U.S. patent application number 16/748130 was filed with the patent office on 2020-12-24 for devices, solutions and methods for sample collection.
This patent application is currently assigned to AboGen, Inc.. The applicant listed for this patent is AboGen, Inc.. Invention is credited to Stephen ANDREWS, Youssef BIADILLAH, Chris BRIDEN, Melvin J. LEEDLE, Benjamin Cooper PRIESS, Bryce G. RUTTER, Jonathan SUNDY.
Application Number | 20200398267 16/748130 |
Document ID | / |
Family ID | 1000005062350 |
Filed Date | 2020-12-24 |
View All Diagrams
United States Patent
Application |
20200398267 |
Kind Code |
A1 |
BIADILLAH; Youssef ; et
al. |
December 24, 2020 |
DEVICES, SOLUTIONS AND METHODS FOR SAMPLE COLLECTION
Abstract
Some embodiments are directed to a bodily fluid sample
collection device for the collection of naturally expressed bodily
fluids and include a cap engageable with a tube to close a mouth of
the tube. The cap includes a chamber for containing a reagent. The
tube defines at least partly a sample collection space for
receiving the naturally expressed bodily fluid. The cap comprises
first and second cap portions relatively movable with respect to
each other. The first and second cap portions are configured such
that, responsive to engagement of the cap on the tube, one of the
cap portions is caused to move integrally relative to the other cap
portion to open the chamber and permit fluid communication between
the chamber and the sample collection space. The reagent in the
chamber is thereby permitted to mix with the bodily fluid in the
sample collection space. A method of organizing and processing
samples is also described.
Inventors: |
BIADILLAH; Youssef; (Geneve,
CH) ; ANDREWS; Stephen; (Falmouth, ME) ;
RUTTER; Bryce G.; (St. Louis, MO) ; LEEDLE; Melvin
J.; (St. Louis, MO) ; SUNDY; Jonathan;
(Columbia, MO) ; PRIESS; Benjamin Cooper; (St.
Charles, MO) ; BRIDEN; Chris; (Coventry, RI) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
AboGen, Inc. |
Portland |
ME |
US |
|
|
Assignee: |
AboGen, Inc.
Portland
ME
|
Family ID: |
1000005062350 |
Appl. No.: |
16/748130 |
Filed: |
January 21, 2020 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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15112677 |
Jul 19, 2016 |
10576468 |
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PCT/US15/12038 |
Jan 20, 2015 |
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16748130 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
B01L 2300/047 20130101;
B65D 51/2892 20130101; B01L 2400/0683 20130101; B65D 55/02
20130101; A61B 10/0051 20130101; A61B 10/0096 20130101; B01L
2300/042 20130101; B65D 51/2871 20130101; A61B 10/007 20130101;
B65D 51/2878 20130101; B01L 3/502 20130101; B65D 25/56 20130101;
B01L 2300/0672 20130101; B65D 41/04 20130101; B65D 51/2835
20130101; B01L 2400/043 20130101 |
International
Class: |
B01L 3/00 20060101
B01L003/00; B65D 51/28 20060101 B65D051/28; A61B 10/00 20060101
A61B010/00; B65D 25/56 20060101 B65D025/56; B65D 41/04 20060101
B65D041/04; B65D 55/02 20060101 B65D055/02 |
Foreign Application Data
Date |
Code |
Application Number |
Jan 20, 2014 |
EP |
14151801.9 |
Jan 20, 2014 |
EP |
14151830.8 |
Mar 17, 2014 |
EP |
14160215.1 |
Jun 23, 2014 |
EP |
14173372.5 |
Sep 29, 2014 |
EP |
14186782.0 |
Nov 10, 2014 |
EP |
14192586.7 |
Nov 11, 2014 |
EP |
14192740.0 |
Jan 12, 2015 |
EP |
15150866.0 |
Claims
1. A bodily fluid sample collection device for the collection of
naturally expressed bodily fluids, comprising a cap engageable with
a tube to close a mouth of the tube, the cap comprising a first cap
portion defining at least partly a chamber for containing a
reagent, and the tube defining at least partly a sample collection
space for receiving the naturally expressed bodily fluid; wherein
the cap further comprises a second cap portion defining a closure
for closing an aperture communicating with the chamber, the second
cap portion being configured, in use responsive to fitting the cap
to the tube, to disengage from the first cap portion, and descend
at least partly into the tube.
Description
RELATED APPLICATIONS
[0001] This application is a continuation of U.S. application Ser.
No. 15/112,677, filed Jul. 19, 2016 (now allowed), which is a 35
U.S.C. .sctn. 371 national stage entry of PCT/US2015/012038, filed
Jan. 20, 2015, which claims priority under 35 U.S.C. .sctn. 119 to
European Patent Application No. 14 151 801.9, filed Jan. 20, 2014
and entitled "DEVICES, SOLUTIONS AND METHODS FOR SAMPLE
COLLECTION"; European Patent Application No. 14 151 830.8, filed
Jan. 20, 2014 and entitled "DEVICES, SOLUTIONS AND METHODS FOR
SAMPLE COLLECTION": European Patent Application No. 14 160 215.1,
filed Mar. 17, 2014 and entitled "DEVICES, SOLUTIONS AND METHODS
FOR SAMPLE COLLECTION"; European Patent Application No. 14 173
372.5, filed Jun. 23, 2014 and entitled "DEVICES, SOLUTIONS AND
METHODS FOR SAMPLE COLLECTION"; European Patent Application No. 14
186 782.0, filed Sep. 29, 2014 and entitled "DEVICES, SOLUTIONS AND
METHODS FOR SAMPLE COLLECTION" European Patent Application No. 14
192 586.7, filed Nov. 10, 2014 and entitled "DEVICES, SOLUTIONS AND
METHODS FOR SAMPLE COLLECTION" European Patent Application No. 14
192 740.0, filed Nov. 11, 2014 and entitled "DEVICES, SOLUTIONS AND
METHODS FOR SAMPLE COLLECTION"; European Patent Application No. 15
150 866.0, filed Jan. 12, 2015 and entitled "DEVICES, SOLUTIONS AND
METHODS FOR SAMPLE COLLECTION"; each of which in turn claims
priority to International Application Publication No.
WO/2012/177656, filed Jun. 19, 2012 and entitled "DEVICES,
SOLUTIONS AND METHODS FOR SAMPLE COLLECTION." The entire contents
of the aforementioned applications are herein expressly
incorporated by reference.
FIELD OF THE DISCLOSURE
[0002] The disclosure relates to devices, solutions and methods for
collecting samples of bodily fluids or other substances, including
hazardous and/or toxic substances, and in some cases, a naturally
expressed bodily fluid (e.g., saliva, urine). Additionally or
alternatively, the disclosure relates generally to functional
genomics and/or to the isolation and preservation of cells from
such bodily fluids, for studies in any of: diagnosis, genetics,
functional genomic, epigenetic studies, and biomarker discovery
(for example). Additionally or alternatively, the disclosure
relates generally to collecting a bodily fluid sample for DNA
analysis.
BACKGROUND
[0003] Personalized medicine is the customization of treatment to
an individual as opposed to the one treatment-for-all model.
Personalized medicine involves categorizing a patient based on his
or her physical condition and designing an optimal healthcare
solution exclusively for that category. The progression of
personalized medicine is dependent on the discovery, validation,
and commercialization of biomarkers to stratify populations for
treatment and for the development of diagnostics for screening and
early detection.
[0004] Epigenetic research has come to the forefront of medical
research and is implicated in the etiology of a number of physical
and mental illnesses including: cancer, obesity, diabetes,
schizophrenia, and Alzheimer's disease. In addition, Epigenetics
may hold particular promise in the many scientific and medical
areas including but not limited to: cancer, diabetes, drug
integrations, drug effectiveness, childhood aggression, suicidal
behaviors, aging, inflammation, pain, obesity, schizophrenia, and
other mental illnesses.
SUMMARY OF THE DISCLOSURE
[0005] Some embodiments of the disclosure may provide safer and/or
easy to use sample collection devices for fluids (for example,
naturally expressed bodily fluids), as well as solutions and
methods for preserving cells of samples collected, and
additionally, methods for isolating specific cells either collected
and/or preserved. Such isolated cells (and even non-isolated
collected cells), can then be analyzed for studies including but
not limited to: functional genomic and epigenetic studies, and
biomarker discovery.
[0006] The sample collection devices according to the present
disclosure can provide several advantages over currently available
sample collection devices. For example, in some embodiments, the
sample collection devices can use a minimum amount of parts and may
not require removal or exchange of a piece or an object thereof. In
some embodiments, the sample collection devices may not require any
additional manipulation by the sample donor apart from depositing
the sample in the sample collection device and closing the sample
collection device. In some embodiments, use of the sample
collection devices can provide improved safety for both the sample
donor and the end user, since, for example, exposed sharp objects
are not included and there is limited to no risk of exposure to
toxic solutions (e.g., sample preservative solutions). Additionally
or alternatively, in some embodiments, the sample collection
devices can at least partly separate functionally a fastening of a
cap, and release of a reagent into the collected sample.
Additionally or alternatively, in some embodiments, the sample
collection devices can avoid accidental premature release of a
reagent before a cap is fully sealed closed.
[0007] In some embodiments of the sample collection device, the
sample collection device can have two main mating bodies, a cap and
a tube. The cap can include a closed chamber holding a reagent for
acting on the collected sample. The cap can mate with the tube to
constitute the closed sample collection device. The tube can be
configured to receive the donor specimen. The cap and tube are
configured so that when the donor deposits the specimen and closes
the tube with the cap, the chamber holding the reagent may be
opened to release the reagent and allow it to mix with the donor
specimen.
[0008] As used herein, the term "reagent" may refer to any kind of
substance for acting on the collected sample to achieve a desired
effect. In some embodiments, the reagent can be a chemical
preservative for preserving at least a component of the sample. For
purposes of the disclosure, "preserving cells" refers to preventing
the cells from having their antigens degraded, such that they can
be purified or enriched based on their antigens, and preventing
alterations in the cellular epigenome. The "epigenome" refers to
the state or pattern of alteration of genomic DNA by covalent
modification of the DNA or of proteins bound to the DNA. Examples
of such alteration can include methylation at the 5 position of
cytosine in a CpG dinucleotide, acetylation of lysine residues of
histones, the binding of proteins to the DNA to initiate
transcription (for example, transcription factors) and other
heritable or non-heritable changes that do not result from changes
in the underlying DNA sequence. In other forms, the reagent may be
configured to preserve DNA, RNA, or protein components of the
sample, suitable for DNA, RNA, or proteomic analysis.
[0009] The reagent may be any suitable form, for example, a fluid
(e.g. liquid, solution, or gas) or a solid (e.g. powder). In some
embodiments, the reagent may be toxic. In such case, it may be
desirable to avoid, to the extent possible, any exposure of the
reagent to the donor donating the sample to the collection
device.
[0010] In some embodiments, a bodily fluid sample collection device
for the collection of naturally expressed bodily fluids is can be
provided, and can include a cap engageable with a tube to close a
mouth of the tube. The cap includes a chamber for containing a
reagent. The tube can define at least partly a sample collection
space for receiving the naturally expressed bodily fluid. The cap
comprises first and second cap portions that are (i) relatively
movable with respect to each other, and/or (ii) in use moved one
relative to the other. The first and second cap portions can be
configured such that, responsive to engagement of the cap on the
tube, one of the cap portions can move (e.g. integrally) relative
to the other cap portion to open the chamber and permit fluid
communication between the chamber and the sample collection space.
The reagent in the chamber is thereby permitted to mix with the
bodily fluid in the sample collection space.
[0011] In some embodiments, relative movement between the first and
second cap portions may be caused or controlled by a coupling
between the cap portions. In other embodiments, the first and
second cap portions may be freely movable with respect to each
other (such as within a predetermined range of operative movement,
and/or notwithstanding friction between the first and second cap
portions), and the relative movement between the cap portions may
be caused by respective different engagement between each cap
portion and the tube.
[0012] In some embodiments, the first and second cap portions can
be rotatably movable with respect to each other. As used herein,
the terms "rotatable" or "rotatably" or "rotate" are used to mean
that one cap portion is able to move at least partly angularly
about an axis with respect to the other portion, whether or not the
angular movement corresponds to a partial turn about the axis, or a
full turn, or more than one full turn, and/or whether or not the
relative movement includes an axial component.
[0013] In some embodiments, the first and second cap portions can
be threadedly coupled together. As used herein, the terms "thread"
or "threaded" are used to mean a coupling that defines an at least
partly helical movement, whether or not the movement includes a
full turn. Relative rotation of one (e.g. cap) portion can cause
relative translation between the portions in a direction parallel
to the axis.
[0014] In some embodiments, the first and second cap portions are
coupled together by a bayonet coupling. As used herein, the term
"bayonet" refers to a type of coupling movement involving first and
second phases, one of which is predominantly rotational, and the
other of which is predominantly axial. An example bayonet coupling
may be formed by a pin slideable in a slot or track. The slot or
track may define an "L" shape, for example, in a circumferential
direction.
[0015] In some embodiments, the first and second cap portions are
relatively movable in a substantially non-rotating manner. For
example, the first and second cap portions may be pushed one
towards the other, or pulled one away from the other, substantially
without rotation.
[0016] In some embodiments, the first and second portions may be
integrally coupled together, for example, by a captive connection
or by a frangible wall portion that breaks in use in response to
the relative movement between the first and second portions.
Breakage of a frangible wall portion may create or open an aperture
or other exit path for releasing the agent from the chamber.
[0017] Whether or not the first and second cap portions are
rotatably movable with respect to each other, in some embodiments,
the cap is rotatably engageable on the tube, for example,
threadedly engageable or by a bayonet connection. The type of
coupling (e.g. threaded; bayonet) between the cap and tube may be
same as, or different from, the type of coupling (e.g. threaded,
bayonet) between the first and second cap portions.
[0018] In some embodiments, the tube comprises a first engager for
engagement by the first cap portion, and a second engager for
engagement by the second cap portion. During fitting of the cap to
the tube, the engagement between each respective cap portion and
engager causes collectively relative movement between the cap
portions optionally in combination with a coupling (e.g. active
coupling) between the cap portions. For example, in some
embodiments, the second engager restrains the second cap portion
against substantial rotational movement while the first cap portion
is being screwed on to the first engager. This generates relative
rotational movement between the cap portions to open the
cavity.
[0019] However, other relative movements are also possible. For
example, the second engager may actively generate movement of the
second cap portion with respect to the tube, in a different manner
from movement of the first cap portion with respect to the
tube.
[0020] In some embodiments, the first and second engagers may be
configured to engage the respective cap portions generally
simultaneously, such that attachment of the cap to the tube
proceeds generally simultaneously with opening of the chamber. In
other embodiments, the first and second engagers may be configured
such that one of the engagers may engage its respective cap portion
before the other engager engages its respective cap portion. The
other engager may engage its respective cap portion after relative
movement between the cap and the tube.
[0021] For example, in some embodiments, the second engager may be
configured to be keyed to engage the second cap portion before
engagement between the first engager and the first cap portion.
Alternatively, the second engager may be configured to engage the
second cap portion after the first cap portion has been fitted to
engage the first engager.
[0022] The nature of the first and second engagers may vary
according to the type of relative movement intended between first
and second cap portions. At least one of the first and second
engagers may comprise at least one selected from: a screw thread; a
non-threaded element engageable with a screw thread; a bayonet
connection track; an element engageable with a bayonet connection
track; a rotation stop; a stop; an abutment; a post; a
projection.
[0023] The first and second cap portions may be integral with each
other, or they may be discrete components.
[0024] Whether or not separate components, in some embodiments, the
first and second cap components may be at least partly separable to
open the chamber. The cap portions may be completely separable or
at least a portion of one cap portion may remain non-separated
(e.g. coupled or joined) to the other.
[0025] Whether or not at least partly separable, and whether or not
separate components, the first and second cap portions may, in some
embodiments, remain coupled together when the chamber is open, for
example, coupled by a captive coupling. Examples of (e.g. captive)
coupling may include: a captive or integral tether; a captive or
integral cage; a captive or integral hinge; a disengagement stop
integrated as part of the coupling; a threaded or bayonet coupling
have a range of movement while still in engaged such that
disengagement of the cap from the tube does not disengage the
threaded or bayonet coupling of the first and second cap
portions.
[0026] In some embodiments, the tube may comprise a support element
for supporting at least a portion of the second cap portion if at
least partly disengaged from the first cap portion. The support
element may be configured to cooperate with the first and/or second
cap portion to prevent the second cap portion from dropping (e.g.
entirely) into the sample collection space.
[0027] In some embodiments, the first cap portion comprises an
outer wall of the cap, and an inner wall defining at least partly
the chamber. The second cap portion comprises a closure engageable
at and/or over a mouth or aperture of the chamber. For example, the
closure may be in the form of a second cap or plug, for example,
positioned in an inverted state at and/or over a downwardly opening
mouth of the chamber. For example, the chamber may have an open
bottom end defining the mouth. The inner wall may depend from an
upper or top wall of the cap.
[0028] In some embodiments, the second cap (portion) may be
relatively short in axial length compared to the inner wall of the
first cap portion so that, for example, the majority of the chamber
may be defined by the inner wall. Alternatively, in some
embodiments, the second cap (portion) may be relatively long
axially (or tall) compared to the inner wall of the first cap
portion so that, for example, the majority of the chamber may be
defined by the second cap (portion). The second cap portion may
have the form of a cup suspended from the first cap portion.
[0029] In some embodiments, the second cap portion is releasably
engageable from the first cap portion to open the chamber. At least
partial separation of the second cap portion from the first cap
portion, and/or movement of at least a portion of the second cap
portion away from the first cap portion may provide a signal to a
user in the form of a visual indication that the chamber has been
opened and/or that the reagent has been successfully dispensed into
the collected bodily fluid sample. In some embodiments, even after
the at least partial separation and/or movement away, the first and
second cap portions may remain coupled, for example, by a captive
or hinged connection. Such a connection may optionally be an
integral joint between the first and second cap portions, or it may
be a non-integral captive connection or joint.
[0030] In some embodiments, the relative movement between the first
and second cap portions causes the second cap portion to translate
progressively in a direction towards the sample collection space.
This may be achieved, for example, by using a screw threaded
coupling (between the first and second cap portions), having a
thread angle that is opposite in sense (or direction) to the screw
threaded coupling between the cap and the tube. The thread angles
may be the same or different in magnitude, yet opposite in sense
(or direction).
[0031] Additionally or alternatively, in some embodiments, the
engagement between the second cap portion and the tube (e.g. second
engager) is configured to cause the second cap portion to translate
progressively, relative to the first cap portion, in a direction
towards the sample collection space.
[0032] Additionally or alternatively to any of the above, in some
embodiments, the collection device may be configured to provide to
the user a first signal indicative of the chamber having been
opened, and a second signal indicative of the cap having reached a
closed and/or locked position.
[0033] In some embodiments, the first signal may be or comprise any
one or a combination of two or more of: a visual signal, an audible
signal, a tactile signal. Additionally or alternatively, the second
signal may be or comprise any one or a combination of two or more
of: a visual signal, an audible signal, a tactile signal. In some
embodiments, the first and second signals may be of the same type
as each other, or include one or more signal components or types
(e.g. visual and/or audible and/or tactile) in common, or be wholly
different.
[0034] In some embodiments, the first signal may be provided by
movement or displacement or dropping down of at least a portion
(for example, substantially all) of the second cap portion towards
or into the tube. If the tube is transparent, the
movement/displacement of the second cap portion may provide a
visual signal to the user. The second cap portion may be colored to
enhance visibility (for example, a color different from other
colors, for example, of at least the majority (and optionally
substantially all) of the first cap portion and/or the tube).
Additionally or alternatively, the user may hear and/or feel
(tactile) the dropping down of the second cap portion towards or
into the tube.
[0035] In some embodiments, the second signal may be provided by a
lock device that operates or engages upon the cap reaching a
predetermined closed condition on the tube. The lock device may,
for example, comprise a ratchet or a resilient latch. As used
herein, the term ratchet is used to mean any device or mechanism
that permits relative movement in a first direction while stopping
(or at least obstructing) movement in a second opposite direction.
The ratchet or latch may, for example, comprise at least one
projection or formation that has a ramp surface for permitting a
second component to pass over the formation by riding over the ramp
surface in the first direction, and an abutment surface for
blocking (or at least obstructing) movement in the second
direction. Additionally or alternatively, the ratchet or latch may,
for example, comprise a cantilever and/or articulated member
configured such that, in use, the member is (i) able to be
displaced by a second component for permitting the second component
to pass the cantilever/articulated member in the first direction,
and (ii) not displaced by the second component when contacted in
the second movement direction.
[0036] With a lock device, the second signal may include audible
and/or tactile signal components generated by the operation of the,
for example, ratchet or latch. For example, the user may feel a
physical "click" upon the lock operating, and/or hear a "click"
sound.
[0037] In some embodiments, the first and second movement
directions may, for example, be generally axial or they may, for
example, be generally circumferential.
[0038] Additionally or alternatively to any of the above, in some
embodiments, the second cap portion is configured, upon relative
movement with respect to the first cap portion, to break the
integrity of a frangible wall portion of the chamber, to open the
chamber. The frangible wall portion may be a part of the first cap
portion and/or a part of the second cap portion and/or a portion
joining the first and second cap portions, or it may be a further
component of the cap.
[0039] In some embodiments, the frangible wall portion is a
membrane that at least partly defines a wall of the chamber. For
example, the membrane may be of plastics (e.g. plastics film), or a
thin metallic sheet (e.g. a foil), or a plastics/metallic laminate.
The frangible wall portion may be fastened to the first cap portion
(for example), by adhesive or welding.
[0040] In some embodiments, the second cap portion may comprise a
metal foil that is welded or glued to the first cap portion. In
use, the chamber is opened in response to relative movement, e.g.
rotation, between the first and second cap portions. The second cap
portion may be disengaged by the weld breaking in response to the
relative movement, and/or the foil may be configured to tear or
rupture as a result of the relative movement. In some embodiments,
such an arrangement may enable the foil to be opened without the
need for a cutting or piercing element.
[0041] Additionally or alternatively to any of the above, the
chamber may be defined by a self-contained chamber module that is
fixed to the cap at least prior to attachment of the cap to the
tube, in use. In some embodiments, the chamber module may be fixed
to the cap as part of manufacture or production, to be supplied to
the user in ready-assembled form. In other embodiments, the chamber
module could be provided separately for a user to assemble to the
cap.
[0042] Production of the chamber as a self-contained module may
provide advantages in some embodiments. For example, the chamber
module may be filled with agent separately from the remainder of
production of the cap. The filling with agent could be performed at
a different site from the cap molding or production site.
Additionally or alternatively, it may allow easier molding of
parts, or a greater variety of possible designs of parts, than
incorporating the chamber at least party by an integral
molding.
[0043] Additionally or alternatively, some embodiments of the
present disclosure may provide a tube of a sample collection device
having a sample collection portion having a smaller interior
cross-sectional area than at a mouth for receiving a cap for
closing the device. Providing a small cross-sectional area enables
a finely graduated fill scale and/or fill line to be provided that
may be easily read and judged for collecting small amounts of
bodily fluid.
[0044] Providing a small cross-sectional area may also provide a
region in which the second cap portion may be prevented from
entering when the second cap portion (in some embodiments) drops
downwardly from the first cap portion, thereby keeping the second
cap portion at least partly away from the sample collection
space.
[0045] Additionally or alternatively to any of the above, in some
embodiments, the cap may comprise first and second chambers, for
containing first and second reagents or first and second reagent
components. Plural chambers may enable plural different reagents to
be stored separately, and/or plural reagent components to be stored
separately. For example, certain reagents or components may have a
longer shelf-life when stored separately than when mixed together,
and/or may be less sensitive to external influence such as
temperature when stored separately, and/or may form an active
reagent that is only active for a limited period of time once mixed
together.
[0046] The first and second chambers may be configured to be opened
to release their contents substantially simultaneously, or one
before the other. Sequential release of one before the other may be
suitable if, for example, it is desirable to have a first of the
reagents or reagent components contact the collected sample before
the other.
[0047] In some embodiments, the cap may comprise respective cap
portions that are movable to open the respective chambers. For
example, a first cap portion may define at least partly one or both
of the first and second chambers; a second cap portion may be
movable with respect to the first cap portion to cause opening of
the first chamber; a third cap portion may be movable with respect
to the first cap portion to cause opening of the second
chamber.
[0048] Alternatively, the same cap portion may be configured to
cause opening of both the first and second chambers, either
substantially simultaneously, or one before the other.
[0049] In some embodiments, the mechanism for opening the first
chamber may be the same as that for the other. In other
embodiments, the mechanisms may be different. For example, at least
one of the mechanisms may use relative rotation, for example, screw
threaded rotation. For example, at least one of the mechanisms may
use a frangible wall portion.
[0050] In some embodiments, a bodily fluid sample collection device
for the collection of naturally expressed bodily fluids is provided
and includes a cap engageable with a tube to close a mouth of the
tube. The tube defines at least partly a sample collection space
for receiving the naturally expressed body fluid. The device
(optionally the cap, or optionally the tube) comprises a chamber
for containing a reagent for mixing with a collected sample. The
cap comprises a first body by which a user manipulates the cap, and
a second body that is rotatably mateable with the tube for securing
the cap to the tube. A coupling between the first and second bodies
may be configured for (i) transmitting torque from the first body
to the second body for permitting rotation of the second body to
secure the second body to the tube, and (ii) permitting slippage
between the bodies after the second body has reached a fully
secured position. A mechanism is operable to cause the chamber to
be opened in response to manual rotation of the first body at least
after the second body has reached the fully secured position.
[0051] The mechanism may be operable to begin to cause the chamber
to be opened only after the second body has reached the fully
secured position, or the mechanism may be operable partly before
the second body has reached the fully secured position. In either
case, the second body may reach the fully secured position before
the chamber has been fully opened. Further manual rotation of the
first body after the second body has reached the fully secured
position, may open or complete the opening of the chamber.
[0052] The second body may be threadedly mateable with the tube,
but other rotatably mateable couplings, such a bayonet coupling,
may be used as desired. As used herein, the terms "rotatable" or
"rotatably" or "rotate" are used to mean that one body or portion
is able to move at least partly angularly about an axis with
respect to another body or portion, whether or not the angular
movement corresponds to a partial turn about the axis, or a full
turn, or more than one full turn, and/or whether or not the
relative movement includes an axial component.
[0053] In some embodiments, the coupling may be a torque-responsive
coupling. In some embodiments, the coupling may be a
torque-limiting coupling that limits the amount of torque
transmissible from the first body to the second body, and permits
relative slippage between the two bodies when the torque exceeds a
threshold. For example, during initial fitting (e.g. screwing) of
the cap, the second body may rotate relatively freely as it mates
with the tube, and the applied torque may be small. Once the second
body reaches a fully secured position, it can no longer rotate
relative to the tube, and the applied torque will therefore
increase. The coupling may be responsive to applied torque to
permit the first body to slip with respect to the second body,
thereby permitting continued rotation of the first body despite the
second body no longer being able to rotate.
[0054] In some embodiments, the coupling may be responsive to the
direction of rotation, so as not to transmit significant torque in
a direction for releasing the second body.
[0055] In some embodiments, the coupling may comprise a ratchet
and/or a clutch.
[0056] In some embodiments, the second body may be substantially
shrouded by the first body, at least during fitting of the cap on
the tube.
[0057] In some embodiments, the mechanism for causing opening of
the chamber may be responsive to relative rotation between the tube
and the first cap portion. Alternatively, the mechanism for causing
opening of the chamber may be responsive to rotation between the
first and second bodies.
[0058] Various mechanisms are envisaged. In one form, the chamber
may comprise an aperture closed by a closure. The closure may be a
third body distinct from the first body, or it may be integral with
the first body. The closure may be rotatable relative to the
chamber to open the chamber. For example, the closure may be
threadedly coupled to the chamber. In some embodiments, the chamber
may be rotatable with the first member. The mechanism may operate
restrain the closure against rotation with respect to the tube
and/or the second body. Rotation of the first body may rotate the
chamber, thereby generating relative rotation between the chamber
and the closure, to move the closure to an open condition with
respect to the chamber aperture.
[0059] Other types of mechanisms for opening the chamber may also
be used, for example, a piercing element that ruptures a frangible
film or wall of the chamber.
[0060] In another aspect, in some embodiments, a bodily fluid
sample collection device for the collection of naturally expressed
bodily fluids is provided and includes a cap engageable with a tube
to close a mouth of the tube. The tube defines at least partly a
sample collection space for receiving the naturally expressed body
fluid. The device (optionally the cap, or optionally the tube)
comprises a chamber for containing a reagent for mixing with a
collected sample. The device (optionally the cap, or optionally the
tube) may further comprise a manually operable actuator operable
from outside the device at least once the cap has been secured to
the tube, for causing the chamber to be opened in response to
manual actuation of the actuator.
[0061] In some embodiments, the device may optionally comprise a
lockout mechanism for preventing actuation of the actuator before
the cap has been placed in a fully secured position.
[0062] In some embodiments, the actuator may be rotatable and/or
pressable and/or depressable.
[0063] In some embodiments, the device may be provided as part of a
kit containing packaging in which the device is intended to be
placed for sending (e.g. by post) to a processing institution for
processing, analysis or research. The packaging may be configured
to accept the device only in a condition in which the actuator has
been actuated to cause the chamber to be opened. For example,
packaging may include a predetermined space (e.g. a well) that is
dimensioned to receive the device only in such a condition. The
actuator may, for example, be depressable, whereby an exterior
dimension of the cap or tube becomes smaller. Prior to depression,
the device may be too large to fit in the predetermined space of
the packaging. The device may only fit once the actuator has been
fully depressed. Such an arrangement can ensure that the user does
not accidentally forget to operate the actuator.
[0064] In another aspect, in some embodiments, a bodily fluid
sample collection device comprises a tube, and a cap securable to a
mouth portion of the tube. The cap may be a separate body from the
mouth portion, and securable thereto to close the mouth portion.
The tube defines at least partly a sample collection space for
receiving the naturally expressed body fluid. The device
(optionally the cap, or optionally the tube) comprises a chamber
for containing a reagent for mixing with a collected sample.
[0065] In some embodiments, the mouth portion may be separable from
a collection portion of the tube, to facilitate opening of the
device after the cap has been secured. For example, the mouth
portion may be coupled to the collection portion by a threaded
connection, or some other mechanical connection, or by a frangible
integral connection.
[0066] The mouth portion may flare towards an open end defining a
mouth of the tube, and/or narrow towards the collection
portion.
[0067] In some embodiments, the cap and the mouth portion together
comprise a mechanical or adhesive lock for locking the cap in its
fully secured condition once the cap has been closed. With such an
arrangement, the ability to separate the mouth portion from the
collection portion of the tube may facilitate ease of access to the
sample contents when the device is received at a processing
installation, while still obstructing accidental reopening of the
cap by the user having deposited a sample.
[0068] Additionally or alternatively, in some embodiments, the cap
may comprise a closure for a chamber for containing reagent. The
closure may be configured to be opened when, or after, the cap may
be secured to the mouth portion, the closure dropping down into the
mouth portion when the closure is opened. The mouth portion may
prevent the closure from dropping into the collection portion of
the tube. With such an arrangement, the ability to separate the
mouth portion from the collection portion of the tube may
facilitate easy access to the sample contents, without having to
manually retrieve the closure from the mouth portion. Instead, by
removing the mouth portion itself, the closure is removed with the
mouth portion.
[0069] Additionally or alternatively, in some embodiments, the
ability to separate the mouth portion from the collection portion
may enable the sample to be handled, processed or stored in a
generally more compact form of the collection portion without a
flared or funnel shaped mouth portion.
[0070] Devices disclosed herein may optionally be used as part of a
kit, that may optionally be provided to a user for collection of a
bodily fluid sample at home or in another non-medical
environment.
[0071] Devices disclosed herein may optionally be used to collect a
sample of naturally expressed bodily fluid, for example, saliva or
urine.
[0072] Devices disclosed herein may optionally be used to collect a
bodily fluid sample, for preservation of cells and/or cellular
components, such as DNA. The collected sample may be subjected to
analysis for the purposes of genetics, epigenetics, diagnostics, or
other purposes.
[0073] In some embodiments, the solution is able to preserve cells
in a naturally expressed bodily fluid sample (for example, saliva
or urine), at least to a predetermined efficacy, for a period of at
least one week, optionally at least two weeks, optionally at least
three weeks, optionally at least a month, optionally at least two
months, optionally at least three months.
[0074] For purposes of the disclosure, "preserving cells" means
preventing the cells from having their antigens degraded, such that
they can be purified or enriched based on their antigens, and
preventing alterations in the cellular epigenome. The "epigenome"
means the state or pattern of alteration of genomic DNA by covalent
modification of the DNA or of proteins bound to the DNA. Examples
of such alteration include methylation at the 5 position of
cytosine in a CpG dinucleotide, acetylation of lysine residues of
histones, and other heritable or non-heritable changes that do not
result from changes in the underlying DNA sequence
[0075] As used herein the term "efficacy" may mean that at least a
predetermined percentage of the cells in the original bodily fluid
sample are preserved. The predetermined percentage may optionally
be at least 50%, at least 55%, at least 60%, at least 65%, at least
70%, optionally at least 75%, optionally at least 80%, optionally
at least 85%, optionally at least 90%, optionally at least 95%.
(The cell concentration per unit volume may be reduced compared to
the original body fluid sample, because the mixing of the original
sample with the preservation solution increases the net volume of
the mixture, thereby diluting the cell concentration.)
[0076] Additionally or alternatively, the efficacy may refer to the
number of cells (e.g. of a certain type, e.g. T-cells) per unit
volume. For example, the number of (e.g. such) cells may be at
least about 5000 per ml, optionally at least about 10000 per ml,
optionally at least about 12000 per ml.
[0077] Additionally or alternatively, in some embodiments, the
solution may have a shelf life at room temperature of at least 1
month, optionally at least two months, optionally at least three
months, optionally at least four months.
[0078] For example, in some embodiments, a solution for preserving
cells in bodily fluids, such as saliva and urine, is provided for
further separation into cell types and downstream analysis that
allows for the cells in saliva to retain their antigenicity and
cellular architecture during storage. The solution can contain at
least one chemical fixing agent, such as but not limited to
paraformaldehyde, and at least one protease inhibitor. In some
embodiments, the solution may further contain, for example, one or
more of: at least one antimicrobial agent, serum proteins from
human and/or other animal species. The solution may be buffered at
a pH between about 6.4 to about 8.4, and in some embodiments,
between about 7.2 to about 7.6.
[0079] In some embodiments, a method for preserving cells in one or
more bodily fluids includes contacting collected cells with a
solution according to one and/or another embodiment of the present
disclosure, which allows the cells to retain their antigenicity and
epigenome, for example.
[0080] In some embodiments, a method for isolating cells from
chemically fixed cells collected from a bodily fluid, e.g., saliva
or urine, and includes centrifuging the cells to separate, for
example, DNA and/or other soluble material from a pellet of cells,
bacteria, and debris, enriching white blood cells from other
contents of the pellet, and isolating specific cells (e.g., white
blood cells) using antibodies conjugated to magnetic beads targeted
to cell specific markers.
[0081] In some embodiments, methods for isolating a particular type
of cell, for example, a type of white blood cell (e.g.,
lymphocytes), from one or more bodily fluids (e.g., saliva and/or
urine), and includes one or more of the following steps (and,
depending upon the embodiment, several or all of the following
steps): providing a sample of bodily fluid comprising chemically
fixed cells, optionally centrifuging the bodily fluid sample to
obtain a pellet comprising cells, optionally re-suspending the
pellet in a buffer, subjecting the re-suspended pellet to density
gradient separation to obtain a layer of a mixture of white blood
cell types (including lymphocytes), contacting the mixture of cell
types with a solution containing specific binding agents for an
epitope found on a particular type of white blood cell, and
separating the particular type of white blood cell (including
lymphocytes) from the mixture of white blood cell types.
[0082] In some embodiments, the specific binding agents may be
magnetic beads coupled to antibodies specific to an epitope found
on a particular type of white blood cell, and in the separation
step may then comprise, for example, magnetically separating the
particular type of white blood cell (including lymphocytes) from
the mixture of white blood cell types (though other cell separation
techniques are within the scope of the disclosure).
[0083] In some embodiments, the bodily fluid (e.g., saliva, urine)
can be mixed with a chemical fixative solution and the mixture can
be removed from the pellet. The pellet can then be re-suspended in
a buffer. The re-suspended pellet may optionally be centrifuged and
washed one or more times in the buffer. The washed pellet may then
be applied to a hydrophilic polysaccharide mixture to form a
gradient. This gradient may be different than that used for blood
because the density of the cells in other bodily fluids (e.g.,
saliva, urine) after chemical fixation for preservation can be
different due to the different density of the preserved cells
requiring an alteration in the time, temperature, and/or density of
the gradient for the cells to be processed through this density
gradient.
[0084] Additionally, in some embodiments, the white blood cells can
form a layer in the gradient. The white blood cell layer can be
extracted from the gradient and placed in another centrifuge tube
where it may be washed in a buffer and re-pelleted to remove the
remaining gradient mixture. The pellet may then be re-suspended and
incubated in a buffer containing antibodies that are conjugated to
magnetic beads and specific to antigens that are specific for a
cell type to be isolated. In some embodiments, the cell type to be
isolated is T-cells and the antigen is a T-cell-specific antigen.
In some embodiments, the antigen is CD4. The re-suspended cells in
the buffer can be bound by the antibody and subjected to a magnetic
field that magnetically attracts the cells bound to the
antibody-conjugated magnetic beads to the side of the tube.
Remaining liquid may then be removed from the tube and the tube is
washed in buffer. Isolated T-cells then remain attracted to the
side of the tube and are ready for further processing, such as
freezing for later downstream experimentation (for example).
[0085] In some embodiments, a method for preserving cells in a
naturally expressed bodily fluid comprises contacting the bodily
fluid with the preservation solution according to any of the
disclosed embodiments.
[0086] The devices, solutions and methods of sample collection,
preservation, isolation and analysis will be better understood in
light of the following drawings, detailed description and claims.
Like reference symbols in the various drawings indicate like
elements.
[0087] It is worth noting that while some embodiments of the sample
collection devices disclosed herein are set forth for use with the
collection of bodily fluids, the same also has particular use with
the collection of any other substance, including hazardous and/or
toxic fluids.
[0088] While certain features and aspects of the embodiments have
been highlighted above and in the appended claims, protection is
claimed for any novel feature or idea described herein and/or
illustrated in the drawings whether or not emphasis has been placed
thereon.
BRIEF DESCRIPTION OF THE DRAWINGS
[0089] FIG. 1 is a schematic section though a sample collection
device comprising a cap and a tube, shown with the cap separated
from the tube, according to some embodiments.
[0090] FIG. 2 is a schematic section similar to FIG. 1, showing the
cap engaged on the tube, according to some embodiments.
[0091] FIG. 3 is a schematic section through a cap of a second
example of sample collection device, according to some
embodiments.
[0092] FIG. 4 is a schematic section through a cap of a further
example of sample collection device, according to some
embodiments.
[0093] FIGS. 5A and 5B are schematic illustrations of a bayonet
style coupling, according to some embodiments.
[0094] FIG. 6 is a schematic section showing the second cap portion
of FIG. 4 in a closed position, according to some embodiments.
[0095] FIG. 7 is a schematic section showing the second cap portion
of FIG. 6 in an open position, according to some embodiments.
[0096] FIG. 8 is a schematic section through a cap of a further
example of sample collection device, according to some
embodiments.
[0097] FIG. 9 is a schematic section through the cap of FIG. 8, but
showing the second cap portion displaced to an open position,
according to some embodiments.
[0098] FIG. 10 is a schematic section through a tube of a further
example of sample collection device, according to some
embodiments.
[0099] FIG. 11 is a schematic section through a tube of a further
example of sample collection device, according to some
embodiments.
[0100] FIG. 12 is a schematic sectional view of a cap in a further
embodiment.
[0101] FIG. 13 is an underside view of the second cap portion of
the cap of FIG. 12, according to some embodiments.
[0102] FIG. 14 is a top view of the mouth of a tube for use with
the cap of FIG. 12, according to some embodiments.
[0103] FIG. 15 is a schematic side section through the tube of FIG.
14, according to some embodiments.
[0104] FIG. 16 is a schematic sectional view of a cap in a further
embodiment.
[0105] FIG. 17 is an underside view of the second cap portion of
the cap of FIG. 16, according to some embodiments.
[0106] FIG. 18 is a top view of the mouth of a tube for use with
the cap of FIG. 16, according to some embodiments.
[0107] FIG. 19 is a schematic side section through the tube of FIG.
18, according to some embodiments.
[0108] FIG. 20 is a schematic section showing a cap in which first
and second cap portions are integrally formed, according to some
embodiments.
[0109] FIG. 21 is an exploded sectional view showing a sample
collection device including a variable volume and/or shape chamber
unit, according to some embodiments.
[0110] FIG. 22 is a schematic section showing the principle of
opening the variable volume and/or shape chamber unit of FIG. 21,
according to some embodiments.
[0111] FIG. 23 is a schematic section showing a cap comprising a
welded foil cap portion, according to some embodiments.
[0112] FIG. 24 is a schematic underside view of the second cap
portion of the cap of FIG. 23, according to some embodiments.
[0113] FIG. 25 is a schematic section showing a cap comprising a
cup-shaped second cap portion, according to some embodiments.
[0114] FIG. 26 is a schematic section showing a cap comprising
plural chambers, according to some embodiments.
[0115] FIG. 27 is a schematic section through a cap comprising
multiple chambers, showing the first cap portion in isolation,
according to some embodiments.
[0116] FIG. 28 is a schematic section showing the cap of FIG. 27
fitted with respective cap portions for closing/opening the plural
chambers, according to some embodiments.
[0117] FIG. 29 is a schematic section through a cap comprising a
modular chamber, according to some embodiments.
[0118] FIG. 30 is a schematic section showing a sample collection
device including a lock device, according to some embodiments.
[0119] FIG. 31 is a schematic drawing illustrating a detail of the
lock device from FIG. 30, according to some embodiments.
[0120] FIG. 32 is a schematic perspective view showing a cap of a
further embodiment, according to some embodiments.
[0121] FIG. 33 is a schematic perspective view showing a collection
tube (optionally usable with the cap of FIG. 32), according to some
embodiments.
[0122] FIG. 34 is a schematic section showing the cap of FIG. 32
and the tube of FIG. 33 just prior to fitting together, according
to some embodiments.
[0123] FIG. 35 is a schematic section along the line X-X of FIG.
34, according to some embodiments.
[0124] FIG. 36 is a schematic perspective section through an
example of second cap portion (plug) for the cap of FIGS. 32 and
34, according to some embodiments.
[0125] FIG. 37 is a schematic perspective section through an
alternative example of second cap portion (plug) for the cap of
FIGS. 32 and 34, according to some embodiments.
[0126] FIG. 38 is a schematic section view showing a second cap
portion (in isolation), with a tether, according to some
embodiments.
[0127] FIG. 39 is a schematic section view showing a first example
of second cap portion having a retrieval magnet, according to some
embodiments.
[0128] FIG. 40 is a schematic section view showing a second example
of second cap portion having a retrieval magnet, according to some
embodiments.
[0129] FIG. 41 is a schematic section view showing a third example
of second cap portion having a retrieval magnet, according to some
embodiments.
[0130] FIG. 42 is a schematic side view of a retrieval tool for use
with the examples of FIG. 39, 40 or 41, according to some
embodiments.
[0131] FIG. 43 is a schematic section view of an alternative
example of mechanical retrieval tool, shown in a non-deployed
state.
[0132] FIG. 44 is a schematic section view of the mechanical
retrieval tool of FIG. 43, but shown in a deployed state, according
to some embodiments.
[0133] FIG. 45 is a schematic section view of a second cap portion
showing a first example of engagement surface for mechanical
retrieval using the tool of FIGS. 43 and 44, according to some
embodiments.
[0134] FIG. 46 is a schematic section view of a second cap portion
showing a second example of engagement surface for mechanical
retrieval using the tool of FIGS. 43 and 44, according to some
embodiments.
[0135] FIG. 47 is a schematic section view of a second cap portion
showing a third example of engagement surface for mechanical
retrieval using the tool of FIGS. 43 and 44, according to some
embodiments.
[0136] FIG. 48 is a schematic section view of a second cap portion
showing a fourth example of engagement surface for mechanical
retrieval using the tool of FIGS. 43 and 44, according to some
embodiments.
[0137] FIG. 49 is a schematic section view showing a cage fitted to
the first cap portion for keeping the second cap portion captive,
according to some embodiments.
[0138] FIG. 50 is a schematic section view showing the cage of FIG.
49 in isolation, according to some embodiments.
[0139] FIG. 51 is a schematic section view showing a further
example of retainer for retaining the second cap portion captive to
the first cap portion, according to some embodiments.
[0140] FIG. 52 is a schematic section of a bodily fluid sample
collection device, including a cap and a tube, according to some
embodiments.
[0141] FIG. 53 is a schematic section showing a further embodiment
of cap with a chamber actuator in a non-actuated position,
according to some embodiments.
[0142] FIG. 54 is a schematic section similar to FIG. 53, but
showing the chamber actuator in an actuated position to open the
chamber, according to some embodiments.
[0143] FIG. 55 is a schematic section similar to FIG. 53 showing
how the cap is too large to be received in packaging, according to
some embodiments.
[0144] FIG. 56 is a schematic section similar to FIG. 54, showing
how the cap is able to fit within the confines of the packaging,
according to some embodiments.
[0145] FIG. 57 is a schematic section showing a further embodiment
of tube.
[0146] FIG. 58 is a graph demonstrating the preservation of T-cells
in a saliva sample contacted by a preservation solution, according
to some embodiments.
[0147] FIG. 59 is a schematic flow diagram illustrating a process
for organizing shipping, filling, and processing of sample
collection devices, according to some embodiments.
DETAILED DESCRIPTION OF THE EMBODIMENTS
[0148] Embodiments of the present disclosure include devices,
solutions and methods for the collection of samples, such as bodily
fluids, as well as methods for isolating one or more cell types
from collected cells (chemically fixed or otherwise). For example,
in some embodiments, the sample collection devices provide several
advantages over currently available sample collection devices, and
in addition, the sample collection devices according to some
embodiments use a minimum amount of parts and the devices do not
require removal or exchange of a piece or an object. Furthermore,
in some embodiments, the sample collection devices may generally
not require additional manipulation by the sample donor apart from
depositing the sample and closing the collection device. The sample
collection devices according to some embodiments include improved
safety of use for both sample donors and end users due, at least in
part, to the elimination of exposed sharp objects and limited risk
of exposure to toxic solutions, as will be described in greater
detail below.
[0149] The same reference numerals are used to denote equivalent or
similar features amongst the different embodiments. Where further
construction detail is needed, or detail of a reagent, or of how
the device may be used, reference may be made to the aforementioned
WO 2012/177656 already incorporated herein by reference in its
entirety.
[0150] Referring to the drawings, some embodiments of the sample
collection device 10 may include two mating bodies, such as a cap
12 and a tube 14. In some embodiments, the cap 12 may include a
closed chamber 16, such as an interior or in-cap space, for holding
a reagent (which may be toxic). The cap 12 may be configured for
mating with the tube 14 to constitute a closed sample collection
device. The tube may 14 be configured to receive a donor specimen,
such as one or more bodily fluids (e.g., saliva, urine) in a
collection space 18. In some embodiments, the cap 12 and/or tube 14
may be configured so that when the donor deposits the specimen and
closes the tube 14 with the cap 12, the chamber 16 in the cap,
which may be holding the reagent, can be opened to release the
reagent and allow it to mix with the donor specimen.
[0151] In the following description, the reagent is described in
the form of a preservative solution for preserving at least a
component of the collected sample for further analysis. In some
embodiments, the preservative solution is a non-lysing preservative
effective to preserve (e.g. chemically fix) entire cells for
epigenetic analysis. However, the principles of the disclosure
encompass other types of reagent, without prejudice to the
preferred preservative solution described. If a different reagent
is to be used, all references to preservative solution are to be
interpreted as applying to that different reagent. Some embodiments
may optionally use a reagent as described later below with respect
to FIG. 58.
[0152] One of skill in the art will appreciate that with respect to
some embodiments of the collection device described herein, such
may be used in combination with accessories that ease specimen
deposit within the collection device, including, for example, mouth
adapters for saliva collection, funnels and hoses for urine
collection, and the like.
[0153] In some embodiments, the sample collection device 10 may
comprise a cap 12 engageable with a tube 14 to close a mouth of the
tube 14. The cap 12 may include a chamber 16 for containing a
preservation fluid. The tube 14 may define at least partly a sample
collection space 18 for receiving naturally expressed bodily fluid.
The cap 12 may comprise first and second cap portions 20 and 22
relatively movable with respect to each other. The first and second
cap portions 20 and 22 may be configured such that, responsive to
engagement of the cap 12 on the tube 14, one of the cap portions
(e.g. the first cap portion 20) is caused to move (e.g. integrally)
relative to the other cap portion (e.g. second cap portion 22) to
open the chamber 16 and permit fluid communication between the
chamber 16 and the sample collection space 18. The preservative
fluid in the chamber 16 may thereby be permitted to mix with the
bodily fluid in the sample collection space 18.
[0154] In some embodiments, the first cap portion 20 and/or the
second cap portion 22 may be a single part, for example, an
integral plastics molding. Additionally or alternatively, the first
cap portion 20 and/or the second cap portion 22 may comprise
multiple parts assembled together. Illustration of the cap portions
20 and 22 as single parts in one or more of the drawings is merely
schematic, and does not limit the scope of the embodiments.
[0155] In some embodiments, relative movement between the first and
second cap portions 20 and 22 may be caused or controlled by a
coupling between the cap portions. Such a coupling may be referred
to herein as an "active" coupling that influences the relative
movement. For example, FIGS. 1-3 illustrate such an "active"
coupling in the form of a screw thread, and FIGS. 4-7 illustrate an
"active" coupling in the form of a bayonet coupling. In other
embodiments, the first and second cap portions may be freely
movable with respect to each other (at least within a predetermined
range of operative movement, and/or notwithstanding friction
between the first and second cap portions), and the relative
movement between the cap portions may be caused by respectively
different engagements between each cap portion and the tube. Such a
coupling between the cap portions may be referred to as a "passive"
coupling, that does not influence the relative movement (for
example see FIGS. 8 and 9.
[0156] In some embodiments, the first and second cap portions 20
and 22 are rotatably movable with respect to each other. In some
embodiments, the first and second cap 20 and 22 portions may be
threadedly coupled together. Relative rotation of one cap portion
causes relative translation between the portions in a direction
parallel to the axis. However, in other embodiments, the first and
second cap portions 20 and 22 may be coupled by a bayonet coupling
(FIGS. 4-7)
[0157] Whether or not the first and second cap portions 20 and 22
are rotatably movable with respect to each other, in some
embodiments, the cap 12 is rotatably engageable on the tube 14, for
example, threadedly engageable or by a bayonet connection. The type
of coupling (e.g. threaded: bayonet) between the cap 12 and tube 14
may be same as, or different from, the type of coupling (e.g.
threaded, bayonet) between the first and second cap portions 20 and
22.
[0158] In some embodiments, the tube 14 may comprise a first
engager 24 for engagement by the first cap portion 20, and a second
engager 26 for engagement by the second cap portion 22. During
fitting of the cap to the tube, the engagement between the
respective cap portions and engagers causes (e.g. collectively)
relative movement between the cap portions, optionally in
combination with a coupling (e.g. active coupling) between the cap
portions.
[0159] For example, in some embodiments, the second engager 26
restrains the second cap portion 22 against substantial rotational
movement while the first cap portion 20 is screwed on to the first
engager 24. This generates relative rotational movement between the
cap portions 20 and 22 to open the chamber or cavity.
[0160] However, other relative movements are also possible. For
example, the second engager 26 may actively generate movement of
the second cap portion 22 with respect to the tube 14, in a
different manner from movement of the first cap portion 20 with
respect to the tube 14.
[0161] The nature of the first and second engagers 24 and 26 may
vary according to the type of relative movement intended between
first and second cap portions. At least one of the first and second
engagers 24 and 26 may comprise at least one selected from: a screw
thread; a non-threaded element engageable with a screw thread; a
bayonet connection track; an element engageable with a bayonet
connection track; a rotation stop; a stop; an abutment; a post; a
projection.
[0162] The first and second cap portions 20 and 22 may be integral
with each other, or they may be discrete components. Integral
components may, for example, be integrally molded together, or be
coupled together by an integral coupling or joint.
[0163] In some embodiments, the first and second cap portions 20
and 22 may be captively coupled to each other, for example, by a
tether (shown at 190 in FIG. 38). The tether may be integral with
at least one of the portions 20 and 22. Additionally or
alternatively, the tether may be non-integral with at least one of
the components (for example, a loop defining a captive coupling).
In the form illustrated in FIG. 38, the tether 190 comprises a
strap having a retainer protrusion or shoulder 192 at at least one
end, optionally at each opposite end. The tether 190 may pass
through one or more apertures, for example aperture 194 shown in
the second cap portion 22. The protrusion(s) may retain the tether
190 captively engaged in the aperture, so that in turn the first
and second cap portions 20 and 22 are relatively movable, but
captively coupled.
[0164] Referring specifically to the example of FIGS. 1 and 2, in
some embodiments, the first cap portion 20 comprises an outer wall
of the cap (for example, a top wall 30, and depending side wall 32
carrying a screw thread 34), and an (e.g. depending) inner wall 36
defining at least partly the chamber 16. The second cap portion 22
comprises a closure engageable at and/or over a mouth or aperture
of the chamber 16. For example, the closure 22 may be in the form
of a second cap or plug, for example, positioned in an inverted
state at and/or over a downwardly opening mouth of the chamber 16.
For example, the chamber may have an open bottom end defining the
mouth. The inner wall 36 may depend from the top wall 30 of the cap
12. Additionally, or alternatively, the closure 22 may be coupled
to the inner wall 36 by a screw threaded connection (not shown). In
some embodiments, where at least a portion of the second cap
portion 22 may fit partly within the aperture, the second cap
portion 22 may be referred to as a plug or plug-like.
[0165] Use of a closure 22 as described herein may facilitate
production of the device 10, and filling of the chamber 16. It is
relatively easy to fill the chamber 16 with the first cap portion
20 in an inverted state, and the chamber 16 presenting an open cup
space. Thereafter, the closure 22 (second cap portion) may be
screwed into place on the first cap portion 20 to close the chamber
16. The closure 22 may use standard capping techniques to ensure a
reliable seal preventing leakage of the preservative solution when
the cap 12 is subsequently placed in an upright (or non-inverted)
orientation, without involving excessive torquing of the closure 22
on to the first cap portion 20.
[0166] In some embodiments, the second cap portion (e.g. closure,
cap or plug) 22 is at least partly disengageable and/or at least
party separable from the first cap portion 20 to open the chamber.
Movement of at least a portion of the second cap portion 22 away
from the first cap portion 20 may provide a signal (first signal)
to a user in the form of a visual indication that the chamber 16
has been opened and/or that the preservation solution has been
successfully dispensed into the collected bodily fluid sample. The
second cap portion 22 (or at least a portion of the second cap
portion 22) may be colored with a contrasting color to aid its
visibility. For example, the color may be different from that of
the first cap portion and/or the tube. The tube (or at least a
portion of the tube) may optionally be transparent or translucent.
In addition to, or as an alternative to a visual signal, the
falling down of the second cap portion 22 into the tube may
generate an audible sound and/or produce a tactile knock, thereby
providing additional/alternative components of a signal to the
user.
[0167] In the illustrated form (FIG. 2), once the closure 22 is
(e.g., at least partly) disengaged from the first cap portion 20,
at least a portion of the closure may drop towards or into the
sample collection space 18, where it is easily visible to the user.
As shown in FIG. 2, in the (e.g., at least partly) disengaged
state, the second cap portion 22 may optionally lie in an inclined
position partly trapped or supported by a support 38. The support
38 may obstruct the second cap portion 22 from falling completely
into the sample collection space 18, where it may interfere with
intermixing of the reagent with the collected sample. In the
illustrated form, the support 38 is a post that wedges the second
cap portion 22 in combination with the inner wall 36. However, many
other forms of support may be used as desired, for example, a cage
or keep (e.g. as described later with respect to FIGS. 49 and 50).
In some embodiments (e.g. described later with respect to FIGS. 10
and 11, and subsequent figs.), the interior cross-sectional area of
the tube may be smaller in the sample collection space, than at the
mouth. The narrowing of the interior cross-section may also act as
a natural support or stop to obstruct the second cap portion from
dropping (e.g. fully) into the sample collection space.
Alternatively, the second cap portion 22 may remain integrally or
captively coupled to the first cap portion 20.
[0168] In some embodiments, the relative movement between the first
and second cap portions 20 and 22 causes the second cap portion 22
to translate progressively in a direction towards the sample
collection space 18. This may be achieved, for example, by using a
screw threaded coupling (between the first and second cap portions
20 and 22), having a thread angle opposite in sense (or direction)
to the screw threaded coupling between the cap 12 and the tube 14.
The thread angles may be the same or different in magnitude, yet
opposite in sense (or direction). As the first cap portion 20 is
screwed on to the tube 14, the closure 22 is restrained from
rotating and "unscrews" in a downward direction until it disengages
from the first cap portion 20, or achieves an open position not
disengaged entirely from first cap portion. For example, the length
of the screw threaded coupling between the first and second cap
portions 20 and 22 may be such that the second cap portion 22 does
not unscrew completely, but instead attains an open position while
remaining threadedly coupled to the first cap portion 20.
[0169] Where a screw threaded coupling is used between the first
and second cap portions, in some embodiments (e.g. shown in FIGS.
1, 2, 3, 26, 28 and 29), a radially inwardly facing thread of the
second cap portion 22 may optionally engage with a radially
outwardly facing thread of the first cap portion 20 (for example,
carried on a radially outwardly facing surface of the inner wall 36
of the first cap portion 20). Alternatively, in some embodiments
(e.g. shown in FIGS. 12, 16, 25, 32, 34, 36 and 37) a radially
outwardly facing thread of the second cap portion 22 may optionally
engage with a radially inwardly facing thread of the first cap
portion 20 (for example, carried on a radially inwardly facing
surface of the inner wall 36 of the first cap portion 20).
[0170] In some embodiments, the first and second engagers 24 and 26
may be configured to engage respective cap portions 20 and 22
substantially simultaneously, such that the relative rotation of
one cap portion with respect to the other commences as soon as the
cap 12 has begun to be screwed on to the tube 14. However, in other
embodiments, the second engager 26, for example, may be configured
not to engage the second cap portion 22 to restrain rotation until
the cap 12 has already been screwed partway on to the tube 14. Such
an arrangement may facilitate establishment of a seal between the
cap 12 and tube 14 before any relative rotation of the cap portions
20 and 22 to open the chamber 16. However, such an arrangement also
reduces the range of rotation between the cap portions 20 and 22
compared to the range of movement between the cap 12 and tube 14.
Alternatively, the second engager 26 for example, may be configured
to engage the second cap portion 22 before the first engager 24
engages the first cap portion 24. The parameters may be varied
according to design preference.
[0171] Referring to an alternative example shown in FIG. 3, in some
embodiments, the chamber in the cap for holding a preservative
solution is at least partly defined or closed by a frangible wall
portion 40. In some embodiments, the frangible wall portion 40 is a
membrane that at least partly defines a wall of the chamber and/or
closes an aperture in the chamber wall. For example, the membrane
may be of plastics (e.g. plastics film), or a thin metallic foil or
sheet, or a plastics/metallic laminate. The frangible wall portion
40 may be a part of one of the cap portions, or it may be a further
component of the cap. The frangible wall portion 40 may be fastened
to one of the cap portions (for example), by adhesive or welding,
or by a mechanical fastening, or held captive by a carrier.
[0172] In the example illustrated in FIG. 3, the frangible wall
portion 40 is mounted to the first cap portion 20. The frangible
wall portion may be in the form of a blister encapsulating the
preservative solution and/or closing an aperture in the chamber
wall. In the case of an encapsulated blister, the blister may be
produced and filled separately using conventional blister
forming/filling techniques, and subsequently mounted.
[0173] In some embodiments, one of the cap portions (e.g. second
cap portion 22) is configured, upon relative movement with respect
to the other cap portion (e.g. first cap portion 20), to break the
integrity of the frangible wall portion 40, to open the chamber.
For example, the second cap portion 22 comprises a cutting or
piercing element 42 for breaking the integrity. A single
cutting/piercing element 42 may be used, or plural cutting/piercing
elements 42 may be used if preferred (for example, two, three,
four, or more).
[0174] As already described, the second cap portion 22 may be
coupled to the first cap portion 20 by a rotating or screw-threaded
coupling. The second cap portion 22 may have the form of a nut with
an interior thread (not shown graphically but denoted at 44) for
connection to an exterior facing thread (not shown graphically, but
denoted at 46) on a depending wall 48 of the first cap portion 20.
Additionally or alternatively, the second cap portion 22 may have
the form of an annular nut carrying the cutting/piercing element
42. Additionally or alternatively, the thread of the nut may be the
cutting/piercing element 42 if the thread profile is sufficiently
sharp. As the first cap portion 20 is screwed into engagement with
the tube, the second cap portion 22 may be restrained against
rotation. The resulting relative rotation between the first and
second cap portions 20 and 22 causes the cutting/piercing element
42 to press against, or wipe across, the frangible wall portion to
break its integrity. For example, the second cap portion 22 may
ride upwardly towards the frangible wall portion 40 (as illustrated
in FIG. 3), or it the second cap portion 22 may be configured to
ride downwardly (in a similar manner to the embodiments of FIGS. 1
and 2) towards a frangible wall portion positioned towards the
lower end of the wall 48.
[0175] It will be appreciated that by incorporating the
cutting/piercing element 42 into the assembly of the cap 12, there
is no need to provide an exposed cutting/piercing element in the
mouth of the tube, where it may pose a risk to the lips, mouth or
other body member of a donor while donating the bodily fluid
sample. Instead, both the chamber of preservative solution (which
may be toxic), and the cutting/piercing element can be shielded
from the donor.
[0176] Various forms of relative movement between the first and
second cap portions 20 and 22 may be envisaged, while still
providing the benefit that the chamber and the cutting/piercing
element 42 are both incorporated in the cap itself. The disclosure
is not limited only to relative rotational movement (including
screw threaded movement) between the first and second cap portions
20 and 22, although relative rotational movement may provide
additional advantages by being related to the movement to screw the
cap on to the tube.
[0177] Referring to the example of FIGS. 4 to 7, the second cap
portion 22 may be similar to that of FIGS. 1 and 2, except that:
[0178] (i) In some embodiments, the second cap portion 22 is
coupled to the first cap portion 20 by a bayonet coupling
(indicated generally at 60 in FIG. 4). The bayonet coupling may
comprise one or pins or projections 62 carried by one cap portion
engageable with a respective complementary track or tracks 64
carried by the other cap portion. Purely by example, the
projection(s) 62 may be carried by the first cap portion 20 and the
track(s) 64 carried by the second cap portion 22, but the two may
be reversed according to design preference. The track 64 may by a
guide rib or fence against which the projection 62 bears, or the
track 64 may be slot within which the projection 62 slides. [0179]
(ii) Whether or not a bayonet connection is used, in some
embodiments, the second cap portion 22 may remain attached to the
first cap portion 20 when the second cap portion 22 is moved to an
open position.
[0180] For example, the cap 12 may comprise a disengagement stop
(indicated generally at 66) to prevent (or at least obstruct)
disengagement of the second cap portion 22 from the first cap
portion 20. The disengagement stop 66 may be integrated into the
bayonet coupling (or other coupling, whether rotational or not), or
the disengagement stop 66 may be a distinct coupling arrangement
between the first and second cap portions 20 and 22.
[0181] Preventing (or at least obstructing) separation of the first
and second cap portions 20 and 22 can stop the second cap portion
22 from dropping down entirely into the sample collection space 18
of the tube 14. As explained above, this can reduce the risk of the
second cap portion interfering with good mixing of the reagent and
the collected sample. [0182] (iii) The cap 12 may comprise an
elastomeric sealing element 68, for example, of silicone. The
sealing element 68 may be compressed when the second cap portion 22
is in its closed state on the first cap portion (FIG. 6). The
sealing element 68 may generate a return force tending to urge the
second cap portion 22 away from the first cap portion 20 when the
bayonet coupling is relaxed (FIG. 7). Such an arrangement may
automatically urge the second cap portion to move towards its open
position.
[0183] In the open position of the second cap portion 22 (FIG. 7),
the reagent may escape from the chamber 16 either through escape
channels formed in the coupling between the first and second cap
portions 20 and 22 (as indicated by the arrows), or through escape
apertures formed in the second cap portion (not shown).
[0184] Referring to the example of FIGS. 8 and 9, in some
embodiments the coupling between the first and second cap portions
20 and 22 may be "passive". The coupling may permit at least a
range of predetermined movement, without the coupling being
response to actively move the second cap portion 22 relative to the
first cap portion.
[0185] For example, the second cap portion 22 may have the form of
a pull-down cover that is displaceable from a closed position (FIG.
8) to an open position (FIG. 9). The cover has a interior seal
surface 70 configured to seal around apertures 72 formed in the
inner wall 36 when the second cap portion 22 is in its closed
position. The inner wall 36 may have a tapered lower end at which
the apertures 72 are positioned. The inner wall 36 may include a
floor defining a closed shape for the chamber 16.
[0186] An additional active displacement mechanism may be provided
for causing the second cap portion 22 to move downwardly with
respect to the first cap portion 20 when the cap 12 is placed on to
a tube. In some embodiments, the active displacement mechanism may,
for example, be a threaded coupling between the exterior surface 74
of the second cap portion, and a complementary thread of the second
engager 26. Alternatively, a lever arrangement (not shown) in the
cap 12 may be responsive to fitting the cap 12 to the tube 14, in
order to generate a force urging the second cap portion 22
downwardly.
[0187] In the open position of the second cap portion 22, the seal
surface 70 is moved away from blocking the aperture 72, thereby
allowing the reagent to escape through the apertures 72. The second
cap portion 22 may include one or more openings 76 through which
the reagent may enter the sample collection space of the tube.
[0188] The coupling between the first and second cap portions 20
and 22 may include a disengagement stop (again indicated generally
at 66 in FIG. 9) for preventing (or at least obstructing)
disengagement of the second cap portion 22 from the first cap
portion.
[0189] As an alternative to the second cap portion 22 displacing
downwardly with respect to the first cap portion, in some
embodiments, the second cap portion 22 may be configured to be
displaced upwardly (for example, by engagement with a second
displacer 26 configured to push upwardly on the second cap portion
22).
[0190] In the example of FIGS. 8 and 9, if preferred, the first and
second cap portions 20 and 22 may be coupled by means of an active
coupling, such as a threaded coupling or a bayonet coupling.
[0191] Referring to FIGS. 10 and 11, whether or not the cap
incorporates any of the above cap features, the tube 14 may have a
shape including a sample collection portion 50 having a smaller
interior cross-sectional area than at the mouth 52 for receiving
the cap (not shown). Providing a small cross-sectional area enables
a finely graduated fill scale and/or fill line to be provided that
may be easily read and judged for collecting small amounts of
bodily fluid. For example, for saliva, the collected sample may be
between about 1 ml and 6 ml in volume. It may be desirable to
indicate a graduation for each 2 ml, or 1 ml, or half ml, or even
smaller. Alternatively, it may be desirable to have only one
graduation indicating either a volume of 2 ml, 4 ml, 6 ml, or any
volume between 1 and 6 ml. In the non-limiting example illustrated,
the scale is graduated between 1 and 4 ml. Alternatively, a (e.g.
single) fill line may also be provided instead of one or more
specific measurement graduations.
[0192] Providing a fill scale and/or fill line that is clear to see
and/or judge is greatly facilitated by having a small interior
cross-sectional area, without compromising the size of the mouth of
the tube.
[0193] A fill scale and/or fill line may be advantageous in some
embodiments disclosed herein, where the second cap portion 22 man
translate towards, or drop towards, the sample collection space. By
avoiding overfilling the sample, any risk of the tube overflowing
may be avoided. Overflow could otherwise result from release of the
reagent into an tube overfilled with the bodily fluid sample (the
reagent may be toxic), and/or from the action of the second cap
portion 22 dropping or translating towards the sample collection
space, potentially reducing the available volume.
[0194] The region of small cross-sectional area may also prevent
(in some embodiments) dropping down of the second cap portion 22
into the small cross-sectional area sample collection space.
[0195] By way of example, the cross-sectional area of the sample
collection portion may be no more than about 50% of the mouth
cross-sectional area, optionally no more than about 45% of the
mouth cross-sectional area, optionally no more than about 40% of
the mouth cross-sectional area, optionally no more than about 35%
of the mouth cross-sectional area, optionally no more than about
30% of the mouth cross-sectional area, optionally no more than
about 25% of the mouth cross-sectional area, optionally no more
than about 20% of the mouth cross-sectional area, optionally no
more than about 15% of the mouth cross-sectional area, optionally
no more than about 10% of the mouth cross-sectional area,
optionally no more than about 5% of the mouth cross-sectional
area.
[0196] Additionally or alternatively, in some embodiments, the
cross-sectional area of the sample collection portion may be at
least about 70 mm.sup.2, optionally at least about 200 mm.sup.2,
optionally at least about 300 mm.sup.2. Additionally or
alternatively to any of these values, in some embodiments, the
cross-sectional area of the sample collection portion may be not
substantially greater than about 700 mm.sup.2, optionally not
substantially greater than about 500 mm.sup.2, optionally not
substantially greater than about 400 mm.sup.2. In some embodiments,
the cross-sectional area may be between about 70 mm.sup.2 and about
700 mm.sup.2, optionally between about 200 mm.sup.2 and about 500
mm.sup.2, optionally between about 300 mm.sup.2 and about 400
mm.sup.2.
[0197] In the example of FIG. 10, the sample collection portion 50
may have a thin columnar shape. In the example of FIG. 11, the
sample collection portion 50 may have an annular or toroid shape
defined (for example) by an inverted-U-shape floor 54 of the tube
14. Such a shape may be more stable than a thin columnar portion of
FIG. 4, and may enable the tube to be placed upright on a table
(for example if desired).
[0198] The concept of a thin columnar shape of sample collection
portion 50 of the tube 14 is also illustrated in some further
examples below, although these further embodiments are not limited
only to such a shape. The tube 14 may have a sample collection
portion 50 of thin columnar shape, and a wider mouth region 52. The
cap 12 may have a first cap portion 20 defining a downwardly
depending chamber 16 with an aperture at the bottom closed by a
second cap portion 22. The second cap portion 22 may be releasable
from the first cap portion 20 by relative rotation between the cap
portions 20 and 22. For example, the second cap portion 22 may be
threadedly coupled to the first cap portion, and unscrewed
therefrom in response to the relative rotation. A first engager 24
on the tube mouth 52 may threadedly engage the first cap portion
20. A second engager 26 on the tube mouth 52 may engage the second
cap portion 22 to restrain the second cap portion 22 against
rotation when the first cap portion 20 is screwed on to the tube
mouth 52.
[0199] Some embodiments address a relationship between (i) ease of
attaching the cap 12 to the tube, and (ii) the angular screw thread
length available for engaging/releasing the second cap portion 22
with respect to the first cap portion 20. The following examples
use a design criterion that a first angular thread length for
securing the cap 12 to the tube 14 (for example, and defining the
engagement between the first cap portion 20 and the first engager
24) corresponds to rotation through about a single turn (e.g. about
360.degree.). Such an engagement thread length may provide good
usability for many different users, while still providing
sufficient engagement to reliably seal the tube 14 closed. However,
longer first thread lengths, for example, about a turn and a half,
or more, or shorter first thread lengths, for example, about a
three-quarter turn, or about a half turn, or less, may also be used
as desired.
[0200] Referring to FIGS. 12-15, in some embodiments, it may be
desirable to have a relatively long second angular engagement
thread length (measured in rotation angle) between the first and
second cap portions 20 and 22, for example, not substantially
shorter than the first engagement thread length referred to above,
for example, corresponding to about one full turn. This may be
facilitated by arranging the second engager 26 to engage the second
cap portion 22 before, or substantially at the same time as, or at
least not substantially later than, engagement between the first
engager 24 and the first cap portion 20. Such relatively early
engagement by the second engager 26 can ensure that the second cap
portion 22 is restrained against rotation almost immediately when
the first cap portion 20 is rotated, and thereby enable at least
the majority, or substantially all, of the rotation movement of the
first cap portion 20 to be available for generating the relative
rotation between the first and second cap portions 20 and 22 for
opening the chamber.
[0201] In FIGS. 12-15, the first cap portion 22 is positioned below
the mouth of the first cap portion 20. In use, abutments 100 of the
second cap portion are manually keyed with an arrangement of
projections 102 defining the second engager 26 in the mouth portion
52 of the tube 14, before the first cap portion 20 engages the
screw thread of the first engager 24. The arrangement of
projections 102 defines angular spaces 104 that are not
substantially larger than the angular or circumferential width of
the abutments 100, to provide engagement without substantial lost
rotation or backlash. For example, the spaces 104 may be less than
twice the angular width of the abutments 100, optionally less than
150%, optionally less than 125%. In use, the user may manually key
the abutments 100 with the spaces 104 between the projections 102
as an initial stage of fitting the cap 12 to the tube 14. The
position of the second cap portion 22 below the mouth of the first
cap portion 20 may facilitate easy viewing to arrange the keyed
alignment. Thereafter, the user may slide the cap 12 axially
further towards the tube 14 to engage the first cap portion 20 with
the first engager 24 and permit screwing of the first cap portion
20 on to the tube 14. As already described, the early engagement
between the second engager 26 and the second cap portion 22 can
avoid significant "lost rotation" in the relative movement between
the first and second cap portions 20 and 22. It can also ensure
that the user feels a generally uniform resistance during screwing
the cap 12 on to the tube 14 because the engagement of the second
engager 26 is not delayed.
[0202] Referring to FIGS. 16-19, in some embodiments, it may be
desirable to accommodate screwing of the cap 12 on to the tube 14
without the user having to manually key together the second engager
26 and the second cap portion 22. This may be facilitated by
increasing the angular spaces 104 between the projections 102,
and/or reducing the number of the projections 102 defining the
second engager 26, and/or by shortening the angular width of the
abutments 100. For example, the number of projections 102 may be
four or less, optionally three or less, optionally two or less,
optionally one. In the example of FIGS. 16-19, two projections 102
are illustrated, separated by angular spaces 104 each of at least
about 170.degree., for example, approaching 180.degree.. Such an
arrangement may provide a large angular position range over which
the abutments 100 may enter a space 104 between the projections 102
to loosely key the second engager 26 and the second cap portion 22.
Such an arrangement may avoid any need for the user to manually key
the second engager 26 and the second cap portion 22, because the
two components can fit together in almost any relative angular
orientation. The second cap portion 22 may be recessed (or at least
non-projecting) with respect the mouth of the first cap portion
20.
[0203] A consequence of the large angular spaces 104 may be that
significant so-called lost rotation or backlash exists between the
second engager 26 and the second cap portion 22, before the second
cap portion 22 is restrained from rotation during screwing of the
cap 12 on to the tube 14. For example, in the illustrated example,
the lost rotation may be up to about a half turn, (for example, up
to between about 170.degree. and about 180.degree.). The second
angular thread length (between the first and second cap portions 20
and 22) may be designed to be less than the first angular thread
length (between the first engager 24 and the first cap portion 20)
by at least a corresponding amount. For example, the first angular
thread length for screwing the cap 12 on the tube 14 may be about
one full turn (e.g. about 360), and the second angular thread
length may be about a half-turn (e.g. about 180). The amount of
relative rotation available for engaging/releasing the first and
second cap portions 20 and 22 may be reduced compared to the
preceding embodiment, but with easier fitting of the cap 12 to the
tube 14 without having to manually key the second cap portion 22
with the second engager 26.
[0204] Referring to FIG. 20, in some embodiments, the first and
second cap portions 20 and 22 may be formed or joined together as a
unitary item. A frangible wall portion 110 (e.g. an integral
frangible wall portion) may be breakable to release the second cap
portion 22 from the first cap portion 20 in response to relative
movement (for example, relative rotation) between the cap portions
20 and 22. The cap portions 20 and 22 may be regarded as being
relatively movable at least in use. Additionally or alternatively,
the cap portions 20 and 22 may be regarded as being in use moved
one relative to the other. The release or opening of the chamber 16
may be similar to a twist-to-break-open design, in which a
frangible wall portion is designed to fail or break in response to
forced twisting of one portion relative to another. The first and
second cap portions 20 and 22 may be formed as an injection molded
body.
[0205] In some embodiments, the second cap portion 22 may comprise
relatively strong and/or large fins 112 to enable sufficient torque
to be applied to the second cap portion 22 by the second engager 26
to restrain the second cap portion 22 from rotation and break the
frangible wall portion 110.
[0206] In some embodiments, a protective sleeve 113 may be provided
for protecting the second cap portion 22 from accidental breakage
prior to intended use. The protective sleeve 113 may be manually
removable by the user at the time of use, or it may be intended to
remain in place, and be received within the mouth portion of the
tube 14.
[0207] In some embodiments, the cap 12 may further comprise a
filling port 114 that is distinct from the aperture for releasing
the reagent, and/or distinct from connection to the second cap
portion 22. Such a filling port 114 may be especially suitable when
the first and second cap portions 20 and 22 are integrally formed
together to define a closed-bottom chamber 16, but the filling port
114 may also be used in any of the other embodiments described
herein. The filling port 114 may enable the reagent to be
introduced into the chamber 16 independently of the dispensing
aperture and/or the second cap portion. In some embodiments, the
filling port 114 may be closed by a press-fit (e.g. snap fit) cover
or plug 115, or by any other suitable closure.
[0208] Referring to FIGS. 21 and 22, in some embodiments, the
second cap portion 22 comprises a movable wall of a closed bladder
or other variable volume and/or variable shape chamber 116. For
example, the chamber 116 may have a bellows or accordion design,
including a wall portion 118 that is intended to fold or collapse
to provide variable volume and/or shape. The cap 12 may further
comprise a cutting and/or piercing element 42 for breaking the
integrity of a frangible wall portion of the chamber 116 in
response to movement of the movable wall (e.g. second cap portion
22). In some embodiments, the cutting/piercing element 42 may be
provided inside the chamber 116. Such an arrangement provides
considerable safety advantages by avoiding any exposed sharp edge
prior to use. Such an arrangement can also accommodate the
cutting/piercing element within a relatively low package profile.
Alternatively, the cutting/piercing element 42 may be arranged
outside the chamber 116.
[0209] In some embodiments, the chamber 116 (and optionally the
cutting/piercing element) may be produced as a self-contained
module independently of a cap shell 120. This can allow the chamber
module to be filled with reagent by a separate operation before the
module is mounted to the cap shell 120. For example, the module may
be attached to a mounting 122 of the cap shell by any suitable
fixing technique, for example, by adhesive, welding, or an
interference fit.
[0210] In use, when the cap 12 is fitted to the tube 22, the
movable wall (second cap portion 22) may bear against an abutment
defining the second engager 26 in the mouth portion 52 of the tube
14. The abutment causes the movable wall to displace upwardly into
contact with the cutting/piercing element 42. The element 42 breaks
the integrity of the movable wall, thereby releasing the reagent
from the chamber 116.
[0211] The cap 12 may be attachable to the tube 14 by any suitable
attachment, for example, a screw thread, a bayonet connection, or a
press-fit (e.g. a snap-fit).
[0212] In some embodiments, a protective sleeve 113 may be provided
for protecting the chamber 116 from accidental deformation or
breakage prior to intended use. The protective sleeve 113 may be
manually removable by the user at the time of use, or it may be
intended to remain in place, and be received within the mouth
portion of the tube 14. Additionally or alternatively, the chamber
116 may be disposed within a protective case (not shown), or behind
a protective wall (not shown). The case or wall may include one or
more apertures through which respective pushers or plungers may
bear on the movable wall without exposing the movable wall itself.
The reagent when released from the chamber 116 may be dispensed
through these (or other) apertures.
[0213] Although the present embodiment illustrates the chamber 116
installed within the cap, in other embodiments, the chamber 116 may
be installed within the tube, and configured to be deformed upon
fitting of the cap to the tube.
[0214] Referring to FIGS. 23 and 24, in some embodiments, the
second cap portion 22 may be provided as a foil or plug that is
welded (at region 140) to the first cap portion 20 (e.g. to the
depending wall 36). The second cap portion 22 may, for example,
comprise a laminate of plastics and metal foil, optionally
reinforced with a plug body or frame. The second cap portion 22 may
be attached to the first cap portion 20 by any suitable welding
technique, such as ultrasonic welding. Welding may provide a
convenient and low-cost technique for establishing a seal closing
the chamber 16. In the illustrated form, the depending wall 36 is
optionally slightly longer than the outer body of the cap 12, in
order to facilitate welding.
[0215] The second cap portion 22 may comprise abutments 100 which
function in the same way as described earlier. In use, when the cap
12 is screwed to the tube (14, not illustrated in FIGS. 23 and 24),
the abutments 100 are engaged by complementary profiles of the tube
14 to restrain the second cap portion 22 from rotation. The
resulting torsion breaks the seal to release the contents of the
chamber 16 into the tube. In some embodiments, the torsion may
break the integrity of the weld join, such that the second cap
portion 22 is disengaged from the first cap portion. Additionally
or alternatively, in some embodiments, the torsion may rupture or
tear the foil material of the second cap portion, thereby creating
openings to release the contents of the chamber 16. Optionally, the
foil may have predetermined lines or zones of weakness defining
intended tear locations.
[0216] Use of a welded second cap portion 22 may provide some
advantages in enabling a reliable seal to be established quickly
and simply, using known food container techniques. In particular,
it may avoid the need and the tooling cost of molding screw threads
for coupling the first and second cap portions. It may also avoid
the need for incorporating any cutting or piercing element.
[0217] Referring to FIG. 25, in some embodiments, second cap
portion 22 may, instead of being relatively flat, have a
substantially cup form. The second cap portion 22 may, for example,
be taller than the depending wall 36 of the first cap portion 20.
The coupling between the first and second cap portions may be
active or passive. The coupling may be rotatable, for example, a
threaded coupling or a bayonet coupling. The second cap portion 22
may, for example, include the abutments 100 referred to above for
cooperating with complementary elements of the tube, to restrain
the second cap portion 22 against rotation during fitting of the
cap 12 to the tube.
[0218] In use, this embodiment may function similarly to the
preceding embodiments. In response to relative movement (e.g.
rotation) between the first and second cap portions 20 and 22 upon
fitting the cap 12 to a tube, the second cap portion 22 may
disengage from the first cap portion 20. Optionally the second cap
portion 22 may drop down at least partly towards or into the tube.
Optionally the second cap portion 22 may lean or tip over to
promote release of the agent into the tube. Optionally, mixing of
the agent with the collected sample may be enhanced by the user
manually shaking the sample collection device after having fitted
the cap 12 to the tube.
[0219] Although not illustrated above, any of the preceding
embodiments may optionally comprise plural chambers 16 (or 116) for
containing plural reagents or plural reagent components. Some
embodiments explicitly incorporating plural chambers 16a and 16b
are shown in FIGS. 26-28.
[0220] In some embodiments, the plural chambers (e.g. first and
second chambers 16a and 16b) are defined by respective compartments
in the first cap portion. In some embodiments, the compartments may
be one above the other (as illustrated). Alternatively or
additionally, compartments may be arranged side by side. The number
of compartments may be two, or three, or more as desired.
[0221] Plural chambers 16a and 16b may enable plural different
reagents to be stored separately, and/or plural reagent components
to be stored separately. For example, certain reagents or
components may have a longer shelf-life when stored separately than
when mixed together, and/or may be less sensitive to external
influence such as temperature when stored separately, and/or may
form an active reagent that is only active for a limited period of
time once mixed together.
[0222] If desired, the cap 12 may be configured to release the
contents of the chambers 16a and 16b generally at the same time as
each other, or sequentially one after the other. Sequential release
may be especially suitable when it is desired to contact the sample
with one reagent or component before the other.
[0223] In some embodiments, the mechanism for opening each chamber
16 to release its contents may be similar to any of the release
mechanisms described above. In particular the cap 12 may comprise
portions that are relatively movable with respect to one another,
and/or in use are moved one relative to another, in response to
fitting the cap 12 to the tube 14. The relative movement between
the cap portions may open each chamber 16a and 16b (optionally
sequentially) to release the chambers' contents.
[0224] Referring to FIG. 26, in some embodiments, each chamber 16a
and 16b may have an aperture in a wall of the first cap portion 20,
closed by a frangible wall portion 40a and 40b, similar to the
frangible wall portion 40 described above. The second cap portion
22 may be coupled to the first cap portion 20 by a rotating or
screw-threaded coupling. The second cap portion 22 may comprise one
or more cutting/piercing elements 42 configured to break the
integrity of the frangible wall portions 40a and 40b as the second
cap portion 22 moves rides upwardly in response to relative
rotation. The second cap portion 22 may optionally be configured to
open the chambers 16a and 16b sequentially one after the other
responsive to the axial movement. Although the second cap portion
22 is illustrated as being initially at the bottom (mouth) of the
cap 12, and configured to ride upwardly into the cap, the second
cap portion 22 may if desired be positioned initially at the upper
end, and configured to ride downwardly towards the cap mouth.
[0225] Referring to the alternative embodiment of FIGS. 27 and 28,
the first cap portion 20 is similar to FIG. 26, except that the
apertures 128a and 128b are not covered by frangible wall portions.
Instead, each aperture is closed by a respective cap portion, for
example, each in the form of a nut or other annular member. The
aperture 128a of chamber 16a may be closed by a second cap portion
22, and the aperture 128b of chamber 16b may be closed by a further
(e.g. third) cap portion 130. The cap portions 22 and 130 may be
configured to move relative to the first cap portion 20, to uncover
the respective apertures of the chambers 16a and 16b when the cap
12 is fitted to the tube 14.
[0226] For example, in some embodiments, the second cap portion 22
may be caused to rotate first upon fitting the cap 12 to the tube
26, to move upwardly into the cap 12, and uncover the aperture 128a
of the first chamber 16a, to release its contents. Continued
relative rotation causes the second cap portion 22 to bear against
and similarly move the third cap portion 130, in order to uncover
the aperture 128b of the second chamber 16b, to release its
contents sequentially after the first chamber 16a. As an
alternative to the above, both the second and third cap portions
could be caused to rotate simultaneously, in order to release the
contents of the chambers 16a and 16b together. As a further
alternative, the second and third cap portions could be replaced by
a single cap portion having an axial length sufficient to cover the
apertures 128a and 128b of both chambers 16a and 16b. The single
cap portion may be shaped to provide simultaneous or sequential
opening of the chambers 16a and 16b in response to relative
rotation, according to design preference.
[0227] Referring to FIG. 29, the principles of producing the agent
containing chamber 116 as a self-contained module independently of
a cap shell 120, and previously described with reference to the
embodiment of FIGS. 21 and 22, may be applied to any of the other
types of chamber 16 and cap portions 20 and 22 described
hereinbefore. FIG. 29 illustrates, for example, generally a chamber
module 116 comprising an inverted cup-shaped body 142, and a second
cap portion 22.
[0228] The coupling between the body 142 and the second cap portion
22 may be active or passive. The coupling may be rotatable, for
example, a threaded coupling or a bayonet coupling. The second cap
portion 22 may, for example, include the abutments 100 referred to
above for cooperating with complementary elements of the tube, to
restrain the second cap portion 22 against rotation during fitting
of the cap 12 to the tube.
[0229] The chamber module 116 may be attached to a mounting 122 of
the cap shell 120 by any suitable fixing technique, for example, by
adhesive, welding, a screw thread, or an interference fit.
Especially in the case of the second cap portion 22 being
responsive to relative rotation, the fixation at the mounting may
optionally be of a non-rotation type that does not, after fixing,
permit relative rotation between the cap shell 120 and the body
142.
[0230] Producing the chamber 116 in a self-contained module form
may provide several potential advantages, in some embodiments. For
example: [0231] (iv) the chamber module 116 can be filled with
re-agent by a separate (e.g. automated) operation before the module
is mounted to the cap shell 120. This may simplify filling
production. [0232] (v) the tooling for molding the components for
the cap 12 may be simplified, because the cap is built from several
parts that are, individually, easier to mold than may be a more
complicated integral molding. [0233] (vi) the technique may permit
modular moldings to be used that may be difficult to mold in
integral form. For example, as illustrated in FIG. 29, the
engagement between the second cap portion 22 and the body 142 may
be on an external face of the body 142. The molding used for the
body 142 may, for example, have an exterior thread. Such an
external thread may be molded more easily when the body 142 is made
separately from the cap shell 120.
[0234] In the embodiments of FIGS. 21, 22 and 29, the cap shell 120
and/or a portion (e.g. 142) of the chamber module 116 to be affixed
to the cap shell 120 may be regarded as a first cap portion. When
both parts in combination are considered to be comprised in the
first cap portion, such an embodiment may illustrate a cap portion
constructed from plural parts assembled together.
[0235] Referring to FIGS. 30 and 31, in some embodiments, and
applicable to any of the above examples, the sample collection
device may further include locking and/or sealing means, such that
the cap cannot be removed from the tube by the donor once the cap
has been connected or screwed onto the tube, such as by the donor.
Suitable locking members can include a wedge on the cap and a
matching flange on the tube or visa-versa. The wedge and flange can
either be on the inside of the cap and tube, or on the outside of
the cap and tube. Suitable sealing means include a sealed cavity
containing a sealing solution, such as a glue, wherein the sealing
solution is released when the cap is pushed, rotated or screwed
onto the tube and thereafter cures in order to prevent
disengagement between the cap and tube. In some embodiments, the
sealing solution may be a two-component glue, such as an epoxy,
with one component being sealed into the cap, and the other
component sealed into the tube, such that the two components mix
within the threads when the cap is screwed onto the tube. In other
embodiments, the sealing solution can be a single component, such
as a cyanoacrylate-based glue, which can be in a sealed cavity in
the cap or tube, such that the sealing solution is released into
the threads when the cap is screwed onto the tube. In some
embodiments, the sealing solution can cure soon after engagement
between the cap and tube such that disengagement between the tube
and cap by the user can be generally prevented.
[0236] Referring to FIGS. 30 and 31, in one form, a locking means
may comprise a ratchet or a resilient latch. The ratchet or latch
may, for example, comprise at least one projection or formation 150
that has a ramp surface 152 for permitting a second component 154
to pass over the formation 150 by riding over the ramp surface 152
in the first direction (corresponding to the rotation direction to
screw the cap 12 to the tube 14), and an abutment surface 156 for
blocking (or at least obstructing) movement in the second direction
(unscrewing direction). The second component 154 may optionally
comprise complementary ramp and abutment surfaces. Additionally or
alternatively, to any of the above, the ratchet or latch may, for
example, comprise a cantilever and/or articulated member 158
configured such that, in use, the member 156 is (i) able to be
displaced by a second component 154 for permitting the second
component 154 to pass the cantilever/articulated member 156 in the
first direction, and (ii) not displaced by the second component 154
when contacted in the second movement direction.
[0237] One component may be arranged on the cap 12, and the other
on the tube 14. For example, as illustrated in FIGS. 30 and 31, a
second component ramp or wedge 154 may be formed on the tube, for
engagement by a latch/ratchet of the cap 12 and defining the
cantilever member 158 and/or the formation 150.
[0238] In some embodiments, the first and second movement
directions may, for example, be generally axial or they may, for
example, be generally circumferential.
[0239] The lock device may generate a signal (second signal) to the
user to indicate that the lock device has locked the cap 12 in its
closed state. The second signal may include audible and/or tactile
signal components generated by the operation of the, for example,
ratchet or latch. For example, the user may feel a physical "click"
upon the lock operating, and/or hear a "click" sound.
[0240] In some embodiments, the collection device may be configured
to provide to the user a first signal indicative of the chamber
having been opened, and a second signal indicative of the cap
having reached a closed and/or locked position.
[0241] As already described, the first signal may result from
dropping down of the second cap portion 22 at least partly into the
tube. The first signal may be at least partly visual, and/or at
least partly tactile, and/or at least partly audible.
[0242] As described recently above, the second signal may result
from operation of a lock device (for example, a latch or ratchet).
The second signal may be at least partly tactile and/or at least
partly audible.
[0243] The combination of the first and second signals generated to
the user can provide intuitive feedback to the user that the cap is
firmly closed, and that the agent has been released.
[0244] Referring to FIGS. 32 to 37, a further embodiment of sample
collection device is illustrated. (In some of these drawings, a
quadrilateral "X" denotes a cut-plane where an item is shown partly
or wholly in cross-section.) The device may have any of the
features described hereinbefore, whether or not illustrated or
described below. In particular, the device 10 may comprise a cap 12
threadedly engageable at and/or over the mouth of a collection tube
14. The cap 12 may comprise a first cap portion 20 having an inner
wall 36 defining a chamber 16 for a reagent, the chamber 16 having
an open lower end. The cap may further comprise a second cap
portion 22 in the form of a closure (or cap or plug) for closing
the open end. The second cap portion 22 may be threadedly coupled
to the first cap portion 20 by a reverse thread (e.g. having an
opposite thread direction to the threaded coupling between the cap
12 and the tube 14).
[0245] In the illustrated form, at least a region of the second cap
portion 22 may have a top hat shape. For example, referring to FIG.
36, the second cap portion 20 may comprise an inverted cup portion
160 defining a hollow cavity 162, and encircled by a flange (or
annular shoulder) 164. The (e.g. reverse) screw thread of the
second cap portion 22 may be radially outwardly facing (e.g.
example, carried on a radially outwardly facing surface of the
inverted cup portion 160) for engaging a radially inwardly facing
screw thread of the first cap portion 20 (e.g. carried on a
radially inwardly facing surface of the inner wall 36). Such a
shape of second cap portion 22, with a cavity 162, may be
especially suitable to be made by injection molding, without
requiring complicated mold parts, or excess plastics.
[0246] The second cap portion 22 may further comprise abutments 100
in the form of lateral extensions of the flange 164. In some
embodiments, two abutments 100 may be provided, generally
diametrically opposed, in a similar manner to the embodiment of
FIGS. 16-19. However, in other embodiments, the number of abutments
100 may be fewer than two, or greater than two, according to design
choice.
[0247] In some embodiments, the contact between the first and
second cap portions 20 and 22 may be sufficient to form a
liquid-tight seal to prevent leakage of the agent prior to intended
use. Additionally or alternatively, a seal gasket 166 may be
provided to effect a seal at an interface between the first and
second cap portions 20 and 22. For example, the seal gasket 166 may
have a closed-loop or washer shape (or optionally an O-ring). When
provided, the seal gasket 166 may be carried by one of the first
and second cap portions 20 and 22, for example, attached to the
second cap portion 22 as indicated by the arrow in FIG. 36. The
gasket 166 may, for example, be adhered to the flange 164.
Alternatively, the gasket 166 could be integrally formed by a
multi-shot molding process. In the modified example of second cap
portion 22 in FIG. 37, the gasket 166 may be retained in place by a
peripheral wall 168 of the second cap portion 22 and/or by one or
more undercut retainers 170 of the second cap portion 22. In the
illustrated example, both the peripheral wall 168 and the retainers
170 are illustrated, but one or the other could be used
independently, and/or in addition to the adhering or multi-shot
molding of the gasket 166 with respect to the second cap portion
22. In the case of undercut retainers 170, the flange 164 may be
formed with openings 172 resulting from, or accommodating, portions
of the mold tooling for forming the undercut retainers 170. As
explained above, the gasket 166 may be omitted altogether if the
contact between the cap portions 20 and 22 themselves is sufficient
to effect a liquid-tight seal for containing the agent with the
compartment 16.
[0248] As may be seen in FIG. 34, in some embodiments, the inner
wall 36 and/or the second cap portion 22 may depend or project
below the periphery of the outer side wall 32. This can facilitate
keying of the abutments 100 and the projections 102 when fitting
the cap 12 to the tube 14. Additionally or alternatively, it can
enable the projections 102 to be placed lower inside the mouth 52
of the tube 14, such that the projections 102 are recessed or
spaced axially away from the open end of the tube 14. Even though
the projections 102 are not sharp, spacing the projections 102 away
from the open end (to be contacted in use, for example, by the
donor's mouth or lips), may enhance further the ergonomics of the
device 10 and avoid any surprising sensation of the projections 102
against the donor's mouth or lips should the donor's lips
accidentally enter the open end while using the device 10.
[0249] In a similar manner to that described previously, when the
cap 12 is fitted to, and tightened by screwing on, the mouth 50,
rotation of the second cap portion 22 relative to the tube 14 is
obstructed once the abutments 100 of the second cap portion 22 abut
the projections 102 of the tube mouth 50. Continued screwing of the
cap 12 (e.g. the first cap portion 20) generates relative rotation
between the first and second cap portions 20 and 22. The reverse
threaded coupling between the first and second cap portions 20 and
22 causes the second cap portion 22 to unscrew from the first cap
portion. Once released, the second cap portion 22 may drop down
from the inner wall 36, thereby opening the compartment 16, and
allowing the reagent in the compartment 16 to be dispensed into the
sample collection space 18 of the tube. The dropping down of the
second cap portion 22 may generate a first signal to the user, that
the reagent has been released as intended. The first signal may,
for example, be at least partly tactile (e.g. the user feeling the
dropping down), and/or at least partly visual (e.g. the user seeing
the second cap portion 22 in its dropped down position if the tube
14 comprises transparent material), and/or at least partly audible
(e.g. if the user hears the second cap portion 22 dropping
down).
[0250] As described for preceding embodiments, the design may be
varied according to design preference regarding the angle of
rotation (e.g. turns) for screwing the cap 12 on to the tube 14,
and/or for unscrewing the second cap portion 22. For example, the
rotation to secure the cap 12 may be made up of (a) a first angle
to bring the thread starts of the first cap portion 20 and the tube
14 into alignment, and (b) a second angle to fully screw the cap 12
on to the tube. In some embodiments, the first cap portion 20 and
the tube 14 may include two thread starts, e.g. diametrically
opposed, such that the angle (a) is up to about half a turn
(depending on an arbitrary orientation of initial fitting, the
worst case is up to a half turn before the thread starts are
aligned). The angle (b) to fully engage the first cap portion 20
may be about a full turn, optionally at least about a full turn,
optionally at least about one and a quarter turns, optionally at
least about one and a half turns. If desired, the first angle (a)
may be reduced by increasing the number of thread starts. For
example, for three thread starts the angle (a) may be up to about a
third of a turn, or for four thread starts the angle (a) may be up
to about a quarter of a turn.
[0251] Within the combined range of movement (a) plus (b) above,
the movement to disengage the second cap portion 22 may also be
accommodated. For example, the motion to disengage the second cap
portion 22 may be made up of (c) a third angle to engage the
abutments 100 with the projections 102, and (d) a fourth angle for
the second cap portion 22 to unscrew once its rotation is
restrained with respect to the tube 14. The third angle (c) may
depend on the number of projections 102 and/or the number of
abutments 100. In the illustrated form, the number of projections
102 is two, and the number of abutments 100 is also two. The third
angle (c) may be up to about half a turn. Depending on an arbitrary
orientation of initial fitting, the worst case is up to about half
a turn before the abutments 100 are aligned to engage the
projections 102. The fourth angle (c) depends on the thread design.
In some embodiments the fourth angle may generally be less than
three-quarters of a turn, optionally not more than about half a
turn, optionally not more than about a quarter of a turn. If
desired, the third angle (c) may be reduced by increasing the
number of abutments 100 and/or the number of projections 102. For
example, by increasing the number of abutments 102 to four, and/or
by increasing the number of projections 100 to four, each uniformly
arranged, the third angle (c) may be reduced to up to about a
quarter of a turn.
[0252] In some embodiments, the cap 12 and tube 14 may be
configured such that the abutments 100 of the second cap portion 22
do not engage the projections 100 of the tube 14 before the first
cap portion 20 has already been threadedly engaged (e.g. the thread
starts have already engaged) with the tube 14. Such an arrangement
may prevent the second cap portion 22 from beginning to unscrew
before the cap 12 is at least partly screwed on to the tube 14. For
example, the abutments 100 may engage the projections 102 only
after the first cap portion 20 has already begun threaded
engagement with the tube 14 through at least about a quarter of a
turn.
[0253] Additionally or alternatively, in some embodiments, the
second cap portion 22 may be configured to disengage from the first
cap portion 20 before the first cap portion 20 has completed fully
being screwed on to the tube 14. This may ensure that the second
cap portion 22 is always reliably disengaged during fitting of the
cap 12. For example, the second cap portion 22 may disengage at
about at least a quarter of a turn before the fully screwed
position of the cap 12 on the tube 14 (optionally at least half a
turn before, optionally at least three-quarters of a turn before).
Such an arrangement can also provide the sequential generation of
first and second indicator signals to the user as described
above.
[0254] Owing to manufacturing (e.g. molding) tolerances, the above
specifications of angles may (in some embodiments) vary by as much
as plus or minus a quarter of a turn.
[0255] The tube 14 may have a shape in which the interior
cross-sectional area may be smaller in the sample collection space
18, than at the mouth 52. The narrowing of the interior
cross-section may act as a natural support or stop to obstruct the
second cap portion 22 from dropping (e.g. fully) into the sample
collection space 18. The small interior cross-section may also
enhance the visibility of the amount of bodily fluid collected,
compared to a target fill line or scale (not shown). The small
interior cross-section may, in some embodiments, be dimensioned at
least to prevent entry of the second cap portion 22.
[0256] The device 10 may be configured with a lock to obstruct
removal of the cap 12 from the tube 14 by the donor once the cap 12
has been connected or screwed on to the tube 14. For example, the
lock may comprise at least one lock wedge 180 on one of the tube 14
and cap 12, and at least one lock keep 182 on the other of the tube
14 and cap 12. In the illustrated form, the tube 14 comprises the
lock wedge(s) 180 (for example, one, two, three, four, or more),
and the cap 12 comprises the lock keep(s) 182 (for example, one,
two, three, four, or more). The number of wedges 180 and keeps 182
may be the same of different, according to design preference. In
the illustrated example, two lock wedges 180 and two lock keeps 182
are provided.
[0257] Each lock wedge 180 may generally comprise a ramp surface
180a, and an abutment surface 180b. Additionally or alternatively,
each keep 182 may generally comprise an opening or recess, and an
abutment edge or surface around the opening or recess. The keep 182
may, for example, comprise a generally rectangular or
inverted-U-shaped cut-out in the cap wall. The wedge 180 and keep
182 are generally configured such that, when the cap 12 is screwed
to a fully closed position on the tube 14, the abutment surface of
the keep 182 can cam or slide progressively over the ramp surface
180a of the wedge. Upon reaching the fully closed position, the
wedge 180 is received at the opening or recess of the keep 182.
Should the user try to unscrew the cap, the abutment surface 180b
of the wedge will abut or strike the abutment edge of the keep 182,
thereby blocking or obstructing such unscrewing motion, and
effectively locking the cap 12 in its fully closed position.
[0258] The engagement of the lock may generate a second signal to
the user, indicative of the cap 12 reaching its fully closed
position. The second signal may, for example, be at least partly
tactile (e.g. the user feeling a click as the wedge 180 enters the
keep 182), and/or at least partly visual (e.g. the user seeing the
wedge 180 captive in the keep 182), and/or at least partly audible
(e.g. if the user hears an audible click as the wedge 180 enters
the keep 182).
[0259] In the illustrated example (as may be seen in FIGS. 32 and
34), the abutments 100 of the second cap portion 12 may be (in the
closed position of the second cap portion 22 with respect to the
first cap portion 20) generally angularly aligned with (e.g. on the
same radius direction as) the lock keeps 182. Especially in the
case of the lock keeps 182 being visible on or from the exterior of
the cap 12, this can enable the lock keeps 182 to be used as a
visual alignment aid, should it be desired to align or key the
abutments 100 with the projections 102 in the mouth 52 of the tube
14 when initially fitting the cap 12 on to the tube 14.
[0260] In some embodiments, in the closed position, the cap 12 may
effect a liquid-tight seal at the mouth of the tube 14. Various
different seal configurations may be used as desired. In the
illustrated example, a very effective seal may be provided by a
depending annular seal lip (or wedge or wiper) 184 (FIG. 34) that
can engage the inner surface of the mouth of the tube 14.
[0261] Alternatively, or in addition, and applicable to any of the
examples described previously, some embodiments may further include
an annular member at the base of the cap that is partially secured
to the cap, such that removal of the cap after it has been screwed
onto the tube breaks the bond between the cap and the annular
member, thereby indicating that the tube has been opened. This
"tamper-evident" embodiment is similar to those used to attach a
cap to a soda bottle.
[0262] As described above, in some embodiments, the second cap
portion 22 may be configured to drop down at least partly into the
tube 14. When the device 10 subsequently is returned to a
laboratory for processing of the preserved sample, it may be
desirable to remove the second cap portion 22 in a manner that does
not interfere with the collected sample. As already described, the
second cap portion 22 may in some embodiments remain captively
coupled to the first cap portion 20 such that, when the first cap
portion 20 is removed to open the device 10, the second cap portion
22 may be withdrawn automatically with the first cap portion 20.
However, in other embodiments in which the second cap portion 22 is
not captively coupled, the second cap portion 22 may remain in the
tube 14 after removal of the first cap portion. The following
examples address how the second cap portion 22 may be retrieved
independently, without interfering with the collected sample.
[0263] Referring to FIGS. 39-41, in some embodiments, the second
cap portion 22 may carry or comprise a magnetic element 200. The
magnetic element 200 may, for example, be a magnet, or it may be of
material that is attractable by a magnet. Different mountings of
the magnetic element 200 are envisaged. For example, referring to
FIG. 39, the magnetic element 200 may be surface mounted on the
second cap portion 22, for example, in the cavity of a plug shaped
second cap portion 22. Alternatively, referring to FIG. 40, the
magnetic element 200 may be received in a suitable recess 202. The
profile of the cap 22 may optionally bulge to one side (shown at
204) to accommodate the recess 202 without requiring thinning of
the cap material. In a further alternative example of FIG. 41, the
magnetic element 200 may be embedded substantially entirely in the
material of the second cap portion, such that the magnetic element
200 has substantially no exposed surface.
[0264] FIG. 42 illustrates a retrieval tool 206 for use to retrieve
the second cap portion 22 of FIGS. 39-41. The retrieval tool 206
may comprise a handle 208 having a magnetic element 210 at one end
configured to magnetically attract the element 200 of the second
cap portion 22. By inserting the end of the tool 206 having the
magnetic element 210 into the tube 14, the second cap portion 22
can easily be magnetically hooked and retrieved, without
interfering with the preserved sample.
[0265] As an alternative to magnetic retrieval, a mechanical
gripping/hooking and retrieval are also envisaged. Various
mechanical arrangements may be used, for example, an "eye" and
"hook" system (not shown) in which the second cap portion is
provided with an open eye capable of being hooked by a suitable
hook provided on a retrieval tool.
[0266] FIGS. 43 and 44 illustrate an alternative mechanical
retrieval tool 220, including a deployable gripper 224 disposed
within a control sleeve 222. The gripper 224 may have distensible
and/or deployable gripper fingers 226. The fingers 226 may be
resiliently biased to a distended state (FIG. 44), but be radially
collapsible to a stowed state when constrained by the control
sleeve 222 (FIG. 43). The gripper 224 and/or the fingers 226 may be
of any suitable elastic or super-elastic material. In one example
use, the tool 220 is advanced in its collapsible condition (FIG.
43), towards a feature of the second cap portion 22. To deploy the
gripper 224, the control sleeve 222 may be retracted (as shown by
the arrows in the upper half of FIG. 44) and/or the gripper 224 may
be advanced relative to the sleeve 222. Once no longer constrained
by the sleeve 222, the fingers 226 are free to distend to engage
the feature of the second cap portion (as described below).
[0267] FIGS. 45 to 48 illustrates examples of second cap portion 22
that include a feature mechanically grippable by the retrieval tool
200. The feature may be a recess or hole 228 (for example a blind
hole) capable of being gripped by the fingers 226 when the
deployment end of the tool 220 is inserted into or positioned
adjacent to the hole 228, depending on the dimensions of the
fingers 226. The fingers 226 may distend into contact with the
sidewall of the hole 228, providing sufficient contact force to
enable the second cap portion 22 to be retrieved. In FIG. 45, the
hole 228 may be the or a cavity 230 on the underside of the plug
shape of the second cap portion 22. In FIG. 46, the hole 228 may be
a smaller recess in the floor of the cavity. In FIGS. 47 and 48,
plural holes 228 may be provided on opposite faces or sides of the
second cap portion 22 to permit retrieval whether the second cap
portion 22 is lying upside down or normally.
[0268] Referring to FIGS. 49 and 50, as previously described,
instead of the second cap portion 22 being free to separate
completely from the first cap portion 20, the first cap portion 20
may be provided be a cage 240 into which the first cap portion 22
may fall, while being retained captive and removable from the tube
14 with the first cap portion 20 when the first cap portion 20 is
removed to open the tube 14.
[0269] In the illustrated form, the cage 240 may comprise a
plurality of depending struts or members 242 configured in use to
depend from the inner wall 36 of the first cap portion, and a
plurality of transverse struts or members 244 that collectively
define a floor, or bottom supports, of the cage 240 on which the
second cap portion 22 may rest once the second cap portion 22 has
opened. In the illustrated form, the depending members 242 and the
transverse members 244 are integrally formed as L-shaped members.
The L-shaped members may be interconnected at the upper end of the
cage 240, to define a tubular shape of the cage 240.
[0270] The cage 240 may include apertures 245 through which the
abutments 100 of the second cap portion 22 may project to engage
the projections 102 defining the second engager 26 previously
described. The apertures 245 may, for example, be defined by spaces
between the depending members 242.
[0271] The cage 240 may optionally define the extent to which the
second cap portion 22 may separate from the inner wall 36 of the
first cap portion 20 when the second cap portion 22 is released.
FIG. 49 may illustrate a relatively shallow cage 24 limiting the
separation FIG. 50 may illustrate a deeper cage 240 permitting
greater separation. It will be appreciated that the dimension may
be varied according to design preference.
[0272] In some embodiments, the cage 240 may be produced separately
from the first cap portion 20, and be securable to the first cap
portion 10 either at the same time as fitting the second cap
portion 22 to seal the chamber, or thereafter. For example, the
cage 240 may clip to the first cap portion 10, or another securing
mechanism may be provided. In the illustrated form, the mouth of
the cage 240 is formed with a radially inwardly projecting undercut
246 which forms an interference fit with a circumferential groove
248 of the inner wall 36. The undercut 246 and the groove 248
optionally may have surfaces designed to permit easy assembly, but
to obstruct disassembly.
[0273] In order to permit expansion of the mouth of the cage 240 to
permit the undercut 246 to ride over the inner wall 36 to the
groove 248, at least one (optionally multiple or all) of depending
members 242 may be formed with axial slits or cuts 250.
[0274] In some embodiments, the cage 240 may be rotatable (e.g.
with the second cap portion 22) about the axis of the chamber. For
example, the cage 240 may be produced (e.g. molded) in its
as-fitted state. The slits 250 may permit temporary expansion of
the mouth of the cage 240 to assemble the cage 240 to the inner
wall 36, after which the cage 240 returns to its undeformed
state.
[0275] Alternatively, in some embodiments, the cage 240 may be
substantially non-rotatable (or rotation may be at least partly
resisted), by circumferential friction between the cage 240 and the
inner wall 36. For example, the cage 240 may be produced (e.g.
molded) in a slightly undersized state. The slits 250 may permit
forced expansion of the mouth of the cage 240 when assembling the
cage 240 to the inner wall 36. Once fitted, the cage 240 may remain
expanded, tending to squeeze against the groove 248 of the inner
wall 36 to produce circumferential friction that at least partly
resists, relative rotation with respect to the first cap portion
20.
[0276] Referring to FIG. 51, in some embodiments, the second cap
portion 22 may be provided with retainer arms 260 extending
upwardly to overlap the inner wall 36 around the chamber. The
retainer arms 260 may have barbs or abutments 262 which engage
behind a beaded lower edge 264 of the inner wall 36 when the second
cap portion 22 drops downwards. The second cap portion 22 may be
rotatable with respect to the first cap portion, but coupled or
retained captively to the first cap portion 20 by the retainer arms
260.
[0277] Referring to FIG. 52 in some embodiments, a bodily fluid
sample collection device 310 for the collection of naturally
expressed body fluids, generally comprises a cap 312 engageable
with a tube 314 to close a mouth 316 of the tube. The tube 314
defines at least partly a sample collection space 318 for receiving
the natural expressed bodily fluid. The device 310 (the cap 312 in
this embodiment, or optionally the tube in other embodiments)
comprises a chamber 320 for containing a reagent for mixing with a
collected sample. The cap comprises a first body 322 by which a
user manipulates the cap, and a second body 324 that is rotatably
mateable with the tube for securing the cap 312 to the tube 314. A
coupling (shown schematically at 326) between the first and second
bodies may be configured for (i) transmitting torque from the first
body to the second body for permitting rotation of the second body
to secure the second body to the tube, and (ii) permitting slippage
between the bodies after the second body has reached a fully
secured position. A mechanism (328a, 328b) is operable to cause the
chamber to be opened in response to manual rotation of the first
body at least after the second body has reached the fully secured
position.
[0278] The mechanism 328a, 328b may be operable to begin to cause
the chamber 320 to be opened only after the second body 324 has
reached the fully secured position, or the mechanism 328a, 328b may
be operable partly before the second body 324 has reached the fully
secured position. In either case, the second body 324 may reach the
fully secured position before the chamber 320 has been fully
opened. Further manual rotation of the first body 322 after the
second body 324 has reached the fully secured position, may open or
complete the opening of the chamber 320.
[0279] The second body 324 may be threadedly mateable with the tube
314, but other rotatably mateable couplings, such a bayonet
coupling, ma be used as desired.
[0280] In some embodiments, the coupling 326 may be a
torque-responsive coupling. In some embodiments, the coupling 326
may be a torque-limiting coupling that limits the amount of torque
transmissible from the first body 322 to the second body 324, and
permits relative slippage between the two bodies 322, 324 when the
torque exceeds a threshold. For example, during initial fitting
(e.g. screwing) of the cap 312, the second body 324 may rotate
relatively freely as it mates with the tube 314, and the applied
torque may be small. Once the second body 324 reaches a fully
secured position on the tube 314, it can no longer rotate relative
to the tube 314, and the applied torque will therefore increase.
The coupling 326 may be responsive to applied torque to permit the
first body 322 to slip with respect to the second body 324, thereby
permitting continued rotation of the first body 322 despite the
second body 324 no longer being able to rotate.
[0281] In some embodiments, the coupling may be responsive to the
direction of rotation, so as not to transmit significant torque
from the first body 322 to the second body 324 in a rotation
direction for releasing the second body 324.
[0282] In some embodiments, the coupling 326 may comprise a ratchet
and/or a clutch.
[0283] In some embodiments, the second body 324 may be
substantially shrouded by the first body 322, at least during
fitting of the cap 312 on the tube 314.
[0284] In some embodiments, the mechanism 328a, 328b for causing
opening of the chamber may be responsive to relative rotation
between the tube 314 and the first cap portion 322. Alternatively,
the mechanism for causing opening of the chamber may be responsive
to rotation between the first and second bodies.
[0285] Various mechanisms are envisaged. In one form, the chamber
320 may comprise an aperture closed by a closure 328a. The closure
may be a third body distinct from the first body 322, or it may be
integral with the first body 322. The closure 328a may be rotatable
relative to the chamber 320 to open the chamber 320. For example,
the closure 328a may be threadedly coupled to the chamber 320. In
some embodiments, the chamber 320 may be rotatable with the first
member 322. The mechanism 328a, 328b may operate to restrain the
closure 328a against rotation with respect to the tube 314 and/or
the second body. For example, the mechanism may comprise abutments
328b in the mouth 316 that engage projections of the closure 328a
to block rotation of the closure 328a. Rotation of the first body
322 may rotate the chamber 320, thereby generating relative
rotation between the chamber 320 and the closure 328a, to move the
closure 328a to an open condition with respect to the chamber
aperture.
[0286] Other types of mechanisms for opening the chamber may also
be used, for example, a piercing element that ruptures a frangible
film or wall of the chamber.
[0287] Referring to FIGS. 53 and 54, a further example of cap 212
is illustrated. The cap may be used with the tube of FIG. 52, or
with the tube of FIG. 57 described later, or with a tube as
illustrated in other drawings herein, or as described in the
aforementioned WO 2012/177656.
[0288] In FIGS. 53 and 54, the sample collection device (optionally
the cap 312 as shown in this embodiment, or optionally the tube in
other embodiments) comprises a chamber 320 for containing a reagent
for mixing with a collected sample. The device (optionally the cap
312 in this embodiment, or optionally the tube in other
embodiments) may further comprise a manually operable actuator 332
operable from outside the device at least once the cap has been
secured to the tube, for causing the chamber 320 to be opened in
response to manual actuation of the actuator 332.
[0289] In some embodiments, the device may optionally comprise a
lockout mechanism (not shown) for preventing actuation of the
actuator 332 before the cap 312 has been placed in a fully secured
position.
[0290] In some embodiments, the actuator 332 may be rotatable
and/or pressable and/or depressable.
[0291] In the illustrated form, the chamber 320 comprises a body
with a frangible wall 334. The actuator 332 comprises a plunger
with a tip 336 shaped for cutting or breaking the wall 334 when the
plunger is depressed (FIG. 54). Opening of the wall 334 permits the
reagent in the chamber 320 to mix with the collected bodily fluid
sample.
[0292] Referring to FIGS. 55 and 56, in some embodiments, the
device may be provided as part of a kit containing packaging
(depicted schematically at 340) in which the device is intended to
be placed for sending (e.g. by post) to a processing institution
for processing, analysis or research. The packaging 340 may be
configured to accept the device only in a condition in which the
actuator has been actuated to cause the chamber to be opened. For
example, the packaging 340 may include a predetermined space (e.g.
a well) that is dimensioned to receive the device only in such a
condition. The actuator may, for example, be depressable, whereby
an exterior dimension of the cap or tube becomes smaller. Prior to
depression (FIG. 55), the device may be too large to fit in the
predetermined space of the packaging 340. The projecting actuator
332 may make the device too tall to fit within the confines of the
packaging 340. Referring to FIG. 56, the device may only fit once
the actuator 332 has been fully depressed. Such an arrangement can
ensure that the user does not accidentally forget to operate the
actuator.
[0293] Referring to FIG. 57, a further example of tube 314 is
illustrated. Although not shown explicitly in FIG. 57, the tube 314
may be used with the cap of any of the preceding embodiments, or as
described in the aforementioned WO 2012/177656. The cap may be
secured to a mouth portion 316 of the tube 314 to seal the
collected bodily fluid sample closed. In some embodiments, the tube
314 defines at least partly a sample collection space 318 for
receiving the naturally expressed bodily fluid. The device
(optionally the cap, or optionally the tube) comprises a chamber
(not shown) for containing a reagent for mixing with a collected
sample.
[0294] In some embodiments, the mouth portion 316 may be separable
from a collection portion 342 of the tube 314, to facilitate
opening of the device after the cap has been secured. The
collection portion 342 of the tube may define the collection space
318. For example, the mouth portion 316 may be coupled to the
collection portion 342 by a threaded connection 344, or some other
mechanically separable connection, or by a frangible integral
connection.
[0295] The mouth portion 316 may flare towards an open end defining
a mouth of the tube, and/or narrow towards the collection portion.
The mouth portion 316 may optionally comprise the abutments 328b
(or other mechanism) for interacting with the chamber to cause the
chamber to be opened, although such abutments are not shown in FIG.
57 for clarity.
[0296] In some embodiments, the cap and the mouth portion together
comprise a mechanical or adhesive lock for locking the cap in its
fully secured condition once the cap has been closed. With an
arrangement as in FIG. 57, the ability to separate the mouth
portion 316 from the collection portion 342 of the tube 314 may
facilitate ease of access to the sample contents when the device is
received at a processing installation, while still obstructing
accidental reopening of the cap by the user having deposited a
sample.
[0297] Additionally or alternatively, in some embodiments, the cap
may comprise a closure for a chamber for containing reagent. The
closure may be configured to be opened when, or after, the cap may
be secured to the mouth portion, the closure dropping down into the
mouth portion 316 when the closure is opened. The mouth portion 316
may prevent the closure from dropping into the collection portion
342 of the tube. With such an arrangement, the ability to separate
the mouth portion 316 from the collection portion 342 of the tube
may facilitate easy access to the sample contents, without having
to manually retrieve the closure from the mouth portion. Instead,
by removing the mouth portion itself, the closure is removed with
the mouth portion.
[0298] Additionally or alternatively, in some embodiments, the
ability to separate the mouth portion 316 from the collection
portion 342 may enable the sample to be handled, processed or
stored in a relatively more compact form of the collection portion
342 absent a flared or funnel shaped mouth portion 316.
[0299] The sample collection devices according to some embodiments
can be made of any suitable plastics, such as polypropylene,
polystyrene and polycarbonate. The dimensions of the device can be
modified to suit the specific processing the sample will be
subjected to. In certain embodiments, typical dimensions include
the following. For the inner chamber of the cap, the volume is from
about 3 ml to about 10 ml, typically about 6 ml. For the lumen of
the tube, the volume is from about 15 ml to about 50 ml, typically
about 25 ml. Other volumes are within the scope of some embodiments
of the present disclosure.
[0300] In some embodiments, a solution for preserving cells in one
or more bodily fluids, such as saliva and urine, is disclosed. The
preservative solution may optionally be used in any of the
embodiments. The solution for preserving cells may be beneficial
for further separation into cell types and downstream molecular
analysis that allows for storage of cells in the body fluid to
retain their antigenicity and cellular architecture. The solution
may contain at least one chemical fixing agent, such as but not
limited to paraformaldehyde, and at least one protease inhibitor.
In some embodiments, the solution may further contain one or more
of at least one antimicrobial agent, and serum proteins from human
and/or other animal species. The solution can be buffered at a pH
from between about 6.4 to about 8.4, preferably from between about
7.2 to about 7.6.
[0301] For purposes of the disclosure, "preserving cells" means
preventing the cells from having their antigens degraded, such that
they can be purified or enriched based on their antigens, and
preventing alterations in the cellular epigenome. The "epigenome"
means the state or pattern of alteration of genomic DNA by covalent
modification of the DNA or of proteins bound to the DNA. Examples
of such alteration include methylation at the 5 position of
cytosine in a CpG dinucleotide, acetylation of lysine residues of
histones, the binding of proteins to the DNA to initiate
transcription (example: transcription factors) and other heritable
or non-heritable changes that do not result from changes in the
underlying DNA sequence.
[0302] In some embodiments, concentrations of agents in the
following description can be those of the sample preserving
solution itself. Depending upon the bodily fluid, and in the case
of saliva, about an equal volume of solution and body fluid can be
mixed together. This preferably results in the cells from the body
fluids retaining their antigenicity and DNA integrity for at least
one week at room temperature.
[0303] In some embodiments of the disclosure, the volume of
preservation solution held within the device and deployed may be
between about 100 and about 500 ml, which is relevant, for example,
for the preservation of cells in urine. As such, the preservation
solution for urine may be anywhere between about ten times
(10.times.) concentrated solution to a one-point five times
(1.5.times.) solution for urine.
[0304] A "chemical fixing agent", according to some embodiments, is
a chemical cross-linking compound used to alter cell components
such that the cells resist degradation. The chemical fixing agents
can also serve to cross-link histones and other DNA-binding
proteins to the DNA. Such agents may be known in the art and
include, without limitation, paraformaldehyde, formaldehyde,
formalin, aldehydes, alcohol, oxidizing agents, Mercurials,
Picrates, Hepes-glutamic acid buffer-mediated organic solvent
protection effect (HOPE), fixative combinations such as Zambonis
fixative, combinations of aldehydes, and synthetic cross-linking
reagents. In some embodiments, the chemical fixing agent is
paraformaldehyde. In some embodiments, the chemical fixing agent is
present at a concentration of about 1% (v/v).
[0305] To protect the cells from degradation by proteases present
in the body fluids, in some embodiments, the solution can contain
at least one protease inhibitor. In some embodiments, the protease
inhibitor can be selected from the group consisting of Aspartic
protease inhibitors, Cysteine protease inhibitors, Metalloprotease
inhibitors, Serine protease inhibitors (e.g., serpins), Threonine
protease inhibitors, Trypsin inhibitors, and Kunitz STI protease
inhibitor. Some specific, non-limiting, examples include sodium
azide, PMSF, Aprotinin, leupeptin, pepstatin, natural or synthetic
proteinase inhibitors, and cocktail mixtures of protease
inhibitors. Suitable concentrations of these inhibitors can
include, without limitation, PMSF (Phenylmethylsulfonyl fluoride)
Serine proteases at about 0.1-1 mM, Benzamidine Serine proteases at
about 1 mM, Pepstatin A Acid proteases at about 1 .mu.g/ml,
Leupeptin Thiol proteases at about 1 .mu.g/ml, Aprotinin Serine
proteases at about 5 .mu.g/ml, and Antipain Thiol proteases at
about 1 .mu.g/ml. In certain embodiments, the protease inhibitor is
sodium azide at a concentration of about 0.01% (w/v).
[0306] To prevent damage to the cells from microbial contamination,
some embodiments of the solution contain at least one antimicrobial
agent. Suitable antimicrobial agents include, without limitation,
antibacterial and antifungal antibiotics.
[0307] Preservation of cell architecture is enhanced by the
presence of serum proteins, which may optionally be added to the
solution in some embodiments. Additionally serum proteins may be
used to neutralize osmotic difference between cells and solution.
These can be from human or other animal sources. In some cases,
whole serum may be used. For example, fetal bovine serum may be
added, in some embodiments at about 1% (v/v).
[0308] The solution according to the present disclosure may include
any combination of the foregoing embodiments.
[0309] In some embodiments of the disclosure, a method for
preserving cells in one or more bodily fluids is disclosed. The
method for preserving the cells can comprise contacting the body
fluids with the solution according to the present disclosure. The
body fluids can contain a variety of cell types and the cells in
the body fluids can be preserved by the solution according to the
present disclosure. While not critical to the present disclosure, a
ratio of solution to body fluids of from about 1 to 1 is typically
used.
[0310] The following examples are intended to further illustrate
some embodiments of the solutions and methods for preserving cells
in body fluids and are not to be construed to limit the scope of
this disclosure.
[0311] For example, a solution of PBS pH 7.4, 1% Paraformaldehyde,
1% FBS, and 0.01% NaN3 can be added at a 1:1 ratio with saliva,
then T-cells can be purified and DNA extracted. The results of such
a process are shown in FIG. 8 of WO 2012/177656. These results can
demonstrate that the integrity of the antigenicity and DNA of
T-cells was maintained for at least one week.
[0312] As shown in the accompanying FIG. 58, further testing has
demonstrated the efficacy of the solution in preserving T-cells in
a saliva sample for extended durations, even at elevated
temperature, and even after an extended shelf life.
[0313] In FIG. 58, the vertical axis represents the number of
T-cells (in thousands) per ml of a saliva sample mixed with the
preservation solution in a 1:1 ratio, as determined by analysis.
The cell concentration is effectively halved compared to the
original saliva sample, as a result of the 1:1 mix with the
preservation solution.
[0314] The first (leftmost) column indicates the number of cells in
three samples stored a room temperature for a few hours after
sample collection and mixing with the preservation solution. The
first column acts as a benchmark for assessing the cell numbers in
other samples.
[0315] The second, third and fourth columns compare the number of
cells in three groups of three samples each, stored at room
temperature for a day, two days and 1 month, respectively, after
sample collection and mixing with the preservation solution. The
second to third columns show very little variation with each other
or with the first column.
[0316] The fifth, sixth, seventh and eighth columns compare the
number of cells in groups of ten samples each, stored for a period
of three months after sample collection and mixing with the
preservative solution, kept respectively at 4.degree. C., room
temperature, 30.degree. C. and 40.degree. C. Ten samples (instead
of three samples) were used, because the test was focused on
long-term preservation. The fifth to eight columns show very little
variation with each other or with the first column.
[0317] The final column repeats the test for the second column,
using a sample group of ten samples, and using a preservation
solution that has been stored (pre-use shelf-term) for 4 months. As
above, ten samples (instead of three samples) were used, because
the test was focused on demonstrating extended shelf life.
[0318] The graph illustrates that the preservative solution is
highly effective, to preserve T-cells in a saliva solution for an
extended duration, over a wide range of temperature conditions, and
even after an extended shelf-term. The solution may have a similar
or corresponding preservation capability for other types of cells.
The deviation amongst the cell numbers in the different columns can
be explained at least by the usual differences in cell numbers from
different people donating the samples and/or different samples even
from the same person. The number of cells per ml is also eminently
satisfactory for permitting downstream cell analysis.
[0319] Further information regarding the construction and use of
the sample collection device, preservative solution, and downstream
analysis may be found in the aforementioned WO 2012/177656 already
incorporated herein by reference in its entirety.
[0320] FIG. 59 depicts one manner in which sample collection
devices (optionally as described herein) may be used to provide a
flexible technique for sample collection from, for example, home
based donors. The diagram depicts how a researcher or diagnostic
professional wishing to conduct cell diagnosis, epigenetic research
or other analysis may be able to benefit from a procedure enabling
sample collection devices to be supplied, collected and
processed
[0321] At step 80, a supply company may provide sample collection
kits including, for example, a tube 14, a cap 12, and instructions
for use. The kits may be supplied to the researcher or diagnosis
professional upon request. At step 82, the researcher/diagnosis
professional may send individual kits to individual donors, for
example, by post or other delivery technique. Each donor may
collect a sample of naturally expressed bodily fluid within the
tube (step 84), and close the tube by fitting the cap (step 86).
The step of fitting the cap releases the reagent within the tube to
preserve cells within the collected sample. The donor may collect
the sample in a home environment. The bodily fluid may, for
example, be saliva.
[0322] After closing the tube, the donor returns the sample
collection device, for example, by post or by other delivery
technique. In some embodiments, the donor may return the device
directly to the supply company (step 88), or via the
researcher/diagnosis professional as an intermediary (step 90). In
the latter case, the researcher/diagnosis professional may collect
returned samples from multiple donors, and forward these in batches
to the supply company.
[0323] The supply company processes the returned devices by
removing the preserved sample from the tube (step 92), isolating
cells from the sample (step 94), and preparing the cells for
sending to the researcher (step 96). The step of removing the
sample from the tube may optionally comprise using automated
machinery to open the sample collection device and extract the
sample. The step of isolating the cells may optionally include any
of the techniques described in the aforementioned WO 2012/177656.
The step 96 of preparing the cells may optionally include freezing
the cells.
[0324] At step 98, the prepared cells may be sent to the
researcher/diagnosis professional for research, diagnosis or
analysis, for example, epigenetic research or analysis.
[0325] In some embodiments, a serial number system may be used for
identifying each sample collection device, and its associated
bodily fluid sample. For example, each sample collection device may
be assigned a serial number. The serial number may optionally be
assigned during manufacture of the sample collection device. The
serial number may, for example, be printed on one or more (or all)
components of the sample collection device during manufacture, or
on a label affixed to the sample collection device. Alternatively,
the serial number may be assigned by the researcher while
processing the kits before sending to individual donors at step 82.
During processing of the collected samples (steps 92-96), the
samples may be identified by the serial number of the collection
device. The same serial number may be used to identify the isolated
and prepared cells finally returned to the researcher for step
98.
[0326] It will be appreciated that the foregoing description is
merely illustrative of preferred embodiments of the disclosed
inventions, and that many improvements, alternatives and/or
equivalents may be used.
[0327] By way of example only, a non-limiting hierarchical summary
of certain features in some embodiments is as follows:
[0328] Item/Embodiment:
[0329] An embodiment represented in a bodily fluid sample
collection device for the collection of naturally expressed bodily
fluids, comprising a cap engageable with a tube to close a mouth of
the tube, the cap comprising a first cap portion defining at least
partly a chamber for containing a reagent, and the tube defining at
least partly a sample collection space for receiving the naturally
expressed bodily fluid; wherein the cap further comprises a second
cap portion defining a closure for closing an aperture
communicating with the chamber, the second cap portion being
configured, in use responsive to fitting the cap to the tube, to
disengage from the first cap portion, and descend at least partly
into the tube.
[0330] The device of embodiment 1, wherein the first and second cap
portions are relatively movable with respect to each other, the
first and second cap portions being configured such that,
responsive to engagement of the cap on the tube, one of the cap
portions is caused to move relative to the other cap portion to
open the chamber and permit fluid communication between the chamber
and the sample collection space, whereby a reagent in the chamber
is permitted to mix with the bodily fluid in the sample collection
space.
[0331] The device of embodiment 2, wherein the second cap portion
is configured, upon relative movement with respect to the first cap
portion, to translate in a direction towards the sample collection
space in response to the relative movement between the first and
second cap portions.
[0332] An embodiment represented in a bodily fluid sample
collection device for the collection of naturally expressed bodily
fluids comprising a cap engageable with a tube to close a mouth of
the tube, the cap comprising a chamber for containing a reagent,
and the tube defining at least partly a sample collection space for
receiving the naturally expressed bodily fluid; wherein the cap
comprises first and second cap portions relatively movable with
respect to each other, the first and second cap portions being
configured such that, responsive to engagement of the cap on the
tube, one of the cap portions is caused to move relative to the
other cap portion to open the chamber and permit fluid
communication between the chamber and the sample collection space,
whereby a reagent in the chamber is permitted to mix with the
bodily fluid in the sample collection space; and wherein the second
cap portion is configured to translate in a direction towards the
sample collection space in response to the relative movement
between the first and second cap portions.
[0333] The device of embodiment 2, 3 or 4, wherein the first and
second cap portions are configured such that, responsive to
engagement of the cap on the tube, one of the cap portions is
caused to move integrally relative to the other cap portion.
[0334] The device of any preceding embodiment, wherein the second
cap portion is integrally coupled to, or captively coupled to, or
integral with, the first cap portion.
[0335] The device of embodiment 7, wherein the second cap portion
is coupled to the first cap portion by a tether.
[0336] The device of embodiment 7 or 8, wherein the first cap
portion is provided with a cage for retaining the second cap
portion captively coupled to the first cap portion.
[0337] The device of embodiment 9, wherein the cage is rotatable
with respect to the first cap portion.
[0338] The device of any preceding embodiment, wherein the tube
comprises a support for preventing the second cap portion from
dropping into the sample collection space.
[0339] The device of any preceding embodiment, wherein the tube has
a sample collection portion having a smaller interior
cross-sectional area than at a mouth for receiving a cap for
closing the device.
[0340] The device of embodiment 12, wherein the cross-section area
of the sample collection space is too small to accommodate the
second cap portion, whereby the second cap portion is obstructed
from dropping down into the sample collection space.
[0341] The device of embodiment 12 or 13, wherein the sample
collection portion has a shape selected from: columnar; annular;
toroid.
[0342] The device of any preceding embodiment, wherein the sample
collection portion bears at least one mark indicating sample volume
and/or a fill level.
[0343] The device of any preceding embodiment, wherein the cap is
securable to a mouth portion of the tube, the mouth portion being
separable from a collection portion the tube, to facilitate opening
of the device after the cap has been secured.
[0344] The device of embodiment 16, wherein the cap is a separate
body from the mouth portion, and securable thereto to close the
mouth portion.
[0345] The device according to any preceding embodiment, wherein
the second cap portion comprises or is provided with a feature for
permitting retrieval of the second cap portion from a dropped down
position in the tube.
[0346] The device according to embodiment 18, wherein feature is a
magnetic element.
[0347] The device according to embodiment 86 or 87, wherein the
feature is a blind hole.
[0348] The device of any preceding embodiment, and configured to
provide to the user a first signal indicative of the chamber having
been opened, and a second signal indicative of the cap having
reached a closed and/or locked position.
[0349] An embodiment represented in an apparatus comprising
[0350] a bodily fluid sample collection device for the collection
of naturally expressed bodily fluids, the device comprising a cap
engageable with a tube to close a mouth of the tube, the cap
comprising a chamber for containing a reagent, and the tube
defining at least partly a sample collection space for receiving
the naturally expressed bodily fluid; wherein the cap comprises
first and second cap portions configured such that, responsive to
engagement of the cap on the tube, one of the cap portions is
caused to drop down into the tube and thereby open the chamber and
permit fluid communication between the chamber and the sample
collection space, whereby a reagent in the chamber is permitted to
mix with the bodily fluid in the sample collection space: and a
retrieval tool for retrieving the second cap portion from the tube
once the first cap portion has been subsequently removed to open
the device to access the collected sample.
[0351] A retrieval tool for retrieving a second cap portion from a
bodily fluid sample collection device of a type comprising a tube
having a mouth closed by a first cap portion, the tube containing a
second cap portion that has at least partly separated from the
first cap portion, and the tube containing a preserved sample of
bodily fluid, the retrieval tool comprising a magnetic and/or
mechanical feature for engaging the second cap portion, for
retrieving the second cap portion from the tube once the first cap
portion has been removed, to permit access to the sample of bodily
fluid.
[0352] The retrieval tool of embodiment 23, wherein the tool
comprises a plurality of distensible fingers for mechanically
engaging a blind hole of the second cap portion.
[0353] The retrieval tool of embodiment 24, wherein the tool
comprises a tubular stem in which a gripper member is reciprocally
movable, the gripper member comprising the distensible fingers.
[0354] A bodily fluids sample collection device for the collection
of naturally expressed bodily fluids comprising a cap engageable
with a tube to close a mouth of the tube, the cap comprising a
chamber for containing a reagent, and the tube defining at least
partly a sample collection space for receiving the naturally
expressed bodily fluid; the device being configured to open the
chamber responsive to engagement of the cap on the tube, for
allowing the reagent to enter the sample collection space: and
wherein the device is configured to provide to the user a first
signal indicative of the chamber having been opened, and a second
signal indicative of the cap having reached a closed and/or locked
position.
[0355] The device of embodiment 21 or 26, wherein the first signal
comprises any one or a combination of two or more of: a visual
signal, an audible signal, a tactile signal.
[0356] The device of embodiment 21, 26 or 27, wherein the second
signal comprises any one or a combination of two or more of: a
visual signal, an audible signal, a tactile signal.
[0357] The device of embodiment 21, 26, 27 or 28, wherein the cap
comprises first and second cap portions together defining at least
partly the chamber, wherein the second cap portion is configured to
drop at least partly into the tube to open the chamber, and the
first signal is provided by the dropping down of the second cap
portion.
[0358] The device of any of embodiments 21 or 26 to 29, wherein the
cap further comprises a lock device engageable upon the cap
reaching a fully closed position of the tube, the lock device
configured for locking the cap in the fully closed position, and
wherein the second signal is generated by operation of the lock
device.
[0359] The device of any of embodiments 1 to 21, or 26 to 29,
wherein the second cap portion comprises at least a portion having
a top-hat shape, comprising a cup portion defining a cavity, and a
flange encircling the cup portion.
[0360] An embodiment represented in a bodily fluid sample
collection device for the collection of naturally expressed bodily
fluids comprising a cap engageable with a tube to close a mouth of
the tube, the cap comprising a chamber for containing a reagent,
and the tube defining at least partly a sample collection space for
receiving the naturally expressed bodily fluid; wherein the cap
comprises first and second cap portions configured such that,
responsive to engagement of the cap on the tube, one of the cap
portions is caused to move relative to the other cap portion to
open the chamber and permit fluid communication between the chamber
and the sample collection space, whereby a reagent in the chamber
is permitted to mix with the bodily fluid in the sample collection
space; wherein the second cap portion comprises at least a portion
having a top-hat shape, comprising a cup portion defining a cavity,
and a flange encircling the cup portion.
[0361] The device of embodiment 31 or 32, wherein the second cap
portion carries a thread on a radially outwardly facing surface,
for engaging a radially inwardly facing thread of the first cap
portion.
[0362] The device of embodiment 31, 32 or 33, wherein the cup
portion is configured for entering the open end of the chamber for
closing the chamber.
[0363] The device of any or embodiments 1 to 21 or 26 to 34,
wherein a first amount of rotation to fully secure the cap to the
tube is not more than three turns, and wherein a second amount of
rotation between the first and second cap portions to open the
chamber is less than the first amount of rotation.
[0364] An embodiment represented in a bodily fluid sample
collection device for the collection of naturally expressed bodily
fluids comprising a cap threadedly engageable with a tube to close
a mouth of the tube, the cap comprising a chamber for containing a
reagent, and the tube defining at least partly a sample collection
space for receiving the naturally expressed bodily fluid; wherein
the cap comprises first and second cap portions threadedly coupled
together and configured such that, responsive to engagement of the
cap on the tube, one of the cap portions is caused to move
rotatably relative to the other cap portion to open the chamber and
permit fluid communication between the chamber and the sample
collection space, whereby a reagent in the chamber is permitted to
mix with the bodily fluid in the sample collection space, wherein a
first amount of rotation to fully secure the cap to the tube is not
more than three turns, and wherein a second amount of rotation
between the first and second cap portions to open the chamber is
less than the first amount of rotation.
[0365] The device of embodiment 35 or 36, wherein the first amount
of rotation is at least one selected from: not more than two and a
half turns; not more than two turns not more than one and a half
turns; not more than one turn.
[0366] The device of embodiment 35, 36 or 37, wherein the second
amount of rotation is at least one selected from: mot more than one
turn; not more than three-quarters of a turn; not more than half a
turn; not more than a quarter of a turn.
[0367] The device of embodiment 35, 36, 37 or 38, wherein the
second amount of rotation comprises a first angular segment for an
engager of the tube to cooperate with the second cap portion to
restrain the second cap portion against rotation with respect to
the tube, and a second angular segment for the threaded coupling
between the first and second cap portions to unscrew.
[0368] The device of embodiment 39, wherein the first angular
segment is selected from: not more than about a quarter of a turn,
or not more than about half a turn; and the second angular segment
is selected from: not more than about a quarter of a turn, or nor
more than about half a turn.
[0369] The device of any of embodiments 1 to 21 or 26 to 40,
wherein the cap comprises a cap shell and a self-contained chamber
module assembled to the cap shell, the self-contained chamber
module defining the chamber.
[0370] An embodiment represented in a bodily fluid sample
collection device, optionally according to any of embodiments 1 to
21 or 26 to 41, the device for the collection of naturally
expressed bodily fluids comprising a cap engageable with a tube to
close a mouth of the tube, the tube defining at least partly a
sample collection space for receiving the naturally expressed body
fluid, the device (optionally the cap, or optionally the tube)
further comprising a chamber for containing a reagent for mixing
with a collected sample; wherein the cap comprises a first body by
which a user manipulates the cap, a second body that is rotatably
mateable with the tube for securing the cap to the tube and a
coupling between the first and second bodies configured for (i)
transmitting torque from the first body to the second body for
permitting rotation of the second body to secure the second body to
the tube, and (ii) permitting slippage between the bodies after the
second body has reached a fully secured position; the device
further comprising a mechanism operable to cause the chamber to be
opened in response to manual rotation of the first body at least
after the second body has reached the fully secured position.
[0371] The device of embodiment 42, wherein the mechanism is
operable to begin to cause the chamber to be opened only after the
second body has reached the fully secured position.
[0372] The device of embodiment 42, wherein the mechanism is
operable partly before the second body has reached the fully
secured position.
[0373] An embodiment represented in a bodily fluid sample
collection device, optionally according to any of embodiments 1 to
21 or 26 to 44, the device for the collection of naturally
expressed bodily fluids comprising a cap engageable with a tube to
close a mouth of the tube, the tube defining at least partly a
sample collection space for receiving the naturally expressed body
fluid, the device comprising a chamber for containing a reagent for
mixing with a collected sample; wherein the device further
comprises a manually operable actuator operable from outside the
device at least once the cap has been secured to the tube, for
causing the chamber to be opened in response to manual actuation of
the actuator.
[0374] The device of embodiment 45, wherein the chamber is disposed
at a position selected from: on the cap; or on the tube.
[0375] The device of embodiment 45 or 46, wherein the manually
operable actuator is disposed at a position selected from: on the
cap; or on the tube.
[0376] An embodiment represented in an apparatus comprising: a
device according to embodiment 47; and packaging in which the
device is intended to be placed, the packaging configured to accept
the device only in a condition in which the actuator has been
actuated to cause the chamber to be opened.
[0377] A bodily fluid sample collection device, optionally
according to any of embodiments 1 to 21 or 26 to 47, the device
comprising a tube, and a cap securable to a mouth portion of the
tube, the tube defining at least partly a sample collection space
for receiving the naturally expressed body fluid, and the device
comprising a chamber for containing a reagent for mixing with a
collected sample; wherein the mouth portion is separable from a
collection portion the tube, to facilitate opening of the device
after the cap has been secured.
[0378] The device of embodiment 49, wherein the chamber is disposed
at a position selected from: on the cap; or on the tube.
[0379] The device of embodiment 49 or 50, further comprising a lock
mechanism for obstructing removal of the cap once the cap has been
fitted to the mouth portion of the tube.
[0380] The device of embodiment 49, 50 or 51, wherein the cap is a
separate body from the mouth portion, and securable thereto to
close the mouth portion.
[0381] A bodily fluid sample collection device, optionally
according to any of embodiments 1 to 21, or 26 to 47, or 49 to 52,
the device for the collection of naturally expressed bodily fluids
comprising a cap engageable with a tube to close a mouth of the
tube, the cap comprising a first cap portion defining at least
partly a chamber for containing a reagent, and the tube defining at
least partly a sample collection space for receiving the naturally
expressed bodily fluid: wherein the cap further comprises a second
cap portion defining a closure for closing an aperture at a lower
end of the chamber, the second cap portion having a cup shape.
[0382] The device of embodiment 53, wherein the second cap portion
is configured to disengage from the first cap portion responsive to
fitting the cap to the tube.
[0383] A bodily fluid sample collection device, optionally
according to any of embodiments 1 to 21, or 26 to 47, or 49 to 54,
the device for the collection of naturally expressed bodily fluids
comprising a cap engageable with a tube to close a mouth of the
tube, the cap comprising a chamber for containing a reagent, and
the tube defining at least partly a sample collection space for
receiving the naturally expressed bodily fluid; wherein the cap
comprises first and second cap portions relatively rotatable with
respect to each other, the first and second cap portions being
configured such that, responsive to engagement of the cap on the
tube, one of the cap portions is caused to rotate relative to the
other cap portion to break the integrity of a frangible wall
portion of the chamber, to open the chamber and permit fluid
communication between the chamber and the sample collection space,
whereby a reagent in the chamber is permitted to mix with the
bodily fluid in the sample collection space.
[0384] A bodily fluid sample collection device, optionally
according to any of embodiments 1 to 21, or 26 to 47, or 49 to 55,
the device for the collection of naturally expressed bodily fluids,
comprising a cap engageable with a tube to close a mouth of the
tube, the device further comprising a chamber for containing a
reagent, and the tube defining at least partly a sample collection
space for receiving the naturally expressed bodily fluid; wherein
the chamber is defined at least partly by a variable volume and/or
shape chamber unit having a frangible wall portion; in use the
chamber is at least partly deformed in response to fitting the cap
to the tube, such that the integrity of the frangible wall portion
is broken, allowing the contents of the chamber to be dispensed
into the sample collection space.
[0385] The device of embodiment 56, further comprising a piercing
element for breaking the integrity of the frangible wall portion
upon the frangible wall portion contacting the piercing element in
response to deformation of the chamber.
[0386] The device of embodiment 57, wherein the piercing element is
provided inside the chamber.
[0387] The device of embodiment 56, 57, or 58, wherein the variable
volume and/or shape chamber unit comprises at least one selected
from: a bladder; a bellows; an accordion.
[0388] The device of any of embodiments 56 to 59, wherein in use
the chamber is at least partly deformed by compression of the
chamber in at least one direction, in response to fitting the cap
to the tube.
[0389] A bodily fluid sample collection device, optionally
according to any of embodiments 1 to 21, or 26 to 47, or 49 to 60,
the device for the collection of naturally expressed bodily fluids
comprising a cap engageable with a tube to close a mouth of the
tube, the cap comprising a chamber for containing a reagent, and
the tube defining at least partly a sample collection space for
receiving the naturally expressed bodily fluid: wherein the cap
comprises first and second cap portions joined by a frangible wall
portion, the first and second cap portions and the frangible wall
portion together defining at least partly the chamber and being
integrally molded together, the cap configured such that,
responsive to engagement of the cap on the tube, one of the cap
portions is caused to move relative to the other cap portion to
break the frangible wall portion and thereby open the chamber and
permit fluid communication between the chamber and the sample
collection space, whereby a reagent in the chamber is permitted to
mix with the bodily fluid in the sample collection space.
[0390] A bodily fluid sample collection device, optionally
according to any of embodiments 1 to 21, or 26 to 47, or 49 to 61,
the device for the collection of naturally expressed bodily fluids
comprising a cap engageable with a tube to close a mouth of the
tube, the cap comprising a chamber for containing a reagent, and
the tube defining at least partly a sample collection space for
receiving the naturally expressed bodily fluid; wherein the cap
comprises first and second cap portions joined by a weld or
adhesive bond, the first and second cap portions together defining
at least partly the chamber and being integrally molded together,
the cap configured such that, responsive to engagement of the cap
on the tube, one of the cap portions is caused to move relative to
the other cap portion to break the weld or adhesive bond and
thereby open the chamber and permit fluid communication between the
chamber and the sample collection space, whereby a reagent in the
chamber is permitted to mix with the bodily fluid in the sample
collection space.
[0391] The device according to any of embodiments 1 to 21, or 26 to
47, or 49 to 62, further comprising a second chamber for containing
a second reagent separately from the reagent of the first
chamber.
[0392] A bodily fluid sample collection device for the collection
of naturally expressed bodily fluids, comprising a cap engageable
with a tube to close a mouth of a tube, the device further
comprising a plurality of chambers for containing reagents or
reagent components separately from one another, and an opener for
opening the chambers to dispense the contents of the chambers into
a sample collection space of the tube when the cap is fitted to
close the mouth of the tube.
[0393] The device of embodiment 63 or 64, wherein the opener is
configured to cause opening of one chamber before another, to
define sequential release of the chambers' contents into the sample
collection space.
[0394] The device of embodiment 63 or 64, wherein the opener is
configured to cause substantially simultaneous opening of one
chamber before another, to define substantially simultaneous
release of the chambers' contents into the sample collection
space.
[0395] The device of embodiment 63, 64, 65 or 66, wherein at least
one, and optionally first and second, of the plurality of chambers
is or are provided in the cap.
[0396] The device of embodiment 63, 64, 65, 66 or 67, wherein the
opener comprises at least one cap portion configured to move
relative to another cap portion when the cap is engaged to the
mouth of the tube.
[0397] A bodily fluid sample collection device, optionally
according to any of embodiments 1 to 21, or 26 to 47, or 49 to 68,
the device for the collection of naturally expressed bodily fluids
comprising a cap engageable with a tube to close a mouth of the
tube, the cap comprising a chamber for containing a reagent, and
the tube defining at least partly a sample collection space for
receiving the naturally expressed bodily fluid; wherein the cap
comprises first and second cap portions relatively movable with
respect to each other, the first and second cap portions being
configured such that, responsive to engagement of the cap on the
tube, one of the cap portions is caused to move integrally relative
to the other cap portion to open the chamber and permit fluid
communication between the chamber and the sample collection space,
whereby a reagent in the chamber is permitted to mix with the
bodily fluid in the sample collection space.
[0398] A bodily fluid sample collection device, optionally
according to any of embodiments 1 to 21, or 26 to 47, or 49 to 69,
the device for the collection of naturally expressed bodily fluids
comprising a cap engageable with a tube to close a mouth of the
tube, the cap comprising a chamber for containing a reagent, and
the tube defining at least partly a sample collection space for
receiving the naturally expressed bodily fluid; wherein the cap
comprises first and second cap portions configured such that,
responsive to engagement of the cap on the tube, one of the cap
portions is caused to move relative to the other cap portion to
open the chamber and permit fluid communication between the chamber
and the sample collection space, whereby a reagent in the chamber
is permitted to mix with the bodily fluid in the sample collection
space.
[0399] The device of embodiment 69 or 70, wherein the first and
second cap portions are rotatably movable with respect to each
other.
[0400] The device of embodiment 71, wherein the first and second
cap portions are threadedly coupled together.
[0401] The device of any of embodiments 69 to 72, wherein the cap
is rotatably engageable on the tube.
[0402] The device of embodiment 73, wherein the cap is threadedly
engageable on the tube.
[0403] The device of any of embodiments 69 to 74, wherein the first
and second cap portions are rotatable about an axis that is
generally parallel with an axis about which the cap is rotatable
when fastening the cap to the tube.
[0404] The device of embodiment 75, wherein the axes are generally
coincident.
[0405] The device of any of embodiments 69 to 76, wherein the tube
comprises a first engager for engagement by the first cap portion,
and a second engager for engagement by the second cap portion.
[0406] The device of embodiment 77, wherein the first engager
comprises a component of a threaded coupling.
[0407] The device of embodiment 77 or 78, wherein the second
engager comprises a restrainer for restraining the second cap
portion from relative rotation with respect to the tube.
[0408] The device of embodiment 77, 78 or 79, wherein in use one of
the first and second engagers is configured to engage a respective
cap portion before the other engager engages its respective cap
portion, said other engager engaging its respective cap portion
after relative movement between the cap and the tube.
[0409] The device of embodiment 80, wherein the second engager is
configured to be keyed to engage the second cap portion before
engagement between the first engager and the first cap portion.
[0410] The device of embodiment 80, wherein the second engager is
configured to engage the second cap portion after the first cap
portion has been fitted to engage the first engager.
[0411] The device of embodiment 77, 78 or 79, wherein the first and
second engagers are configured to engage the respective cap
portions generally simultaneously during engagement of the cap with
the tube.
[0412] The device of any of embodiments 69 to 83, wherein the tube
is configured to engage the first and second cap portions such
that, during fastening of the cap to the tube, one of the first and
second cap portions is at least partly restrained against movement
relative to the tube while the other cap portion moves relative to
the tube.
[0413] The device of any of embodiments 69 to 84, wherein the first
and second cap portions are coupled together by a coupling which
causes or permits relative axial displacement between the cap
portions responsive to relative rotation.
[0414] The device of any of embodiments 69 to 85, wherein the
second cap portion is releasable from the first cap portion to open
the chamber.
[0415] The device of any of embodiments 69 to 85, wherein the
second cap portion is integrally coupled to, or captively coupled
to, or integral with, the first cap portion.
[0416] The device of embodiment 87, wherein the second cap portion
is coupled to the first cap portion by a tether.
[0417] The device of embodiment 87 or 88, wherein the first cap
portion is provided with a cage for retaining the second cap
portion captively coupled to the first cap portion.
[0418] The device of embodiment 89, wherein the cage is rotatable
with respect to the first cap portion.
[0419] The device of any of embodiments 69 to 90, wherein the
second cap portion comprises a closure for closing an aperture of
the chamber.
[0420] The device of embodiment 91, wherein the second cap portion
has or comprises a generally cup-shape.
[0421] The device of embodiment 91 or 92, wherein the chamber has
an open lower end.
[0422] The device of embodiment 91, 92 or 93, wherein at least a
portion of the second cap portion drops into or towards the sample
collection space of the tube when the second cap portion is
disengaged from the first cap portion.
[0423] The device of any of embodiments 69 to 94, wherein the
second cap portion is configured to translate in a direction
towards the sample collection space in response to the relative
movement between the first and second cap portions.
[0424] The device of any of embodiments 69 to 95, wherein the
second cap portion is configured, upon relative movement with
respect to the first cap portion, to break the integrity of a
frangible wall portion of the chamber, to open the chamber.
[0425] The device of embodiment 96, wherein the frangible wall
portion comprises material selected from: plastics; metal; a
plastics/metal laminate.
[0426] The device of embodiment 96 or 97, wherein the frangible
wall portion is an integral wall portion joining the first and
second cap portions.
[0427] The device of embodiment 96, 97 or 98, wherein the second
cap portion comprises a piercing and/or cutting element for
breaking the integrity of the frangible wall portion.
[0428] The device of any of embodiments % to 99, wherein the
frangible wall portion is selected as one or more of: a blister
defining the chamber; a closure sealed to close an aperture of the
chamber; an integral part of at least one of the cap portions: a
foil welded or glued at an aperture of the chamber.
[0429] The device of any of embodiments % to 100, wherein the
chamber is defined by a variable volume and/or shape chamber unit
having at least one movable wall portion.
[0430] The device of embodiment 101, wherein the frangible wall
portion is a wall portion of the variable volume and/or shape
chamber unit.
[0431] The device of embodiment 101, wherein the frangible wall
portion is a said movable wall portion of the variable volume
and/or shape chamber unit.
[0432] The device of any of embodiments 101 to 103, wherein the
variable volume and/or shape chamber unit comprises at least one
selected from: a bladder; a bellows; an accordion.
[0433] The device of any of embodiments 101 to 104, further
comprising a cutting and/or piercing element for breaking the
integrity of the frangible wall portion.
[0434] The device of embodiment 105, wherein the cutting and/or
piercing element for breaking the integrity of the frangible wall
portion is provided inside the variable volume and/or shape chamber
unit.
[0435] The device of embodiment 105 or 106, wherein the cutting
and/or piercing element is configured to break the integrity of the
movable wall portion of the variable volume and/or shape chamber
unit when the movable wall portion moves in response to compression
of the chamber.
[0436] The device of any of embodiments 69 to 107, wherein the
first and second cap portions are joined by adhesive or welding,
the join being configured to break in response to said relative
movement between the first and second cap portions when the cap is
engaged on the tube.
[0437] The device of any of embodiments 69 to 107, wherein the cap
comprises a cap shell and a self-contained chamber module assembled
to the cap shell, the self-contained chamber module defining the
chamber.
[0438] The device of any of embodiments 69 to 108, and configured
to provide to the user a first signal indicative of the chamber
having been opened, and a second signal indicative of the cap
having reached a closed and/or locked position.
[0439] The device of embodiment 109, wherein at least one of the
first and second signals comprises any one or a combination of two
or more of: a visual signal, an audible signal, a tactile
signal.
[0440] The device of embodiment 109 or 110, wherein the first
signal is generated by dropping down of the second cap portion at
least partly into the tube.
[0441] The device of embodiment 109, 110 or 111, wherein the second
signal is generated by engagement of a lock mechanism operative to
lock the cap in a fully closed condition.
[0442] The device of embodiment 112, wherein the lock mechanism
comprises at least one selected from: a latch; a ratchet.
[0443] The device of any of embodiments 69 to 113, wherein the tube
has a sample collection portion having a smaller interior
cross-sectional area than at a mouth for receiving a cap for
closing the device.
[0444] The device of embodiment 114, wherein the sample collection
portion bears at least one mark indicating sample volume and/or a
fill level.
[0445] The device of embodiment 114 or 115, wherein the sample
collection portion has a shape selected from: columnar; annular;
toroid.
[0446] The device of embodiment 114, 115 or 116, wherein the
interior cross-sectional area of the sample collection portion is
sufficiently small that it prevents the second cap portion from
entering the sample collection portion.
[0447] The device of any of embodiments 69 to 117, wherein the
reagent comprises a preservation solution.
[0448] The device of any of embodiments 69 to 118, further
comprising a second chamber for containing a second reagent
separately from the reagent of the first chamber.
[0449] The device of embodiment 119, wherein the second chamber is
configured to be opened in use by one or more of relative movement
of the second cap portion; relative movement of a third cap
portion.
[0450] The device of embodiment 119 or 120, wherein the second
chamber is configured to be opened substantially at the same time
as the first chamber, or in sequence before or after opening of the
first chamber.
[0451] An embodiment represented in a solution for preserving cells
in bodily fluid for further separation into cell types and
downstream epigenetic analysis that allows for storage of cells in
bodily fluid to retain their antigenicity and cellular
architecture, the solution comprising at least one chemical fixing
agent and at least one protease inhibitor, buffered at a pH from
about 6.4 to about 8.4, wherein the solution is effective to
preserve cells for a duration of at least 1 week.
[0452] The solution of embodiment 122, wherein the solution is
effective to preserve cells for a duration selected from: at least
two weeks; or at least three weeks, or at least a month, or at
least two months; or at least three months.
[0453] The solution of embodiment 122 or 123, wherein the solution
is effective to preserve cells when kept at a temperature selected
as at least one of the following temperatures or temperature
ranges: between 4.degree. C. and 40.degree. C.; between 4.degree.
C. and 30.degree. C.; about room temperature; about 4.degree. C.;
about 30.degree. C.; about 40.degree. C.
[0454] The solution of embodiment 122, 123 or 124, wherein the
solution has a shelf-life selected from at least one of the
following: at least 1 month; at least two months: at least three
months; at least four months.
[0455] The solution of embodiment 125, wherein the shelf-life is
shelf-life at room temperature.
[0456] The solution of any of embodiments 122 to 126, wherein the
solution is effective to preserve at least a predetermined
percentage of cells from an original sample of the body fluid, the
predetermined percentage being selected from: at least 50%, at
least 55%, at least 60%, at least 65%, at least 70%, at least 75%,
at least 80%, at least 85%, at least 90%, at least 95%.
[0457] The solution of any of embodiments 122 to 127, wherein a
number of preserved cells or a predetermined type, per ml is at
least about 5000, or at least about 10000, or at least about
12000.
[0458] The solution of any of embodiments 122 to 128, wherein the
cells are T-cells.
[0459] The solution according to any of embodiments 122 to 129,
further comprising one or more of at least one antimicrobial agent
and serum proteins from human and/or other animal species.
[0460] The solution according to any of embodiments 122 to 130,
wherein the chemical fixing agent is selected from the group
consisting of aldehydes.
[0461] The solution according to embodiment 131, wherein the
chemical fixing agent is paraformaldehyde.
[0462] The solution according to any of embodiments 122 to 132,
wherein the chemical fixing agent is present at a concentration of
about 1% (v/v).
[0463] The solution according to any of embodiments 122 to 133,
wherein the antimicrobial agent is selected from the group
consisting of antibacterial and antifungal antibiotics.
[0464] The solution according to any of embodiments 122 to 134,
wherein the protease inhibitor is selected from the group
consisting of: Aspartic protease inhibitors, Cysteine protease
inhibitors, Metallo protease inhibitors, Serine protease
inhibitors, Threonine protease inhibitors, Trypsin inhibitors,
Kunitz STI protease inhibitor and a combination of any of the
foregoing.
[0465] The solution according to any of embodiments 122 to 135,
wherein the protease inhibitor is selected from the group
consisting of: sodium azide, PMSF, aprotinin, leupeptin, pepstatin,
natural or synthetic proteinase inhibitors, mixtures of protease
inhibitors both natural and synthetic, and any combination of the
foregoing.
[0466] The solution according to any of embodiments 122 to 136,
wherein the protease inhibitor is sodium azide.
[0467] The solution according to any of embodiments 122 to 137,
wherein the solution is buffered at a pH of from about 7.2 to about
7.6.
[0468] The solution according to any of embodiments 122 to 138,
wherein the buffer is selected from the group consisting of:
barbital, trisphosphate, citrate, cacodylate, other non-phosphate
buffers and any combination of the foregoing.
[0469] The solution according to any of embodiments 122 to 139,
wherein the buffer is a phosphate buffer.
[0470] A method for preserving cells in a naturally expressed
bodily fluid comprising contacting the bodily fluid with the
preservation solution according to any of embodiments 122 to
140.
[0471] A sample collection device, optionally according to any of
embodiments 1 to 21, or 26 to 47, or 49 to 121, the device for
collection of a naturally expressed bodily fluid, the sample
collection device containing a preservation solution according to
any of embodiments 122 to 140.
[0472] A sample collection kit including a solution as defined in
any of embodiments 122 to 140.
[0473] A sample collection kit including a sample collection device
as defined in any of embodiments 1 to 21, or 26 to 47, or 49 to
121.
[0474] The kit of embodiment 143 or 144 for collection of a bodily
fluid sample from which cells and/or DNA may be isolated for
analysis.
[0475] The kit of embodiment 145, further comprising a reagent in
the device, the reagent configured to preserve cells and/or cell
components.
[0476] Use of a device as defined in any of embodiments 1 to 21, or
26 to 47, or 49 to 121, for collecting a bodily fluid sample for
analysis of cells or cellular components, the analysis selected
from: genetics; epigenetics, diagnostics; or other purposes.
[0477] An embodiment represented in a method comprising: providing
at least one sample collection kit for collecting a naturally
expressed sample of bodily fluid, the kit optionally according to
any of embodiments 143 to 146, the sample collection kit comprising
a sample collection device and instructions for use, the sample
collection device comprising a tube, a cap engageable with the tube
to close a mouth of the tube, and a preservative for preserving
cells of the donated bodily fluid sample, the preservative being
contained in a chamber of the device that is configured to be
opened automatically upon fitting the cap to the tube, to release
the preservative into the tube; shipping the at least one sample
collection kit: receiving at least one sample collection device
contained a bodily fluid sample; extracting the bodily fluid sample
from the collection device: processing the sample to isolate cells
for epigenetic analysis or diagnostic purpose; and preparing the
isolated cells for shipping.
[0478] The method of embodiment 148 wherein the collected bodily
fluid is saliva.
[0479] The method of embodiment 148 or 149, wherein the step of
preparing the isolated cells comprises freezing the cells.
[0480] A bodily fluid sample collection device for the collection
of naturally expressed bodily fluids comprising a cap engageable
with a tube to close a mouth of the tube, the cap comprising a
chamber for containing a reagent, and the tube defining at least
partly a sample collection space for receiving the naturally
expressed bodily fluid; wherein the cap comprises first and second
cap portions relatively movable with respect to each other, the
first and second cap portions being configured such that,
responsive to engagement of the cap on the tube, one of the cap
portions is caused to move integrally relative to the other cap
portion to open the chamber and permit fluid communication between
the chamber and the sample collection space, whereby a reagent in
the chamber is permitted to mix with the bodily fluid in the sample
collection space.
[0481] A bodily fluid sample collection device for the collection
of naturally expressed bodily fluids comprising a cap engageable
with a tube to close a mouth of the tube, the cap comprising a
chamber for containing a reagent, and the tube defining at least
partly a sample collection space for receiving the naturally
expressed bodily fluid; wherein the cap comprises first and second
cap portions configured such that, responsive to engagement of the
cap on the tube, one of the cap portions is caused to move relative
to the other cap portion to open the chamber and permit fluid
communication between the chamber and the sample collection space,
whereby a reagent in the chamber is permitted to mix with the
bodily fluid in the sample collection space.
[0482] The device of embodiment 151 or 152, wherein the first and
second cap portions are rotatably movable with respect to each
other.
[0483] The device of embodiment 153, wherein the first and second
cap portions are threadedly coupled together.
[0484] The device of any of embodiments 151 to 154, wherein the cap
is rotatably engageable on the tube.
[0485] The device of embodiment 155, wherein the cap is threadedly
engageable on the tube.
[0486] The device of any of embodiments 151 to 156, wherein the
first and second cap portions are rotatable about an axis that is
generally parallel with an axis about which the cap is rotatable
when fastening the cap to the tube.
[0487] The device of embodiment 157, wherein the axes are generally
coincident.
[0488] The device of any of embodiments 151 to 158, wherein the
tube comprises a first engager for engagement by the first cap
portion, and a second engager for engagement by the second cap
portion.
[0489] The device of embodiment 159, wherein the first engager
comprises a component of a threaded coupling.
[0490] The device of embodiment 159 or 160, wherein the second
engager comprises a restrainer for restraining the second cap
portion from relative rotation with respect to the tube.
[0491] The device of embodiment 159, 160 or 161, wherein in use one
of the first and second engagers is configured to engage a
respective cap portion before the other engager engages its
respective cap portion, said other engager engaging its respective
cap portion after relative movement between the cap and the
tube.
[0492] The device of embodiment 162, wherein the second engager is
configured to be keyed to engage the second cap portion before
engagement between the first engager and the first cap portion.
[0493] The device of embodiment 162, wherein the second engager is
configured to engage the second cap portion after the first cap
portion has been fitted to engage the first engager.
[0494] The device of embodiment 159, 160 or 161, wherein the first
and second engagers are configured to engage the respective cap
portions generally simultaneously during engagement of the cap with
the tube.
[0495] The device of any of embodiments 151 to 165 wherein the tube
is configured to engage the first and second cap portions such
that, during fastening of the cap to the tube, one of the first and
second cap portions is at least partly restrained against movement
relative to the tube while the other cap portion moves relative to
the tube.
[0496] The device of any of embodiments 151 to 166, wherein the
first and second cap portions are coupled together by a coupling
which causes or permits relative axial displacement between the cap
portions responsive to relative rotation.
[0497] The device of any of embodiments 151 to 167, wherein the
second cap portion is releasable from the first cap portion to open
the chamber.
[0498] The device of any of embodiments 151 to 167, wherein the
second cap portion is integrally coupled to, or captively coupled
to, or integral with, the first cap portion.
[0499] The device of embodiment 169, wherein the second cap portion
is coupled to the first cap portion by a tether.
[0500] The device of embodiment 169 or 170, wherein the first cap
portion is provided with a cage for retaining the second cap
portion captively coupled to the first cap portion.
[0501] The device of embodiment 171, wherein the cage is rotatable
with respect to the first cap portion.
[0502] The device of any of embodiments 151 to 172, wherein the
second cap portion comprises a closure for closing an aperture of
the chamber.
[0503] The device of embodiment 173, wherein the second cap portion
has or comprises a generally cup-shape.
[0504] The device of embodiment 173 or 174, wherein the chamber has
an open lower end.
[0505] The device of embodiment 173, 174 or 175, wherein at least a
portion of the second cap portion drops into or towards the sample
collection space of the tube when the second cap portion is
disengaged from the first cap portion.
[0506] The device of any of embodiments 151 to 176, wherein the
second cap portion is configured to translate in a direction
towards the sample collection space in response to the relative
movement between the first and second cap portions.
[0507] The device of any of embodiments 151 to 177, wherein the
second cap portion is configured, upon relative movement with
respect to the first cap portion, to break the integrity of a
frangible wall portion of the chamber, to open the chamber.
[0508] The device of embodiment 178, wherein the frangible wall
portion comprises material selected from: plastics; metal; a
plastics/metal laminate.
[0509] The device of embodiment 178 or 179, wherein the frangible
wall portion is an integral wall portion joining the first and
second cap portions.
[0510] The device of embodiment 178, 179 or 180, wherein the second
cap portion comprises a piercing and/or cutting element for
breaking the integrity of the frangible wall portion.
[0511] The device of any of embodiments 178 to 181, wherein the
frangible wall portion is selected as one or more of: a blister
defining the chamber: a closure sealed to close an aperture of the
chamber; an integral part of at least one of the cap portions; a
foil welded or glued at an aperture of the chamber.
[0512] The device of any of embodiments 178 to 182, wherein the
chamber is defined by a variable volume and/or shape chamber unit
having at least one movable wall portion.
[0513] The device of embodiment 183, wherein the frangible wall
portion is a wall portion of the variable volume and/or shape
chamber unit.
[0514] The device of embodiment 182, wherein the frangible wall
portion is a said movable wall portion of the variable volume
and/or shape chamber unit.
[0515] The device of any of embodiments 183 to 185, wherein the
variable volume and/or shape chamber unit comprises at least one
selected from: a bladder; a bellows; an accordion.
[0516] The device of any of embodiments 183 to 186, further
comprising a cutting and/or piercing element for breaking the
integrity of the frangible wall portion.
[0517] The device of embodiment 187, wherein the cutting and/or
piercing element for breaking the integrity of the frangible wall
portion is provided inside the variable volume and/or shape chamber
unit.
[0518] The device of embodiment 187 or 188, wherein the cutting
and/or piercing element is configured to break the integrity of the
movable wall portion of the variable volume and/or shape chamber
unit when the movable wall portion moves in response to compression
of the chamber.
[0519] The device of any of embodiments 151 to 189, wherein the
first and second cap portions are joined by adhesive or welding,
the join being configured to break in response to said relative
movement between the first and second cap portions when the cap is
engaged on the tube.
[0520] The device of any of embodiments 151 to 190, wherein the cap
comprises a cap shell and a self-contained chamber module assembled
to the cap shell, the self-contained chamber module defining the
chamber.
[0521] The device of any of embodiments 151 to 191, and configured
to provide to the user a first signal indicative of the chamber
having been opened, and a second signal indicative of the cap
having reached a closed and/or locked position.
[0522] The device of embodiment 192, wherein at least one of the
first and second signals comprises any one or a combination of two
or more of: a visual signal, an audible signal, a tactile
signal.
[0523] The device of embodiment 192 or 193, wherein the first
signal is generated by dropping down of the second cap portion at
least partly into the tube.
[0524] The device of embodiment 192, 193 or 194, wherein the second
signal is generated by engagement of a lock mechanism operative to
lock the cap in a fully closed condition.
[0525] The device of embodiment 195, wherein the lock mechanism
comprises at least one selected from: a latch; a ratchet.
[0526] The device of any of embodiments 151 to 196, wherein the
tube has a sample collection portion having a smaller interior
cross-sectional area than at a mouth for receiving a cap for
closing the device.
[0527] The device of embodiment 197, wherein the sample collection
portion bears at least one mark indicating sample volume and/or a
fill level.
[0528] The device of embodiment 197 or 198, wherein the sample
collection portion has a shape selected from: columnar; annular;
toroid.
[0529] The device of embodiment 197, 198 or 199, wherein the
interior cross-sectional area of the sample collection portion is
sufficiently small that it prevents the second cap portion from
entering the sample collection portion.
[0530] The device of any of embodiments 151 to 200, wherein the
reagent comprises a preservation solution.
[0531] The device of any of embodiments 151 to 201, further
comprising a second chamber for containing a second reagent
separately from the reagent of the first chamber.
[0532] The device of embodiment 202, wherein the second chamber is
configured to be opened in use by one or more of: relative movement
of the second cap portion; relative movement of a third cap
portion.
[0533] The device of embodiment 202 or 203, wherein the second
chamber is configured to be opened substantially at the same time
as the first chamber, or in sequence before or after opening of the
first chamber.
[0534] An embodiment represented in a bodily fluid sample
collection device for the collection of naturally expressed bodily
fluids comprising a cap engageable with a tube to close a mouth of
the tube, the cap comprising a first cap portion defining at least
partly a chamber for containing a reagent, and the tube defining at
least partly a sample collection space for receiving the naturally
expressed bodily fluid; wherein the cap further comprises a second
cap portion defining a closure for closing an aperture
communicating with the chamber, the second cap portion being
configured, in use responsive to fitting the cap to the tube, to
disengage from the first cap portion, and descend at least partly
into the tube.
[0535] A bodily fluid sample collection device for the collection
of naturally expressed bodily fluids comprising a cap engageable
with a tube to close a mouth of the tube, the cap comprising a
first cap portion defining at least partly a chamber for containing
a reagent, and the tube defining at least partly a sample
collection space for receiving the naturally expressed bodily
fluid; wherein the cap further comprises a second cap portion
defining a closure for closing an aperture at a lower end of the
chamber, the second cap portion having a cup shape, and optionally
being configured to disengage from the first cap portion responsive
to fitting the cap to the tube.
[0536] A bodily fluid sample collection device for the collection
of naturally expressed bodily fluids comprising a cap engageable
with a tube to close a mouth of the tube, the cap comprising a
chamber for containing a reagent, and the tube defining at least
partly a sample collection space for receiving the naturally
expressed bodily fluid; wherein the cap comprises first and second
cap portions relatively rotatable with respect to each other, the
first and second cap portions being configured such that,
responsive to engagement of the cap on the tube, one of the cap
portions is caused to rotate relative to the other cap portion to
break the integrity of a frangible wall portion of the chamber, to
open the chamber and permit fluid communication between between the
chamber and the sample collection space, whereby a reagent in the
chamber is permitted to mix with the bodily fluid in the sample
collection space.
[0537] An embodiment represented in a bodily fluid sample
collection device for the collection of naturally expressed bodily
fluids comprising a cap engageable with a tube to close a mouth of
the tube, the cap comprising a chamber for containing a reagent,
and the tube defining at least partly a sample collection space for
receiving the naturally expressed bodily fluid; wherein the tube
has a sample collection portion having a smaller interior
cross-sectional area than at a mouth for receiving a cap for
closing the device.
[0538] The device of embodiment 208, wherein the sample collection
portion bears at least one mark indicating sample volume and/or a
fill level.
[0539] The device of embodiment 208 or 209, wherein the sample
collection portion has a shape selected from: columnar; annular;
toroid.
[0540] An embodiment represented in a bodily fluid sample
collection device for the collection of naturally expressed bodily
fluids, comprising a cap engageable with a tube to close a mouth of
a tube, the device further comprising a plurality of chambers for
containing reagents or reagent components separately from one
another, and an opener for opening the chambers to dispense the
contents of the chambers into a sample collection space of the tube
when the cap is fitted to close the mouth of the tube.
[0541] The device of embodiment 211, wherein the opener is
configured to cause opening of one chamber before another, to
define sequential release of the chambers' contents into the sample
collection space.
[0542] The device of embodiment 211, wherein the opener is
configured to cause substantially simultaneous opening of one
chamber before another, to define substantially simultaneous
release of the chambers' contents into the sample collection
space.
[0543] The device of embodiment 211, 212 or 213, wherein at least
one, and optionally first and second, of the plurality of chambers
is or are provided in the cap.
[0544] The device of embodiment 211, 212, 213 or 214, wherein the
opener comprises at least one cap portion configured to move
relative to another cap portion when the cap is engaged to the
mouth of the tube.
[0545] An embodiment represented in a bodily fluid sample
collection device for the collection of naturally expressed bodily
fluids, comprising a cap engageable with a tube to close a mouth of
the tube, the device further comprising a chamber for containing a
reagent, and the tube defining at least partly a sample collection
space for receiving the naturally expressed bodily fluid; wherein
the chamber is defined at least partly by a variable volume and/or
shape chamber unit having a frangible wall portion; in use the
chamber is at least partly deformed in response to fitting the cap
to the tube, such that the integrity of the frangible wall portion
is broken, allowing the contents of the chamber to be dispensed
into the sample collection space.
[0546] The device of embodiment 216, further comprising a piercing
element for breaking the integrity of the frangible wall portion
upon the frangible wall portion contacting the piercing element in
response to deformation of the chamber.
[0547] The device of embodiment 217, wherein the piercing element
is provided inside the chamber.
[0548] The device of embodiment 216, 217, or 218, wherein the
variable volume and/or shape chamber unit comprises at least one
selected from: a bladder; a bellows; an accordion.
[0549] The device of any of embodiments 216 to 219, wherein in use
the chamber is at least partly deformed by compression of the
chamber in at least one direction, in response to fitting the cap
to the tube.
[0550] An embodiment represented in a bodily fluid sample
collection device for the collection of naturally expressed bodily
fluids comprising a cap engageable with a tube to close a mouth of
the tube, the cap comprising a chamber for containing a reagent,
and the tube defining at least partly a sample collection space for
receiving the naturally expressed bodily fluid; wherein the cap
comprises first and second cap portions joined by a frangible wall
portion, the first and second cap portions and the frangible wall
portion together defining at least partly the chamber and being
integrally molded together, the cap configured such that,
responsive to engagement of the cap on the tube, one of the cap
portions is caused to move relative to the other cap portion to
break the frangible wall portion and thereby open the chamber and
permit fluid communication between the chamber and the sample
collection space, whereby a reagent in the chamber is permitted to
mix with the bodily fluid in the sample collection space.
[0551] An embodiment represented in a bodily fluid sample
collection device for the collection of naturally expressed bodily
fluids comprising a cap engageable with a tube to close a mouth of
the tube, the cap comprising a chamber for containing a reagent,
and the tube defining at least partly a sample collection space for
receiving the naturally expressed bodily fluid: wherein the cap
comprises first and second cap portions joined by a weld or
adhesive bond, the first and second cap portions together defining
at least partly the chamber and being integrally molded together,
the cap configured such that, responsive to engagement of the cap
on the tube, one of the cap portions is caused to move relative to
the other cap portion to break the weld or adhesive bond and
thereby open the chamber and permit fluid communication between the
chamber and the sample collection space, whereby a reagent in the
chamber is permitted to mix with the bodily fluid in the sample
collection space.
[0552] An embodiment represented in a bodily fluids sample
collection device for the collection of naturally expressed bodily
fluids comprising a cap engageable with a tube to close a mouth of
the tube, the cap comprising a chamber for containing a reagent,
and the tube defining at least partly a sample collection space for
receiving the naturally expressed bodily fluid; the device being
configured to open the chamber responsive to engagement of the cap
on the tube, for allowing the reagent to enter the sample
collection space; and wherein the device is configured to provide
to the user a first signal indicative of the chamber having been
opened, and a second signal indicative of the cap having reached a
closed and/or locked position.
[0553] The device of embodiment 223, wherein the first signal
comprises any one or a combination of two or more of: a visual
signal, an audible signal, a tactile signal.
[0554] The device of embodiment 223 or 224, wherein the second
signal comprises any one or a combination of two or more of: a
visual signal, an audible signal, a tactile signal.
[0555] The device of embodiment 223, 224 or 225, wherein the cap
comprises first and second cap portions together defining at least
partly the chamber, wherein the second cap portion is configured to
drop at least partly into the tube to open the chamber, and the
second signal is provided by the dropping down of the second cap
portion.
[0556] The device of any of embodiments 222 to 226, wherein the cap
further comprises a lock device engageable upon the cap reaching a
fully closed position of the tube, the lock device configured for
locking the cap in the fully closed position, and wherein the
second signal is generated by operation of the lock device.
[0557] An embodiment represented in a bodily fluid sample
collection device for the collection of naturally expressed bodily
fluids comprising a cap threadedly engageable with a tube to close
a mouth of the tube, the cap comprising a chamber for containing a
reagent, and the tube defining at least partly a sample collection
space for receiving the naturally expressed bodily fluid; wherein
the cap comprises first and second cap portions threadedly coupled
together and configured such that, responsive to engagement of the
cap on the tube, one of the cap portions is caused to move
rotatably relative to the other cap portion to open the chamber and
permit fluid communication between the chamber and the sample
collection space, whereby a reagent in the chamber is permitted to
mix with the bodily fluid in the sample collection space, wherein a
first amount of rotation to fully secure the cap to the tube is not
more than three turns, and wherein a second amount of rotation
between the first and second cap portions to open the chamber is
less than the first amount of rotation.
[0558] The device of embodiment 228, wherein the first amount of
rotation is at least one selected from: not more than two and a
half turns; not more than two turns; not more than one and a half
turns: not more than one turn.
[0559] The device of embodiment 228 or 229, wherein the second
amount of rotation is at least one selected from: mot more than one
turn; not more than three-quarters of a turn; not more than half a
turn; not more than a quarter of a turn.
[0560] The device of embodiments 228, 229 or 230, wherein the
second amount of rotation comprises a first angular segment for an
engager of the tube to cooperate with the second cap portion to
restrain the second cap portion against rotation with respect to
the tube, and a second angular segment for the threaded coupling
between the first and second cap portions to unscrew.
[0561] The device of embodiment 231, wherein the first angular
segment is selected from: not more than about a quarter of a turn,
or not more than about half a turn; and the second angular segment
is selected from: not more than about a quarter of a turn, or nor
more than about half a turn.
[0562] An embodiment represented in a bodily fluid sample
collection device for the collection of naturally expressed bodily
fluids comprising a cap engageable with a tube to close a mouth of
the tube, the cap comprising a chamber for containing a reagent,
and the tube defining at least partly a sample collection space for
receiving the naturally expressed bodily fluid; wherein the cap
comprises first and second cap portions configured such that,
responsive to engagement of the cap on the tube, one of the cap
portions is caused to move relative to the other cap portion to
open the chamber and permit fluid communication between the chamber
and the sample collection space, whereby a reagent in the chamber
is permitted to mix with the bodily fluid in the sample collection
space; wherein the second cap portion comprises at least a portion
having a top-hat shape, comprising a cup portion defining a cavity,
and a flange encircling the cup portion.
[0563] The device of embodiment 233, wherein the second cap portion
carries a thread on a radially outwardly facing surface, for
engaging a radially inwardly facing thread of the first cap
portion.
[0564] The device of embodiment 233, wherein the cup portion is
configured for entering the open end of the chamber for closing the
chamber.
[0565] The device according to any preceding embodiment, wherein
the second cap portion comprises or is provided with a feature for
permitting retrieval of the second cap portion from a dropped down
position in the tube.
[0566] The device according to embodiment 236, wherein feature is a
magnetic element.
[0567] The device according to embodiment 236 or 237, wherein the
feature is a blind hole.
[0568] An embodiment represented in an apparatus comprising a
bodily fluid sample collection device for the collection of
naturally expressed bodily fluids, the device comprising a cap
engageable with a tube to close a mouth of the tube, the cap
comprising a chamber for containing a reagent, and the tube
defining at least partly a sample collection space for receiving
the naturally expressed bodily fluid; wherein the cap comprises
first and second cap portions configured such that, responsive to
engagement of the cap on the tube, one of the cap portions is
caused to drop down into the tube and thereby open the chamber and
permit fluid communication between the chamber and the sample
collection space, whereby a reagent in the chamber is permitted to
mix with the bodily fluid in the sample collection space: and a
retrieval tool for retrieving the second cap portion from the tube
once the first cap portion has been subsequently removed to open
the device to access the collected sample.
[0569] An embodiment represented in a retrieval tool for retrieving
a second cap portion from a bodily fluid sample collection device
of a type comprising a tube having a mouth closed by a first cap
portion, the tube containing a second cap portion that has at least
partly separated from the first cap portion, and the tube
containing a preserved sample of bodily fluid, the retrieval tool
comprising a magnetic and/or mechanical feature for engaging the
second cap portion, for retrieving the second cap portion from the
tube once the first cap portion has been removed, to permit access
to the sample of bodily fluid.
[0570] The retrieval tool of embodiment 240, wherein the tool
comprises a plurality of distensible fingers for mechanically
engaging a blind hole of the second cap portion.
[0571] The retrieval tool of embodiment 241, wherein the toll
comprises a tubular stem in which a gripper member is reciprocally
movable, the gripper member comprising the distensible fingers.
[0572] An embodiment represented in a method comprising: providing
at least one sample collection kit for collecting a naturally
expressed sample of bodily fluid, the sample collection kit
comprising a sample collection device and instructions for use, the
sample collection device comprising a tube, a cap engageable with
the tube to close a mouth of the tube, and a preservative for
preserving cells of the donated bodily fluid sample, the
preservative being contained in a chamber of the device that is
configured to be opened automatically upon fitting the cap to the
tube, to release the preservative into the tube; shipping the at
least one sample collection kit: receiving at least one sample
collection device contained a bodily fluid sample; extracting the
bodily fluid sample from the collection device; processing the
sample to isolate cells for epigenetic analysis or diagnostic
purpose; and preparing the isolated cells for shipping.
[0573] The method of embodiment 243 wherein the collected bodily
fluid is saliva.
[0574] The method of embodiment 243 or 244, wherein the step of
preparing the isolated cells comprises freezing the cells.
[0575] An embodiment represented in a bodily fluid sample
collection device for the collection of naturally expressed bodily
fluids comprising a cap engageable with a tube to close a mouth of
the tube, the tube defining at least partly a sample collection
space for receiving the naturally expressed body fluid, the device
(optionally the cap, or optionally the tube) further comprising a
chamber for containing a reagent for mixing with a collected
sample; wherein the cap comprises a first body by which a user
manipulates the cap, a second body that is rotatably mateable with
the tube for securing the cap to the tube and a coupling between
the first and second bodies configured for (i) transmitting torque
from the first body to the second body for permitting rotation of
the second body to secure the second body to the tube, and (ii)
permitting slippage between the bodies after the second body has
reached a fully secured position: the device further comprising a
mechanism operable to cause the chamber to be opened in response to
manual rotation of the first body at least after the second body
has reached the fully secured position.
[0576] The device of embodiment 246, wherein the mechanism is
operable to begin to cause the chamber to be opened only after the
second body has reached the fully secured position.
[0577] The device of embodiment 246, wherein the mechanism is
operable partly before the second body has reached the fully
secured position.
[0578] An embodiment represented in a bodily fluid sample
collection device for the collection of naturally expressed bodily
fluids comprising a cap engageable with a tube to close a mouth of
the tube, the tube defining at least partly a sample collection
space for receiving the naturally expressed body fluid, the device
(optionally the cap, or optionally the tube) comprising a chamber
for containing a reagent for mixing with a collected sample;
wherein the device (optionally the cap, or optionally the tube)
further comprises a manually operable actuator operable from
outside the device at least once the cap has been secured to the
tube, for causing the chamber to be opened in response to manual
actuation of the actuator.
[0579] An embodiment represented in apparatus comprising: a device
according to embodiment 249; and packaging in which the device is
intended to be placed, the packaging configured to accept the
device only in a condition in which the actuator has been actuated
to cause the chamber to be opened.
[0580] An embodiment represented in a bodily fluid sample
collection device comprising a tube, and a cap securable to a mouth
portion of the tube, the tube defining at least partly a sample
collection space for receiving the naturally expressed body fluid,
and the device (optionally the cap, or optionally the tube)
comprising a chamber for containing a reagent for mixing with a
collected sample: wherein the mouth portion is separable from a
collection portion the tube, to facilitate opening of the device
after the cap has been secured.
[0581] The device of embodiment 251, wherein the cap is a separate
body from the mouth portion, and securable thereto to close the
mouth portion.
[0582] An embodiment represented in a kit for collection of a
bodily fluid sample from which cells and/or DNA may be isolated for
analysis, the kit comprising apparatus or device as defined in any
preceding embodiment.
[0583] The kit of embodiment 253, further comprising a reagent in
the device, the reagent configured to preserve cells and/or cell
components.
[0584] Use of a sample bodily fluid sample collection device as
defined in any of embodiments 246 to 249, 250 or 251, for
collecting of a bodily fluid sample for analysis of cells or
cellular components, the analysis selected from: genetics;
epigenetics; diagnostics; or other purposes.
[0585] An embodiment represented in a solution for preserving cells
in bodily fluid for further separation into cell types and
downstream epigenetic analysis that allows for storage of cells in
bodily fluid to retain their antigenicity and cellular
architecture, the solution comprising at least one chemical fixing
agent and at least one protease inhibitor, buffered at a pH from
about 6.4 to about 8.4, wherein the solution is effective to
preserve cells for a duration of at least 1 week.
[0586] The solution of embodiment 256, wherein the solution is
effective to preserve cells for a duration selected from: at least
two weeks; or at least three weeks, or at least a month, or at
least two months; or at least three months.
[0587] The solution of embodiment 256 or 257, wherein the solution
is effective to preserve cells when kept at a temperature selected
as at least one of the following temperatures or temperature
ranges: between 4.degree. C. and 40.degree. C.; between 4.degree.
C. and 30.degree. C.; about room temperature; about 4.degree. C.;
about 30.degree. C.; about 40.degree. C.
[0588] The solution of embodiment 256, 257 or 258, wherein the
solution has a shelf-life selected from at least one of the
following: at least 1 month; at least two months; at least three
months; at least four months.
[0589] The solution of embodiment 259, wherein the shelf-life is
shelf-life at room temperature.
[0590] The solution of any of embodiments 256 to 260, wherein the
solution is effective to preserve at least a predetermined
percentage of cells from an original sample of the body fluid, the
predetermined percentage being selected from: at least 50%, at
least 55%, at least 60%, at least 65%, at least 70%, at least 75%,
at least 80%, at least 85%, at least 90%, at least 95%.
[0591] The solution of any of embodiments 256 to 261, wherein a
number of preserved cells or a predetermined type, per ml is at
least about 5000, or at least about 10000, or at least about
12000.
[0592] The solution of any of embodiments 256 to 262, wherein the
cells are T-cells.
[0593] The solution according to any of embodiments 256 to 263,
further comprising one or more of at least one antimicrobial agent
and serum proteins from human and/or other animal species.
[0594] The solution according to any of embodiments 256 to 264,
wherein the chemical fixing agent is selected from the group
consisting of aldehydes.
[0595] The solution according to embodiment 265, wherein the
chemical fixing agent is paraformaldehyde.
[0596] The solution according to any of embodiments 256 to 266,
wherein the chemical fixing agent is present at a concentration of
about 1% (v/v).
[0597] The solution according to any of embodiments 256 to 267,
wherein the antimicrobial agent is selected from the group
consisting of antibacterial and antifungal antibiotics.
[0598] The solution according to any of embodiments 256 to 268,
wherein the protease inhibitor is selected from the group
consisting of: Aspartic protease inhibitors, Cysteine protease
inhibitors, Metallo protease inhibitors, Serine protease
inhibitors, Threonine protease inhibitors, Trypsin inhibitors,
Kunitz STI protease inhibitor and a combination of any of the
foregoing.
[0599] The solution according to any of embodiments 256 to 269,
wherein the protease inhibitor is selected from the group
consisting of: sodium azide. PMSF, aprotinin, leupeptin, pepstatin,
natural or synthetic proteinase inhibitors, mixtures of protease
inhibitors both natural and synthetic, and any combination of the
foregoing.
[0600] The solution according to any of embodiments 256 to 270,
wherein the protease inhibitor is sodium azide.
[0601] The solution according to any of embodiments 256 to 271,
wherein the solution is buffered at a pH of from about 7.2 to about
7.6.
[0602] The solution according to any of embodiments 256 to 272,
wherein the buffer is selected from the group consisting of:
barbital, trisphosphate, citrate, cacodylate, other non-phosphate
buffers and any combination of the foregoing.
[0603] The solution according to any of embodiments 256 to 273,
wherein the buffer is a phosphate buffer.
[0604] An embodiment represented in a method for preserving cells
in a naturally expressed bodily fluid comprising contacting the
bodily fluid with the preservation solution according to any of
embodiments 256 to 274.
[0605] A sample collection device for collection of a naturally
expressed bodily fluid, the sample collection device containing a
preservation solution according to any of embodiments 256 to
274.
[0606] A sample collection kit including a solution as defined in
any of embodiments 256 to 274.
[0607] Any and all references to publications or other documents,
including but not limited to, patents, patent applications,
articles, webpages, books, etc., presented anywhere in the present
application, are herein incorporated by reference in their
entirety.
[0608] Example embodiments of the devices, systems and methods have
been described herein. As may be noted elsewhere, these embodiments
have been described for illustrative purposes only and are not
limiting. Other embodiments are possible and are covered by the
disclosure, which will be apparent from the teachings contained
herein. Thus, the breadth and scope of the disclosure should not be
limited by any of the above-described embodiments but should be
defined only in accordance with features and claims supported by
the present disclosure and their equivalents. Moreover, embodiments
of the subject disclosure may include methods, systems and devices
which may further include any and all elements/features from any
other disclosed methods, systems, and devices, including any and
all features corresponding to user-experience
functionality/systems/methods, including the manufacture and use
thereof. In other words, features from one and/or another disclosed
embodiment may be interchangeable with features from other
disclosed embodiments, which, in turn, correspond to yet other
embodiments. Moreover, embodiments, or features thereof, disclosed
in the instant application may be combined with features and/or
embodiments disclosed in the incorporated by reference information
and yield yet other embodiments of the present disclosure.
[0609] One or more features/elements of embodiments supported by
the present disclosure may be removed and still result in
patentable subject matter (and thus, resulting in yet more
embodiments of the subject disclosure). Furthermore, some
embodiments of the present disclosure may be distinguishable from
the prior art by specifically lacking one and/or another feature,
functionality or structure which is included in the prior art
(i.e., claims directed to such embodiments may include "negative
limitations").
* * * * *