U.S. patent application number 11/920462 was filed with the patent office on 2009-02-12 for sampling system.
This patent application is currently assigned to APROVIX AB. Invention is credited to Ulf Lundkvist, Soren Nygren, Berndt Sjoberg, Erik Wilander.
Application Number | 20090043224 11/920462 |
Document ID | / |
Family ID | 37064671 |
Filed Date | 2009-02-12 |
United States Patent
Application |
20090043224 |
Kind Code |
A1 |
Lundkvist; Ulf ; et
al. |
February 12, 2009 |
Sampling System
Abstract
A sampling system comprises a mailing package; a cell sampling
device comprising a flexible shaft having a handle at one end,
wherein the shaft is configured to allow an individual to self
collect a cell sample from mucous tissue, and a sample collecting
element removably connectable with the other end of the shaft and
operable to collect a cell sample from mucous tissue of an
individual; and a sealable unit, wherein the unit is configured to
store the sample collecting element having a cell sample thereon
and to be received within the mailing package in its sealed form.
The system may optionally further include a transport package
configured to receive the remaining components of the system for
delivery to a user.
Inventors: |
Lundkvist; Ulf; (Uppsala,
SE) ; Sjoberg; Berndt; (Sodertalje, SE) ;
Wilander; Erik; (Uppsala, SE) ; Nygren; Soren;
(Knivsta, SE) |
Correspondence
Address: |
DINSMORE & SHOHL, LLP
1900 CHEMED CENTER, 255 EAST FIFTH STREET
CINCINNATI
OH
45202
US
|
Assignee: |
APROVIX AB
Uppsala
SE
|
Family ID: |
37064671 |
Appl. No.: |
11/920462 |
Filed: |
May 26, 2006 |
PCT Filed: |
May 26, 2006 |
PCT NO: |
PCT/IB2006/001723 |
371 Date: |
November 15, 2007 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
60685892 |
May 31, 2005 |
|
|
|
Current U.S.
Class: |
600/562 |
Current CPC
Class: |
A61B 2010/0074 20130101;
A61B 2017/00473 20130101; A61B 10/0051 20130101; A61B 10/0291
20130101; A61B 10/0096 20130101; A61B 2010/0003 20130101 |
Class at
Publication: |
600/562 |
International
Class: |
A61B 10/00 20060101
A61B010/00 |
Claims
1. A sampling system comprising: a) a mailing package; b) a cell
sampling device comprising: i) a flexible shaft having a handle at
one end, wherein the shaft is configured to allow an individual to
self collect a cell sample from mucous tissue, and ii) a sample
collecting element removably connectable with the other end of the
shaft and operable to collect a cell sample from mucous tissue of
an individual; and c) a sealable unit, wherein the unit is
configured to store the sample collecting element having a cell
sample thereon and to be received within the mailing package in its
sealed form.
2. The system of claim 1, wherein the shaft is configured to allow
an individual to self collect a cell sample from a cervix
location.
3. The system of claim 1, further comprising a transport package
configured to receive components a)-c) for delivery to an
individual for use of the system.
4. The system of claim 3, wherein the transport package and the
unit each have an identification element.
5. The system of claim 4, wherein the identification element
includes a bar code.
6. The system of claim 1, wherein a portion of the shaft is
rigid.
7. The system of claim 1, wherein the shaft is formed of polymer
comprising polypropylene, polyethylene, or a mixture thereof.
8. The system of claim 1, wherein the sample collecting element is
generally cylindrical and has a diameter of from about 2 to about
20 mm.
9. The system of claim 1, wherein the sample collecting element
comprises at least one raised portion.
10. The system of claim 1, wherein the raised portion forms a
plurality of cell and mucous collecting segments.
11. The system of claim 10, wherein the sample collecting element
further comprises at least one groove which is from about 0.01 to
about 2 mm in width for maintaining a cell and mucous sample
therein.
12. The system of claim 11, wherein the raised portion forms an
edge at the groove capable of scraping tissue to collect a
sample.
13. The system of claim 12, wherein the raised portion and grooves
are configured to collect a sample by insertion in a body orifice
and to hold a collected sample during withdrawal of the device from
a body orifice.
14. The system of claim 1, wherein the sample collecting element
comprises an abrasive surface.
15. The system of claim 14, wherein the abrasive surface has a
surface roughness of from about 1 to about 100 .mu.m.
16. The system of claim 1, wherein the sealable unit comprise a
unit cover for sealing the unit.
17. The system of claim 1, wherein the sample collecting element,
the shaft and the sealable unit are configured to allow the sample
collecting element to be at least partially inserted within the
sealable unit and separated from the shaft without contact of the
sample collecting element by an individual.
18. The system of claim 17, wherein the connection comprises a
snap-fit mechanism.
19. The system of claim 16, wherein the unit and the unit cover
form an air-tight seal.
20. The system of claim 1, further comprising an instruction
sheet.
21. A sampling system comprising: a) a preaddressed mailing
package; b) an instruction sheet; c) a flexible shaft; d) a sample
collecting element removably connectable with an end of the shaft
and having a plurality of raised portions and grooves; e) a bar
coded unit including an air tight unit cover and configured to
receive the sample collecting element therein and to be received in
the mailing package; and f) a transport package configured to
receive components a)-e) for delivery to a user.
22. The sampling system of claim 21, wherein the sample collecting
element is configured for snap-fit connection and removal with the
shaft.
23. The sampling system of claim 22, wherein the cell sampling
device is configured to allow an individual to self collect a
sample.
24. The sampling system of claim 23, wherein the cell sampling
device is configured to allow an individual to collect a sample
from mucous tissue.
25. The sampling system of claim 24, wherein the mucous tissue
resides in the gynecological tract.
26. The sampling system of claim 24, wherein the mucous tissue
resides in the mouth.
Description
FIELD OF THE INVENTION
[0001] The present invention relates generally to the field of
screening and health control. More specifically the invention
relates to a novel sampling system and associated methods suitable,
for example, in testing to detect virus-associated cervical cancer,
microbial infections and pathological changes.
BACKGROUND OF THE INVENTION
[0002] Cervical cancer is the second most common form of cancer in
women world-wide. Invasive cervical carcinoma develops by
progression of less severe epithelial changes, known as dysplacia
and cervical intraepithelial neoplacia (CIN I-II-III), into
cervical carcinomas in situ (CIS).
[0003] Using vaginal aspirates (Pap smears), the epithelial changes
can be detected and classified by common cytological methods. It is
particularly important to notice that invasive cervical carcinoma
is preceded by its dysplastic precursor lesions, which can be
present for months or years before cervical carcinoma develops.
Furthermore, progression to carcinoma can effectively be stopped by
a simple operation (conization) if the precursor lesions are
detected.
[0004] Many developed countries have experienced up to a 50%
reduction in the incidence of and mortality from invasive cervical
carcinoma after the introduction of organized screening programs.
Despite this fact, about 500,000 women in the world are struck by
cervical cancer each year. In the U.S., close to 5,000 women die
each year from this disease. This number would drop further if more
women were tested on a regular basis.
[0005] Of those who die of cervical cancer, 50% have not had a Pap
test done in 5 or more years. Indeed, those women who do not
participate in the gynecological health control and those who show
false negative cytology are the highest risk groups for cervical
cancer. The efficacy and reliability of the sampling method and the
sample's analysis are therefore primary issues. This involves, in
the first place, reaching those women who do not now participate in
the gynecological screening by providing a simple and reliable
device for sampling, and secondly, to increase the discriminating
efficacy of the analytical methods to diagnose infections,
precancerous lesions or cancerous lesions.
[0006] Association between papillomavirus (HPV) infection and
cervical carcinoma was postulated in the 1970's. The International
Biological Study on Cervical Cancer reported a world-wide
prevalence of infection with HPV of 93% in women with invasive
cervical cancer. In addition, the subtypes HPV 16 and HPV 18 are
the most significant risk factors in its aetiology. HPV infection
is also an important risk factor for progression of CIN.
[0007] Recent studies with improved methods of polymerase chain
reaction (PCR) imply an overall HPV prevalence of almost 100% and
that the PCR results correlate with the histological findings.
These results reinforce the rational for HPV testing in combination
with, or even instead of, cytology in population-based screening
programs.
[0008] Determination of squamous intraepithelial lesions, or
cervical dysplacia, is commonly used as an indication of
progression to cervical cancer. Alternatively, the presence of HPV
nucleic acid in a patient sample, following amplification by PCR,
is taken as a risk factor for progression to cervical cancer. From
the above, it is obvious that cytology and PCR analysis of HPV
infection provide very efficient means to detect individuals at
risk to develop cervical cancer.
[0009] Recently published evidence-based consensus guidelines for
the management of women with cervical cytological abnormalities and
cervical cancer precursors state that women with atypical squamous
cells of undetermined significance (ASCUS) should be managed using
a program of 2 repeat cytology tests, immediate colposcopy, or DNA
testing for high-risk types of HPV. Testing for HPV DNA is the
preferred approach when liquid-based cytology is used for
screening.
[0010] The limiting factor in order to further decrease the
incidence of and mortality from cervical cancer appears therefore
to be related to reaching the non attending women and providing a
simple sampling device giving relevant samples for HPV analysis
and/or cytology.
[0011] Traditionally, sampling of vaginal smear requires scraping
of a woman's cervix with a sampling device, such as a spatula or a
brush. This sampling is generally performed by medical
professionals like gynecologists, midwifes or nurses in a clinical
environment. Many women, who now refrain from such gynecological
testing, would participate if the sampling could be carried out at
home and/or by the women themselves. Self and home sampling would
therefore increase the participation in the gynecological
screening, and by that means, decrease the incidence of cervical
cancer.
[0012] In addition to the above, sampling systems are also in
demand for DNA analysis. Law enforcement officials, paternity
agents, etc. are constantly taking DNA samples to help solve
crimes, determine paternity, etc. As the results of the tests done
on these samples dramatically affect people's lives and may be
desired as evidence in legal proceedings, the sampling must be done
in a manner in which the sample contamination is reduced or
avoided. As such, there is a need for an improved sampling
system.
SUMMARY OF THE INVENTION
[0013] In view of the need for an improved sampling device and a
system easily adaptable to present health screening procedures, the
present invention therefore provides improvement over the currently
available devices and systems.
[0014] In one embodiment, the present invention comprises a
sampling system comprising: a) a mailing package; b) a cell
sampling device comprising: i) a flexible shaft having a handle at
one end, wherein the shaft is configured to allow an individual to
self collect a cell sample from mucous tissue, and ii) a sample
collecting element removably connectable with the other end of the
shaft and operable to collect a cell sample from mucous tissue of
an individual; and c) a sealable unit, wherein the unit is
configured to store the sample collecting element having a cell
sample thereon and to be received within the mailing package in its
sealed form. The sampling system may optionally further include a
transport package configured to receive components a)-c) for
delivery to a user.
[0015] In another embodiment, the present invention comprises a
sampling system comprising: a) a mailing package; b) an instruction
sheet; c) a flexible shaft; d) a sample collecting element
connected with an end of the shaft and having a plurality of raised
portions and grooves; e) a bar coded unit including an air tight
cover and configured to receive the sample collecting element
therein and to be received in the mailing package; and f) a
bar-coded transport package configured to receive components a)-e)
for delivery to a user.
[0016] The sampling systems of the invention may be used by medical
personnel for patient sampling and/or may be used by individuals
for self-sampling. The sampling systems are particularly
advantageous for use by an individual in conduct self-sampling in
testing to detect, for example, virus-associated cervical cancer,
microbial infections and pathological changes. These and additional
embodiments and advantages may be more fully apparent in view of
the detailed description.
BRIEF DESCRIPTION OF THE DRAWINGS
[0017] The present invention will be more fully understood from the
detailed description, given herein below and the accompanying
drawings which are given for illustration, and thus not limiting
the scope of the invention, and wherein
[0018] FIGS. 1A and 1B are, respectively, a front view of mailing
package and a rear view of a bar-coded transport package included
in one embodiment of the sampling system according to the
invention;
[0019] FIG. 2 is a top view of a sampling device and a sealable
unit held in a protective plastic tray, in accordance with one
embodiment of the sampling system of the invention;
[0020] FIGS. 3A-3J show schematic plan and cross-sectional views of
a sampling device included in one embodiment of a sampling system
according to the invention; and
[0021] FIG. 4 is an illustration of an instruction sheet suitable
for use in accordance with one embodiment of the sampling system of
the invention.
[0022] The embodiments set forth in the drawings are illustrative
in nature and are not intended to be limiting of the invention
defined by the claims. Moreover, individual features of the
drawings and the invention will be more fully apparent and
understood in view of the following detailed description.
DETAILED DESCRIPTION
[0023] The present invention provides a sampling system that
overcomes disadvantages of prior art devices, instruments and
procedures for obtaining cell samples from mucous tissue such as,
but not limited to, the gynecological tract and the mouth.
[0024] In a first aspect, the present invention provides a sampling
system which may be employed by an individual to easily and
reliably, at home or at a visit to a medical location, under
hygienic conditions, take cell smears and samples, for example,
gynecological samples, from mucous tissues. The samples can be
transported without risk of contamination or transmission of
infective agents, and thereafter be analyzed by chemical methods,
such as PCR, or by other microbiological methods.
[0025] With reference to FIGS. 1-4, the sampling system according
to one embodiment of the present invention includes a cell sampling
device 2 for taking cell samples, a mailing package 14 for
returning a sample to, for example, a laboratory for testing, and a
sealable unit 7. Optionally, the sampling system may include a
transport package 3 for delivery of the sampling system components
to a user. One embodiment of the transport package 3 is shown in
FIG. 1B, and includes a bar code, for use as described in further
detail below. One embodiment of the mailing package 14, including a
printed address for mailing a sample to the appropriate medical
professional, on the front side thereof is shown in FIG. 1A. It
will be appreciated that the transport package 3 and the mailing
package 14 may be provided with this exemplary information, or
other information as desired, in any suitable arrangement. The
mailing package 14 allows return of the sealable unit 7 and
contents thereof to the appropriate facility, for example, by mail,
courier or the like, without compromising the sealable unit or its
contents.
[0026] In one embodiment, the cell sampling device 2 comprises a
shaft 4 having a handle 5 at one end. The handle may include a
lower lip 5a as shown to facilitate the ease of use of the device.
The shaft 4 is configured to allow an individual to self collect a
cell sample from mucous tissue. In a specific embodiment, the shaft
4 is configured to allow an individual to self collect a sample
from a cervix location. In an additional embodiment, at least a
portion of the shaft is flexible, and in a further embodiment, a
portion of the shaft 4 is rigid. Alternatively, the shaft may be
entirely flexible. Reference to a flexible shaft is intended to
mean at least a portion of the shaft is flexible. In another
embodiment, the shaft 4 is formed of a polymer, including, for
example, polypropylene, polyethylene, or a mixture thereof.
[0027] The cell sampling device 2 further comprises a sample
collecting element 6 removably connectable with the other end of
the shaft 4 opposite the handle. The element 6 is operable to
collect a cell sample from mucous tissue of an individual. FIGS. 3A
and 3B show the sample collecting element 6 removable connected
with the shaft 4, while FIGS. 3C and 3E show the shaft 4 without
the sample collecting element 6 thereon and FIGS. 3H and 3I show
the sample collecting element 6 apart from the shaft 4. FIG. 3D
shows a cross-sectional view taken along line D-D in FIG. 3C; FIGS.
3F and 3G show cross-sectional views taken along lines F-F and G-G
in FIG. 3E, respectively, and FIG. 3J shows a cross-sectional view
taking along line J-J in FIG. 3I.
[0028] The sealable unit 7 is configured to store the sample
collection element 6 having a cell sample thereon, preferably in a
manner which prevents contamination of the element 6, i.e., in an
air tight manner, and to be received within the mailing package 14
in its sealed form. In one specific embodiment, the unit 7 is a
sealable tube.
[0029] In an additional embodiment, the transport package 3 and the
unit 7 each have an identification element 8, for example
correlating to the individual from which a sample is made. In a
further embodiment, the identification element 8 consists of a bar
code.
[0030] The shaft 4, the adsorbing sample collecting element 6, the
sealable unit 7, and the unit cover 12 can be manufactured of any
suitable materials as desired. For example, these components may be
formed of the same or different plastic materials. In a further
embodiment, a plastic material of the cell sampling device 2,
preferentially polypropylene, is selected with a flexural modulus
giving the shaft 4 flexibility to follow the anatomy of the vagina
to reach portio vaginalis and at the same time rigid enough to get
a close contact between the sample collecting element 6 and the
mucous tissue ectocervix.
[0031] In a specific embodiment as shown in FIGS. 3A, 3B and 3H-3J,
the sample collecting element 6 is generally cylindrical. The
element 6 may be configured and sized as desired for a particular
sample collection. In one embodiment, the element 6 is generally
cylindrical as shown and has a diameter from about 2 to about 20
mm. In one embodiment as shown in FIGS. 3A, 3B, 3H and 3I, the
front part of the sample collecting element 6 is rounded and may be
made very smooth, so as to render it more tissue friendly and
easier for introduction into the sensitive tissue of the
vagina.
[0032] In a further embodiment, the sample collecting element 6
comprises at least one raised portion 9. In another embodiment, the
raised portions of the sample collecting element 6 form a plurality
of cell and mucous adsorbing segments 10. The segments 10 are
separated by at least one groove 11 or a plurality of grooves 11.
In a specific embodiment, the grooves 11 are from about 0.01 to 2
mm in width and in another embodiment, the raised portions 9
include an edge at the groove 11 capable of scraping tissue to
collect a sample. In an additional embodiment, the raised portions
9 forming the segments 10 and the grooves 11 are configured to
collect a cell sample and hold the sample within the grooves 11
even during withdrawal of the device 2 from a body orifice. In a
specific embodiment, the segments 10 of the sample collecting
element 6 have an unpolished surface and, in a specific embodiment,
comprise an abrasive surface, for example having a surface
roughness of about 1 to 100 .mu.m, to facilitate release of
cell-containing mucous, for example, from ectocervix tissue.
[0033] In one embodiment, the raised portions 9 form segments 10
which are essentially rectangular in shape by providing the grooves
11 in the longitudinal and transversal directions on the sample
collecting element 6. However, it is of course possible to provide
grooves 11 in other geometries, e.g. in spiral or zigzag patterns.
In one embodiment, the grooves 11 are substantially narrower than
the width of the raised portions 9. In one embodiment the width of
the grooves 11 does not exceed about 2 mm, and in another
embodiment, the width is from about 0.5 to about 0.1 mm.
Importantly, the grooves 11 should be able to absorb mucous liquid
and cells therein, and maintain these materials in place during
retraction of the device from the body orifice.
[0034] The sample collecting element 6 is removably connected with
one end of the shaft 4. Thus, the sample collecting element 6 may
be connected with the shaft to facilitate obtaining a mucous
sample, for example from ectocervix tissue, and may then be removed
from the shaft 4 for insertion in the sealable unit 7. One of
ordinary skill in the art will appreciate that various connection
configurations may be employed to facilitate the removable
connection of the sample collecting element 6 with the end of the
shaft 4. In the specific embodiments shown in FIG. 3A-3J, an end of
the sample collecting element 6 is provided with an extension 13
having protrusions 15. The end of the shaft 4 is correspondingly
provided with extensions 16 having grooves adapted to receive
protrusions 15 therein in a snap-fit manner. Thus, the extension 13
is inserted between the extensions 16 in a male-female type manner
in which the protrusions 15 are snap fit within grooves contained
in the extension 16 at the end of the shaft 4. The protrusions are
released from the grooves contained in extension 16 by rotation of
the sample collecting element 6 as shown in FIG. 3B. As a result,
the sample collecting element 6 may be removed from the shaft 4 to
the unit 7 and preferably sealed therein, for example with a unit
cover 12 as shown in FIG. 2. Advantageously, to prevent
contamination of the sample collecting element 6 once a mucous
sample is adhered thereto, the sample collecting element may be at
least partially inserted within the unit 7, prior to removal of the
sample collecting element 6 from the shaft 4. The unit 7 may then
be moved to rotate the sample collecting element as shown in FIG.
3B and release the sample collecting element from extension 16 of
the shaft 4. After release of the sample collecting element from
its connection with the shaft 4, the remainder of the sample
collecting element is then inserted into the unit 7, for example by
gravity by holding the sample collection unit an upright vertical
position, or by pushing the sample collected element further into
the unit with the end of the shaft 4. The unit is then sealed with
the appropriate cover, preferably to form an airtight seal.
[0035] The sealed unit 7, having the sample collecting element 6
therein, may then be placed in the mailing package 14 which is
designed to protect the sealed unit during return transport of the
sealed unit to a medical facility, for example a doctor's office,
hospital or laboratory, for appropriate testing of the collected
sample therein.
[0036] In one embodiment, the sample collecting system further
comprises an instruction sheet 20, particularly useful when the
sampling system is adapted for self sampling by an individual.
[0037] In one embodiment, the sampling system of the invention is
configured to allow an individual to self-collect a sample. In an
additional embodiment, the self-sampling device is configured to
allow an individual to collect a sample from mucous tissue. In
another embodiment, the mucous tissue resides in the gynecological
tract and in another embodiment the mucous tissue resides in the
mouth, (e.g. cheek). The sampling system may be used by
distribution to a patient, who conducts sampling and returns the
sample for final laboratory analysis according to the present
invention.
EXAMPLE
[0038] This example examines if the same result will be obtained
when gynecological smears are taken by hospital staff using
previous standard procedures or using the sampling system according
to the present invention, as well as if patients themselves use the
sampling system.
[0039] Thirty six women are requested to come to the hospital for
regular gynecological control and participate in the study. The
hospital staff secure gynecological smears from the portio area
with the use of a cytobrush. One sample is used for conventional
cytological screening and the other for HPV analysis. The women
take one sample themselves with the present invention following the
written information as shown in FIG. 4. This sample is used for HPV
analysis.
[0040] All samples are sent to the Department of Pathology,
University of Uppsala. The smears collected with cytobrush by the
gynecological staff and the smears collected by the women
themselves with the device are analyzed for presence of HPV with
the Hybrid Capture II method (Digene Diagnostics Inc., Silver
Spring, Md., USA). The cytological smears are, after screening,
examined for HPV using a PCR based technique.
[0041] All samples taken with previous standard procedures are
scraped into test tubes and PCR buffer and proteinase K is added.
When samples are taken with the device according to the present
invention, the PCR buffer and proteinase K are simply added into
the sealable unit, either by the user, or prior to delivery of the
sampling system to a user, or upon return of the unit to, for
example, a testing facility. The cells are digested at 60.degree.
C. and the DNA fraction recovered with standard methods.
[0042] The PCR amplification is performed in 100 .mu.l volume
containing standard amplification reagents. Type-specific PCR
amplification is performed under conditions described by Brule et
al. using GP5+/GP6+ general primers. Samples with HPV DNA
amplicones are sequenced with an ABI PRISM 310 Genetic Analyzer
(Applied Biosystems, Foster City, Calif.) after which the HPV type
can be determined.
[0043] The results from these studies demonstrate that the women
themselves can readily secure gynecological samples with the device
according to the present invention. Furthermore, both cytological
and PCR analysis of the samples give essentially the same result as
when medical staff take the samples either using the present device
or other previously well established sampling methods. It is
demonstrated that the analysis can be carried out with satisfactory
results three days after sampling with the device.
[0044] Thus, the sampling system is particularly advantageous for
self-sampling for gynecological samples, and particularly HPV
analysis. After self sampling at home, the device may be rapidly
returned by mail to a hospital laboratory for HPV analysis. The
sampling system according to the present invention is surprisingly
well accepted, and is particularly useful for self sampling at
home.
[0045] The sampling system will increase participation in the
gynecological screening programs evaluating the risk of developing
cervical cancer in situ. Self and home sampling will be positive
from a health-economic point of view, but more importantly,
increased participation will decrease the incidence of cervical
cancer and also decrease the number of women who die of this
disease.
[0046] The specific illustrations and embodiments described herein
are exemplary only in nature and are not intended to be limiting of
the invention defined by the claims. Further embodiments and
examples will be apparent to one of ordinary skill in the art in
view of this specification and are within the scope of the claimed
invention.
* * * * *