
between the first and second seals.
21. The method of claim 20, wherein the filter is comprised of a
resilient material.
22. The method of claim 20, wherein the filter is gas
permeable.
23. The method of claim 22, wherein the filter is constructed and
arranged to trap an aerosol and/or bubbles.
24. The method of claim 15, wherein the cap does not include a
filter interposed between the first and second seals.
25. The method of claim 15, wherein the first and second seals are
torn in step (a), thereby forming the air passageways between the
pipette tip and the first and second seals.
26. The method of claim 15, wherein the .[.collection device.].
.Iadd.closed system .Iaddend.contains a specimen-retrieval device
within an interior space of the .[.collection device.].
.Iadd.closed system.Iaddend..
27. The method of claim 15 further comprising, after step .[.(c).].
.Iadd.(d).Iaddend., the step of amplifying a target nucleic acid
sequence present in the fluid substance removed from the
.[.collection device.]. .Iadd.closed system .Iaddend.in step
.[.(c).]. .Iadd.(d).Iaddend..
28. The method of claim 15, wherein the second seal is welded to
the core structure.
29. The method of claim 15, wherein the second seal is affixed to
the core structure with an adhesive.
30. The cap of claim 1, wherein the second seal is welded to the
core structure.
31. The cap of claim 1, wherein the second seal is affixed to the
core structure with an adhesive.
.Iadd.32. The cap of claim 1, wherein the second seal comprises a
foil layer..Iaddend.
.Iadd.33. The cap of claim 32, wherein the foil layer is an
aluminum foil..Iaddend.
.Iadd.34. The cap of claim 32, wherein the second seal further
comprises a heat seal layer and a brittle layer..Iaddend.
.Iadd.35. The cap of claim 32, wherein the first and second seals
tear when penetrated by a plastic pipette tip, thereby forming air
passageways between the pipette tip and the first and second
seals..Iaddend.
.Iadd.36. The cap of claim 32 further comprising a filter
interposed between the first and second seals..Iaddend.
.Iadd.37. The cap of claim 32, wherein the cap does not include a
filter interposed between the first and second seals..Iaddend.
.Iadd.38. The cap of claim 1, wherein the first seal comprises
score lines..Iaddend.
.Iadd.39. The cap of claim 38, wherein the second seal comprises a
foil layer..Iaddend.
.Iadd.40. The cap of claim 39, wherein the foil layer is an
aluminum foil..Iaddend.
.Iadd.41. The cap of claim 39, wherein the second seal further
comprises a heat seal layer and a brittle layer..Iaddend.
.Iadd.42. The cap of claim 39, wherein the first and second seals
tear when penetrated by a plastic pipette tip, thereby forming air
passageways between the pipette tip and the first and second
seals..Iaddend.
.Iadd.43. The cap of claim 39 further comprising a filter
interposed between the first and second seals..Iaddend.
.Iadd.44. The cap of claim 39, wherein the cap does not include a
filter interposed between the first and second seals..Iaddend.
.Iadd.45. The method of claim 15, wherein the second seal comprises
a foil layer..Iaddend.
.Iadd.46. The method of claim 45, wherein the foil layer is an
aluminum foil..Iaddend.
.Iadd.47. The method of claim 45, wherein the second seal further
comprises a heat seal layer and a brittle layer..Iaddend.
.Iadd.48. The method of claim 45, wherein the first and second
seals are torn in step (a), thereby forming the air passageways
between the pipette tip and the first and second
seals..Iaddend.
.Iadd.49. The method of claim 45 further corn risin a filter
interposed between the first and second seals..Iaddend.
.Iadd.50. The method of claim 45, wherein the cap does not include
a filter interposed between the first and second
seals..Iaddend.
.Iadd.51. The method of claim 15, wherein the first seal comprises
score lines..Iaddend.
.Iadd.52. The method of claim 51, wherein the second seal comprises
a foil layer..Iaddend.
.Iadd.53. The method of claim 52, wherein the second seal comprises
an aluminum foil layer..Iaddend.
.Iadd.54. The method of claim 52, wherein the second seal further
comprises a heat seal layer and a brittle layer..Iaddend.
.Iadd.55. The method of claim 52, wherein the first and second
seals are torn in step (a), thereby forming the air passageways
between the pipette tip and the first and second
seals..Iaddend.
.Iadd.56. The method of claim 52 further comprising a filter
interposed between the first and second seals..Iaddend.
.Iadd.57. The method of claim 52, wherein the cap does not include
a filter interposed between the first and second seals..Iaddend.
Description
FIELD OF THE INVENTION
The present invention relates to caps for use in combination with
fluid-holding vessels, such as those designed to receive and retain
biological specimens for clinical analysis, patient monitoring or
diagnosis. In particular, the present invention relates to a cap
which is penetrable by a fluid transfer device used to transfer
fluids to or from a fluid-holding vessel, where the vessel and cap
remain physically and sealably associated during a fluid
transfer.
INCORPORATION BY REFERENCE
All references referred to herein are hereby incorporated by
reference in their entirety. The incorporation of these references,
standing alone, should not be construed as an assertion or
admission by the inventors that any portion of the contents of all
of these references, or any particular reference, is considered to
be essential material for satisfying any national or regional
statutory disclosure requirement for patent applications.
Notwithstanding, the inventors reserve the right to rely upon any
of such references, where appropriate, for providing material
deemed essential to the claimed invention by an examining authority
or court. No reference referred to herein is admitted to be prior
art to the claimed invention.
BACKGROUND OF THE INVENTION
Collection devices are a type of cap and vessel combination
commonly used for receiving and storing biological specimens for
delivery to clinical laboratories, where the specimens may be
analyzed to determine the existence or state of a particular
condition or the presence of a particular infectious agent, such as
a virus or bacterial microorganism. Types of biological specimens
commonly collected and delivered to clinical laboratories for
analysis include blood, urine, sputum, saliva, pus, mucous and
cerebrospinal fluid. Since these specimen-types may contain
pathogenic organisms, it is important to ensure that collection
devices are constructed to be substantially leak-proof during
transport from the site of collection to the site of analysis. This
feature of collection devices is especially important when the
clinical laboratory and the collection facility are remote from one
another, increasing the likelihood that the collection device will
be inverted or severely jostled during transport and potentially
subjected to substantial temperature and pressure fluctuations.
To prevent specimen leakage, and possible contamination of the
surrounding environment, collection device caps are typically
designed to be screwed, snapped or otherwise frictionally fitted or
welded onto the vessel component, thereby forming a substantially
leak-proof seal between the cap and the vessel. In addition to
preventing fluid specimen from leaking, a substantially leak-proof
seal formed between the cap and the vessel components of a
collection device may also aid in ameliorating exposure of the
specimen to potentially contaminating influences from the immediate
environment. This aspect of a leak-proof seal is important for
preventing the introduction of contaminants into the collection
device that could alter the qualitative or quantitative results of
an assay.
While a leak-proof seal should prevent specimen seepage during
transport, the actual removal of the cap from the vessel prior to
specimen analysis presents another potential opportunity for
contamination. When removing the cap, specimen which may have
collected on the underside of the cap during transport could come
into contact with a clinician, possibly exposing the clinician to a
harmful pathogen present in the fluid sample. And if the specimen
is proteinaceous or mucoid in nature, or if the transport medium
contains detergents or surfactants, then a film or bubbles could
form around the mouth of the vessel during transport which could
burst when the cap is removed from the vessel, thereby
disseminating specimen into the testing environment. Another risk
associated with cap removal is the potential for creating a
contaminating aerosol which may lead to false positives or
exaggerated results in other specimens being simultaneously or
subsequently assayed in the same general work area through
cross-contamination. It is also possible that specimen residue from
one collection device, which may have been inadvertently
transferred to a gloved hand of a clinician, will come into contact
with specimen from another collection device through routine or
careless removal of caps and handling of the collection
devices.
Concerns with cross-contamination are especially acute when the
assay being performed involves nucleic acid detection and includes
an amplification procedure such as the well known polymerase chain
reaction (PCR), or a transcription-based amplification system such
as transcription-mediated amplification (TMA). (A review of several
amplification procedures currently in use, including PCR and TMA,
is provided in HELEN H. LEE ET AL., NUCLEIC ACID AMPLIFICATION
TECHNOLOGIES (1997).) Since amplification is intended to enhance
assay sensitivity by increasing the quantity of targeted nucleic
acid sequences present in a specimen, transferring even a minute
amount of pathogen-bearing specimen from one vessel, or target
nucleic acid from a positive control sample, to another vessel
containing an otherwise negative specimen could result in a
false-positive result.
To minimize the potential for creating contaminating specimen
aerosols, and to limit direct contact between specimens and humans
or the environment, it is desirable to have a collection device cap
which can be penetrated by a fluid transfer device (e.g., a pipette
tip which can be used with an air displacement pipette) while the
cap remains physically and sealably associated with the vessel. The
material and construction of the penetrable aspect of the cap
should facilitate the venting of air displaced from the interior
space of the collection device to ensure accurate fluid transfers
and to prevent a rapid release of aerosols as the fluid transfer
device is being inserted into or withdrawn from the collection
device. And, because air is vented from the interior space of the
collection device after the cap has been penetrated, it would be
particularly helpful if means were included for minimizing aerosol
release through the cap once it was penetrated by the fluid
transfer device. Also, to limit the amount of potentially
contaminating fluid present on the exterior of the fluid transfer
device after it is has been withdrawn from the collection device,
it would be advantageous if the cap also included means for wiping
or absorbing fluid present on the outside of the fluid transfer
device as it is being withdrawn from the collection device. To
prevent damage to the fluid transfer device which could affect its
ability to predictably and reliably dispense or draw fluids, and to
facilitate its use in manual pipetting applications, the cap should
also be designed to limit the forces necessary for the fluid
transfer device to penetrate the cap. Ideally, the collection
device could be used in both manual and automated formats and would
be suitable for use with disposable pipette tips made of a plastic
material.
Collection device caps which can be penetrated by a fluid transfer
device will have other advantages, as well, including the
time-savings resulting from clinicians not having to manually
remove caps from vessels before retrieving sample aliquots from the
collection devices for assaying. Another advantage of penetrable
collection device caps would be the reduction in repetitive motion
injuries suffered by clinicians from repeatedly unscrewing
caps.
SUMMARY OF THE INVENTION
The present invention solves the potential contamination problems
associated with conventional collection devices by providing a
penetrable cap for use with a vessel component of a collection
device which includes: (i) a closed side wall having an inner
surface, an outer surface, a top surface and a bottom surface; (ii)
attachment means for fixing the cap to an open end of the vessel in
sealing engagement; (iii) a ledge which extends in a radial and
inward direction from an inner surface of the side wall of the cap
and has an end surface which defines an aperture sized to receive a
fluid transfer device, where the inner surface of the side wall of
the cap and a top surface of the ledge define a first bore; (iv) a
frangible seal for preventing the passage of a fluid from an
interior space of the vessel into the first bore when the cap is
fixed to the vessel in sealing engagement, where the seal is
affixed to either the top surface or a bottom surface of the ledge;
(v) filtering means for impeding or preventing the release of an
aerosol or bubbles from the interior space of the vessel to the
atmosphere, where the filtering means is positioned substantially
within the first bore; and (vi) retaining means for containing the
filtering means within the first bore. (A "closed side wall" is one
which lacks fully exposed end surfaces.) The retaining means is
preferably affixed to a top wall of the cap. The side wall, the
flange and the ledge of the cap are molded from a plastic material
and preferably form a unitary piece.
In an alternative and preferred embodiment, the penetrable cap
includes a skirt which depends from the bottom surface of the
ledge, where an inner surface of the skirt defines a second bore
having a diameter or width smaller than that of the first bore. The
skirt may be included, inter alia, to further prevent a fluid from
leaking from the interior of the vessel when the cap is fixed to
the vessel in sealing engagement. (By "sealing engagement" is meant
touching contact between solid surfaces which is intended to
prevent or impede the passage of a fluid.) An outer surface of the
skirt preferably includes a seal bead which is in frictional
contact with an inner surface of the vessel. With this embodiment,
the frangible seal may be affixed to either the top surface of the
ledge or to a bottom surface of the skirt. The side wall, the
flange, the ledge and the skirt of the cap of this embodiment are
molded from a plastic material and preferably form a unitary
piece.
In another embodiment of the present invention, the retaining means
is a second frangible seal. The second frangible seal may comprise
the same or a different material than the frangible seal affixed to
the top or bottom surface of the ledge, or to the bottom surface of
the skirt. Both seals are penetrable by a fluid transfer device
with the application of moderate manual force and each seal
preferably comprises a foil.
In still another embodiment of the present invention, the retaining
means comprises a foil ring having a centrally located hole which
is sized to receive a fluid transfer device and which is
substantially axially aligned with the first bore and the second
bore, if present. The diameter or width of this hole is smaller
than the diameter or width of a filter contained within the first
bore so that the foil ring can function to contain the filter
within the cap. The foil ring of this embodiment may be affixed to
the top wall of the cap by means of an adhesive or by means of a
plastic liner which has been applied to the foil ring and which can
be welded to the surface of the top wall of the cap.
In yet another embodiment of the present invention, the retaining
means includes a plastic disc having a hole formed therein which is
sized to receive a fluid transfer device and which is substantially
axially aligned with the first bore and the second bore, if
present. The retaining means of this embodiment functions to
contain a filter within the first bore. The disc may be affixed to
the top wall of the cap or the top wall may be adapted to include a
seat for receiving the disc in, for example, a frictional or snap
fit.
In a further embodiment, the retaining means comprises a removable
seal which is designed to limit exposure of a filter to
environmental contaminants and may include a tab for easy removal
prior to penetrating the cap. Because this seal may be removed
prior to penetration of the cap, it is not a requirement that this
particular retaining means be comprised of a frangible material
which can be pierced by a fluid transfer device applying moderate
manual force. Since the removable seal can function to protect the
filter against external contaminants during shipping, the removable
seal may be applied, for example, to the fixed disc described above
for retaining the filter within the first bore.
In still another embodiment, the cap is provided as part of a
collection device which includes a vessel for containing fluids.
When provided as a part of a collection device, the cap preferably
includes the skirt feature described above, which is positioned
adjacent to an inner surface of an open end of the vessel to impede
the passage of a fluid from the interior space of the vessel to the
environment outside of the collection device. Including a seal bead
on an outer surface of the skirt further facilitates this objective
by increasing the pressure which is exerted by the skirt on the
inner surface of the vessel. The collection device may contain, for
example, a dry powder, pellets of chemical reagents, buffers,
stabilizers, or a transport medium for preserving a specimen while
it is being shipped from a collection location to a site for
analysis. The collection device may also be provided in packaged
combination with a specimen retrieval device (e.g., a swab) for
obtaining a specimen from a human, animal, water, environmental,
industrial, food or other source. Instructional materials may
additionally be included with the collection device which detail
proper use of the collection device when obtaining or transporting
a specimen or appropriate techniques for retrieving a fluid sample
from the collection device at the site of analysis. When in
packaged combination, the recited items are provided in the same
container (e.g., a mail or delivery container for shipping), but do
not need to be per se physically associated with one another in the
container or combined in the same wrapper or vessel within the
container.
In yet another embodiment, the cap can be used in a method for
retrieving a fluid substance from the vessel component of a
collection device with a plastic pipette tip for use with an air
displacement pipette. When the cap is penetrated by the pipette
tip, air passageways are formed between the pipette tip and the
frangible seal or seals of the cap, thereby facilitating the
venting of air from within the vessel. After fluid is removed from
the collection device, at least some portion of the fluid sample
may be exposed to amplification reagents and conditions permitting
a targeted nucleic acid sequence which may be present in the fluid
sample to be amplified. Various amplification procedures, and their
associated reagents and conditions, are well known to those skilled
in the art of nucleic acid diagnostics.
In still another embodiment, a method is provided for removing a
fluid substance contained in a closed system comprising a cap and a
fluid-holding vessel. In addition to the cap and vessel components,
the phrase "closed system" is used herein to refer to a cap that is
fixed to a vessel in sealing engagement to prevent the fluid
contents of the system from escaping into the surrounding
environment. The method includes penetrating first and second
frangible seals affixed to the cap with a fluid transfer device,
where the second seal is axially aligned below the first seal.
Penetration of the first and second seals by the fluid transfer
device results in the formation of air passageways between the
seals and the fluid transfer device which aid in venting air from
the interior space of the system. The fluid transfer device is
preferably a plastic pipette tip for use with an air displacement
pipette. In a preferred mode, the method further includes passing
the fluid transfer device through a filter contained within the cap
and interposed between the first and second seals.
Once fluid has been removed from the system in this method, some or
all of the fluid sample may be exposed to amplification reagents
and conditions permitting a targeted nucleic acid sequence which
may be present in the fluid sample to be amplified. As noted above,
a variety of amplification procedures are well known to those
skilled in the art of nucleic acid diagnostics, and appropriate
reagents and conditions for use with any of these amplification
procedures could be determined without engaging in undue
experimentation.
In yet a further embodiment of the present invention, a method is
provided for depositing substances into the collection devices and
other closed systems of the present invention by means of a
substance transfer device capable of transporting fluids (e.g.,
specimen or assay reagents) or solids (e.g., particles, granules or
powders). This embodiment of the present invention is particularly
useful for diagnostic assays which can be performed in a single
reaction vessel and where it is desirable to maintain the contents
of the vessel in a substantially closed environment. The steps of
this embodiment are similar to those of other preferred methods
described herein, except that one or more substances would be
deposited into the vessel component rather than retrieving a fluid
sample contained therein.
The methods of the presently claimed invention may be performed
manually or adapted for use with a semi-automated or fully
automated instrument. Examples of instrument systems which could be
readily adapted for use with the collection devices or other closed
systems of the present invention include the DTS.RTM. 400 System
(detection only) and the DTS.RTM. 1600 System (amplification and
detection) (Gen-Probe Incorporated; San Diego, Calif.). See Acosta
et al., "Assay Work Station," U.S. Pat. No. 6,254,826. Other fully
automated instrument systems are disclosed by Ammann et al.,
"Automated Process for Isolating and Amplifying a Target Nucleic
Acid Sequence," U.S. Pat. No. 6,335,166.
These and other features, aspects, and advantages of the present
invention will become apparent to those skilled in the art after
considering the following detailed description, appended claims and
accompanying drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is an exploded perspective view of the cap and vessel
components of a preferred collection device of the present
invention.
FIG. 2 is an enlarged top plan view of the core cap of FIG. 1.
FIG. 3 is an enlarged bottom view of the core cap of FIG. 1.
FIG. 4 is an enlarged partial section side view of the collection
device of FIGS. 1-3 (showing core cap only), taken along the 4-4
line thereof.
FIG. 5 is an enlarged partial section side view of another
collection device according to the present invention.
FIG. 6 is an enlarged section side view of the cap of FIG. 1.
FIG. 7 is an enlarged section side view of another cap according to
the present invention.
FIG. 8 is an enlarged section side view of a frangible seal
according to the present invention.
FIG. 9 is an enlarged section side view of another frangible seal
according to the present invention.
FIG. 10 is an enlarged top plan view of the core cap and filter of
FIG. 1.
FIG. 11 is a top plan view of the cap of FIGS. 6 and 7 showing
perforations in the frangible seal.
FIG. 12 is an enlarged top plan view of a further cap according to
the present invention.
FIG. 13 is an enlarged section side view of yet another cap
according to the present invention.
FIG. 14 is a top plan view of the cap of FIG. 13.
FIG. 15 is an enlarged section side view of still another cap
according to the present invention.
FIG. 16 is a top plan view of the cap of FIG. 15.
FIG. 17 is a partial section side view of the collection device of
FIG. 1, after it has been penetrated by a fluid transfer
device.
FIG. 18 is a top plan view of the cap and fluid transfer device of
FIG. 17.
DETAILED DESCRIPTION OF THE INVENTION
While the present invention may be embodied in a variety of forms,
the following description and accompanying drawings are merely
intended to disclose some of these forms as specific examples of
the present invention. Accordingly, the present invention is not
intended to be limited to the forms or embodiments so described and
illustrated. Instead, the full scope of the present invention is
set forth in the appended claims.
With reference to the figures, preferred caps 30A-E of the present
invention are shown alone or in combination with a vessel 20 which
can be used for receiving and storing fluid specimens for
subsequent analysis, including analysis with nucleic acid-based
assays or immunoassays diagnostic for a particular pathogenic
organism. When the desired specimen is a biological fluid, the
specimen can be, for example, blood, urine, saliva, sputum, mucous
or other bodily secretion, pus, amniotic fluid, cerebrospinal fluid
or seminal fluid. However, the present invention also contemplates
materials other than these specific biological fluids, including,
but not limited to, water, chemicals and assay reagents, as well as
solid substances which can be dissolved in whole or in part in a
fluid milieu (e.g., tissue specimens, stool, environmental samples,
food products, powders, particles and granules). The vessel 20 is
preferably capable of forming a substantially leak-proof seal with
the cap 30A-E and can be of any shape or composition, provided the
vessel is shaped to receive and retain the material of interest
(e.g., fluid specimen or assay reagents). Where the vessel 20
contains a specimen to be assayed, it is important that the
composition of the vessel be essentially inert so that it does not
significantly interfere with the performance or results of an
assay. A preferred vessel 20 is formed of polypropylene and has a
generally cylindrical shape which measures approximately 13
mm.times.82 mm.
As illustrated in the figures, particularly preferred caps 30A-E of
the present invention include an integrally molded core structure
31A (referred to herein as the "core cap") which comprises: (i) a
generally cylindrical side wall 35; (ii) a flange 36 depending from
a bottom surface 37 of the side wall and having an inner surface 38
adapted to grip an outer surface 21 of a generally cylindrical side
wall 22 of an open-ended vessel 20; (iii) a ledge 39 extending
radially inwardly from an inner surface 40 of the side wall 35
above the flange 36; and (iv) a generally cylindrical skirt 41
depending from a bottom surface 42 of the ledge in a substantially
parallel orientation to the flange. The inner surface 40 of the
side wall 35 and a top surface 43 of the ledge 39 define a first
bore 44, as shown in FIG. 4, which is sized to receive a filter 33,
as shown in FIGS. 6 and 7, that may be frictionally fitted or
otherwise immobilized within the first bore. In a preferred
embodiment, the ledge 39 aids in retaining the filter 33 within the
first bore 44 during penetration of the cap 30A-E by a fluid
transfer device. The ledge 39 can also function as a surface for
affixing a frangible seal 32, as depicted in FIG. 6. An inner
surface 45 of the skirt 41 beneath the top surface 43 of the ledge
39 defines a second bore 46 which is smaller in diameter than the
first bore 44 and is sized to permit movement therethrough of a
fluid transfer device. (The proximal portion of the skirt 41, where
the top surface 43 of the ledge 39 meets the inner surface 45 of
the skirt, may be chamfered to deflect a misaligned fluid transfer
device during penetration of the cap 30A-E, provided sufficient
surface area remains on the top surface of the ledge for affixing
the frangible seal 32 thereto.) As shown in FIG. 7, the skirt 41
includes a bottom surface 47 which may serve as an alternate
location for affixing the frangible seal 32.
In an alternative core cap 31B embodiment shown in FIG. 5, the
skirt 41 is eliminated from the core cap 31A structure shown in
FIG. 4. In this embodiment, the frangible seal 32 may be affixed to
either the bottom surface 42 or the top surface 43 of the ledge 39.
However, since the skirt 41 aids in preventing fluids from leaking
from a collection device 10, it may be desirable to include an
alternative fluid retainer for this core cap 31B embodiment, such
as a neoprene O-ring (not shown) fitted between the bottom surface
37 of the side wall 35 and an annular top surface 23 of the vessel
20.
While the ledge 39 of the core cap 31B shown in FIG. 5 forms a
flange structure having bottom and top surfaces 42, 43, this
embodiment may be modified so that the inner surface 40 of the side
wall 35 is extended radially inward until an end surface 62 of the
ledge and the inner surface of the side wall are co-extensive. In
this modified form of the core cap 31B (not shown), the ledge 39 is
defined by the bottom surface 37 of the side wall 35, since the top
surface 43 of the ledge is eliminated. Because the bore 44 of this
embodiment is defined solely by the inner surface 40 of the side
wall 35, the frangible seal 32 must be affixed to the bottom (or
sole) surface 42 of the ledge 39.
A similar modification may be made to the preferred core cap 31A,
whereby the inner surface 40 of the side wall 35 is extended
radially inward until the inner surface 45 of the skirt 41 is
co-extensive with the inner surface of the side wall. This modified
form of the core cap 31A (not shown) eliminates the ledge 39,
transforms the first and second bores 44, 46 into a single bore,
and requires that the frangible seal 32 be affixed to the bottom
surface 47 of the skirt 41. The disadvantage of these modified
forms of the core caps 31A, 31B is that the alteration or
elimination of the ledge 39 makes it is more difficult to maintain
the filter 33 within the cap 30A-E when the cap is penetrated by a
fluid transfer device. This problem may be overcome by adhering the
filter 33 to the side wall 35 of the cap 30A-E, the frangible seal
32 or the retaining means 34A-C, for example.
The core cap 31A-B may be integrally molded from a number of
different polymer and heteropolymer resins, including, but not
limited to, polyolefins (e.g., high density polyethylene ("HDPE"),
low density polyethylene ("LDPE"), a mixture of HDPE and LDPE, or
polypropylene), polystyrene, high impact polystyrene and
polycarbonate. A currently preferred material for forming the core
cap 31A-B is an HDPE material sold under the tradename Alathon
M5370 by GE Polymerland of Huntersville, N.C. Skilled artisans will
readily appreciate that the range of acceptable cap resins will, in
part, depend upon the nature of the resin used to form the vessel,
since the properties of the resins used to form these two
components will affect how well the cap 30A-E and vessel 20
components of a collection device 10 can form a leak proof seal and
the ease with which the cap can be securely screwed onto the
vessel. As with the vessel 20 component, the material of the core
cap 31A-B should be essentially inert with respect to a fluid
substance (including assay reagents) contained in the collection
device 10 so that the material of the core cap does not
significantly interfere with the performance or results of an
assay.
The core cap 31A-B is injection molded as a unitary piece using
procedures well-known to those skilled in the art of injection
molding. After the core cap 31A-B has been formed and cured for a
sufficient period of time, the following components are added to
the core cap in the indicated manner and in any practicable order:
(i) the frangible seal 32 to the top surface 43 of the ledge 39 of
either core cap 31A-B, to the bottom surface 42 of the ledge of the
alternative core cap 31B, or to the bottom surface 47 of the skirt
41 of the preferred core cap 31A; (ii) a filter 33 within the first
bore 44; and (iii) a retainer 34A-D to the annular top wall 48.
The frangible seal 32 is included to provide a substantially
leak-proof barrier between the fluid contents of a collection
device 10 and the filter 33 contained in the first bore 44. For
this reason, it is not critical whether the frangible seal 32 is
affixed to a surface 42, 43 of the ledge 39 or to the bottom
surface 47 of the skirt 41. According to a preferred embodiment of
the present invention, the width of the annular top surface 43 of
the ledge 39 is about 0.08 inches (2.03 mm), the thickness of the
ledge (the distance between the top and bottom surfaces 43, 42 of
the ledge) is about 0.038 inches (0.97 mm), the combined width of
the annular bottom surface 42 of the ledge and the exposed bottom
surface 37 of the side wall 35 is about 0.115 inches (2.92 mm), and
the width of the annular bottom surface 47 of the skirt 41 is about
0.025 inches (0.635 mm). The dimensions of these features of the
core cap 31A-B may vary, of course, provided sufficient surface
area exists for affixing the frangible seal 32 to the core cap in a
substantially leak-proof manner.
The frangible seal 32 may be made of a plastic film (e.g., thin
monoaxially or biaxially oriented plastic film) or, preferably, of
a foil (e.g., aluminum foil or other foil exhibiting low water
vapor transmission), which can be affixed to a surface 42, 43 of
the ledge 39 or to the bottom surface 47 of the skirt 41 by means
well known to those skilled in the art, including adhesives. The
frangible seal 32 is preferably not an integral component of the
core cap 31A-B. If the frangible seal 32 comprises a foil, it may
further include a compatibilizer, such as a thin veneer of plastic
applied to one or both surfaces of the foil, which will promote a
substantially leak-proof attachment of the frangible seal to a
surface of the core cap 31A-B with the application of thermal
energy. A heat sealer or heat induction sealer may be used to
generate the requisite thermal energy. (To avoid the potentially
deleterious effects of corrosion, it is recommended that all
portions of a metallic frangible seal 32 which might become exposed
to the fluid contents of a collection device 10 during routine
handling be coated with a plastic liner.) A TOSS Machine heat
sealer (Packworld USA; Nazareth, Pa.; Model No. RS242) is preferred
for attaching the frangible seal 32 to a surface 42, 43 of the
ledge 39 or to the bottom surface 47 of the skirt 41. Ultrasonic
and radio frequency welding procedures known to those skilled in
the art may also be used to affix the frangible seal 32 to the core
cap 31A-B.
To further promote attachment of the frangible seal 32 to the core
cap 31A-B, a surface 42, 43 of the ledge 39 or the bottom surface
47 of the skirt 41 may be modified during injection molding of the
core cap to include an energy director, such as an annular ring or
series of protuberances. By limiting contact between the frangible
seal 32 and a plastic surface of the ledge 39 or skirt 41, an
energy director allows the frangible seal 32 to be affixed to the
ledge or skirt in less time and using less energy than would be
required in its absence when an ultrasonic welding procedure is
followed. This is because the smaller surface area of the
protruding energy director melts and forms a weld with the plastic
material of the frangible seal 32 more quickly than is possible
with a flat, unmodified plastic surface. An energy director of the
present invention is preferably a continuous surface ring which is
triangular in cross-section.
In order to facilitate the venting of air from within a collection
device 10, the frangible seal 32 is preferably constructed so that
it tears when the seal is penetrated by a fluid transfer device,
thereby forming air passageways 70 between the seal and the fluid
transfer device, as described in detail infra. To achieve this
tearing, the seal 32 preferably includes a brittle layer comprised
of a hard plastic material, such as a polyester. (See CHARLES A.
HARPER, HANDBOOK OF PLASTICS, ELASTOMERS, AND COMPOSITES
.sctn.1.7.13 (1997 3d ed.) for a discussion of the properties of
polyesters.) As shown in FIG. 8, the preferred seal 32 of the
present invention is a co-laminate that includes a foil layer, a
heat seal layer and an intervening brittle layer (Unipac; Ontario,
Canada; Product No. SG-75M (excluding the pulp board and wax layers
typically included with this product)). With this preferred seal
32, the foil layer is an aluminum foil having a thickness of about
0.001 inches (0.0254 mm), the heat seal layer is a polyethylene
film having a thickness of about 0.0015 inches (0.0381 mm), and the
brittle layer is a polyester having a thickness of about 0.0005
inches (0.0127 mm). Because this particular seal 32 design would
have a metallic surface exposed to the contents of a collection
device 10 after sealing--if applied to the bottom surface 42 of the
ledge 39 or to the bottom surface 47 of the skirt 41--it is
preferred that this seal 32 be applied to the top surface 43 of the
ledge, as shown in FIGS. 6, 13, 15 and 17. In this way, the cap
30A, C, D and E of these embodiments will have no metallic surfaces
exposed to the fluid contents of an associated vessel 20. While the
diameter of the seal 32 will depend upon the dimensions of the cap
30A-E, the presently preferred seal has a diameter of about 0.5
inches (12.70 mm).
An alternative frangible seal 32 embodiment is depicted in FIG. 9,
which shows a top foil layer with a lower combined brittle/heat
seal layer comprised of an epoxy resin. The epoxy resin is selected
for its mechanical strength, which will promote formation of the
desired air passageways 70 discussed above when the material is
penetrated by a fluid transfer device. And, so that this seal 32
can be affixed to a plastic surface using a commonly practiced
thermoplastic welding procedure, the epoxy layer further includes a
compatibilizer dispersed within the epoxy resin, as shown in FIG.
9. A preferred compatibilizer of this seal 32 embodiment is a
polyethylene.
As illustrated in the figures, the filter 33 is positioned within
the first bore 44 above the ledge 39 and is incorporated to retard
or block the movement of an escaping aerosol or bubbles after the
seal has been pierced by a fluid transfer device. The filter 33 can
also be constructed to perform a wiping action on the outside of a
fluid transfer device as the fluid transfer device is being removed
from a collection device 10. In a preferred mode, the filter 33
functions to draw fluids away from the outside of a fluid transfer
device by means of capillary action. As used herein, however, the
term "filter" refers generally to a material which performs a
wiping function to remove fluids present on the outside of a fluid
transfer device and/or an absorbing function to hold or otherwise
sequester fluids removed from the outside of a fluid transfer
device. For reasons discussed below, the filters 33 of the present
invention are composed of a material or combination of materials
having pores or interstices which admit the passage of a gas.
Examples of filter 33 materials which may be used with the cap
30A-E of the present invention include, but are not limited to,
pile fabrics, sponges, foams (with or without a surface skin),
felts, sliver knits, a GORE-TEX.RTM. fabric, a fabric containing a
LYCRA.RTM. fiber, and other materials and blends, both natural and
synthetic. These materials may also be mechanically or chemically
treated to further improve the intended functions of the filter 33.
For example, napping may be used to increase the surface area and,
therefore, the fluid holding capacity of a filter 33. The material
of the filter 33 may also be pre-treated with a wetting agent, such
as a surfactant, to lower the surface tension of a fluid present on
an outer surface of a fluid transfer device. An acrylic binder
might be used, for example, to actually bind the wetting agent to
the filter 33 material. Additionally, the filter 33 may include a
super-absorbent polymer, (see, e.g., Sackmann et al., "Pre-Formed
Super Absorbers with High Swelling Capacity," U.S. Pat. No.
6,156,848), to prevent a fluid from escaping from a penetrated
collection device 10.
To limit the unobstructed passage of air from within a collection
device 10 to the environment, the filter 33 is preferably made of a
resilient material whose original shape is restored, or
substantially restored, as a fluid transfer device is being removed
from the collection device. This characteristic of the filter 33 is
especially important when the fluid transfer device has a
non-uniform diameter, as is the case with most pipette tips used
with standard air displacement pipettes. Thus, materials such as
pile fabric, sponges, foams, and fabrics containing LYCRA.RTM.
fibers are preferred because they tend to quickly restore their
original shape after exposure to compressive forces. Pile fabric is
a particularly preferred filter 33. An example of a preferred pile
fabric is an acrylic material having a thickness of about 0.375
inches (9.53 mm) which is available from Roller Fabrics of
Milwaukee, Wis. as Part No. ASW112. Examples of other acceptable
pile fabrics include those made of acrylic and polyester materials
and which range in size from about 0.25 inches (6.35 mm) to about
0.3125 inches (7.94 mm). Such pile fabrics are available from Mount
Vernon Mills, Inc. of LaFrance, S.C. as Part Nos. 0446, 0439 and
0433. The filter 33 material is preferably inert with respect to a
fluid substance contained within the vessel 20.
Because the filter 33 is intended to remove fluid from the exterior
of a fluid transfer device and to capture fluid in the form of an
aerosol or bubbles, it is best if the material and dimensions of
the filter material are chosen so that the filter does not become
saturated with fluid during use. If the filter 33 does become
saturated, fluid may not be adequately wiped from the exterior of
the fluid transfer device and bubbles may be produced as the fluid
transfer device passes through the filter or as air is displaced
from within the collection device 10. Thus, it is important to
adapt the size and adsorptive properties of the filter 33 in order
to achieve adequate wiping and aerosol or bubble containment.
Considerations when selecting a filter 33 will include the cap
configuration, the shape and size of the fluid transfer device and
the nature and amount of fluid substance contained in the vessel
20, especially in view of the number of anticipated fluid transfers
for a given collection device 10. As the amount of fluid a filter
33 is likely to be exposed to increases, the volume of the filter
material or its absorptive properties may need to be adjusted so
that the filter does not become saturated during use.
It is also important that the filter 33 be constructed and arranged
in the cap 30A-E so that the flow of air out of the collection
device 10 remains relatively unimpeded as the cap is being
penetrated by a fluid transfer device. In other words, the material
of the filter 33 and its arrangement within the cap 30A-E should
facilitate the venting of air displaced from within the collection
device 10. Of course, this venting property of the filter 33 needs
to be balanced with the requirement that the filter material have
sufficient density to trap an escaping aerosol or bubbles.
Consequently, those skilled in the art will appreciate the need to
select or design filter 33 materials having matrices that are
capable of trapping an aerosol or bubbles, while simultaneously
permitting air to be vented from within the collection device 10
once the underlying seal 32 has been pierced by a fluid transfer
device.
As the figures show, the filter 33 is preferably sized to fit
within the first bore 44 beneath the horizontal plane of the
annular top wall 48. In a preferred cap 30A-E of the present
invention, the filter 33 also rests substantially or completely
above the ledge 39, even though the seal 32 may be affixed to the
bottom surface 47 of the skirt 41, as illustrated in FIG. 7. To
better ensure that the filter 33 is not substantially moved from
its position within the first bore 44 by frictional contact with a
fluid transfer device penetrating or being removed from the cap
30A-E, the filter may be bound to the top surface 43 of the ledge
39 or to the inner surface 40 of the side wall 35 using an inert
adhesive. Notwithstanding, the filter 33 is preferably a pile
fabric which is snugly fitted in the first bore 44 and retained
there by means of the seal 32 and the retainer 34A-D, without the
use of an adhesive. In preferred cap 30A-E embodiments, the first
bore 44 is about 0.50 inches (12.70 mm) in diameter and has a
height of about 0.31 inches (7.87 mm).
The material and configuration of the filter 33 should be such that
it creates minimal frictional interference with a fluid transfer
device as it is being inserted into or withdrawn from the
collection device 10. In the case of a sponge or foam, for example,
this may require boring a hole or creating one or more slits in the
center of the filter 33 (not shown) which are sized to minimize
frictional interference between the filter and a fluid transfer
device, while at the same time providing enough interference so
that aerosol or bubble transmission is limited and the wiping
action is performed by the filter material. If a pile fabric is
employed as the filter 33, the pile fabric is preferably arranged
in the manner shown in FIG. 10, such that the free ends of
individual fibers (shown as squiggles, but not specifically
identified with a reference number) are oriented radially inwardly
toward the longitudinal axis 80 of the cap 30A-E and away from the
pile fabric backing 49 which is in touching or fixed contact with
the inner surface 40 of the side wall 35. When rolling the pile
fabric for insertion into the first bore 44, care should be taken
not to wind the pile fabric so tightly that it will create
excessive frictional interference with a fluid transfer device
penetrating the cap 30A-E, thereby substantially impeding movement
of the fluid transfer device. A particularly preferred pile fabric
is available from Mount Vernon Mills, Inc. as Part No. 0446, which
has a thickness of about 0.25 inches (6.35 mm) and is cut to have a
length of about 1.44 inches (36.58 mm) and a width of about 0.25
inches (6.35 mm).
To immobilize the filter 33 within the first bore 44, the caps
30A-E of the present invention include a retainer 34A-D positioned
above the filter, preferably on the annular top wall 48. In a
preferred embodiment shown in FIGS. 6 and 7, the retainer 34A is a
solid, generally circular frangible seal which may be of the same
or a different material than the frangible seal 32 positioned
beneath the filter 33. Preferably, the retainer 34A includes the
same materials as the preferred seal 32 described above, which
comprises an aluminum foil layer, a polyester brittle layer, and a
polyethylene heat seal layer (Unipac; Ontario, Canada; Product No.
SG-75M (excluding the pulp board and wax layers typically included
with this product)). This retainer 34A can be applied to the
annular top wall 48 with a heat sealer or heat induction sealer in
the same manner that the seal 32 is applied to a surface 42, 43 of
the ledge 39 or to the bottom surface 47 of the skirt 41. Like the
preferred seal 32, the preferred retainer 34A has a foil layer
thickness of about 0.001 inches (0.0254 mm), a brittle layer
thickness of about 0.0005 inches (0.0127 mm), and a heat seal layer
thickness of about 0.0015 inches (0.0381 mm). The diameter of the
preferred retainer is about 0.625 inches (15.88 mm). Of course, the
diameter of this preferred retainer 34A may vary and will depend
upon the dimensions of the annular top wall 48.
As illustrated in FIG. 11, the retainer 34A may be adapted to
facilitate penetration by including one or more series of
perforations 50 which extend radially outwardly from a center point
51 of the retainer. The center point 51 of these radiating
perforations 50 is preferably positioned to coincide with the
expected entry point of a fluid transfer device. Also contemplated
by the present invention are other types of adaptations that would
reduce the tensile strength of the retainer 34A, including creases,
score lines or other mechanical impressions applied to the material
of the retainer. The same adaptations may also be made to the seal
32, provided the seal will continue to exhibit low water vapor
transmission characteristics after the collection device 10 is
exposed to normal shipping and storage conditions.
Besides providing a means for keeping the filter 33 fixed within
the first bore 44 prior to and during a fluid transfer, a seal
retainer 34A can protect the underlying filter from external
contaminants prior to penetration of the cap 30A. Moreover, a cap
30A designed to completely seal the filter 33 within the first bore
44 may be sterilized prior to use by, for example, gamma
irradiation. Additionally, the retainer 34 of such a cap 30A could
be wiped with a disinfectant or the entire collection device 10
could be irradiated with ultraviolet light prior to penetration to
facilitate a sterile fluid transfer.
In those instances where the potential presence of contaminants on
the filter would not be of significant concern, however, the
retainer may comprise a foil ring, for example, which includes a
centrally located hole which is sized to receive a fluid transfer
device. As illustrated in FIG. 12, a cap 30C having a retainer 34B
with a centrally located hole 52 could aid in retaining the filter
33 within the first bore 44, while at the same time limiting the
number of surfaces that a fluid transfer device would have to
pierce in order to fully penetrate the cap. To retain the filter 33
within the first bore 44, the diameter of the hole 52 would have to
be smaller than the diameter of the filter when the hole and the
filter are substantially axially aligned.
Another cap 30D embodiment is illustrated in FIGS. 13 and 14. The
retainer 34C of this cap 30D is a plastic disc which includes a
centrally located hole 53 sized to receive a fluid transfer device.
The disc 34C may be affixed to the annular top wall 48 by means of
an adhesive or welded by heat, ultrasound or other appropriate
welding method known to skilled artisans. Alternatively, the
annular top wall 48 may be modified to include a seat 54 which is
sized to receive the disc 34C in, for example, a frictional or snap
fit. While this particular cap 30D embodiment does not provide the
filter 33 with a completely sealed environment, the disc retainer
34C can nevertheless function to contain the filter 33 within the
first bore 44 during transport of the collection device 10, as well
as during a fluid transfer. If it is important to protect the
filter 33 from potential contaminants prior to use, then the cap
30D of this embodiment could further include a seal, such as the
frangible seal 34A described supra, affixed to a top 55 or a bottom
surface 56 of the disc 34C so that the hole 53 is fully and
sealably covered. As illustrated in FIGS. 15 and 16, one such seal
34D could include a tab 57 for easy removal. With this design, the
seal 34D of a cap 30E could be removed just before penetration of
the cap with a fluid transfer device, allowing the filter 33 to be
protected from external contaminants immediately prior to use. An
advantage of this cap 30E over, for example, the cap 30A-B
embodiments shown in FIGS. 6 and 7 is that penetration of the cap
will require less force since there is only one seal 32, as opposed
to the two seals 32, 34A of those embodiments, that the fluid
transfer device needs to pierce.
When a cap 30A-E of the present invention is pierced by a fluid
transfer device 90 which is used to retrieve at least a portion of
a fluid sample 100 contained in a collection device 10, as shown in
FIG. 17, one or more tears are preferably formed in the frangible
seal 32 and, if comprised of a frangible seal, the retainer 34A. As
FIG. 18 illustrates, these tears in the frangible seal form air
passageways 70 which facilitate the venting of air displaced from
within a collection device 10 as the fluid transfer device 90
enters the interior space 11 (defined as the space below the cap
30A-E and within inner surfaces 24, 25 of the side wall 22 and a
bottom wall 26 of the vessel 20) of the collection device 10. By
providing means for venting air displaced from within a collection
device 10, the volume accuracy of fluid transfers (e.g., pipetting)
will likely be improved. While a variety of fluid transfer devices
can be used with the present invention, including hollow metal
needles and conventional plastic pipette tips having beveled or
flat tips, a preferred fluid transfer device is the Genesis series
1000 .mu.l Tecan-Tip (with filter), available from
Eppendorf-Netherler-Hinz GmbH of Hamburg, Germany as Part No.
612-513. Fluid transfer devices of the present invention are
preferably able to penetrate the frangible seal 32 with the
application of less than about 3 pounds force (13.34 N), more
preferably less than about 2 pounds force (8.90 N), even more
preferably less than about 1 pound force (4.45 N), and most
preferably less than about 0.5 pounds force (2.22 N).
The insertion force, which is the total or additive force required
to pierce all penetrable surfaces of a cap 30A-E according to the
present invention (i.e., the frangible seal 32, the filter 33 and,
optionally, the retainer 34A) with a fluid transfer device, is
preferably less than about 8 pounds force (35.59 N), more
preferably less than about 6.5 pounds force (28.91 N), even more
preferably less than about 5 pounds force (22.24 N), and most
preferably less than about 4.5 pounds force (20.02 N). The
withdrawal force, which is the force required to completely
withdraw a fluid transfer device from the collection device 10
after the cap 30A-E has been completely penetrated, is preferably
less than about 4 pounds force (17.79 N), more preferably less than
about 3 pounds force (13.34 N), even more preferably less than
about 2 pounds force (8.90 N), and most preferably less than about
1 pound force (4.45 N). The forces exerted on the fluid transfer
device as it is being withdrawn from a collection device 10 should
be minimized to avoid stripping the fluid transfer device from, for
example, the mounting probe of a vacuum pipette. Insertion and
withdrawal forces can be determined using conventional force
measurement instruments, such as a motorized test stand (Model No.
TCD 200) and digital force gauge (Model No. DFGS-50) available from
John Chatillon & Sons, Inc. of Greensboro, N.C.
A cap 30A-E according to the present invention is generally
provided in combination with a fluid-holding vessel 20 as
components of a collection device 10. The cap 30A-E and vessel 20
of the collection device 10 can be joined by means of mated threads
which allow the cap to be screwed, snapped or otherwise
frictionally fitted onto an outer surface 21 of the side wall 22 at
the open end of the vessel. When the cap 30A-E is frictionally
fitted onto the vessel 20, the bottom surface 37 of the side wall
35 of the cap is preferably in contact with the annular top surface
23 of the vessel to provide an interference fit, thereby
facilitating the essentially leak-proof seal discussed above. The
cap 30A-E can be modified to further improve resistance of the
collection device 10 to leaking by providing an annular seal bead
58 to an outer surface 59 of the skirt 41, as shown in FIG. 4. If
the seal bead 58 is included, it should be sized so that it will be
in frictional contact with the inner surface 24 of the side wall 22
of the vessel 20 but will not substantially interfere with joining
of the cap 30A-E and vessel. The annular center 60 of the preferred
seal bead 58 is about 0.071 inches (1.80 mm) from the bottom
surface 37 of the side wall 35 and extends radially outwardly about
0.0085 inches (0.216 mm) from the outer surface 59 of the skirt 41,
where the thickness of the skirt 41 above the seal bead 58 is about
0.052 inches (1.32 mm). The skirt 41 preferably includes a beveled
base 61 below the seal bead 58 to facilitate joining of the cap
30A-E and vessel 20. In a preferred embodiment, the skirt 41
extends downward a vertical distance of about 0.109 inches (2.77
mm) from the annular center 60 of the seal bead 58 to the bottom
surface 47 of the skirt and uniformly decreases in thickness from
about 0.0605 inches (1.54 mm) to about 0.025 inches (0.635 mm)
between the annular center of the seal bead and the bottom surface
of the skirt. The second bore 46 of this preferred embodiment has a
diameter of about 0.340 inches (8.64 mm) and a height of about
0.218 inches (5.54 mm).
When provided as a component of a kit, the collection device 10 of
the present invention preferably includes a specimen retrieval
device for obtaining a sample to be analyzed, where the specimen
retrieval device has preferably been sized to fit within the
interior space 11 of the collection device after the cap 30A-E and
vessel 20 have been joined. A preferred specimen retrieval device
is a swab, such as the swab disclosed by Pestes et al., "Cell
Collection Swab," U.S. Pat. No. 5,623,942. This particular swab is
preferred because it is manufactured to include a score line which
is positioned on the stem of the swab, allowing the swab to be
manually snapped in two after a specimen has been obtained, leaving
the lower, specimen-bearing portion of the swab entirely inside the
vessel 20 component of the collection device 10. When the specimen
is being transported to a clinical laboratory, the collection
device 10 also preferably includes a transport medium for
preserving the sample prior to analysis. Transport mediums are well
known in the art and will vary depending upon the sample type and
whether cell lysis prior to analysis is necessary.
Additionally, a kit according to the present invention may include
instructions recorded in a tangible form (e.g., contained on paper
or an electronic medium) which explain how the components of the
collection device 10 are to be manipulated when obtaining a fluid
sample or how the cap 30A-E is to be secured onto the vessel 20
prior to transporting the collection device to a clinical
laboratory. Alternatively, or in addition to, the instructions may
detail proper pipetting techniques for retrieving at least a
portion of the sample from the collection device 10 prior to
analysis. These instructions may include information about types of
fluid transfer devices that can be used to penetrate the cap 30A-E,
positioning of a fluid transfer device for penetrating the cap
and/or the amount of force needed to penetrate the cap. The
instructional materials may also detail proper use of the
collection device when the sample is to be exposed to reagents and
conditions useful for amplifying a nucleic acid sequence targeted
for detection.
Amplification prior to detection is particularly desirable in
diagnostic assays where the initial population of targeted nucleic
acid sequences in a sample is expected to be relatively small,
making detection of the targeted nucleic acid sequences more
difficult. There are many procedures for amplifying nucleic acids
which are well known in the art, including, but not limited to, the
polymerase chain reaction (PCR), (see, e.g., Mullis, "Process for
Amplifying, Detecting, and/or Cloning Nucleic Acid Sequences," U.S.
Pat. No. 4,683,195), transcription-mediated amplification (TMA),
(see, e.g., Kacian et al., "Nucleic Acid Sequence Amplification
Methods," U.S. Pat. No. 5,399,491), ligase chain reaction (LCR),
(see, e.g., Birkenmeyer, "Amplification of Target Nucleic Acids
Using Gap Filling Ligase Chain Reaction," U.S. Pat. No. 5,427,930),
and strand displacement amplification (SDA), (see, e.g., Walker,
"Strand Displacement Amplification," U.S. Pat. No. 5,455,166). The
particular reagents (e.g., enzymes and primers) and conditions
selected by practitioners will vary depending upon the particular
nucleic acid sequence being targeted for detection and the specific
amplification procedure to be followed. Those skilled in the art of
nucleic acid diagnostics, however, will be able to select
appropriate reagents and conditions for amplifying a specific
targeted nucleic acid sequence following a particular amplification
procedure without having to engage in undue experimentation.
While the present invention has been described and shown in
considerable detail with reference to certain preferred
embodiments, those skilled in the art will readily appreciate other
embodiments of the present invention. Accordingly, the present
invention is deemed to include all modifications and variations
encompassed within the spirit and scope of the following appended
claims.
* * * * *