Note: Descriptions are shown in the official language in which they were submitted.
WO 95/30484 2 1 7 Q 9 9 ~ PCT/US95/05889
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SALIVA SAMPLE COLLECTION SYSTEM
Back~oul-d of the Invention:
Field of the Invention:
The invention relates to a system for collecting and
storing samples of saliva for body fluid constituent
analysis.
Description of the Related Art:
Saliva testing has recently come to the forefront as a
preferred option in body fluid constituent analysis. The
collection procedure is non-invasive, and saliva has been
found to be a very reliable carrier of analyte indicators.
For instance, PKU tests on infants are now regularly done,
drug abuse is tested in many circumstances, HIV testing may
be relatively reliably performed with saliva, and levels of
therapeutic drugs may be ascertained through saliva
testing.
A recent advance in saliva collection and test preparation
is disclosed in U.S. Patent No. 5,103,836 to Goldstein et
al. An absorbent pad which is impregnated with a salt of a
hypertonic solution is inserted into the mouth and saliva
is brushed off from the cavity walls. After having absorbed
a sufficient amount of saliva, the pad is removed and
stored in a vial for later testing. The test kit is suited
for immunoglobulin collection and testing for immunological
infor~ation in the body fluid. That prior art test provides
enough saliva for only a single test, i.e. the saliva is
not collected for general, multiple testing.
Another saliva collector is disclosed in U.S. Patent No.
5,268,148 to Seymour. A portion of filter paper is exposed
so that, when enough saliva is collected, the paper will
W095t30484 2 ~ 7 0 9 9 8 PCT~S95/05889 ~
provide an indication that the collected amount is
adequate.
The method and apparatus described in U.S. Patent No.
4,774,962 to Hebel et al. allows extracting saliva from the
human body in that a sponge member is chewed for a certain
amount of time. The method may be acceptable for adult
saliva collection. Such a free sponge, however, is
essentially unsuitable for infant testing due to the danger
of ingestion and it is also not acceptable in view of the
proposed utilization thereof in HIV and hepatitis testing.
The prior art devices have in common that the collection of
saliva sample is rather cumbersome, it exposes the medical
worker to dangerous substances, and/or the amount of saliva
thus collected is inadequate to perform various tests.
Also, none of the prior art devices provide a convenient
method and kit for collecting large amount of saliva for
body fluid constituent analysis. Finally, saliva collection
from very small infants, for instance for PKU testing, is
guite difficult and virtually always accompanied by forcing
the infant's mouth open during the procedure.
Summary of the Invention:
It is accordingly an object of the invention to provide a
saliva sample collection system, which overcomes the
hereinafore-mentioned disadvantages of the heretofore-known
devices of this general type and which provides a self-
contained collection and test kit as well as a reliable and
convenient method of collecting saliva samples for general,
multiple testing. The method and collection kit, in one
mode and embodiment thereof, further make use of a
centrifuge, which is st~n~rd equipment in any test lab
establishment. Finally, it is an object to provide a fully
integrated, sterile package, which allows collecting,
~ ~a9~8,
WO9S/30484 PCT~S95/05889
filtering, handling and centrifuging without any danger of
exposure to the medical worker.
With the foregoing and other objects in view there is
provided, in accordance with the invention, a method of
collecting saliva samples for body fluid analysis. The
method comprises the following steps:
placing absorptive means into a patient's oral cavity and
absorbing saliva into the absorptive means;
removing the absorptive means from the patient's oral
cavity and placing the absorptive means into fluidic
communication with a collection container;
In a first mode of the invention, the method is continued
with a step of squeezing the saliva from the absorptive
means t collecting the squeezed-out saliva at the bottom of
the collection container, and then harvesting the saliva
from the bottom of the container by opening a fluidic
conduit at the bottom and utilizing the thus harvested
saliva in a saliva testing method.
In a second mode of the invention, the method is continued
with a step of centrifuging the absorptive means in fluidic
communication with the collection container and driving the
saliva out of the absorptive means and into the collection
container; and
removing the absorptive means from the collection container
and testing the saliva driven out of the absorptive means
in the centrifuging step.
In accordance with a preferred mode of the invention, a
filter assembly is placed between the absorptive means and
W095/30484 2 1 7 0 9 ~ 8 PCT~S95/05889 ~
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the collection container for molecular weight-selective
collecting of saliva in the centrifuging step.
With the foregoing and other objects in view, there is also
provided, in accordance with the invention, an assembly for
collecting saliva for body fluid analysis, comprising:
absorptive means for placing into a patient's oral cavity
and for absorbing saliva therein;
a collection and centrifuging assembly having a cavity
formed therein for receiving the absorptive means, the
collection and centrifuging assembly including
a holder section for receiving and holding therein the
absorptive means;
a collection section attached to and fluidically
communicating with the holder section, the collection
section receiving the saliva from the absorptive means
when the collection and centrifuging assembly is
centrifuged; and
cap means for closing off the collection section after
the holder section has been removed therefrom, for
facilitating storage and shipping of the saliva
collected in the collection section during
centrifuging.
In accordance with another feature of the invention, the
assembly includes a filter assembly disposed between the
2S holder section and the collection section for filtering the
saliva prior to collection in the collection section.
WosS/30484 2 t ~ 8 PCT~S9S/05889
In accordance with an added feature of the invention, the
filter assembly includes a substantially annular wall for
fluid-tightly connecting between the holder section and the
collection section, a wire support permanently attached to
the s~bstantially annular wall, and a molecular weight
membrane for selectively filtering the saliva of materials
with a molecular weight greater than a rating of the
molecular weight membrane.
In accordance with an additional feature of the invention,
the absorptive means include a cap member for placing on
the holder section and fluid-tightly sealing a top of the
holder section, and a sponge member for absorbing the
saliva permanently attached to the cap. The sponge member
is preferably formed as a pacifier nipple.
In accordance with yet another feature of the invention,
the assembly includes a safety flange attached to the cap
member for preventing ingestion of the absorptive means
when the sponge member is placed into the patient's oral
cavity. The collection assembly is ~uite similar to a
pacifier, with the essential difference that the nipple
portion is formed of absorptive material, so as to absorb
saliva while the nipple placed in the patient's mouth.
In accordance with a concomitant feature of the invention,
the absorptive means are impregnated with a flavor
substance for stimulating a patient's saliva production.
Appropriate flavors for stimulating the gland may be lemon,
lime, orange, or similar flavors.
In accordance with a preferred embodiment of the invention
there is provided an alternative system which comprises:
,.
woss/3o484 2 1 7 0~ ~ 8 PCT~S95/05889 ~
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absorptive means for placing into a patient's oral cavity
and for absorbing saliva therein:
a collection cont~; ner defining a cavity adapted to
receiving the absorptive means, the collection contA i ner
having resilient walls adapted to collapse towards one
another upon being squeezed and to drive the saliva from
the absoptive means when the absorptive means is disposed
in the collection container.
In accordance with another feature of the invention, the
walls of the collection container are elastically
resilient.
In accordance with a final feature of the invention, the
collection container further comprises a dispensing end in
a vicinity of which the saliva is collected, the dispensing
~5 end having a nipple formed thereon through which the saliva
is removed from the collection container.
Other features which are considered as characteristic for
the invention are set forth in the appended claims.
Although the invention is illustrated and described herein
as embodied in a saliva sample collection system, it is
nevertheless not intended to be limited to the details
shown, since various modifications and structural changes
may be made therein without departing from the spirit of
the invention and within the scope and range of equivalents
of the claims.
The construction of the invention, however, together with
additional objects and advantages thereof will be best
understood from the following description of the specific
W095/304~4 2 t 7 ~ i PCT~S95/05889
embodiment when read in connection with the accompanying
drawings.
A
Brief DescriPtion of the Drawings:
, Fig. 1 is a sectional view of a cap and sponge collection
assembly according to the invention;
Fig. 2 is an exploded, partly broken-away, side-elevational
view of a three-component assembly according to the
invention;
Fig. 3 is a bottom-plan view of a filter insert;
Fig. 4 is a side-elevational view of a centrifuge vial,
i.e. the bottom component shown in Fig. 2, with a closure
cap;
Fig. 5 is a view similar to Fig. 2 of an alternative
embodiment of the invention; and
Fig. 6 is a view similar to Fig. 1 of another alternative
embodiment.
~escription of the Preferred Embodiments:
Referring now to the figures of the drawing in detail and
first, particularly, to Fig. 1 thereof, there is seen a cap
and sponge assembly 1 (the collection component), which
includes a cap 2, an optional handle 3, an optional safety
flange 4 and a æponge 5. As will become amply clear in the
following, the essential components of the assembly 1 are
the cap 2 and the sponge 5. The handle 3 may be provided
for easier handling of the assembly 1, and it may be
integrally formed on the cap 2 or it may be glued thereon.
The safety flange 4 is specifically recommended for infant
testing. The safety flange 4 may be removable, and for that
W O 95/30484 ~ 3 9 8 PCTrUS95/05889
purpose it would be spot-welded (spot weld 6) to the cap 2
or provided with a safety ring similar to those found on
plastic closures of milk jugs. Generally speaking, the cap
and sponge assembly 1 is quite similar to an infant
pacifier, and the assembly, and particularly the sponge 5,
may be shaped in all possible pacifier shapes.
The sponge 5 is permanently locked into the inside of the
cap, so as to allow a liquid-tight seal when the cap is
placed on the components illustrated in Fig. 2. The sponge
5 is either polypropylene, polyethylene, polyurethane,
cellulose, or blends thereof. More specifically, the sponge
is formed of water-catalyzed polyurethane and more
specifically it is preferably formed of HYPOL, available
from Hampshire Chemical Corporation. That material has very
high absorption density and excellent tensile strength.
Similar materials may be used. Factors to be considered,
however, are that the material must be largely inert, it
must not easily break so as to prevent any ingestion of
solid material, and it must have good absorptive qualities.
Additionally, as will become clear from the following
description, it should be able to withstand centrifugation
and be able to release all or most of the saliva previously
collected.
After saliva has been absorbed in the sponge 5 (after an
exposure time between 20 seconds and 5 minutes in the mouth
of the test patient), the cap and sponge assembly 1 is
placed on a sponge holder section 7, in that the sponge 5
is inserted and the cap 2 is securely fastened thereto. A
simple friction fit between the sponge holder section 7 and
the cap 2 will in most cases suffice. It is also possible,
however, to provide the cap 2 and the sponge holder section
7 with mutually r ?~:h;rlg threads. The sponge holder section
7 is preferably formed as a polypropylene, polyethylene or
W095/30484 ~ PCT~S9~/05889
styrene cylinder and it is provided with an attachment
flange 9 at its bottom.
A filter assembly 8 is attached at the flange 9 at the
bottom of the sponge holder section 7. The filter assembly
is preferably attached by a substantially circumferential
ultrasonic weld. The filter 8 and the sponge holder 7,
therefore, form a liquid-tight seal. The filter assembly 8
has a molecular weight cut-off membrane 10 supported on a
simple wire mesh 11. The membrane 10 may be adjusted to any
mesh density. By way of example, a 10,000 MW (molecular
weight) membrane may be used for cleaning the saliva. Other
mesh sizes are also possible, depending on the specimen
requirements.
A bottom stub portion of the filter assembly 8 inserts
tightly into a centrifuge container 12, i.e. a saliva
collection tube 12 or collection container 12. The filter 8
may come attached to the collection tube 12, so as to
provide an integrated system of the components 7, 8 and 12.
The filter assembly 8 may be attached to the collection
tube 12 by means of a ultrasonic spot weld 13, or the like.
It is important, in this respect, that the strength of the
bond between the filter 8 and the collection tube 12 be
smaller than that between the filter 8 and the sponge
holder section 7. This ensures that, after centrifugation,
the filter assembly 8 (together with the sponge holder 7
and the cap and sponge assembly 1 detaches from the
collection tube 12. After separation, then, the collection
tube 12 is closed and sealed with a st~ rd threaded cap
14.
The preferred ~ n~ions of the assembly according to the
invention match those of standard centrifuge equipment. For
instance, the cylindrical tubes have an outer diameter of
W095/30484 2 ~ 7 ~ 9 9 8 PCT~S95/05889 ~
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1/2 inch, the length of the collection tube is 2.125
inches, the length of the filter assembly is 5/16 of an
inch and the sponge holder with the attached cap is 1.75
inches.
The collection tube 12 is also formed of a polypropylene or
a similar material, and it is conical on the bottom. This
facilitates sample withdrawal. The threaded cap ensures
that the collected sample can be stored and shipped without
drying or spilling.
A frosted area 15 may be provided on the collection tube
12, so as to allow proper labelling.
In a further embodiment, the assembly is provided for a
specific test application. In that case, the bottom of the
collection tube 12 holds a certain chemical reactant. When
the saliva is centrifuged into contact with the reaction
chemical, an indication is triggered. That i n~; cAtion may,
for instance, be in the form of a colorimetric reaction.
For that purpose it is clear that the collection tube 12 is
formed of transparent or translucent material, or that a
viewing window is provided. General information on saliva
testing is available from "Saliva as a Diagnostic Fluid",
Malamud and Tabak, Editors; Annals of the New York Academy
of Sciences; Vo. 694; Sept. 20, 1993.
With reference to Fig. 5, we have also provided a much
simplified, yet integrated system for saliva collection and
analysis. The embodiment is particularly based on the
premise that saliva testing by colorimetry and the like has
recently seen a flurry of novel developments which are all
hindered by the fact that the prior art systems for
collecting the saliva are typically cumbersome and slow,
and/or the amount of saliva thus harvested is often not
W095/30484 2 ~ ~ 0 9 9 ~ PCT~S95/05889
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sufficient. The recent call for full disposability of such
devic,es is answered as well with the embodiment of Fig. 5.
The nipple 5 of Fig. 5 may also be formed of HYPOL material
which is directly glued to a lid 16. The adhesive
connection is indicated at 17 and it is preferably formed
by a LO~K'1'1'1'~ system (primer, accelerator, adhesive), a
cyano-acrylic medical grade adhesive. The lid 16 is
internally threaded so that it can be screwed onto the tube
12. In this embodiment, the tube 12 is formed of thin, i.e.
squee~able material. Accordingly, when the sponge 5 is
disposed in the tube 12 and the tube 12 is laterally
squeezed, the saliva is driven from the sponge 5 and it
collects at the bottom of the tube 12.
The bottom of the tube 12 is provided with a nipple 18. The
nipple 18 can be severed (e.g. cut off with scissors) and
the saliva exits from the nipple and into/onto any desired
surface on which the saliva testing (e.g. HIV, Hepatitis,
Drug of Abuse, PSA, etc.) may be performed. Instead of
rec~uiring a cutting tool, the nipple 18 may be provided
with a twist-off cap 19.
With reference to Fig. 6, the sponge nipple 5 may be
directly molded into the cap 16 without requiring an
adhesive layer 17. In such a molding process, the directly
molded foam rubber, after being molded, is allowed to vent
through a casting hole vent 20. A cap plug 21, which is
placed onto the cap 6 after the nipple has been molded into
the cap 6, is provided with a vent opening 22 as well. A
mold opening 23 in the cap 16 is undercut so as to
positively and form-lockingly retain the nipple 5 structure
in the cap 16.
.,
