U.S. patent application number 16/079406 was filed with the patent office on 2019-01-24 for method and device for ctc diagnosis using patch.
The applicant listed for this patent is NOUL CO., LTD.. Invention is credited to Kyung Hwan Kim, Dong Young Lee, Chan Yang Lim.
Application Number | 20190025281 16/079406 |
Document ID | / |
Family ID | 59923756 |
Filed Date | 2019-01-24 |
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United States Patent
Application |
20190025281 |
Kind Code |
A1 |
Lee; Dong Young ; et
al. |
January 24, 2019 |
METHOD AND DEVICE FOR CTC DIAGNOSIS USING PATCH
Abstract
According to an aspect of the present application, there is
provided a diagnostic method for performing diagnosis on tumor
cells included in a sample by using a patch which is provided as a
gel type having a net-like structure forming micro-cavities, the
diagnostic method including placing the sample on a plate, and
using the patch that contains reagents used to detect cancer to
provide the reagents contained in the patch to the plate.
Inventors: |
Lee; Dong Young; (Yongin,
Gyeonggi-do, KR) ; Lim; Chan Yang; (Seongnam,
Gyeonggi-do, KR) ; Kim; Kyung Hwan; (Yongin,
Gyeonggi-do, KR) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
NOUL CO., LTD. |
Yongin, Gyeonggi-do |
|
KR |
|
|
Family ID: |
59923756 |
Appl. No.: |
16/079406 |
Filed: |
February 23, 2017 |
PCT Filed: |
February 23, 2017 |
PCT NO: |
PCT/KR2017/002027 |
371 Date: |
August 23, 2018 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
62298959 |
Feb 23, 2016 |
|
|
|
Current U.S.
Class: |
1/1 |
Current CPC
Class: |
G01N 15/14 20130101;
G01N 33/52 20130101; G06T 7/0014 20130101; G01N 33/5304 20130101;
G01N 15/06 20130101; G01N 2015/0065 20130101; C12Q 1/686 20130101;
G01N 2021/7723 20130101; G01N 33/4833 20130101; B01L 3/505
20130101; C07K 16/3061 20130101; Y02P 20/582 20151101; G01N 1/30
20130101; G01N 33/558 20130101; G01N 1/312 20130101; B01L 7/52
20130101; G01N 2021/7786 20130101; B01F 13/0093 20130101; C12Q
1/701 20130101; G01N 33/49 20130101; G01N 33/60 20130101; B01L 3/00
20130101; G06T 7/0012 20130101; G01N 2001/302 20130101; G01N 1/31
20130101; G01N 21/77 20130101; G01N 2015/0693 20130101; C12Q 1/6844
20130101; C12Q 1/6848 20130101; G01N 33/533 20130101; G01N 33/5082
20130101; C12Q 1/6848 20130101; C12Q 2563/159 20130101; C12Q
2565/625 20130101; C12Q 1/6844 20130101; C12Q 2563/159 20130101;
C12Q 2565/518 20130101 |
International
Class: |
G01N 33/49 20060101
G01N033/49; G01N 1/31 20060101 G01N001/31; G01N 15/14 20060101
G01N015/14; C07K 16/30 20060101 C07K016/30; G01N 33/60 20060101
G01N033/60 |
Foreign Application Data
Date |
Code |
Application Number |
Jun 4, 2016 |
KR |
10-2016-0069936 |
Jun 4, 2016 |
KR |
10-2016-0069937 |
Jun 4, 2016 |
KR |
10-2016-0069938 |
Jul 27, 2016 |
KR |
10-2016-0095739 |
Sep 13, 2016 |
KR |
10-2016-0118462 |
Nov 1, 2016 |
KR |
10-2016-0144551 |
Feb 23, 2017 |
KR |
10-2017-0024388 |
Claims
1. A diagnostic method for performing diagnosis on tumor cells
included in a sample by using a patch which is provided as a gel
type having a net-like structure forming micro-cavities, the
diagnostic method comprising: placing the sample on a plate; and
providing a reagent included in the patch to the plate with using
the patch that contains the reagent used to detect cancer.
2. The diagnostic method of claim 1, wherein the placing the sample
on the plate includes providing the sample in a single layer on the
plate.
3. The diagnostic method of claim 1, wherein the sample is
blood.
4. The diagnostic method of claim 2, wherein the placing the sample
on the plate includes fixating the sample on the plate.
5. The diagnostic method of claim 1, wherein the reagent contained
in the patch include an antibody that reacts specifically with the
tumor cells.
6. The diagnostic method of claim 5, further comprising providing a
substrate on the plate in order to identify an antibody bound to
the tumor cells.
7. The diagnostic method of claim 5, wherein the antibody that
reacts specifically with the tumor cells is applied on the
plate.
8. The diagnostic method of claim 1, wherein the reagent contained
in the patch includes a staining reagent used in staining cells in
order to stain the tumor cells.
9. The diagnostic method of claim 8, wherein the staining reagent
targets at least one of a nucleus of the cells, a cytoplasm of the
cells, and DNA distributed in the cells.
10. The diagnostic method of claim 9, further comprising adjusting
a temperature of the sample in order to provide a reaction
environment for the staining reagent.
11. The diagnostic method of claim 1, wherein the reagent contained
in the patch includes a nutrient reagent used in cell culturing in
order to diagnose the cancer by culturing the tumor cells.
12. The diagnostic method of claim 1, wherein the providing the
reagent contained in the patch includes contacting the patch and
the plate.
13. The diagnostic method of claim 1, further comprising acquiring
an image of the plate on which the sample is placed in order to
perform diagnosis of the tumor cells.
14. A diagnostic method for performing diagnosis on tumor cells
included in a sample by using a patch which is provided as a gel
type having a net-like structure forming micro-cavities, the
diagnostic method comprising: placing the sample on a plate;
providing a first reagent contained in a first patch to the plate
with using the first patch containing the first reagent used to
detect cancer; and providing a second reagent contained in a second
patch to the plate with using the second patch containing the
second reagent used to detect the cancer.
15. The diagnostic method of claim 14, wherein the providing the
reagent contained in the first patch is performed prior to the
providing the reagent contained in the second patch.
16. The diagnostic method of claim 14, wherein: the first reagent
includes an antibody that reacts specifically with the tumor cells;
and the second reagent includes at least one of an antibody that
binds to the antibody reacting specifically with the tumor cells, a
nutrient reagent that is used in cell culturing in order to
diagnose the cancer by culturing the tumor cells, includes a
staining reagent that is used for cell staining in order to stain
the tumor cells and an antibody that reacts specifically with white
blood cells.
17. The diagnostic method of claim 14, wherein: the first reagent
includes an antibody that reacts specifically with the tumor cells;
and the second reagent includes an antibody that reacts
specifically with white blood cells, and the diagnostic method
further comprising, between the providing the reagent contained in
the first patch and the providing the reagent contained in the
second patch, acquiring an image of the sample.
18. The diagnostic method of claim 14, wherein: the first reagent
includes a reagent used for removing a cell membrane of a cell in
order to extract DNA of the tumor cells; and the second reagent
includes a reagent used in a polymerase chain reaction (PCR).
19. A diagnostic apparatus for performing diagnosis on tumor cells
included in a sample by using a patch which is provided as a gel
type having a net-like structure forming micro-cavities and
contains reagent used to detect cancer, the diagnostic device
comprising: a relative movement adjusting module configured to
relatively move the patch and a region in which the sample is
provided to each other to provide the reagent contained in the
patch to the sample; and an image acquiring module configured to
acquire an image of the sample for cancer diagnosis.
20. The diagnostic apparatus of claim 19, further comprising a
temperature adjusting module configured to adjust the temperature
of the sample.
Description
TECHNICAL FIELD
[0001] The present application relates to a method of and device
for Circulating Tumor Cell (CTC) diagnosis using a patch, and more
particularly, to a method of and device for CTC diagnosis using a
patch for detecting tumor cells that float in blood and performing
cancer diagnosis.
BACKGROUND ART
[0002] Circulating Tumor Cell (CTC) testing is for detecting
circulating tumor cell that float in the blood, and various
diagnostic methods for blood may be used.
[0003] In the case of conventional cancer diagnosis, various
diagnoses are performed using a biopsy sample which is a piece of
tissue removed from a person subject to diagnosis. Generally, a
biopsy sample being acquired through surgery has sometimes been a
cause of unwillingness to receive cancer screening felt by a person
subject to diagnosis. Such a complex procedure and psychological
burden make it more difficult to detect cancer at an early
stage.
[0004] CTC testing is non-invasive testing for performing cancer
diagnosis using a blood sample collected from the blood of a person
subject to diagnosis. Therefore, a simple cancer diagnosis may be
possible without procedures like surgery. Further, since CTC
testing has an advantage of being able to predict whether cancer
metastasis will occur, research has been more vigorously carried
out on CTC testing.
[0005] In conventional CTC testing, a general immunoassay is
performed on the blood to identify the onset of cancer. For
example, in a process in which an antibody is injected into the
blood to detect an antigen to be diagnosed, a washing process in
which a large amount of washing solution is poured on a plate or
the like to rinse it in order to remove unbound antibodies or other
factors that interfere with the detection is necessarily required.
Accordingly, there are problems in that a large amount of washing
solution is wasted, and binding between an antibody and an antigen
is re-separated.
[0006] Therefore, a means for improving the accuracy of diagnosis
while minimizing an amount of reagents used in the diagnosis is
required for CTC testing.
SUMMARY
[0007] An aspect of the present disclosure is to provide a patch
capable of storing a substance.
[0008] An aspect of the present disclosure is to provide a patch
capable of providing a reaction space for a substance.
[0009] An aspect of the present disclosure is to provide a patch
capable of providing a substance.
[0010] An aspect of the present disclosure is to provide a patch
capable of absorbing a substance.
[0011] An aspect of the present disclosure is to provide a patch
capable of providing an environment.
[0012] An aspect of the present disclosure is to provide a
Circulating Tumor Cell (CTC) testing method.
[0013] According to an aspect of the present application, there is
provided a diagnostic method for performing diagnosis on tumor
cells included in a sample by using a patch which is provided as a
gel type having a net-like structure forming micro-cavities, the
diagnostic method including placing the sample on a plate and using
the patch, which contains reagents used to detect cancer, to
provide the reagents contained in the patch to the plate.
[0014] According to another aspect of the present application,
there is provided a diagnostic method for performing diagnosis on
tumor cells included in a sample by using a patch which is provided
as a gel type having a net-like structure forming micro-cavities,
the diagnostic method including placing the sample on a plate,
using a first patch, which contains a first reagent used to detect
cancer, to provide the reagent contained in the first patch to the
plate, and using a second patch, which contains a second reagent
used to detect the cancer, to provide the reagent contained in the
second patch to the plate.
[0015] According to still another aspect of the present
application, there is provided a diagnostic device for performing
diagnosis on tumor cells included in a sample by using a patch
which is provided as a gel type having a net-like structure forming
micro-cavities and contains reagents used to detect cancer, the
diagnostic device including a relative movement adjusting module
configured to relatively move the patch and a region in which the
sample is provided to each other to provide the reagents contained
in the patch to the sample, and an image acquiring module
configured to acquire an image of the sample for cancer
diagnosis.
[0016] According to the present disclosure, containing, delivery,
and absorption of a substance can be easily performed.
[0017] According to the present disclosure, a reaction region for a
substance can be provided, or a predetermined environment can be
provided to a target region.
[0018] According to the present disclosure, delivery and absorption
of a substance can be properly adjusted using a patch, and an
amount of reagents used in diagnosis can be significantly
reduced.
[0019] According to the present disclosure, a more accurate
diagnosis result can be acquired by performing multiple diagnostic
methods.
[0020] Aspects of the present disclosure are not limited to those
mentioned above, and unmentioned aspects will be clearly understood
by those of ordinary skill in the art to which the present
disclosure pertains from the present specification and the
accompanying drawings.
BRIEF DESCRIPTION OF DRAWINGS
[0021] FIG. 1 illustrates an example of a patch in detail according
to the present application.
[0022] FIG. 2 illustrates an example of a patch in detail according
to the present application.
[0023] FIG. 3 illustrates providing a reaction space as an example
of a function of a patch according to the present application.
[0024] FIG. 4 illustrates providing a reaction space as an example
of a function of a patch according to the present application.
[0025] FIG. 5 illustrates providing a substance as an example of a
function of a patch according to the present application.
[0026] FIG. 6 illustrates providing a substance as an example of a
function of a patch according to the present application.
[0027] FIG. 7 illustrates providing a substance as an example of a
function of a patch according to the present application.
[0028] FIG. 8 illustrates providing a substance as an example of a
function of a patch according to the present application.
[0029] FIG. 9 illustrates providing a substance as an example of a
function of a patch according to the present application.
[0030] FIG. 10 illustrates providing a substance as an example of a
function of a patch according to the present application.
[0031] FIG. 11 illustrates providing a substance as an example of a
function of a patch according to the present application.
[0032] FIG. 12 illustrates providing a substance as an example of a
function of a patch according to the present application.
[0033] FIG. 13 illustrates providing a substance as an example of a
function of a patch according to the present application.
[0034] FIG. 14 illustrates absorbing of a substance as an example
of a function of a patch according to the present application.
[0035] FIG. 15 illustrates absorbing of a substance as an example
of a function of a patch according to the present application.
[0036] FIG. 16 illustrates absorbing of a substance as an example
of a function of a patch according to the present application.
[0037] FIG. 17 illustrates absorbing of a substance as an example
of a function of a patch according to the present application.
[0038] FIG. 18 illustrates absorbing of a substance as an example
of a function of a patch according to the present application.
[0039] FIG. 19 illustrates absorbing of a substance as an example
of a function of a patch according to the present application.
[0040] FIG. 20 illustrates absorbing of a substance as an example
of a function of a patch according to the present application.
[0041] FIG. 21 illustrates absorbing of a substance as an example
of a function of a patch according to the present application.
[0042] FIG. 22 illustrates absorbing of a substance as an example
of a function of a patch according to the present application.
[0043] FIG. 23 illustrates providing an environment as an example
of a function of a patch according to the present application.
[0044] FIG. 24 illustrates providing an environment as an example
of a function of a patch according to the present application.
[0045] FIG. 25 illustrates providing an environment as an example
of a function of a patch according to the present application.
[0046] FIG. 26 illustrates performance of absorbing and providing a
substance as an embodiment of a patch according to the present
application.
[0047] FIG. 27 illustrates performance of absorbing and providing a
substance as an embodiment of a patch according to the present
application.
[0048] FIG. 28 illustrates performance of absorbing and providing a
substance as an embodiment of a patch according to the present
application.
[0049] FIG. 29 illustrates performance of absorbing and providing a
substance as an embodiment of a patch according to the present
application.
[0050] FIG. 30 illustrates performance of absorbing and providing a
substance as an embodiment of a patch according to the present
application.
[0051] FIG. 31 illustrates performance of absorbing and providing a
substance and providing an environment as an embodiment of a patch
according to the present application.
[0052] FIG. 32 illustrates performance of absorbing and providing a
substance and providing an environment as an embodiment of a patch
according to the present application.
[0053] FIG. 33 illustrates an implementation of a plurality of
patches as an embodiment of a patch according to the present
application.
[0054] FIG. 34 illustrates an implementation of a plurality of
patches and a plate having a plurality of target regions as an
embodiment of a patch according to the present application.
[0055] FIG. 35 is a view for describing performance of
morphological diagnosis using a staining technique in cancer
diagnosis according to an embodiment of the present
application.
[0056] FIG. 36 is a view for describing performance of
morphological diagnosis using a staining technique in which a
plurality of stains are used in cancer diagnosis according to an
embodiment of the present application.
[0057] FIG. 37 is a view for describing performance of
morphological diagnosis using a 4,6-diamidino-2-phenylindole (DAPI)
staining technique in cancer diagnosis according to an embodiment
of the present application.
[0058] FIG. 38 is a view for describing performance of immunoassay
in cancer diagnosis according to an embodiment of the present
application.
[0059] FIG. 39 is a view for describing a method of detecting
cancer using a substrate-enzyme reaction when immunoassay is
performed in cancer diagnosis according to an embodiment of the
present application.
[0060] FIG. 40 is a view for describing a method of detecting
cancer using a substrate-enzyme reaction when immunoassay is
performed in cancer diagnosis according to an embodiment of the
present application.
[0061] FIG. 41 is a view for describing a method of detecting
cancer using a fluorescent substance when immunoassay is performed
in cancer diagnosis according to an embodiment of the present
application.
[0062] FIG. 42 is a view for describing a method of performing
immunoassay using multiple types of antibodies in cancer diagnosis
according to an embodiment of the present application.
[0063] FIG. 43 is a view for describing a method of performing
immunoassay using a primary antibody and a secondary antibody in
cancer diagnosis according to an embodiment of the present
application.
[0064] FIG. 44 is a view for describing a method of performing
immunoassay using a first antibody that has been applied on a plate
and a second antibody that is provided to a sample in cancer
diagnosis according to an embodiment of the present
application.
[0065] FIG. 45 is a view for describing performance of cell
culturing in cancer diagnosis according to an embodiment of the
present application.
[0066] FIG. 46 is a view for describing a process in which cells,
which are included in a sample, proliferate in cancer diagnosis
according to an embodiment of the present application.
[0067] FIG. 47 is a view for describing a process in which cells
included in a sample proliferate in cancer diagnosis according to
an embodiment of the present application.
[0068] FIG. 48 is a view for describing performance of a polymerase
chain reaction (PCR) process in cancer diagnosis according to an
embodiment of the present application.
[0069] FIG. 49 is a view for describing a method of using a patch
to decompose a cell membrane of cells included in a sample when a
PCR process is performed in cancer diagnosis according to an
embodiment of the present application.
[0070] FIG. 50 is a view for describing performance of a PCR
process in cancer diagnosis according to an embodiment of the
present application.
[0071] FIG. 51 is a view for describing multiple types of
diagnostic methods for a sample in cancer diagnosis according to an
embodiment of the present application.
[0072] FIG. 52 is a view for describing multiple types of
diagnostic methods for a sample in cancer diagnosis according to an
embodiment of the present application.
[0073] FIG. 53 is a view for describing multiple types of
diagnostic methods for a sample in cancer diagnosis according to an
embodiment of the present application.
[0074] FIG. 54 is a view for describing multiple types of
diagnostic methods for a sample in cancer diagnosis according to an
embodiment of the present application.
[0075] FIG. 55 is a view for describing multiple types of
diagnostic methods for a sample in cancer diagnosis according to an
embodiment of the present application.
[0076] FIG. 56 is a view for describing multiple types of
diagnostic methods for a sample in cancer diagnosis according to an
embodiment of the present application.
[0077] FIG. 57 is a view for describing multiple types of
diagnostic methods for a sample in cancer diagnosis according to an
embodiment of the present application.
[0078] FIG. 58 is a view for describing multiple types of
diagnostic methods for a sample in cancer diagnosis according to an
embodiment of the present application.
[0079] FIG. 59 is a block diagram of a diagnostic device according
to an embodiment of the present application.
[0080] FIG. 60 is a conceptual diagram illustrating an example in
which a structure of a diagnostic device is moved due to a relative
movement operation of a relative position adjusting module
according to an embodiment of the present application.
DETAILED DESCRIPTION
[0081] Since embodiments described herein are for clearly
describing the spirit of The present disclosure to those of
ordinary skill in the art to which the present disclosure pertains,
the present disclosure is not limited to the embodiments described
herein, and the scope of the present disclosure should be construed
as including revised examples or modified examples not departing
from the spirit of the present disclosure.
[0082] General terms currently being used as widely as possible
have been selected as terms used herein in consideration of
functions in the present disclosure, but the terms may be changed
according to intentions and practices of those of ordinary skill in
the art to which the present disclosure pertains or the advent of
new technologies, etc. However, instead, when a particular term is
defined as a certain meaning and used, the meaning of the term will
be separately described. Consequently, the terms used herein should
be construed on the basis of substantial meanings of the terms and
content throughout the present specification instead of simply on
the basis of names of the terms.
[0083] The accompanying drawings herein are for easily describing
the present disclosure. Since shapes illustrated in the drawings
may have been exaggeratedly depicted as much as necessary to assist
in understating the present disclosure, the present disclosure is
not limited by the drawings.
[0084] When detailed description of a known configuration or
function related to the present disclosure is deemed to obscure the
gist of the present disclosure in the present specification, the
detailed description related thereto will be omitted as
necessary.
[0085] According to an aspect of the present application, there is
provided a diagnostic method for performing diagnosis on tumor
cells included in a sample by using a patch which is provided as a
gel type having a net-like structure forming micro-cavities, the
diagnostic method including placing the sample on a plate and using
the patch that contains reagents used to detect cancer to provide
the reagents contained in the patch to the plate.
[0086] The placing of the sample on the plate may include providing
the sample in a single layer on the plate.
[0087] The sample may be blood.
[0088] The placing of the sample on the plate may include fixating
the sample on the plate.
[0089] The reagents contained in the patch may include an antibody
that reacts specifically with the tumor cells.
[0090] The diagnostic method may include providing a substrate on
the plate in order to identify an antibody bound to the tumor
cells.
[0091] An antibody that reacts specifically with the tumor cells
may be applied on the plate.
[0092] The reagents contained in the patch may include a staining
reagent used in staining cells in order to stain the tumor
cells.
[0093] The staining reagent may target at least one of a nucleus of
the cells, a cytoplasm of the cells, and DNA distributed in the
cells.
[0094] The diagnostic method may include adjusting a temperature of
the sample in order to create a reaction environment for the
staining reagent.
[0095] The reagents contained in the patch may include a nutrient
reagent used in cell culturing in order to diagnose the cancer by
culturing the tumor cells.
[0096] The providing the reagents contained in the patch may
include bringing the patch and the plate into contact.
[0097] The diagnostic method may further include acquiring an image
of the plate on which the sample is placed in order to perform
diagnosis of the tumor cells.
[0098] The image of the plate on which the sample is placed may be
a fluorescence image.
[0099] The reagents contained in the patch may include a reagent
used in removal of a cell membrane of cells in order to extract DNA
of the tumor cells.
[0100] According to another aspect of the present application,
there is provided a diagnostic method for performing diagnosis on
tumor cells included in a sample by using a patch which is provided
as a gel type having a net-like structure forming micro-cavities,
the diagnostic method including placing the sample on a plate,
using a first patch that contains a first reagent used to detect
cancer to provide the reagent contained in the first patch to the
plate, and using a second patch, which contains a second reagent
used to detect the cancer, to provide the reagent contained in the
second patch to the plate.
[0101] The providing the reagent contained in the first patch may
be performed prior to the providing the reagent contained in the
second patch.
[0102] The first reagent may include an antibody that reacts
specifically with the tumor cells, and the second reagent may
include an antibody that binds to the antibody reacting
specifically with the tumor cells.
[0103] The first reagent may include an antibody that reacts
specifically with the tumor cells, and the second reagent may
include a nutrient reagent that is used in cell culturing in order
to diagnose the cancer by culturing the tumor cells
[0104] The first reagent may include an antibody that reacts
specifically with the tumor cells, and the second reagent may
include a staining reagent that is used for cell staining in order
to stain the tumor cells.
[0105] The first reagent may include an antibody that reacts
specifically with the tumor cells, and the second reagent may
include an antibody that reacts specifically with white blood
cells.
[0106] The diagnostic method may further include, between the
providing the reagent contained in the first patch and the
providing the reagent contained in the second patch, acquiring an
image of the sample.
[0107] The first reagent may include a reagent used in removal of a
cell membrane of cells in order to extract DNA of the tumor cells,
and the second reagent may include a reagent used in a polymerase
chain reaction (PCR).
[0108] The diagnostic method may further include adjusting a
temperature of the sample in order to cause the PCR.
[0109] According to still another aspect of the present
application, there is provided a diagnostic device for performing
diagnosis on tumor cells included in a sample by using a patch
which is provided as a gel type having a net-like structure forming
micro-cavities and contains reagents used to detect cancer, the
diagnostic device including a relative movement adjusting module
configured to relatively move the patch and a region in which the
sample is provided to each other to provide the reagents contained
in the patch to the sample, and an image acquiring module
configured to acquire an image of the sample for cancer
diagnosis.
[0110] The diagnostic device may further include a temperature
adjusting module configured to adjust the temperature of the
sample.
[0111] 1. Patch
[0112] 1.1 Meaning of Patch
[0113] In the present application, a patch for managing a liquid
substance is disclosed.
[0114] The liquid substance may mean a substance which is in a
liquid state and can flow.
[0115] The liquid substance may be a substance formed of a single
component having fluidity. Alternatively, the liquid substance may
be a mixture that includes a substance formed of a plurality of
components.
[0116] When the liquid substance is a substance formed of a single
component, the liquid substance may be a substance formed of a
single chemical element or a compound including a plurality of
chemical elements.
[0117] When the liquid substance is a mixture, a portion of the
substance formed of a plurality of components may serve as a
solvent, and the other portion may serve as a solute. That is, the
mixture may be a solution.
[0118] A plurality of components constituting the mixture which
forms the substance may be uniformly distributed. Alternatively,
the mixture including the substance formed of a plurality of
components may be a uniformly mixed mixture.
[0119] The substance formed of a plurality of components may
include a solvent and a substance that is not dissolved in the
solvent and is uniformly distributed.
[0120] A portion of the substance formed of a plurality of
components may be non-uniformly distributed. The non-uniformly
distributed substance may include non-uniformly distributed
particle components in the solvent. In this case, the non-uniformly
distributed particle components may be in a solid phase.
[0121] For example, a substance that may be managed using the patch
may be in a state of 1) a liquid formed of a single component, 2) a
solution, or 3) a colloid, or according to circumstances, may be in
a state in which 4) solid particles are non-uniformly distributed
within another liquid substance.
[0122] Hereinafter, the patch according to the present application
will be described in more detail.
[0123] 1.2 General Nature of Patch
[0124] 1.2.1 Configuration
[0125] FIGS. 1 and 2 are views illustrating an example of a patch
according to the present application. The patch according to the
present application will be described below with reference to FIGS.
1 and 2.
[0126] Referring to FIG. 1, a patch PA according to the present
application may include a mesh structural body NS and a liquid
substance.
[0127] As the liquid substance, a base substance BS and an additive
substance AS may be taken into consideration separately.
[0128] The patch PA may be in a gel state (gel type). The patch PA
may be implemented as a gel-type structural body in which colloidal
molecules are bound and mesh tissues are formed.
[0129] The patch PA according to the present application is a
structure for managing a liquid substance SB, and may include a
three-dimensional mesh (net-like) structural body NS. The mesh
structural body NS may be a continuously distributed solid
structure. The mesh structural body NS may have a mesh structure in
which a plurality of micro-threads are intertwined. However, the
mesh structural body NS is not limited to the mesh form in which
the plurality of micro-threads are intertwined, and may also be
implemented in the form of an arbitrary three-dimensional matrix
that is formed by connection of a plurality of micro-structures.
For example, the mesh structural body NS may be a frame structural
body that includes a plurality of micro-cavities. In other words,
the mesh structural body NS may form a plurality of micro-cavities
MC.
[0130] FIG. 2 illustrates a structure of a patch according to an
embodiment of the present application. Referring to FIG. 2, the
mesh structural body of the patch PA may have a sponge structure
SS. The mesh structural body of the sponge structure SS may include
a plurality of micro-holes MH. Hereinafter, the terms micro-holes
MH and the micro-cavities MC may be used interchangeably, and
unless particularly mentioned otherwise, the term micro-cavities MC
is defined as encompassing the concept of the micro-holes MH.
[0131] The mesh structural body NS may have a regular or irregular
pattern. Furthermore, the mesh structural body NS may include both
a region having a regular pattern and a region having an irregular
pattern.
[0132] A density of the mesh structural body NS may have a value
within a predetermined range. Preferably, the predetermined range
may be set within a limit in which the form of the liquid substance
SB captured in the patch PA is maintained in a form that
corresponds to the patch PA. The density may be defined as a degree
to which the mesh structural body NS is dense or a mass ratio, a
volume ratio, or the like that the mesh structural body NS occupies
in the patch.
[0133] The patch according to the present application may manage
the liquid substance SB by having a three-dimensional mesh
structure.
[0134] The patch PA according to the present application may
include the liquid substance SB, and the fluidity of the liquid
substance SB included in the patch PA may be limited by the form of
the mesh structural body NS of the patch PA.
[0135] The liquid substance SB may freely flow within the mesh
structural body NS. In other words, the liquid substance SB is
placed in the plurality of micro-cavities formed by the mesh
structural body NS. An exchange of liquid substance SB may occur
between neighboring micro-cavities. In this case, the liquid
substance SB may be present in a state in which the liquid
substance SB permeating into a frame structural body that forms the
mesh tissues. In such a case, nano-sized pores into which the
liquid substances SB may permeate may be formed in the frame
structural body.
[0136] Further, whether to the liquid substance SB is filled in the
frame structural body of the mesh structure may be determined
depending on a molecular weight or a particle size of the liquid
substance SB to be captured in the patch PA. A substance having a
relatively large molecular weight may be captured in the
micro-cavities, and a substance having a relatively small molecular
weight may be captured by the frame structural body and filled in
the micro-cavities and/or the frame structural body of the mesh
structural body NS.
[0137] In the present specification, the term "capture" may be
defined as a state in which the liquid substance SB is placed in
the plurality of micro-cavities and/or nano-sized holes formed by
the mesh structural body NS. As described above, the state in which
the liquid substance SB is captured in the patch PA is defined as
including a state in which the liquid substance SB may flow between
the micro-cavities and/or the nano-sized holes.
[0138] As in the following, the base substance BS and the additive
substance AS may be taken into consideration separately as the
liquid substance SB.
[0139] The base substance BS may be a liquid substance SB having
fluidity.
[0140] The additive substance AS may be a substance that is mixed
with the base substance BS and has fluidity. In other words, the
base substance BS may be a solvent. The additive substance AS may
be a solute that is dissolved in the solvent or may be particles
that are not melted in the solvent.
[0141] The base substance BS may be a substance capable of flowing
inside a matrix formed by the mesh structural body NS. The base
substance BS may be uniformly distributed in the mesh structural
body NS or may be distributed only in a partial region of the mesh
structural body NS. The base substance BS may be a liquid having a
single component.
[0142] The additive substance AS may be a substance that is mixed
with the base substance BS or dissolved in the base substance BS.
For example, the additive substance AS may serve as a solute while
the base substance BS is a solvent. The additive substance AS may
be uniformly distributed in the base substance BS.
[0143] The additive substance AS may be fine particles that are not
dissolved in the base substance BS. For example, the additive
substance AS may include colloidal molecules and fine particles
such as microorganisms.
[0144] The additive substance AS may include particles larger than
the micro-cavities formed by the mesh structural body NS. When the
size of the micro-cavities is smaller than the size of the
particles included in the additive substance AS, fluidity of the
additive substance AS may be limited.
[0145] According to an embodiment, the additive substance AS may
include a component that is selectively included in the patch
PA.
[0146] The additive substance AS does not necessarily refer to a
substance that is lower in quantity or inferior in function in
comparison to the above-described base substance BS.
[0147] Hereinafter, characteristics of the liquid substance SB
captured in the patch PA may be presumed as characteristics of the
patch PA. That is, the characteristics of the patch PA may depend
on characteristics of a substance captured in the patch PA.
[0148] 1.2.2 Characteristics
[0149] As described above, the patch PA according to the present
application may include the mesh structural body NS. The patch PA
may manage the liquid substance SB through the mesh structural body
NS. The patch PA may allow the liquid substance SB captured in the
patch PA to maintain at least some of its unique
characteristics.
[0150] For example, diffusion of a substance may occur in a region
of the patch PA in which the liquid substance SB is distributed,
and a force such as surface tension may come into action.
[0151] The patch PA may provide a liquid environment in which
diffusion of a target substance is caused due to thermal motion of
a substance or a difference in density or concentration thereof.
Generally, "diffusion" refers to a phenomenon in which particles
that constitute a substance are spread from a side at which
concentration is high to a side at which a concentration is low due
to a difference in concentration. Such a diffusion phenomenon may
be basically understood as a phenomenon that occurs due to motion
of molecules (translational motion in a gas or liquid, vibrational
motion in a solid, and the like). In the present application, in
addition to referring to the phenomenon in which particles are
spread from a side at which a concentration is high toward a side
at which a concentration is low due to a difference in
concentration or density, "diffusion" also refers to a phenomenon
in which particles move due to irregular motion of molecules that
occurs even when a concentration is uniform. The expression
"irregular motion" may also have the same meaning as "diffusion"
unless particularly mentioned otherwise. The diffused substance may
be a solute that is dissolved in the liquid substance SB, and the
diffused substance may be provided in a solid, liquid, or gas
state.
[0152] More specifically, a non-uniformly-distributed substance in
the liquid substance SB captured by the patch PA may be diffused in
a space provided by the patch PA. In other words, the additive
substance AS may be diffused in a space defined by the patch
PA.
[0153] The non-uniformly-distributed substance or the additive
substance AS in the liquid substance SB managed by the patch PA may
be diffused within the micro-cavities provided by the mesh
structural body NS of the patch PA. A region in which the
non-uniformly-distributed substance or the additive substance AS
may be diffused may be changed by the patch PA being connected or
coming into contact with another substance.
[0154] Even when, after the concentration of the substance or the
additive substance AS has become uniform, as a result of diffusion
of the non-uniformly-distributed substance or the additive
substance AS within the patch PA or within an external region
connected to the patch PA, the substance or the additive substance
AS may continuously move due to irregular motion of molecules
inside the patch PA and/or within the external region connected to
the patch PA.
[0155] The patch PA may be implemented to exhibit a hydrophilic or
hydrophobic property. In other words, the mesh structural body NS
of the patch PA may have a hydrophilic or hydrophobic property.
[0156] When properties of the mesh structural body NS and the
liquid substance SB are similar, the mesh structural body NS may be
able to manage the liquid substance SB more effectively.
[0157] The base substance BS may be a polar hydrophilic substance
or a nonpolar hydrophobic substance. The additive substance AS may
exhibit a hydrophilic or hydrophobic property.
[0158] The properties of the liquid substance SB may be related to
the base substance BS and/or the additive substance AS. For
example, when both the base substance BS and the additive substance
AS are hydrophilic, the liquid substance SB may be hydrophilic, and
when both the base substance BS and the additive substance AS are
hydrophobic, the liquid substance SB may be hydrophobic. When
polarities of the base substance BS and the additive substance AS
are different, the liquid substance SB may be hydrophilic or
hydrophobic.
[0159] When polarities of both the mesh structural body NS and the
liquid substance SB are hydrophilic or hydrophobic, an attractive
force may come into action between the mesh structural body NS and
the liquid substance SB. When polarities of the mesh structural
body NS and the liquid substance SB are opposite, e.g., when the
polarity of the mesh structural body NS is hydrophobic and the
polarity of the liquid substance SB is hydrophilic, a repulsive
force may act between the mesh structural body NS and the liquid
substance SB.
[0160] On the basis of the above-described properties, the patch PA
may be solely used, a plurality of patches PA may be used, or the
patch PA may be used with another medium to induce a desired
reaction. Hereinafter, functional aspects of the patch PA will be
described.
[0161] However, hereinafter, for convenience of description, the
patch PA is assumed as being a gel type that may include a
hydrophilic solution. In other words, unless particularly mentioned
otherwise, the mesh structural body NS of the patch PA is assumed
to have a hydrophilic property.
[0162] However, the scope of the present application should not be
interpreted as being limited to the gel-type patch PA having a
hydrophilic property. In addition to a gel-type patch PA that
includes a solution exhibiting a hydrophobic property, a gel-type
patch PA from which a solvent is removed and even a sol-type patch
PA, as long as it is capable of implementing functions according to
the present application, may belong to the scope of the present
application.
[0163] 2. Functions of Patch
[0164] Due to the above-described characteristics, the patch
according to the present application may have some useful
functions. In other words, by capturing the liquid substance SB,
the patch may become involved in behavior of the liquid substance
SB.
[0165] Accordingly, hereinafter, in accordance with forms of
behavior of the substance with respect to the patch PA, a reservoir
function in which a state of the substance is defined in a
predetermined region formed by the patch PA and a channeling
function in which a state of the substance is defined in a region
including an external region of the patch PA will be separately
described.
[0166] 2.1 Reservoir
[0167] 2.1.1 Meaning
[0168] As described above, the patch PA according to the present
application may capture the liquid substance SB. In other words,
the patch PA may perform a function as a reservoir.
[0169] The patch PA may capture the liquid substance SB in the
plurality of micro-cavities formed in the mesh structural body NS
using the mesh structural body NS. The liquid substance SB may
occupy at least a portion of the fine micro-cavities formed by the
three-dimensional mesh structural body NS of the patch PA or be
penetrated in the nano-sized pores formed in the mesh structural
body NS.
[0170] The liquid substance SB placed in the patch PA does not lose
properties of a liquid even when the liquid substance SB is
distributed in the plurality of micro-cavities. That is, the liquid
substance SB has fluidity even in the patch PA, and diffusion of a
substance may occur in the liquid substance SB distributed in the
patch PA, and an appropriate solute may be dissolved in the
substance.
[0171] The reservoir function of the patch PA will be described
below in more detail.
[0172] 2.1.2 Containing
[0173] In the present application, the patch PA may capture a
target substance due to the above-described characteristics. The
patch PA may have resistance to a change in an external environment
within a predetermined range. In this way, the patch PA may
maintain a state in which the substance is captured therein. The
liquid substance SB, which is a target to be captured, may occupy
the three-dimensional mesh structural body NS.
[0174] Hereinafter, for convenience, the above-described function
of the patch PA will be referred to as "containing."
[0175] However, "the patch PA containing the liquid substance" is
defined to encompass a case in which the liquid substance is
contained in a space formed by the mesh structure and/or a case in
which the liquid substance is contained in the frame structural
body constituting the mesh structural body NS.
[0176] The patch PA may contain the liquid substance SB. For
example, the patch PA may contain the liquid substance SB, due to
an attractive force that acts between the mesh structural body NS
of the patch PA and the liquid substance SB. The liquid substance
SB may be bound to the mesh structural body NS with an attractive
force of a predetermined strength or higher and contained in the
patch PA.
[0177] Properties of the liquid substance SB contained in the patch
PA may be classified in accordance with properties of the patch PA.
More specifically, when the patch PA exhibits a hydrophilic
property, the patch PA may be bound to a hydrophilic liquid
substance SB which is polar in general and contain the hydrophilic
liquid substance SB in the three-dimensional micro-cavities.
Alternatively, when the patch PA exhibits a hydrophobic property,
the hydrophobic liquid substance SB may be contained in the
micro-cavities of the three-dimensional mesh structural body
NS.
[0178] The amount of substance that may be contained in the patch
PA may be proportional to a volume of the patch PA. In other words,
the amount of substance contained in the patch PA may be
proportional to an amount of three-dimensional mesh structural body
NS that serves as a support body that contributes to the form of
the patch PA. However, there is no constant proportional factor
between the amount of substance that may be contained in the patch
PA and the volume of the patch PA, and thus the relationship
between the amount of substance that may be contained in the patch
PA and the volume of the patch PA may be changed in accordance with
the design or manufacturing method of the mesh structure.
[0179] The amount of substance contained in the patch PA may be
reduced due to evaporation, loss, etc. with time. The substance may
be additionally injected into the patch PA to increase or maintain
the content of the substance contained in the patch PA. For
example, a moisture keeping agent for suppressing evaporation of
moisture may be added to the patch PA.
[0180] The patch PA may be implemented in a form in which it is
easy to store the liquid substance SB. This signifies that, when
the substance is affected by environmental factors such as humidity
level, amount of light, and temperature, the patch PA may be
implemented to minimize denaturalization of the substance. For
example, to prevent the patch PA from being denaturalized due to
external factors such as bacteria, the patch PA may be treated with
a bacteria inhibitor.
[0181] A liquid substance SB having a plurality of components may
be contained in the patch PA. In this case, the substance formed of
a plurality of components may be placed together in the patch PA
before a reference time point, or a primarily-injected substance
may be first contained in the patch PA and then a secondary
substance may be contained in the patch PA after a predetermined
amount of time. For example, when a liquid substance SB formed of
two components is contained in the patch PA, the two components may
be contained in the patch PA upon manufacturing the patch PA, only
one component may be contained in the patch PA upon manufacturing
the patch PA and the other component may be contained therein
later, or the two components may be sequentially contained in the
patch PA after the patch PA is manufactured.
[0182] As described above, the substance contained in the patch may
exhibit fluidity, and the substance may move irregularly or be
diffused due to molecular motion in the patch PA.
[0183] 2.1.3 Providing of Reaction Space
[0184] FIGS. 3 and 4 are views illustrating providing a reaction
space as an example of a function of the patch according to the
present application.
[0185] As illustrated in FIGS. 3 and 4, the patch PA according to
the present application may perform a function of providing a
space. In other words, the patch PA may provide a space in which
the liquid substance SB may move through a space formed by the mesh
structural body NS and/or a space constituting the mesh structural
body NS.
[0186] The patch PA may provide a space for activity other than
diffusion of particles and/or irregular motion of particles
(hereinafter referred to as activity other than diffusion). The
activity other than diffusion may refer to a chemical reaction, but
is not limited thereto, and may also refer to a physical state
change. More specifically, the activity other than diffusion may
include a chemical reaction in which a chemical composition of the
substance changes after the activity, a specific binding reaction
between components included in the substance, homogenization of
solutes or particles included in the substance and non-uniformly
distributed therein, condensation of some components included in
the substance, or a biological activity of a portion of the
substance.
[0187] When a plurality of substances become involved in the
activity, the plurality of substances may be placed together in the
patch PA before a reference time point. The plurality of substances
may be sequentially inserted into the patch PA.
[0188] By changing environmental conditions of the patch PA,
efficiency of the function of providing a space for activities
other than diffusion in the patch PA may be enhanced. For example,
the activity may be promoted or a start of the activity may be
induced by changing a temperature condition of the patch PA or
adding an electrical condition thereto.
[0189] According to FIGS. 3 and 4, a first substance SB1 and a
second substance SB2 placed in the patch PA may react inside the
patch PA and be deformed into a third substance SB3 or generate the
third substance SB3.
[0190] 2.2 Channel
[0191] 2.2.1 Meaning
[0192] Movement of a substance may occur between the patch PA and
an external region. The substance may be moved from the patch PA to
the external region of the patch PA or may be moved from the
external region to the patch PA.
[0193] The patch PA may form a substance movement path or get
involved in movement of the substance. More specifically, the patch
PA may become involved in movement of the liquid substance SB
captured in the patch PA or become involved in movement of an
external substance through the liquid substance SB captured in the
patch PA. The base substance BS or the additive substance AS may
move out from the patch PA, or an external substance may be
introduced from an external region to the patch PA.
[0194] The patch PA may provide a substance movement path. That is,
the patch PA may become involved in movement of the substance and
provide a substance movement channel. The patch PA may provide a
substance movement channel based on unique properties of the liquid
substance SB.
[0195] In accordance with whether the patch PA is connected to the
external region, the patch PA may be in a state in which the liquid
substance SB is movable between the patch PA and the external
region or a state in which the liquid substance SB is immovable
between the patch PA and the external region. When channeling
between the patch PA and the external region begins, the patch PA
may have unique functions.
[0196] Hereinafter, the state in which the substance is movable and
the state in which the substance is immovable will be described
first, and the unique functions of the patch PA will be described
in detail in connection with whether the patch PA and the external
region are connected.
[0197] Basically, irregular motion and/or diffusion of the
substance are fundamental causes of movement of the liquid
substance SB between the patch PA and the external region. However,
controlling an external environmental factor (e.g., controlling a
temperature condition, controlling an electrical condition, or the
like) in order to control movement of a substance between the patch
PA and the external region has already been described.
[0198] 2.2.2 Movable State
[0199] In the state in which the substance is movable, a flow may
occur between the liquid substance SB captured in the patch PA
and/or the substance placed in the external region. In the state in
which the substance is movable, substance movement may occur
between the liquid substance SB captured in the patch PA and the
external region.
[0200] For example, in the state in which the substance is movable,
the liquid substance SB or some components of the liquid substance
SB may be diffused to the external region or moved due to irregular
motion. Alternatively, in the state in which the substance is
movable, an external substance placed in the external region or
some components of the external substance may be diffused to the
liquid substance SB in the patch PA or moved due to irregular
motion.
[0201] The state in which the substance is movable may be caused by
contact. The contact may refer to connection between the liquid
substance SB captured in the patch PA and the external region.
Contact may refer to at least a partial overlap between a flow
region of the liquid substance SB and the external region. The
contact may refer to the external substance being connected to at
least a portion of the patch PA. It may be understood that the
range in which the captured liquid substance SB may flow is
expanded in the state in which the substance is movable. In other
words, in the state in which the substance is movable, the range in
which the liquid substance SB may flow may be expanded to include
at least a portion of the external region of the captured liquid
substance SB. For example, when the liquid substance SB is in
contact with the external region, the range in which the captured
liquid substance SB may flow may be expanded to include at least a
portion of the external region in contact. More specifically, when
the external region is an external plate, the region in which the
liquid substance SB may flow may be expanded to include a region of
the external plate in contact with the liquid substance SB.
[0202] 2.2.3 Immovable State
[0203] In the state in which the substance is immovable, substance
movement may not occur between the liquid substance SB captured in
the patch PA and the external region. However, substance movement
may respectively occur in the liquid substance SB captured in the
patch PA and in external substance placed in the external
region.
[0204] The state in which the substance is immovable may be a state
in which the contact is released. In other words, in the state in
which contact between the patch PA and the external region is
released, substance movement is not possible between the liquid
substance SB remaining in the patch PA and the external region or
the external substance.
[0205] More specifically, the state in which the contact is
released may refer to a state in which the liquid substance SB
captured in the patch PA is not connected to the external region.
The state in which the contact is released may refer to a state in
which the liquid substance SB is not connected to an external
substance placed in the external region. For example, the state in
which movement of the substance is impossible may be caused by
separation between the patch PA and the external region.
[0206] In the present specification, although "movable state" has a
meaning differentiated from that of "immovable state," a transition
may occur between the states due to an elapse of time, an
environmental change, and the like. In other words, the patch PA
may be in the immovable state after being in the movable state, in
the movable state after being in the immovable state, or may be in
the movable state again, after being in the immovable state after
being in the movable state.
2.2.4 Differentiation of Functions
2.2.4.1 Delivery
[0207] In the present application, due to the above-described
characteristics, the patch PA may deliver at least a portion of the
liquid substance SB captured in the patch PA to a desired external
region. The delivery of the substance may refer to separation of a
portion of the liquid substance SB captured in the patch PA from
the patch PA due to a predetermined condition being satisfied. The
separation of the portion of the liquid substance SB may refer to
the portion of the substance being extracted, emitted, or released
from a region that is affected by the patch PA. This is a concept
subordinate to the above-described channeling function of the patch
PA, and may be understood as defining transfer (delivery) of the
substance placed in the patch PA to the outside of the patch
PA.
[0208] The desired external region may be another patch PA, a dried
region, or a liquid region.
[0209] The predetermined condition for the delivery to occur may be
set as an environmental condition such as a temperature change, a
pressure change, a change in an electrical characteristic, and a
change in a physical state. For example, when the patch PA is in
contact with an object whose force of binding to the liquid
substance SB is larger than a force of binding to the mesh
structural body NS of the patch PA, the liquid substance SB may be
chemically bound with the object in contact, and as a result, at
least a portion of the liquid substance SB may be provided to the
object.
[0210] Hereinafter, for convenience, the above-described function
of the patch PA will be referred to as "delivery."
[0211] The delivery may occur between the patch PA and the external
region, via the state in which the liquid substance SB is movable
and the state in which the liquid substance SB is immovable between
the patch PA and the external region.
[0212] More specifically, when the liquid substance SB is in the
movable state, the liquid substance SB may be diffused between the
patch PA and the external region or may be moved to the external
region due to irregular motion. In other words, the base solution
and/or the additive substance AS included in the liquid substance
SB may be moved from the patch PA to the external region. In the
state in which the liquid substance SB is immovable, the liquid
substance SB is unable to move between the patch PA and the
external region. In other words, due to a transition from the
movable state to the immovable state, a portion of the substance
that has moved from the patch PA to the external region due to
diffusion and/or irregular motion of the liquid substance SB become
unable to move back to the patch PA. Thus, a portion of the liquid
substance SB may be provided to the external region.
[0213] The delivery may be performed due to a difference between an
attractive force between the liquid substance SB and the mesh
structural body NS and an attractive force between the liquid
substance SB and the external region or the external substance. The
attractive force may be caused by similarity between polarities or
a specific binding relationship.
[0214] More specifically, when the liquid substance SB is
hydrophilic and the external region or the external substance is
more hydrophilic than the mesh structural body NS, at least a
portion of the liquid substance SB captured in the patch PA may be
provided to the external region via the movable state and the
immovable state.
[0215] The delivery of the liquid substance SB may also be
performed selectively. For example, when a specific binding
relationship exists between some components included in the liquid
substance SB and the external substance, some of the ingredients
may be selectively delivered via the state in which the substance
is movable and the state in which the substance is immovable.
[0216] More specifically, when it is assumed that the patch PA
provides a substance to an external plate PL, which is in a form of
a flat plate, a substance that binds specifically to a portion of
the liquid substance SB captured in the patch PA (e.g., a portion
of a solute) may be applied on the external plate PL. In this case,
the patch PA may selectively deliver a portion of the solute that
binds specifically to the substance applied on the external plate
PL from the patch PA to the plate PL via the movable state and the
immovable state.
[0217] The delivery as a function of the patch PA will be described
below according to a few examples of different regions to which the
substance is moved. However, in giving the detailed description,
the concepts of "release" of the liquid substance SB and "delivery"
of the liquid substance SB may be interchangeably used. Here, a
case in which the liquid substance SB is provided from the patch PA
to a separate external plate PL will be described. For example, a
case in which the substance is moved from the patch PA to a plate
PL, such as a slide glass, may be taken into consideration.
[0218] As the patch PA and the plate PL come into contact, at least
a portion of the liquid substance SB captured in the patch PA is
diffused to the plate PL or moved due to irregular motion. When the
contact between the patch PA and the plate PL is released, the
portion of the substance that has been moved from the patch PA to
the plate PL (that is, the portion of the liquid substance SB) may
become unable to move back to the patch PA. As a result, the
portion of the substance may be provided from the patch PA to the
plate PL. In this case, the portion of the substance being provided
may be the additive substance AS. For a substance in the patch PA
to be "provided" by the contact and separation, an attractive force
and/or binding force that acts between the substance and the plate
PL should be present, and the attractive force and/or the binding
force should be larger than the attractive force acting between the
substance and the patch PA. Therefore, if the above-described
"delivery condition" is not satisfied, delivery of a substance may
not occur between the patch PA and the plate PL.
[0219] The delivery of a substance may be controlled by providing a
temperature condition or an electrical condition to the patch
PA.
[0220] The movement of a substance from the patch PA to the plate
PL may depend on an extent of a contact area between the patch PA
and the plate PL. For example, the substance movement efficiency
between the patch PA and the plate PL may be increased or decreased
in accordance with an extent of an area in which the patch PA and
the plate PL come into contact.
[0221] When the patch PA includes a plurality of components, only
some of the components may be selectively moved to the external
plate PL. More specifically, a substance that binds specifically to
some of the plurality of components may be fixed to the external
plate PL. In this case, the substance fixed to the external plate
PL may be in a liquid or solid state, or may be fixed to a
different region. In this case, a portion of the substance of the
plurality of components moves to the plate PL and binds
specifically to the plate PL due to contact between the patch PA
and the different region, and when the patch PA is separated from
the plate PL, only some of the components may be selectively
released to the plate PL.
[0222] FIGS. 5 to 7 illustrate delivery of a substance from the
patch PA to the external plate PL as an example of delivery of a
substance from among the functions of the patch PA according to the
present application. According to FIGS. 5 to 7, by the patch PA
coming into contact with the external plate PL, a portion of a
substance contained in the patch PA may be provided to the plate
PL. In this case, providing the substance may become possible by
the patch PA coming into contact with the plate so that the
substance is movable. In this case, a water film WF may be formed
in the vicinity of a contact surface at which the plate and the
patch PA come into contact, and the substance may be movable
through the formed water film WF.
[0223] Here, a case in which the liquid substance SB is provided
from the patch PA to a substance having fluidity SL will be
described. The substance having fluidity SL may be a liquid
substance that is held in other containing space or that is
flowing.
[0224] As the patch PA and the substance having fluidity come into
contact (for example, the patch PA is put into a solution), at
least a portion of the liquid substance SB captured in the patch PA
may be diffused or moved due to irregular motion to the substance
having fluidity SL. When the patch PA and the substance having
fluidity SL are separated, a portion of the liquid substance SB
that has been moved from the patch PA to the substance having
fluidity become unable to move back to the patch PA so that a
portion of the substance in the patch PA may be provided to the
substance having fluidity.
[0225] The substance movement between the patch PA and the
substance having fluidity SL may depend on an extent of a contact
area between the patch PA and the substance having fluidity SL. For
example, the substance movement efficiency between the patch PA and
the substance having fluidity SL may be increased or decreased in
accordance with an extent of an area at which the patch PA and the
substance having fluidity SL come into contact (for example, a
depth at which the patch PA is immersed into a solution or the
like).
[0226] The substance movement between the patch PA and the
substance having fluidity SL may be controlled through physical
separation between the patch PA and the substance having
fluidity.
[0227] A partial concentration of the additive substance AS in the
liquid substance SB and a partial concentration of the additive
substance AS in the substance having fluidity may be different, and
the additive substance AS may be provided from the patch PA to the
substance having fluidity.
[0228] However, in the patch PA providing the liquid substance SB
to the substance having fluidity SL, the physical separation
between the patch PA and the substance having fluidity SL is not
essential. For example, when a force (driving force/casual force)
that causes a substance to move from the patch PA to a liquid
having fluidity disappears or is decreased to a reference value or
lower, the movement of the substance may be stopped.
[0229] In "delivery" between the patch PA and the substance having
fluidity SL, the above-described "delivery condition" between the
patch PA and the substance having fluidity SL may not be required.
It may be understood that substances that have already moved to the
substance having fluidity SL are diffused and/or moved due to
irregular motion in the substance having fluidity SL, and the
substance has been provided to the substance having fluidity SL
when a distance between the moved substance and the patch PA become
larger a predetermined distance. Since, while in the case of the
plate PL, a movable range expanded due to the contact is extremely
limited, and thus the attractive force between the patch PA and the
substances that have moved to the plate PL may be significant, in
the relationship between the patch PA and the substance having
fluidity, a movable range expanded due to contact between the patch
PA and the plate PL is relatively much wider, and thus the
attractive force between the patch PA and the substances that have
moved to the substance having fluidity SL is insignificant.
[0230] FIGS. 8 to 10 illustrate delivery of a substance from the
patch PA to the substance having fluidity as an example of delivery
of a substance from among the functions of the patch PA according
to the present application. According to FIGS. 8 to 10, the patch
PA may deliver a portion of a substance contained in the patch PA
to an external substance having fluidity. The delivery of the
portion of the contained substance may be performed by the patch PA
being inserted into or coming into contact with the substance
having fluidity so that substance movement is possible between the
liquid substance SB captured in the patch PA and the substance
having fluidity.
[0231] Here, it is assumed that a substance is moved from the patch
PA to another patch PA. In a contact region in which the patch PA
and the other patch PA are in contact, at least a portion of the
liquid substance B provided in the patch PA may be moved to the
other patch PA.
[0232] In the contact region, the liquid substance SB provided in
each patch PA may be diffused and moved to the other patch PA. In
this case, due to the movement of the substance, a concentration of
the liquid substance SB provided in each patch PA may be changed.
Also in the present embodiment, as described above, the patch PA
and the other patch PA may be separated, and a portion of the
liquid substance SB in the patch PA may be provided to the other
patch PA.
[0233] The substance movement between the patch PA and the other
patch PA may be performed through a change in an environmental
condition including a change in a physical state.
[0234] The substance movement between the patch PA and another
patch PA may depend on an extent of a contact area between the
patch PA and the other patch PA. For example, the substance
movement efficiency between the patch PA and the other patch PA may
be increased or decreased in accordance with an extent of an area
where the patch PA comes into contact with the other patch PA.
[0235] FIGS. 11 to 13 illustrate delivery of a substance from a
patch PA1 to another patch PA2 as an example of delivery of a
substance among the functions of the patch PA according to the
present application. According to FIGS. 11 to 13, the patch PA1 may
deliver a portion of a substance contained in the patch PA1 to the
other patch PA2. The delivery of the portion of the substance may
be performed by the patch PA1 coming into contact with the other
patch PA2 and becoming a state in which a liquid substance SB
captured in the patch PA1 and a substance captured in the other
patch PA2 are exchangeable.
[0236] 2.2.4.2 Absorption
[0237] Prior to description, it should be noted that, among the
functions of the patch PA according to the present application,
"absorption" may be managed similarly as the above-described
"delivery" in some embodiments. For example, in a case in which a
substance moves due to a concentration differences between
substances, the "absorption" may be similar to the "delivery" in
that a concentration of the liquid substance SB, particularly, a
concentration of the additive substance AS, may be changed to
control a direction in which the substance is moved. The
"absorption" may also be similar to "delivery" in terms of
controlling movement and selective absorption of a substance
through a release of physical contact with the patch PA, and this
may be clearly understood by those of ordinary skill in the art to
which the present application pertains.
[0238] Due to the above-described characteristics, the patch PA
according to the present application may capture an external
substance. The patch PA may pull in an external substance present
outside a region defined by the patch PA toward a region affected
by the patch PA. The pulled external substance may be captured
along with the liquid substance SB of the patch PA. The pulling of
the external substance may be caused by an attractive force between
the external substance and the liquid substance SB already captured
in the patch PA. Alternatively, the pulling of the external
substance may be caused by an attractive force between the external
substance and a region of the mesh structural body NS not occupied
by the liquid substance SB. The pulling of the external substance
may be caused by a force of surface tension.
[0239] Hereinafter, for convenience, the above-described function
of the patch PA will be referred to as "absorption." Absorption may
be understood as a concept subordinate to the above-described
channeling function of the patch PA, the concept defining movement
of an external substance to the patch PA.
[0240] The absorption may occur by the patch PA via a state in
which the substance is movable and a state in which the substance
is immovable.
[0241] A substance that is absorbable by the patch PA may be in a
liquid or solid state. For example, when the patch PA comes into
contact with an external substance including a solid state
substance, absorption of the substance may be performed due to an
attractive force between the solid state substance included in the
external substance and the liquid substance SB placed in the patch
PA. As another example, when the patch PA comes into contact with a
liquid external substance, the absorption may be performed due to
binding between the liquid external substance and the liquid
substance SB placed in the patch PA.
[0242] The external substance absorbed into the patch PA may be
moved to the inside of the patch PA through the micro-cavities of
the mesh structural body NS forming the patch PA or may be
distributed on a surface of the patch PA. Positions at which the
external substance is distributed may be set on the basis of a
molecular weight or a particle size of the external substance.
[0243] While the absorption is performed, the form of the patch PA
may be changed. For example, the volume, color, and the like of the
patch PA may be changed. While the absorption into the patch PA is
being performed, the absorption into the patch PA may be activated
or delayed by adding external conditions such as a temperature
change and a physical state change to an absorption environment of
the patch PA.
[0244] The absorption will be described below as a function of the
patch PA according to some examples of an external region that
provides a substance to be absorbed into the patch PA when the
absorption occurs.
[0245] Hereinafter, it will be assumed that the patch PA absorbs an
external substance from a external plate PL. An example of the
external plate may include a plate PL in which the external
substance may be placed while the external substance is not
absorbed thereinto.
[0246] A substance may be applied on the external plate PL.
Particularly, a substance may be applied in a form of powder on the
plate PL. The substance applied on the plate PL may be a single
component or a mixture of a plurality of components.
[0247] The plate PL may have the shape of a flat plate. The shape
of the plate PL may be deformed for improvement in ability to
contain the substance or the like. For example, a well may be
formed to improve the ability to contain the substance, a surface
of the plate PL may be deformed by engraving or embossing, or a
patterned plate PL may be used to improve contact with the patch
PA.
[0248] The absorption of a substance from the plate PL by the patch
PA according to the present application may be performed through
contact between the plate PL and the patch PA. In this case, in a
contact region in the vicinity of a contact surface between the
plate PL and the patch PA, a water film WF may be formed due to the
liquid substance SB captured in the patch PA and/or the substance
applied on the plate PL. When the water film (aquaplane,
hydroplane) WF is formed in the contact region, the substance
applied on the plate PL may be captured by the water film WF. The
substance captured in the water film WF may freely flow within the
patch PA.
[0249] When the patch PA is spaced a predetermined distance or more
apart and separated from the plate PL, the water film WF may be
moved along with the patch PA, and the substance applied on the
plate PL may be absorbed into the patch PA. The substance applied
on the plate PL may be absorbed into the patch PA as the patch PA
is separated a predetermined distance or more apart from the plate
PL. When the patch PA and the plate PL are spaced apart and
separated, the liquid substance SB provided to the patch PA may not
be moved to the plate PL, or only an insignificant amount thereof
may be absorbed into the patch PA.
[0250] A portion of or the entire substance applied on the plate PL
may react specifically with a portion of or the entire substance
captured in the patch PA. In this respect, absorption of a
substance from the plate PL by the patch PA may be selectively
performed. Particularly, the absorption may be performed
selectively when the patch PA has a stronger attractive force than
the plate PL with respect to a portion of the substance captured in
the patch PA.
[0251] As an example, a portion of the substance may be fixed to
the plate PL. In other words, a portion of the substance may be
fixed to the plate PL while another portion of the substance is
applied to have fluidity or not be fixed. In this case, when the
patch PA and the plate PL are brought into contact and separated,
the substance, excluding the portion of the substance fixed to the
plate PL of the substance applied on the plate PL, may be
selectively absorbed into the patch PA. Instead, the selective
absorption may also occur due to polarities of a substance placed
on the plate PL and a substance captured in the patch PA regardless
of whether the substance is fixed.
[0252] As another example, when the liquid substance SB captured in
the patch PA is bound specifically to at least a portion of a
substance applied on the plate PL, only the portion of the
substance applied on the plate PL bound specifically to the liquid
substance SB may be absorbed into the patch PA when the patch PA is
brought into contact with and then separated from the substance
applied on the plate PL.
[0253] As yet another example, a portion of the substance applied
on the plate PL may react specifically with a substance fixed to
the plate PL in advance. In this case, only a remaining substance,
excluding the substance that reacts specifically with the substance
fixed to the plate PL in advance of the substance being applied to
the plate PL, may be absorbed into the patch PA.
[0254] FIGS. 14 to 16 illustrate absorption of a substance from an
external plate PL by the patch PA as an example of absorption of a
substance from among the functions of the patch PA according to the
present application. According to FIGS. 14 to 16, the patch PA may
absorb a portion of a substance placed on the external plate PL
from the external plate PL. The absorption of the substance may be
performed by the patch PA coming into contact with the external
plate PL, the water film WF being formed in the vicinity of a
contact region between the external plate PL and the patch PA, and
the substance being movable to the patch PA through the water film
WF.
[0255] Here, it will be assumed that a substance is absorbed into
the patch PA from the substance having fluidity SL. The substance
having fluidity SL may refer to a liquid external substance that is
held in other containing space or that is flowing. More
specifically, by having an environment in which the substance
having fluidity SL and the liquid substance SB captured in the
patch PA may flow to and from each other, a portion of or the
entire substance having fluidity SL may be absorbed into the patch
PA. In this case, the environment in which the substance having
fluidity SL and the liquid substance SB may flow to and from each
other may be formed by the patch PA coming into contact with at
least a portion of the substance having fluidity SL.
[0256] When the patch PA comes into contact with the substance
having fluidity SL, the patch PA may be in a state in which a
substance is movable from the substance having fluidity SL. When
the patch PA is separated from the substance having fluidity SL, at
least a portion of the substance having fluidity SL may be absorbed
into the patch PA.
[0257] The absorption of a substance into the patch PA from the
substance having fluidity SL may depend on a concentration
difference between the substance captured in the patch PA and the
substance having fluidity SL. In other words, when the
concentration of the liquid substance SB captured in the patch PA
with respect to a predetermined additive substance AS is lower than
the concentration of the substance having fluidity SL with respect
to the predetermined additive substance AS, the predetermined
additive substance AS may be absorbed into the patch PA.
[0258] When a substance is absorbed into the patch PA from the
substance having fluidity SL, in addition to the absorption
depending on the concentration difference while the patch PA and
the substance having fluidity SL are in contact as described above,
the absorption into the patch PA may also be controlled by adding
an electrical factor or changing a physical condition. Further,
without direct contact between the substance captured in the patch
PA and a substance to be absorbed, the absorption of a substance
may also be performed through indirect contact therebetween via a
medium.
[0259] FIGS. 17 to 19 illustrate absorption of a substance from the
substance having fluidity SL by the patch PA as an example of
absorption of a substance from among the functions of the patch PA
according to the present application. According to FIGS. 17 to 19,
the patch PA may absorb a portion of the substance having fluidity
SL. The absorption of a substance may be performed by the patch PA
being immersed into the substance having fluidity SL or coming into
contact with the substance having fluidity SL so that the liquid
substance SB captured in the patch PA and the substance having
fluidity SL are movable to and from each other.
[0260] Here, it will be assumed that the patch PA absorbs an
external substance from another patch PA.
[0261] The absorption of an external substance from another patch
PA by the patch PA may be performed due to a difference in binding
force between the absorbed external substance and the substance
already captured in the patch PA and between the absorbed external
substance and the external substance not absorbed into the patch
PA. For example, when the absorbed substance exhibits hydrophilic
property, the patch PA exhibits hydrophilic property, and an
attractive force between the absorbed substance and the patch PA is
stronger than an attractive force between the other patch PA and
the absorbed substance (that is, when the patch PA is more
hydrophilic than the other patch PA), at least a portion of the
external substance may be absorbed into the patch PA when the patch
PA and the other patch PA are separated after being brought into
contact.
[0262] FIGS. 20 to 22 illustrate absorption of a substance from
another patch PA4 by a patch PA3 as an example of absorption of a
substance among the functions of the patch PA according to the
present application. According to FIGS. 20 to 22, the patch PA3 may
absorb a portion of a substance placed in the other patch PA4. The
absorption of the substance may be performed by the patch PA3
coming into contact with the other patch PA4 so that a liquid
substance SB captured in the patch PA3 and a liquid substance SB
captured in the other patch PA4 are exchangeable.
[0263] A binding force of the patch PA to the external substance
absorbed thereinto may be changed in accordance with a proportion
of a frame structural body of the three-dimensional mesh structural
body NS constituting the patch PA with respect to the total volume
of the patch PA. For example, as the proportion of a volume
occupied by the frame structural body in the entire patch PA
increases, the amount of substance captured in the structural body
may be reduced. In this case, a binding force between the patch PA
and a target substance may be reduced due to a reason such as
reduction in a contact area between the target substance and the
substance captured in the patch PA.
[0264] In relation to this, ratios of materials that constitutes
the mesh structural body NS may be adjusted during manufacturing
process of the patch PA so that polarity of the patch PA is
controlled. For example, in the case of a patch PA manufactured
using agarose, a concentration of the agarose may be controlled to
adjust a degree of the absorption.
[0265] When the certain region has a weaker binding force than the
patch PA with respect to a substance provided from the patch PA,
and the patch PA and another patch PA are brought into contact and
then separated, the absorbed external substance may be separated
from the other patch PA along with the patch PA.
[0266] 2.2.4.3 Providing of Environment
[0267] Due to the above-described characteristics, the patch PA
according to the present application may perform a function of
adjusting an environmental condition of a desired region. The patch
PA may provide an environment due to the patch PA to the desired
region.
[0268] The environmental condition due to the patch PA may depend
on the liquid substance SB captured in the patch PA. The patch PA
may create a desired environment in a substance placed in an
external region on the basis of characteristics of a substance
accommodated in the patch PA or for a purpose of making the
environment correspond to characteristics of the substance
accommodated in the patch PA.
[0269] The adjustment of the environment may be understood as
changing an environmental condition of the desired region. The
changing of the environmental condition of the desired region may
be implemented in a form in which a region affected by the patch PA
is expanded to include at least a portion of the desired region or
a form in which an environment of the patch PA is shared with the
desired region.
[0270] Hereinafter, for convenience, the above-described function
of the patch PA will be referred to as "providing an
environment."
[0271] The providing an environment by the patch PA may be
performed in a state in which a substance is movable between the
patch PA and an external region subject to provide the environment.
The providing an environment by the patch PA may be performed
through contact. For example, when the patch PA comes into contact
with a desired region (for example, an external substance, a plate
PL, or the like), a specific environment may be provided to the
desired region by the patch PA.
[0272] The patch PA may adjust an environment of a target region TA
by providing an environment with an appropriate pH, osmotic
pressure, humidity level, concentration, temperature, and the like.
For example, the patch PA may provide fluidity (liquidity) to the
target region TA or a target substance. Such providing fluidity may
occur due to movement of a portion of a substance captured in the
patch PA. A moist environment may be provided to the target region
TA through the liquid substance SB or the base substance BS
captured in the patch PA.
[0273] The environmental factors provided by the patch PA may be
constantly maintained in accordance with a purpose. For example,
the patch PA may provide homeostasis to the desired region. As
another example, as a result of providing an environment, the
substance captured in the patch PA may be adapted to an
environmental condition of the desired region
[0274] The providing an environment by the patch PA may result from
diffusion of the liquid substance SB included in the patch PA. That
is, when the patch PA and the desired region come into contact, a
substance may be movable through a contact region that is formed
due to contact between the patch PA and the desired region. In
relation to this, an environmental change due to an osmotic
pressure, an environmental change due to a change in ionic
concentration, providing a moist environment, and a change in a pH
level may be implemented in accordance with a direction in which
the substance is diffused.
[0275] FIGS. 23 to 25 illustrate providing a predetermined
environment to an external plate PL by the patch PA as an example
of providing an environment among the functions of the patch PA
according to the present application. According to FIGS. 23 to 25,
the patch PA may provide a predetermined environment to an external
plate PL on which a fourth substance SB4 and a fifth substance SB5
are placed. For example, the patch PA may provide a predetermined
environment to the plate PL for the fourth substance SB4 and the
fifth substance SB5 to react and form a sixth substance SB6. The
providing the environment may be performed by the patch PA coming
into contact with the plate PL so that a water film WF is formed in
the vicinity of a contact region and the fourth substance SB4 and
the fifth substance SB5 are captured in the water film WF.
[0276] 3. Application of Patch
[0277] The patch PA according to the present application may be
implemented to perform various functions by suitably applying the
above-described functions of the patch PA.
[0278] The technical spirit of the present application will be
described below by disclosing some embodiments. However, the
technical scope to which functions of the patch PA disclosed by the
present application are applied may be interpreted in a broad sense
within the scope that may be easily derived by those of ordinary
skill in the art, and the scope of the present application should
not be interpreted as being limited by the embodiments disclosed
herein.
[0279] 3.1. In-Patch
[0280] The patch PA may provide a reaction region for a substance.
In other words, a reaction of a substance may occur in at least a
portion of a spatial region affected by the patch PA. In this case,
the reaction of a substance may be a reaction between liquid
substances SB captured in the patch PA and/or a reaction between
the captured liquid substance SB and a substance provided from the
outside of the patch PA. The providing a reaction region for a
substance may activate or promote a reaction of a substance.
[0281] In this case, the liquid substance SB captured in the patch
PA may include at least one of a substance added upon manufacturing
the patch PA, a substance additive into the patch PA after the
manufacturing of the patch PA and contained in the patch PA, and a
substance temporarily captured in the patch PA. In other words,
regardless of a form in which a substance is captured in the patch
PA, any substance captured in the patch PA at a time point at which
a reaction in the patch PA is activated may react in the patch PA.
Further, a substance injected after the manufacturing of the patch
PA may also act as a reaction initiator.
[0282] The providing a reaction region for a reaction related to
the liquid substance SB captured in the patch PA may be a concept
subordinate, in terms of embodiment, to the above-described Section
2.1.3 (that is, providing reaction space). Alternatively, the
providing a reaction region for a reaction related to the liquid
substance SB captured in the patch PA may consist of multiple
concepts that perform combined functions of the above-described
Section 2.1.3 and Section 2.2.4.2 (that is, absorption). The
providing a reaction region for a reaction related to the liquid
substance SB captured in the patch PA is not limited thereto and
may be implemented in the form in which two or more functions are
combined.
[0283] 3.1.1 First Embodiment
[0284] Hereinafter, description will be given by assuming that the
function of absorption into the patch PA and the function of
providing a reaction space (hereinafter referred to as "providing
function") are performed by a single patch PA. In this case, the
absorption function and the providing function may be
simultaneously-performed functions, functions performed at
different time points, or functions sequentially performed to
perform another function. The patch PA further including other
functions in addition to the absorption and providing functions may
also be considered as belonging to the present embodiment.
[0285] As described above, the patch PA may perform a function of
capturing a substance, and the substance may have fluidity even
when the substance is captured. When some components of the liquid
substance SB are non-uniformly distributed, the non-uniform
components may be diffused. Even when components of the liquid
substance SB are uniformly distributed, the liquid substance SB may
have a predetermined level of mobility due to irregular motion of
particles. In this case, a reaction between substances, for
example, specific binding between substances, may occur inside the
patch PA.
[0286] For example, in the patch PA, in addition to a reaction
between captured substances, a reaction in a form in which a
substance having fluidity that is newly captured in the patch PA
and the substance that has been captured in the patch PA bind
specifically to each other may also be possible.
[0287] The reaction between the substance having fluidity and the
substance that has been captured in the patch PA may also occur
after the substance patch being separated from an space that has
been provided. For example, after the patch PA absorbs the
substance having fluidity from an arbitrary space, the patch PA may
be separated from the arbitrary space, and a reaction between the
absorbed substance and the substance that has been captured in the
patch PA may occur in the patch PA.
[0288] In addition, the patch PA may allow a reaction of a
substance captured therein to occur by performing the absorption
function with respect to a substance having fluidity. In other
words, the absorption of the substance having fluidity by the patch
PA may act as a trigger for a reaction between the absorbed
substance and the substance that has been captured in the patch PA.
The reaction may occur inside a space defined by the patch PA.
[0289] A composition of the liquid substance SB captured in the
patch PA may be changed due to the reaction occurring inside the
patch PA. When, particularly, a substance captured inside the patch
PA is a compound, a chemical composition thereof may be changed
before and after a reaction. Alternatively, a composition
distribution of a substance may be changed in accordance with a
position of the substance in the patch PA. For example, this may be
due to diffusion or particles having an attractive force specific
to another substance.
[0290] When the composition of the liquid substance SB is changed
due to a reaction inside the patch PA, a portion of the substance
may be absorbed into the patch PA due to a concentration difference
between the patch PA and a substance outside the patch PA (when a
substance in contact with the patch PA is present, the
corresponding substance), or the substance may be released from the
patch PA to the substance outside the patch PA.
[0291] 3.1.2 Second Embodiment
[0292] Hereinafter, an embodiment in which the containing function
of the patch PA and the function of providing a reaction space for
a substance are performed together for at least a predetermined
amount of time will be described. More specifically, the patch PA
may perform a function of providing a space for at least a portion
of the liquid substance SB contained in the patch PA to react.
[0293] The patch PA may contain a substance and provide a reaction
space for the contained substance. In this case, the reaction space
provided by the patch PA may be the micro-cavities formed by the
mesh structural body NS of the patch PA or a surface region of the
patch PA. Particularly, when a substance contained in the patch PA
and a substance applied on a surface of the patch PA react, the
reaction space may be the surface region of the patch PA.
[0294] The reaction space provided by the patch PA may serve to
provide a specific environmental condition. While a reaction occurs
in the liquid substance SB placed in the patch PA, an environmental
condition of the reaction may be adjusted by the patch PA. For
example, the patch PA may serve as a buffer solution.
[0295] By containing a substance through a mesh structure, the
patch PA does not require a container, separately. When the
reaction space of the patch PA is a surface of the patch PA, a
reaction may be easily observed through the surface of the patch
PA. For this, the shape of the patch PA may be deformed into a
shape that facilitates the observation.
[0296] The liquid substance SB contained in the patch PA may be
denaturalized or react with a different type of substance. The
composition of the liquid substance SB contained in the patch PA
may be changed with time.
[0297] The reaction may refer to a chemical reaction in which a
chemical formula is changed, a physical state change, or a
biological reaction. In this case, the liquid substance SB
contained in the patch PA may be a substance formed of a single
component or a mixture including a plurality of components.
[0298] 3.2 Providing of Movement Path (Channeling)
[0299] Hereinafter, the patch PA that performs a function of
providing a substance movement path will be described. More
specifically, as described above, the patch PA may capture, absorb,
release, and/or contain a substance having fluidity. Various
embodiments of the patch PA that performs the function of providing
a substance movement path may be implemented by each of the
above-described functions of the patch PA or a combination thereof.
However, a few embodiments will be disclosed for a better
understanding.
[0300] 3.2.1 Third Embodiment
[0301] The patch PA may be implemented to perform functions
described in Section 2.2.4.1 (that is, the section related to
delivery) and Section 2.2.4.2 (that is, the section related to
absorption) among the above-described functions of the patch PA. In
this case, the absorption function and the delivery function may be
provided together or sequentially provided.
[0302] The patch PA may perform the absorption and delivery
functions together to provide a substance movement path.
Particularly, the patch PA may absorb an external substance and
provide the absorbed external substance to an external region,
thereby providing a movement path to the external substance.
[0303] The providing the movement path of the external substance by
the patch PA may be performed by absorbing the external substance
and releasing the external substance. More specifically, the patch
PA may come into contact with the external substance, absorb the
external substance, come into contact with the external region, and
deliver the external substance to the external region. In this
case, the capturing of the external substance and the delivery of
the captured external substance to the external region by the patch
PA may be performed through a process similar to those of the
above-described absorption and delivery.
[0304] The external substance absorbed into the patch PA and
provided may be in a liquid phase or a solid phase.
[0305] In this way, the patch PA may allow a portion of the
external substance to be provided to another external substance.
The external substance and the other external substance may
simultaneously come into contact with the patch PA. The external
substance and the other external substance may come into contact
with the patch PA at different time points.
[0306] The external substance and the other external substance may
come into contact with the patch PA at different time points. When
the external substances come into contact with the patch PA at
different time points, the external substance may come into contact
with the patch PA first, and after the external substance and the
patch PA are separated, the patch PA and the other external
substance may come into contact. In this case, the patch PA may
temporarily contain a substance captured from the external
substance.
[0307] The patch PA may simultaneously provide a substance movement
path and additionally provide a time delay. The patch PA may
perform a function of suitably adjusting an amount of substance
provided to another external substance and a speed of such
providing.
[0308] Such a series of processes may be carried out in one
direction with respect to the patch PA. As a specific example,
absorption of a substance may be performed through a surface of the
patch PA, an environment may be provided in an inner space of the
patch PA, and the substance may be released through another surface
facing the surface.
[0309] 3.2.2 Fourth Embodiment
[0310] The patch PA may perform the absorbing and releasing of a
substance among the above-described functions of the patch PA and
the providing a reaction space for the substance simultaneously. In
this case, the absorption and release of the substance and the
providing the reaction space may be performed simultaneously or
sequentially.
[0311] According to an embodiment, in performing the processes of
absorbing and releasing an external substance, the patch PA may
provide a reaction space to the absorbed external substance for at
least a predetermined amount of time. The patch PA may provide a
specific environment for at least some time to the liquid substance
SB captured in the patch PA, including the absorbed external
substance.
[0312] The liquid substance SB that has been captured in the patch
PA and the external substance captured in the patch PA may react
inside the patch PA. The external substance absorbed into the patch
PA may be affected by an environment provided by the patch PA. The
substance released from the patch PA may include at least a portion
of a substance generated through the reaction. The external
substance may be released from the patch PA after the composition,
characteristics, and the like of the external substance are
changed.
[0313] The absorbed substance may be released from the patch PA.
The external substance being absorbed into the patch PA and being
released from the patch PA may be understood as the external
substance passing through the patch PA. The external substance that
has passed through the patch PA may lose integrity due to a
reaction inside the patch PA or an influence of an environment
provided by the patch PA.
[0314] The above-described processes of absorption of an external
substance, reaction of a substance, and providing the substance may
be carried out in one direction. In other words, the absorption of
a substance may be performed at one position of the patch PA, the
providing an environment may be performed at another position of
the patch PA, and the release of the substance may be performed at
yet another position of the patch PA.
[0315] FIGS. 26 to 28 illustrate providing a substance movement
path between two plates PL as an embodiment of the patch PA
according to the present application. According to FIGS. 26 to 28,
the patch PA may provide a substance movement path between a plate
PL1 on which a seventh substance SB7 is applied and a plate PL2 on
which an eighth substance SB8 is applied. As a specific example,
when the seventh substance SB7 is capable of binding to the eighth
substance, and the eighth substance is fixed to the plate PL2, the
patch PA may come into contact with the plates PL1 and PL2 so that
the seventh substance SB7 is moved through the patch PA and bound
to the eighth substance SB8. The seventh substance SB7 and the
eighth substance SB8 may be connected to the patch PA through a
water film WF formed by the patch PA coming into contact with the
plates PL1 and PL2.
[0316] FIGS. 29 and 30 illustrate providing a substance movement
path between two patches as an embodiment of the patch PA according
to the present application. According to FIGS. 29 and 30, a patch
PA6 configured to provide the movement path may be in contact with
a patch PA5 configured to contain a substance to be moved, and a
patch PA7 configured to receive the substance to be moved. The
patch PA6 configured to provide the movement path may come into
contact with the patch PA5 configured to contain the substance to
be moved and the patch PA7 configured to receive the substance to
be moved, and the substance to be moved may be moved to the patch
PA7 configured to receive the substance to be moved. The movement
of the substance between the patches may be performed by a water
film WF formed in the vicinity of a contact region between the
patches.
[0317] FIGS. 31 and 32 illustrate providing a substance movement
path between two patches as an embodiment of the patch according to
the present application. According to FIGS. 29 and 30, a patch PA9
configured to provide the movement path may be in contact with a
patch PA8 configured to contain a ninth substance SB9 and a patch
PA10 configured to receive a substance. The patch PA9 providing the
movement path may come into contact with the patch PA8 configured
to contain the ninth substance SB9 to absorb the ninth substance
SB9. The absorbed ninth substance SB9 may react with a tenth
substance SB10 contained in the patch PA9, which is configured to
provide the movement path, and generate an eleventh substance. An
eleventh substance SB11 may be provided from the patch PA9
configured to provide the movement path to the patch PA10
configured to receive the substance. The movement of a substance
between the patches PA may be performed through a water film WF
formed in the vicinity of a contact region between the patches
PA.
[0318] 3.3 Multi-Patch
[0319] A patch PA may be solely used, or a plurality of patches PA
may be used together. In this case, the plurality of patches PA
being able to be used together includes a case in which the
plurality of patches PA are sequentially used as well as a case in
which the plurality of patches PA are used simultaneously.
[0320] When the plurality of patches PA are used simultaneously,
the patches PA may perform different functions. Although each patch
PA of the plurality of patches PA may contain the same substance,
the plurality of patches PA may also contain different
substances.
[0321] When the plurality of patches PA are used simultaneously,
the patches PA may not come into contact with each other such that
substance movement does not occur between the patches PA, or a
desired function may be performed in a state in which substances
contained in the patches PA are exchangeable.
[0322] Although the plurality of patches PA used together may be
manufactured in shapes similar to each other or in the same size,
the plurality of patches PA may be used together even when the
plurality of patches PA have different shapes. Each patch PA
constituting the plurality of patches PA may be manufactured such
that densities of the mesh structural bodies NS are different or
components constituting the mesh structural bodies NS are
different.
[0323] 3.3.1 Contact with Plurality of Patches
[0324] When a plurality of patches PA are used, the plurality of
patches PA may come into contact with a single target region TA.
The plurality of patches PA may come into contact with the single
target region TA and perform a desired function.
[0325] When a plurality of target regions TA are present, the
plurality of patches PA may come into contact with different target
regions TA. When the plurality of target regions TA are present,
the plurality of patches PA may respectively come into contact with
corresponding target regions TA and perform a desired function.
[0326] The plurality of patches PA may come into contact with a
substance applied on the target region TA. In this case, the
substance applied on the target region TA may be fixed or have
fluidity.
[0327] The desired function may be a function of providing or
absorbing the substance. However, each patch PA does not
necessarily provide the same substance or absorb the same
substance, and the patches PA may provide different substances to
the target region TA or absorb different components from a
substance placed in the target region TA.
[0328] The desired function may be different for each patch PA
constituting the plurality of patches PA. For example, one patch PA
may perform the function of providing a substance to the target
region TA, and another patch PA may perform the function of
absorbing the substance from the target region TA.
[0329] The plurality of patches PA may include different
substances, and the different substances may be provided to a
single target region TA and used to induce a desired reaction. When
a plurality of components of a substance is required for the
desired reaction to occur, the plurality of components may be
contained in a plurality of patches PA respectively and provided to
the target region TA. Such use of the plurality of patches PA may
be particularly useful when properties of substances required for a
desired reaction are lost or altered when the substances required
for the reaction being mixed for reasons such as being contained in
a single patch PA.
[0330] According to an embodiment, when the plurality of patches PA
include substances formed of different components, and the
substances formed of different components have different specific
binding relationships, the substances formed of different
components may be provided to the target region TA. The plurality
of patches PA may be used to detect a plurality of specific
bindings from the substances applied on the target region TA, by
providing the substances including different components.
[0331] According to another embodiment, the plurality of patches PA
may include substances formed of the same component, but each patch
PA may have a different concentration with respect to the substance
formed of the same component. The plurality of patches PA including
the substances formed of the same component may come into contact
with the target region TA and be used to determine an influence in
accordance with a concentration of the substance included in the
plurality of patches PA.
[0332] When the plurality of patches PA are used as described
above, the patches PA may be grouped into more efficient forms and
used. In other words, the configuration of the plurality of patches
PA being used may be changed every time the plurality of patches PA
are used. The plurality of patches PA may be manufactured in the
form of a cartridge and used. In this case, the form of each patch
PA being used may be suitably standardized and manufactured.
[0333] The plurality of patches PA in the form of a cartridge may
be suitable when patches PA configured to contain a plurality of
types of substances are manufactured to be used by being chosen as
necessary.
[0334] Particularly, when attempting to detect a specific reaction
of each substance from the target region TA using a plurality of
types of substances, a combination of specific reactions to be
detected may be changed every time the detection is performed.
[0335] FIG. 33 illustrates a case in which the plurality of patches
PA are used together as an embodiment of the patch PA according to
the present application. According to FIG. 33, the plurality of
patches PA according to an embodiment of the present application
may simultaneously come into contact with a target region TA placed
on a plate PL. The patches PA constituting the plurality of patches
PA may have a standardized form. The plurality of patches PA may
include a first patch and a second patch, and a substance contained
in the first patch may be different from a substance contained in
the second patch.
[0336] FIG. 34 illustrates a case in which the plurality of patches
PA are used and the plate PL includes a plurality of target regions
TA. According to FIG. 34, the plurality of patches PA according to
an embodiment of the present application may simultaneously come
into contact with the plurality of target regions TA placed on the
plate PL. The plurality of patches PA may include a first patch PA
and a second patch PA, the plurality of target regions TA may
include a first target region and a second target region, and the
first patch may come into contact with the first target region and
the second patch may come into contact with the second target
region.
[0337] 3.3.2 Fifth Embodiment
[0338] The plurality of patches PA may perform a plurality of
functions. As described above, the patches PA may simultaneously
perform a plurality of functions, and the patches PA may also
simultaneously perform different functions. However, embodiments
are not limited to the above, and the functions may also be
combined and performed in the plurality of patches PA.
[0339] First, in the case in which the patches PA simultaneously
perform the plurality of functions, the patches PA may perform both
containing and release of a substance. For example, the patches PA
may contain different substances and release substances contained
in the target regions TA. In this case, the contained substances
may be simultaneously or sequentially released.
[0340] Next, in the case in which the patches PA simultaneously
perform different functions, the patches PA may separately perform
containing and release of a substance. In this case, only some of
the patches PA may come into contact with a target region TA and
release a substance to the target region TA.
[0341] 3.3.3 Sixth Embodiment
[0342] When a plurality of patches PA are used, as described above,
the plurality of patches PA may perform a plurality of functions.
First, the patches PA may simultaneously perform containing,
releasing, and absorbing of substances. Alternatively, the patches
PA may also separately perform the containing, releasing, and
absorbing of the substances. However, embodiments are not limited
thereto, and the functions may also be combined and performed in
the plurality of patches PA.
[0343] For example, at least some of the plurality of patches PA
may contain a substance and release the contained substance to the
target region TA. In this case, at least a remainder of the
plurality of patches PA may absorb a substance from the target
region TA. Some of the plurality of patches PA may release a
substance that binds specifically to a substance placed in the
target region TA. In this case, specific binding may be detected by
absorption of a substance that has not formed specific binding from
the substance placed in the target region TA using another patch
PA.
[0344] 3.3.4 Seventh Embodiment
[0345] When a plurality of patches PA are used, the patches PA may
simultaneously perform containing and release of a substance and
providing an environment. Alternatively, the patches PA may
separately perform the containing and release of a substance and
providing an environment. However, embodiments are not limited
thereto, and the functions may also be performed in combination in
the plurality of patches PA.
[0346] For example, a patch PA among the plurality of patches PA
may release a substance contained therein to the target region TA.
In this case, another patch PA may provide an environment to the
target region TA. Here, the providing an environment may be
implemented in the form in which an environmental condition of a
substance contained in the other patch PA is provided to the target
region TA. More specifically, a reacting substance may be provided
to the target region TA by the patch PA, and the other patch PA may
come into contact with the target region TA and provide a buffering
environment.
[0347] As another example, the plurality of patches PA may be in
contact with each other. In this case, at least one patch PA may
contain a substance and release the substance contained therein to
another patch PA configured to provide an environment. In the
present embodiment, the patch PA configured to provide an
environment may release a substance, come into contact with at
least one other patch PA that is not in contact with the patch PA
configured to provide an environment, and absorb a substance from
the patch PA.
[0348] 4. Circulating Tumor Cell (CTC) Diagnosis
[0349] 4.1 CTC
[0350] A patch PA according to the present application may be used
in cancer diagnosis. Particularly, the patch PA may be used in CTC
testing.
[0351] Tumor cells CE are known to destroy normal cells CE and
metastasize through blood vessels or lymphatic vessels. The blood
vessels and the lymphatic vessels are connected to organs located
in the human body. The tumor cells CE can move to tissues which are
in distance (such as a lymphatic gland, liver, or a lung) along a
flow of blood or lymph and form new tumor tissue.
[0352] In relation to this, CTC testing is performed on tumor cells
CE that float in the blood of a person subject to diagnosis
(hereinafter, "circulating tumor cell CE"). Circulating tumor cell
CE refers to tumor cells CE that move along the blood or lymph.
[0353] CTC testing has an advantage of being capable of detecting
tumor cells CE even when tumor cells CE are not detected in
computerized tomography (CT) or an imaging examination. That is,
even when a metastasized tumor tissue has not grown to an extent
that the tumor tissue may be detected in an imaging examination,
the tumor cells CE moving through the blood for metastasis may be
detected when CTC testing is used.
[0354] Also, CTC testing has an advantage of being capable of
simply diagnosing cancer by using the blood without collecting a
biopsy specimen. In relation to the fact that cancer is a disease
that requires continuous monitoring even after a full recovery,
being able to perform cancer diagnosis through a simple procedure
is a very important advantage.
[0355] Hereinafter, prior to describing various embodiments related
to a method in which a patch PA is used to detect circulating tumor
cell CE, a method of diagnosing the circulating tumor cell CE will
be described first.
[0356] 4.2 Diagnostic Method
[0357] In order to detect circulating tumor cell CE and diagnose
cancer, general diagnostic methods that are performed to detect
cells CE may be applied.
[0358] For example, there is a method in which the morphology of
circulating tumor cell CE is detected. By identifying the cells CE
distributed in the blood and considering the sizes and morphology
of the cells CE, detecting the presence of tumor cells CE as well
as sorting out the danger group of tumor cells CE may be
performed.
[0359] Also, for more accurate detection of tumor cells CE,
staining cells CE distributed in the blood may be additionally
performed. For example, staining a cytoplasm of cells CE
distributed in the blood or staining a nucleus of the cells CE may
be performed.
[0360] In another example, there is a method in which immunoassay
is performed on the circulating tumor cell CE. Using a tumor marker
of the tumor cells CE, detection of the presence of tumor cells CE
in the blood may be performed. The tumor marker may be an antibody
AB that reacts specifically with epithelial cells CE or tumor cells
CE.
[0361] In yet another example, there is a method in which culturing
of the circulating tumor cell CE is performed.
[0362] While normal cells CE generally stop cell CE division at an
arbitrary time point and go through apoptosis, tumor cells CE
proliferate infinitely. Also, speed of cell division of the tumor
cells CE is known to be higher than that of the normal cells
CE.
[0363] Due to such differences, blood may be cultured to detect
tumor cells CE in the blood. More specifically, tumor cells CE may
be detected by identifying a speed of cell division of the cells CE
in the blood and a time point at which the cell division has
ended.
[0364] In still another example, there is a method in which
extracting DNA from the circulating tumor cell CE and a PCR process
using the extracted DNA is performed.
[0365] Diagnosis of cancer may be performed by amplifying a target
DNA using primer to which a base sequence of DNA expressed in a
tumor tissue is reflected, and identifying whether extracted DNA
has been amplified by using a label or the like mentioned above. In
some cases, the method for diagnosis of cancer using DNA mentioned
above may also be used to determine the type of cancer expressed in
the sample SA.
[0366] 5. Performance of Diagnosis
[0367] 5.1 Preparation of Sample SA
[0368] 5.1.1 Providing Sample SA
[0369] The cancer diagnosis according to the present application
may be performed on blood in order to detect circulating tumor cell
CE. Although not essential, in consideration of an average
proportion of circulating tumor cell CE found in the blood of
cancer patients, about 60 ml of blood may be used for an effective
cancer diagnosis.
[0370] The sample SA may be provided on a plate PL. Also, the
sample SA may be provided in a single layer on the plate PL if
necessary. To provide the sample SA in a single layer, smearing the
sample SA on the plate PL or printing the sample SA by adjusting a
discharge speed and a discharge position of the sample SA may be
used.
[0371] When the sample SA is provided in a single layer, some cells
CE in the sample SA (for example, white blood cells and red blood
cells) may be arranged in a two-dimensional array.
[0372] When the sample SA is provided in a single layer on the
plate PL, the number of overlapping cells CE may be reduced in
comparison to when the sample SA is discharged using a dropping
pipet or provided in multiple layers on the plate PL. As a result,
when the sample SA is provided in a single layer, the cell-counting
result of the tumor cells CE in the sample SA may become more
accurate.
[0373] The sample SA provided on the plate PL may be fixated. For
example, a sample SA smeared on the plate PL may be fixated on the
plate PL. As another example, a sample SA printed on the plate PL
may be fixated on the plate PL. As yet another example, a sample SA
discharged using a dropping pipet may be fixated on the plate
PL.
[0374] The sample SA being fixated on the plate PL refers to a
state in which a force of resistance has been generated to allow
the sample SA to stay on the plate PL until a force of a reference
strength is applied to the sample SA. As a result, even when the
patch PA and the plate PL are contacted or separated, the sample SA
may not be absorbed into the patch PA.
[0375] The sample SA may be fixated on the plate PL using any
methods that is used in the art related to the present application.
For example, a method of providing methanol in the sample SA and
volatilizing the methanol may be used to fixate the sample SA on
the plate PL.
[0376] The cancer diagnosis according to the present application
may be performed on a DNA sample extracted from the blood. The
extracted DNA may comprise DNA acquired by decomposing a cell
membrane of circulating tumor cell CE, which float in the
blood.
[0377] In relation to this, for extraction of DNA, a lysis patch PA
that comprises a lysozyme for decomposing a cell membrane may be
used. This will be described in more detail below.
[0378] The cancer diagnosis according to the present application
may also be performed to detect DNA of tumor cells CE that float in
the blood (hereinafter "CtDNA").
[0379] The CtDNA may be released from tumor cells CE that have
ruptured and died. A portion of CtDNA released to the blood may not
be removed by macrophages and, due to its characteristics of
proliferating rapidly and having a large size, may stay in blood
instead. The CtDNA staying in blood may be used in cancer diagnosis
by detecting DNA in blood.
[0380] Detecting DNA of tumor cells CE that float in the blood is
the same as detecting DNA of tumor cells CE from an extracted DNA
sample in that cancer diagnosis is performed using DNA. Therefore,
the above-described detecting DNA of tumor cells CE floating in the
blood may be performed similarly to the detecting DNA of tumor
cells CE from an extracted DNA sample.
[0381] Hereinafter, for detecting circulating tumor cell CE, a
method in which cancer diagnosis is performed on the blood will be
described in detail. In describing it will be assumed but not
restricted that the sample SA is provided on the plate PL.
[0382] Also, in describing detecting DNA for cancer diagnosis, a
method for detecting DNA of circulating tumor cell CE by
pre-processing the blood will be described in detail. However, the
method for detecting DNA which floats in blood in order to detect
the CtDNA will be easily understood through understanding of the
method for detecting DNA by pre-processing the blood.
[0383] 5.1.2 Cell Filtering
[0384] The cancer diagnosis according to the present application
may be performed on a sample SA that has gone through filtering. In
performing the cancer diagnosis, a filtering procedure may be
additionally performed in which sorting is carried out using the
size, density, specific marker, or the like of tumor cells CE.
[0385] The filtering has an advantage of improving the detection
efficiency through sorting out cells that are highly likely to
become tumor cells CE considering that circulating tumor cell CE
which should be detected in the cancer diagnosis according to the
present application are distributed in very small amounts in
blood.
[0386] However, the above description merely clarifies that the
cancer diagnosis according to the present application may be
performed on a sample SA that has gone through the filtering
procedure if necessary, and does not necessarily mean that the
filtering procedure must be performed.
[0387] Hereinafter, a patch PA that may be used in performing the
cancer diagnosis according to the present application will be
described.
[0388] 5.2 Preparation of Patch
[0389] 5.2.1 Morphology
[0390] For the cancer diagnosis according to the present
application, the patch PA may be used in analyzing the morphology
of cells CE included in the blood. By contacting it to the plate
PL, the patch PA may enable a substance contained in the patch PA
to move to the plate PL.
[0391] The cancer diagnosis may be performed by analyzing the
morphology in relation to sample SA. More specifically, the cancer
diagnosis may be performed by identifying the size and the shape of
a nucleus of cells CE in the blood.
[0392] However, for more accurate morphological diagnosis, the
tumor cells CE may be stained.
[0393] The patch may contain a staining reagent. Here, the stain
may be changed in various ways in accordance with a purpose of a
blood test or a staining technique to be performed. Typical
examples of the staining reagent may be staining solutions which
are used in Romanowsky staining techniques such as acetocarmine,
methylene blue, eosin, acid fuchsin, safranin, Janus Green B,
hematoxylin, Giemsa solution, Wright solution, and Wright-Giemsa
solution, or Leishman staining solution, Gram staining solution,
carbol-fuchsin, and Ziehl-Neelsen solution.
[0394] Of course, the staining reagent in the present disclosure is
not limited to the above-mentioned examples, and various other
substances for staining blood may also be used as a staining
reagent if necessary. For example, the staining reagent may be
4,6-diamidino-2-phenylindole (DAPI), which exhibits a
fluorescence.
[0395] The patch PA may contain a single staining reagent. In
another embodiment, the patch PA may simultaneously contain two or
more types of stains. In relation to this, in a staining technique
using multiple types of staining reagents, the patch PA may contain
only some of the above multiple types of staining reagents.
[0396] The patch PA may contain a washing solution. For example,
the washing solution may be a tris buffered saline (TBS) or
phosphate buffered saline (PBS) with Tween 20. The patch PA which
contains the washing solution may absorb a substance on the plate
PL by contacting with and being separated from the plate PL.
[0397] The patch PA may contain a buffer solution. The patch PA may
perform a function of providing an environment by contacting with
the plate, and an environment suitable for the staining may be
created in the sample SA located on the plate PL. A solution having
an optimal pH for each staining technique may be used as the buffer
solution.
[0398] 5.2.2 Immunochemistry
[0399] The patch PA may be used in performing immunoassay on blood
for cancer diagnosis according to the present application. By
contacting it with the plate PL, the patch PA may enable a
substance contained in the patch PA to move to the plate PL.
[0400] The patch PA may contain an antigen. The patch PA may
contain a biopsy specimen (that is, sample SA) that includes an
antigen.
[0401] The patch PA may contain an antibody AB. For example, an
antigen which the antibody AB detects may be an epithelial cell
adhesion molecule (EpCAM) or cytokeratin that is known as being
distributed on surfaces of the tumor cells CE.
[0402] According to an indirect technique, the antibody AB
contained in the patch PA may be a primary antibody AB or a
secondary antibody AB. The patch PA may contain either the primary
antibody AB or the secondary antibody AB or may contain both the
primary antibody AB and the secondary antibody AB.
[0403] The patch PA may contain a substrate SU. The substrate SU
may perform a reaction that is catalyzed by an enzyme, and a
substrate SU may be changed in accordance with an enzyme or a
detecting means being used. For example, the substrate SU may be
3-ethylbenzothiazoline-6-sulphonic acid (ABTS),
3,3',5,5'-Tetramethylbenzidine (TMB), or the like.
[0404] The patch PA may contain a washing solution. As described
above, the patch PA which contains the washing solution may absorb
a substance on the plate PL by contacting with and then being
separated from the plate PL. In this case, the sample SA fixated on
the plate PL and some substances bound to the sample SA may not be
absorbed.
[0405] The patch PA may contain a buffer solution. The patch PA may
perform a function of providing an environment by contacting with
the plate PL, and an environment suitable for each step of the
immunoassay may be created in the sample SA located on the plate
PL. As an example of the buffer solution, a peroxide buffer may be
used upon chemiluminescence detection.
[0406] The patch PA containing the washing solution (hereinafter,
"washing patch PA") and the patch PA containing the buffer solution
(hereinafter, "buffer patch PA") may be partially similar to a
washing patch PA and a buffer patch PA that are used in
morphological diagnosis.
[0407] 5.2.3 Culture
[0408] A patch PA may be used in performing a method of culturing
cells CE for the cancer diagnosis according to the present
application. By contacting it with the plate PL, the patch PA may
enable a substance contained in the patch PA to move to the plate
PL.
[0409] The patch PA may contain a nutrient substance NT
(hereinafter, "nutrient patch PA"). The nutrient substance NT may
be a component required for culturing cells CE. For example, the
patch PA may contain amino acids, vitamins, trace elements, and the
like. As another example, the patch PA may contain proteins,
peptides, hormones, minerals, and the like.
[0410] The patch PA may contain a washing solution. As described
above, the patch PA which contains the washing solution may absorb
a substance on the plate PL by contacting with and then being
separated from the plate PL.
[0411] The patch PA may contain a buffer solution. The patch PA may
perform a function of providing an environment by contacting with
the plate PL. In other words, due to contact between the patch PA
and the plate PL, an environment suitable for cell culturing may be
created in the sample SA located on the plate PL. For example, the
patch PA may be used to adjust a pH composition of a sample that is
changed as cells CE are cultured.
[0412] The patch PA containing the washing solution (hereinafter,
"washing patch PA") and the patch PA containing the buffer solution
(hereinafter, "buffer patch PA") may be partially similar to a
washing patch PA and a buffer patch PA that are used in
morphological diagnosis and immunoassay.
[0413] 5.2.4 PCR
[0414] A patch PA may be used in performing a PCR method for
amplifying DNA for the cancer diagnosis according to the present
application. By contacting it with the plate PL, the patch PA may
enable a substance contained in the patch PA to move to the plate
PL.
[0415] The patch PA may contain a lysozyme. The patch PA may enable
the lysozyme contained therein to move to the sample SA by
contacting with the plate PL, and as a result, a cell membrane of
circulating tumor cell CE in the sample SA may be destroyed.
[0416] When the cell membrane of the circulating tumor cell CE is
destroyed, DNA inside the tumor cells CE may be discharged to the
sample. Consequently, the patch PA may enable the DNA of the
circulating tumor cell CE to be discharged to the plate PL.
[0417] The patch PA may contain a primer. The primer may be
produced to correspond to some known DNA sequences of a cancer
patient. The primer may move from the patch PA to the plate PL, and
in the annealing step, the primer may bind to some sequences of DNA
in the sample SA.
[0418] The patch PA may contain a deoxynucleoside triphosphate
(dNTP). The dNTP may move from the patch PA to the plate PL, and in
the extension step, the dNTP may bind to a target DNA of the sample
SA.
[0419] The patch PA may contain a DNA polymerase. The DNA
polymerase may perform a function of enabling the dNTP to bind to
the DNA which is bound to the primer. For example, the DNA
polymerase may be Taq polymerase.
[0420] The patch PA may contain a buffer solution. The patch PA may
perform a function of providing an environment by contacting with
the plate PL, and an environment suitable for each step of the PCR
may be created in the sample SA located on the plate PL.
[0421] The patch PA which contains the buffer solution
(hereinafter, "buffer patch PA") may be partially similar to a
buffer patch PA used in the morphological diagnosis, the
immunoassay, and the cell culture diagnosis.
[0422] The patch PA may contain a coenzyme. The coenzyme may be
changed in accordance with the above DNA polymerase. For example,
when the DNA polymerase is Taq polymerase, the coenzyme may be
MgCl.sub.2. The patch PA may contact with the plate PL and provide
an environment for activating the DNA polymerase.
[0423] Hereinafter, a few diagnostic methods that are performed for
the cancer diagnosis according to the present application will be
described.
[0424] 5.3 Diagnostic Methods
[0425] 5.3.1 Morphology
[0426] In the cancer diagnosis according to the present
application, a morphological diagnosis using a patch PA and a plate
PL may be performed.
[0427] More specifically, taking into consideration that the shape
of the nucleus of tumor cells CE is different from that of normal
cells CE, cancer may be diagnosed through the shape of the nucleus
of the tumor cells CE. Alternatively, taking into consideration
that the size of tumor cells CE is larger than that of normal cells
CE, cancer may be diagnosed through an external morphology of the
tumor cells CE.
[0428] In case of cancer diagnosis in which the morphological
analysis is performed, it can be performed by smearing the sample
SA, acquiring an image of the sample SA, and analyzing the acquired
image of the sample SA. However, for more accurate diagnosis,
staining of the sample SA may be performed.
[0429] A method of performing the staining of the sample SA will be
briefly described below.
[0430] The morphological diagnosis using the patch PA and the plate
PL may be performed through staining. The sample SA provided on the
plate PL may be fixated, and a staining matter may be provided.
Providing the staining matter may be performed by a patch PA which
contains a staining reagent (hereinafter, "staining patch PA").
[0431] When the staining reagent contained in the patch PA moves to
the sample SA, a cytoplasm or nucleus of the cells CE in the sample
may be stained. Alternatively, when the staining reagent contained
in the patch PA moves to the blood, the DNA located inside the
cells CE in the sample SA may also be stained.
[0432] More specifically, a patch PA that contains a nucleus
staining reagent may stain a nucleus of the cells CE in the blood.
A basic PH staining reagent is mostly used as the nucleus staining
reagent, and typical examples thereof include methylene blue,
toluidine blue, hematoxylin, and the like.
[0433] A patch PA that contains a cytoplasm staining reagent may
stain a cytoplasm of cells CE in blood or an outer structure of the
cells CE. An acidic pH staining reagent is mostly used as the
cytoplasm staining reagent, and typical examples thereof include
eosin, acid fuchsin, orange G, and the like.
[0434] Further, the shape of stained cells CE and/or position of a
nucleus of the cells CE can be identified by staining DNA inside
the cells CE in the blood. For this, the patch PA may contain
membrane-permeable DAPI. The DAPI may stain the cells CE by
permeating through a cell membrane and binding to DNA distributed
in the cell membrane.
[0435] By providing a buffer solution to the sample SA after the
staining reagent is provided to the sample SA, a suitable
environment that is required for staining may be created. Providing
the buffer solution may be performed by a buffer patch PA which
contains the buffer solution. This may beto improve the efficiency
of staining the sample SA.
[0436] By providing a washing solution to the sample SA after the
staining reagent is provided to the sample SA, remaining staining
matter which is not required after staining may be removed.
Providing the washing solution may be performed by a washing patch
PA which contains the washing solution. This may be to acquire a
clearer image of the sample SA.
[0437] The morphological diagnosis using stained blood may be
performed by various means. For example, the morphological
diagnosis may be performed by acquiring an image related to the
stained blood and analyzing the acquired image. In the analysis of
the image, a process may be performed by counting the number of
tumor cells CE danger group in the acquired image and analyzing and
sorting the types of the tumor cells CE.
[0438] Here, it may be preferable that the plate PL is prepared
with a material through which light that is emitted from a light
source may permeate as readily as possible. Also, the light source
may emit white light or light having a wavelength in a specific
band.
[0439] 5.3.2 Immunochemistry
[0440] In the cancer diagnosis according to the present
application, an immunoassay using a patch PA and a plate PL may be
performed. Unless otherwise indicated, "Antibody AB" which will be
described below may bind specifically to proteins attached to
surfaces of circulating tumor cell CE.
[0441] The immunoassay using the patch PA and the plate PL may be
performed by a direct technique. A sample SA (or an antigen)
provided on the plate PL may be fixated, and antibodies AB that
bind specifically to antigens to be detected may be provided. This
may be performed by a patch that contains the above-described
antibodies AB (hereinafter, "antibody patch PA"). Labels for
identification may have been attached to the antibodies AB. After
the antibodies AB are provided, a procedure for removing antibodies
AB which are not bound to the antigens provided on the plate PL may
be performed. This may be performed by the above-described patch PA
which contains a washing solution (hereinafter, "washing patch
PA").
[0442] The immunoassay using the patch PA and the plate PL may be
performed by an indirect technique. A sample SA (or antigen)
provided on the plate PL may be fixated, and a primary antibody AB
that binds specifically to antigens to be detected may be provided.
This may be performed by the above-described antibody patch PA. The
primary antibody AB may not have a label for identification
attached. After the primary antibody AB is provided, a secondary
antibody AB that binds specifically to the primary antibody AB may
be provided on the plate PL. This may be performed by the
above-described antibody patch PA. The second antibody AB may have
a label for identification attached. After the secondary antibody
AB is provided, a procedure for removing the primary antibody AB
which is not bound to the antigens provided on the plate PL and the
secondary antibody AB which is not bound to the primary antibody AB
may be performed. This may be performed by the above-described
washing patch PA.
[0443] The immunoassay using the patch PA and the plate PL may be
performed by a sandwich technique. Antibodies AB that bind
specifically to antigens to be detected may be provided on the
plate PL. On the above plate PL on which the antibodies AB are
provided a sample SA may be provided. After the sample SA is
provided, antibodies AB that bind specifically to the antigens may
be provided on the plate PL. This may be performed by the
above-described antibody patch PA. After the antibodies AB are
provided, a procedure for removing antibodies AB, which are not
bound to the antigens provided on the plate PL, may be performed.
This may be performed by the above-described patch which contains a
washing solution (hereinafter, "washing patch PA"). The antibodies
AB mentioned above may have labels for identification attached.
[0444] Cancer detection through the immunoassay method may be
performed using various means. For example, color development
through an enzyme-substrate SU reaction may be detected,
fluorescence of a fluorescence label may be detected, or light
through a chemical reaction may be detected.
[0445] A method of using an enzyme-substrate SU reaction or using a
fluorescence label will be described in more detail below as a
typical example.
[0446] For example, by detecting color development through the
enzyme-substrate SU reaction the presence of antigens in the sample
SA may be identified. The antibodies AB in the above-described
direct technique or the secondary antibody AB in the
above-described indirect technique may have enzymes attached as
labels. After antibodies AB are provided to the sample SA, a
substrate SU may be provided to the sample SA. This may be
performed by a patch PA that includes the substrate SU
(hereinafter, "substrate patch PA"). The enzymes attached to the
antibodies AB mentioned above may catalyze a chemical reaction of
the substrate SU and generate a product. Color development may be
detected from the sample through the generated product.
[0447] When color development is detected by the generated product,
by measuring the color development, specific binding between the
antibodies AB and the antigens may be quantitatively measured.
Measuring of the color development may be performed by detecting
light that has been emitted from a light source and has passed
through the plate PL. In other words, measuring of the color
development may be performed by measuring light absorption. When
measuring the color development a spectrophotometer may be used. In
this case, the plate PL may be a transparent and flat plate.
[0448] As another example, by detecting fluorescence of the
fluorescence label the presence of antigens in the sample SA can be
identified. The antibodies AB in the above-described direct
technique or the secondary antibody AB in the above-described
indirect technique may have fluorescent substances attached as
labels.
[0449] When the fluorescence detecting is used, fluorescence of the
sample SA may be measured in order to quantitatively measure
specific binding between the antibodies AB and the antigens.
Measuring of the fluorescence may be performed by making light be
incident on the plate PL and measuring fluorescence emitted from
the plate PL. When measuring the fluorescence a fluorometer to
which a filter is attached may be used. Preferably, when measuring
the fluorescence an opaque black plate or an opaque white plate may
be used as the plate PL.
[0450] The above-described color development or fluorescence may be
detected through an image. An image of each part may be acquired,
and the acquired images may be combined into a single image. From
the image positions at which target antigens/antibodies AB are
distributed, shape of cells CE, distribution of target proteins, or
the like may be identified.
[0451] 5.3.3 Culture
[0452] In the cancer diagnosis according to the present
application, culturing cells CE may be performed using a patch PA
and a plate PL. A nutrient patch PA which will be described below
may contain nutritional components required for culturing tumor
cells CE.
[0453] In culturing of cells CE using the patch PA and the plate
PL, the sample SA may be provided on the plate PL, and a nutrient
substance NT may be provided to the sample SA, providing the
nutrient substance NT to the sample SA may be performed by the
above-described nutrient patch PA.
[0454] When a predetermined time has elapsed after the nutrient
substance is provided to the sample SA, cells CE in the sample may
proliferate.
[0455] Analysis on the proliferated cells CE may be performed by
various means. For example, an image of a sample SA on which
culturing cells CE has been completed for a predetermined amount of
time may be acquired, and the image may be analyzed. For another
example, an image of a sample SA on which the culturing cells CE is
in progress may be acquired, and the image may be analyzed.
[0456] The analysis of the image may be performed in consideration
of a speed of cell division of the cells CE and a time at which the
cell division of the cells CE has ended. In other words, taking
into consideration that a speed of cell division of tumor cells CE
is faster than that of normal cells CE and the tumor cells CE may
proliferate infinitely while division of the normal cells CE ends
at an arbitrary point in time, cells CE that continuously divide
while dividing at a relatively higher speed may be identified in
order to identify whether cancer has developed.
[0457] Even in this case, it may be preferable for the plate PL to
be prepared with a material through which light emitted from a
light source may permeate as readily as possible.
[0458] 5.3.4 PCR
[0459] In the cancer diagnosis according to the present
application, a PCR may be performed using a patch PA and a plate
PL. A primer which will be described below may be produced to
correspond to a DNA sequence of a cancer patient.
[0460] The PCR using the patch PA and the plate PL may be performed
on a sample SA provided on the plate PL. The sample SA may be a DNA
sample that has been extracted from the blood. The DNA sample may
be heated at the temperature in which two strands of DNA in the DNA
sample are separated (hereinafter, "denaturation temperature").
[0461] A primer may be provided to the heated DNA sample. Providing
of the primer may be performed by a patch PA that contains the
primer. The DNA sample to which the primer has been provided may be
adjusted to the temperature in which the primer can bind to the DNA
(hereinafter, "annealing temperature"). The primer may have a label
for identification attached.
[0462] After the primer binds to the DNA, a dNTP, a DNA polymerase,
a buffer solution, and a coenzyme may be provided to the sample.
This may be performed by a patch PA that contains the dNTP, a patch
PA that contains the DNA polymerase, a patch PA that contains the
buffer solution, and a patch PA that contains the coenzyme.
Alternatively, this may be performed by a patch PA that contains at
least two or more of the above-mentioned dNTP, DNA polymerase,
buffer solution, and coenzyme. When temperature of the sample
mentioned above is adjusted to the temperature at which the DNA
bounds to the primer may extend (hereinafter, "extension
temperature"), the DNA bound to the primer may extend.
[0463] The cancer diagnosis through the PCR process may be
performed by various means. For example, fluorescence of a
fluorescence label may be detected, or electrophoresis may also be
used. Also, in accordance with a point in time at which the sample
SA is analyzed, detecting a target DNA may be performed from a
sample SA on which the PCR process has been completed, or a target
DNA may be detected from a sample SA on which the PCR process is in
progress.
[0464] An identification label attached to the above-described
primer may be a fluorescent substance. Also, the fluorescent
substance may be a substance that exhibits fluorescence until
fluorescence is consumed or a substance that is designed to exhibit
fluorescence when the primer and the DNA are bound.
[0465] Since the detection means using the fluorescence label has
already been described in detail above in relation to the
immunoassay, detailed description thereof will be omitted.
[0466] As described above, cancer diagnosis according to an
embodiment of the present application may be performed through the
morphological diagnosis, the immunoassay, the culture progress
diagnosis, and the DNA diagnosis (that is, PCR testing).
[0467] Hereinafter, to assist in understanding the present
application, a method of performing cancer diagnosis using a patch
PA will be described in detail for each diagnostic method using a
few embodiments.
[0468] 6. Embodiments Related to Diagnostic Processes Using
Patch
[0469] 6.1 Morphology
[0470] FIG. 35 is a view for describing performance of
morphological diagnosis using a staining technique in cancer
diagnosis according to an embodiment of the present application.
The morphological diagnosis according to an embodiment of the
present application may be performed through providing a sample SA
on a plate PL (S1100), providing a staining reagent on the plate PL
(S1200), and acquiring an image of the stained sample SA (S1300).
This may correspond to performing morphological diagnosis using a
simple staining technique.
[0471] In the morphological diagnosis for the cancer diagnosis
according to the present application, as described above, a nucleus
and/or a cytoplasm of tumor cells CE may be stained.
[0472] The providing the sample SA on the plate PL (S1100) may
refer to placing the sample SA on the plate PL. For example, the
sample SA may be smeared or printed on the plate PL. Also, the
sample SA may be fixated on the plate PL. The sample SA may have a
predetermined force of resistance and be fixated on the plate PL so
that absorption of the sample SA into a patch PA due to contact or
separation between the patch PA and the plate PL is prevented.
[0473] A staining patch PA may be used for the providing the
staining reagent on the plate PL (S1200). A single staining reagent
may be contained in the patch PA.
[0474] Due to contact between the patch PA and the plate PL, a
staining reagent that has been contained in the patch PA may move
to the plate PL. To provide a staining reagent on the plate PL, the
patch PA and the plate PL may be brought into contact. Also, the
patch PA and the plate PL may be separated after having been in
contact.
[0475] In the present step, to implement a predetermined
environment in the sample SA, the buffer patch PA may also be used
as necessary.
[0476] Also, in the present step, washing may be performed to
remove a non-required staining reagent provided in the sample SA.
The washing may be performed by the washing patch PA which contains
a washing solution.
[0477] After the providing the staining reagent, the acquiring of
the image of the stained sample SA located on the plate PL (S1300)
may be performed. When an image of the sample SA is acquired,
analysis may be performed on the image.
[0478] By analyzing the image, the sizes and morphologies of cells
CE included in the blood may be compared. Since the size of tumor
cells CE is larger than that of normal cells CE and the morphology
of the tumor cells CE is different from that of the normal cells
CE, the tumor cells CE may be detected through the image analysis,
and the number of tumor cells CE may be counted.
[0479] FIG. 36 is a view for describing performance of
morphological diagnosis using a staining technique in which a
plurality of staining reagents are used in cancer diagnosis
according to an embodiment of the present application.
[0480] In the providing the staining reagent on the plate PL
(S1200), at least two or more stains may be delivered. In this
case, to deliver at least two or more stains to the sample SA, a
plurality of staining patches PA that each contain one of the
plurality of staining reagents may be used.
[0481] However, hereinafter, for convenience of description,
description will be given which assumes that two staining patches
PA, i.e., a first staining patch PA and a second staining patch PA,
are used to stain a sample using two staining reagents.
[0482] However, the number of staining patches PA is not limited to
two in the present embodiment, and three or more staining patches
PA may also be used. Since those of ordinary skill in the art may
easily understand that, without inventive thinking, a modified
example in which three or more staining patches PA are used is
applicable to the following description, such a modified example
should be understood as belonging to the present embodiment.
[0483] The providing the staining reagent on the plate PL (S1200)
may include providing a first staining reagent on the plate PL
(S1210) and providing a second staining reagent on the plate PL
(S1220).
[0484] Here, the first staining reagent and the second staining
reagent may stain different target substances in the blood. For
example, the first staining reagent may be any one of a basic
staining reagent that stains a nucleus and an acidic staining
reagent that stains a cytoplasm, and the second staining reagent
may be the other of the two. Alternatively, the opposite may be
possible. Specifically, the first staining reagent may be methylene
blue, and the second staining reagent may be eosin. Of course, it
should be noted that the types of the first staining reagent and
the second staining reagent are not limited to the above-given
examples.
[0485] When the first staining patch PA is brought into contact
with the plate PL, the first staining reagent may move to the plate
PL. Therefore, the staining patch PA that contains the first
staining reagent may stain a first target substance included in the
sample SA. When the second staining patch PA is contacted with the
plate PL, the second staining reagent may move to the plate PL.
Therefore, the staining patch PA that contains the second staining
reagent may stain a second target substance included in the sample
SA. Here, the first target substance may be any one of a nucleus
and a cytoplasm of cells CE, and the second target substance may be
the other of the two.
[0486] FIG. 37 is a view for describing performance of
morphological diagnosis using a DAPI staining technique in cancer
diagnosis according to an embodiment of the present
application.
[0487] In providing a staining reagent on the plate PL (S1240), a
fluorescence staining reagent may be provided on the plate PL. For
example, the fluorescence staining reagent may be DAPI.
[0488] A patch PA that contains the staining reagent may be
contacted with the plate PL, and due to contact between the patch
PA and the plate PL, the staining reagent contained in the patch PA
may move to the plate PL.
[0489] The staining reagent may permeate through a cell membrane
and be introduced into the cells CE. Although the efficiency of
staining using DAPI may be further improved when the cell membrane
is destroyed, the staining reagent may be introduced into the cells
CE even when the cell membrane is present in the case of the DAPI
staining technique.
[0490] A pH value of the sample SA may be adjusted as necessary.
The pH of the sample SA may be adjusted by a buffer patch PA that
contains a buffer solution.
[0491] Also, temperature of the sample SA may be adjusted.
Preferably, after the staining reagent is provided to the sample
SA, the temperature of the sample SA may be maintained at
approximately 37.degree. C. for about 15 minutes so that a
sufficient reaction time is provided to the sample SA.
[0492] The acquiring of the image of the stained sample SA (S1300)
may be performed. However, in the present embodiment, taking into
consideration that a staining reagent being used is a fluorescence
reagent, a fluorescence image may be acquired. Therefore, light in
an arbitrary wavelength band may have to be provided to the sample
SA for acquiring the fluorescence image.
[0493] Since the fluorescence image using the DAPI staining
technique has a high resolution, there may be an advantage in that
a more accurate cancer diagnosis is possible.
[0494] 6.2 Immunochemistry
[0495] FIG. 38 is a view for describing performance of immunoassay
in cancer diagnosis according to an embodiment of the present
application. An immunoassay method according to an embodiment of
the present application may be performed through providing a sample
SA on a plate PL (S2100), providing antibodies AB on the plate PL
(S2200), and identifying antibodies AB that have bound specifically
to antigens (S2300). This may correspond to performing immunoassay
through a direct technique.
[0496] In performing immunoassay for the cancer diagnosis according
to the present application, as described above, antibodies AB that
bind specifically to the EpCAM or cytokeratin may be used.
[0497] The providing the sample SA on the plate PL (S2100) may be
performed similarly to the above-described Step S1100.
[0498] An antibody patch PA may be used to provide the antibodies
AB on the plate PL (S2200). Due to contact between the patch PA and
the plate PL, the antibodies AB contained in the patch PA may move
to the plate PL. The antibodies AB may bind specifically to
antigens included in the sample SA provided on the plate PL.
[0499] When the antibodies AB are provided on the plate PL, the
identifying of the antibodies AB that have bound specifically to
the antigens (S2300) may be performed. Prior to the present step, a
washing patch PA may be used as necessary to remove antibodies AB
that failed to bind to the sample SA.
[0500] The antibodies AB that have bound specifically to the
antigens may be identified through various methods.
[0501] For example, a substrate SU-enzyme reaction may be used to
identify the antibodies AB that have bound specifically to the
antigens.
[0502] FIGS. 39 and 40 are views for describing a method of
detecting cancer using a substrate SU-enzyme reaction when
immunoassay is performed in cancer diagnosis according to an
embodiment of the present application.
[0503] When the antibodies AB are provided by the patch PA, an
enzyme may be bound to the antibodies AB. Labels bound to the
antibodies AB may be enzymes. The sample SA, to which the
antibodies AB are provided by the patch PA, may be bound to some of
the antibodies AB provided by the patch PA.
[0504] A substrate patch PA may be provided to the sample SA. When
the substrate patch PA is provided to the sample SA, the enzymes
attached to the antibodies AB, which are bound to the sample, may
react with the substrate SU. More specifically, a product may be
generated due to a reaction that is catalyzed by the substrate. The
presence of circulating tumor cell CE in the sample SA may be
identified based on whether the product is generated.
[0505] In this case, the substrate patch PA may perform a function
of providing a reaction space in which the enzyme and the substrate
SU may react. This has been described in detail above in the
description of functions of the patch PA.
[0506] As another example, a fluorescent substance may be used to
identify antibodies AB that have bound specifically to the
antigens.
[0507] FIG. 41 is a view for describing a method of detecting
cancer using a fluorescent substance when immunoassay is performed
in cancer diagnosis according to an embodiment of the present
application.
[0508] When antibodies AB are provided by a patch PA, a fluorescent
substance may be bound to the antibodies AB. Labels bound to the
antibodies AB may be a fluorescent substance. The sample SA to
which the antibodies AB are provided by the patch PA may be bound
to some of the antibodies AB provided by the patch PA.
[0509] The contact between the patch PA and the plate PL may be
released. The contact may be released to prevent fluorescence
development by antibodies AB contained in the patch PA (that is,
antibodies AB that have not yet bound to the sample SA).
[0510] After the contact between the patch PA and the plate PL is
released, the presence of tumor cells CE in the sample SA may be
identified in accordance with whether light is emitted from the
fluorescent substance attached to the antibodies AB which are bound
to the sample SA.
[0511] When the above-described fluorescent substance is used to
identify the antibodies AB that bind specifically to the antigens,
a fluorescence image of the sample SA may be acquired to identify
positions at which the antibodies AB are attached. The positions at
which the antibodies AB are attached may be analyzed to count tumor
cells CE distributed in the blood.
[0512] A plurality of images of the sample SA may be acquired with
time. Diagnosis on a plurality of targets may be performed through
a comparison between changes in a previously-acquired image and a
subsequently-acquired image from among the plurality of images.
[0513] FIG. 42 is a view for describing a method of performing
immunoassay using multiple types of antibodies AB in cancer
diagnosis according to an embodiment of the present
application.
[0514] For example, when the sample SA is provided on the plate PL
(S2100), a third antibody AB that binds specifically to white blood
cells (for example, CD45) may be provided to the sample SA (S2250).
The providing the third antibody AB may be performed by a patch PA
that contains the third antibody AB.
[0515] After the third antibody AB is provided to the sample SA,
antigens that bind specifically to the third antibody AB may be
identified (S2350). That is, after the providing the third antibody
AB, an image of the sample SA may be acquired, and the image may be
analyzed to count the number of white blood cells included in the
sample SA.
[0516] A fourth antibody AB related to tumor cells CE may be
provided on the plate PL (S2260). The providing the fourth antibody
AB may be performed by a patch PA that contains the fourth antibody
AB.
[0517] After the fourth antibody AB is provided to the sample SA,
antigens that bind specifically to the fourth antibody AB may be
identified (S2360). That is, after the providing the fourth
antibody AB, an image of the sample SA may be acquired, and the
image may be analyzed. In relation to the image, by identifying a
position at which fluorescence is displayed in a currently-acquired
image and then performing analysis in consideration of a position
at which fluorescence is displayed in a previously-acquired image,
the number of tumor cells CE included in the sample SA may be
counted.
[0518] FIG. 43 is a view for describing a method of performing
immunoassay using a primary antibody AB and a secondary antibody AB
in cancer diagnosis according to an embodiment of the present
application. This may correspond to performing immunoassay through
an indirect technique.
[0519] In a modified example of the above-described embodiment, the
providing the antibodies AB on the plate PL (S2200) may include
providing a first antibody AB on the plate PL (S2210) and providing
a second antibody AB on the plate PL (S2220).
[0520] The first antibody AB may be an antibody AB that binds
specifically to tumor cells CE. The second antibody AB may be an
antibody AB that binds specifically to the first antibody AB. In
this case, the specific binding between the first antibody AB and
the second antibody AB may be species-specific binding instead of
epitope-specific binding. The immunoassay method using the first
antibody AB and the second antibody AB may be used for convenience
of producing a specific antibody AB.
[0521] The first antibody AB may be provided by a patch PA that
contains the first antibody AB. The second antibody AB may be
provided by a patch PA that contains the second antibody AB.
Alternatively, the first antibody AB and the second antibody AB may
be provided by a patch PA that contains both the first antibody AB
and the second antibody AB.
[0522] To provide the first antibody AB on the plate PL, a patch PA
which contains the first antibody AB may be brought into contact
with the plate PL. To provide the second antibody AB on the plate
PL, a patch PA which contains the second antibody AB may be
contacted with the plate PL.
[0523] Alternatively, to provide the first antibody AB and the
second antibody AB on the plate PL, the patch PA that contains both
the first antibody AB and the second antibody AB may be contacted
with the plate PL. To provide the first antibody AB and the second
antibody AB on the plate PL, the patch PA which contains the first
antibody AB may be contacted with the plate PL, and the patch PA
which contains the second antibody AB may be contacted with the
first antibody AB.
[0524] After the providing the antibodies AB on the plate PL, a
washing patch PA may be used as necessary to remove antibodies AB
that have been provided by the patch PA but have not bound to the
sample SA.
[0525] FIG. 44 is a view for describing a method of performing
immunoassay using a first antibody AB that has been applied on a
plate PL and second antibody AB that is provided to a sample SA in
cancer diagnosis according to an embodiment of the present
application. This corresponds to performing immunoassay through a
sandwich technique.
[0526] By a conventional method, a first antibody AB may be placed
on the plate PL (S2020). For example, a method in which the first
antibody is applied on the plate and then frozen and dried may be
applied. The first antibody AB may be an antibody AB that binds
specifically to tumor cells CE.
[0527] The first antibody AB may be fixated on the plate PL. The
fixating of the first antibody AB may be performed through a method
of drying the antibody AB or using a coating buffer solution.
Alternatively, the fixating of the antibody AB on the plate PL may
include forming a thin film on the plate PL. The thin film may be
manufactured in advance to be attached to the plate PL.
[0528] The sample SA may be provided on the plate PL on which the
first antibody AB is located (S2100). The providing the sample SA
on the plate PL may include applying the blood. The applying of the
blood may include applying the blood in a thin layer in
consideration to a reaction area with the antibody AB fixated on
the plate PL. Preferably, the blood may be applied in a single
layer.
[0529] A second antibody AB may be provided on the plate PL
(S2200). The second antibody AB may be an antibody AB that binds
specifically to white blood cells. Alternatively, the second
antibody AB may be an antibody AB that binds specifically to tumor
cells CE. In this case, the second antibody AB may be different
from the first antibody AB.
[0530] The second antibody AB may be provided by the
above-described direct technique or indirect technique. In other
words, the providing the second antibody AB on the plate PL may
include providing an antibody AB that binds specifically to
antigens which are to be detected, or may include providing a
primary antibody AB that bind specifically to antigens which are to
be detected and a second antibody AB that binds specifically to the
primary antibody AB.
[0531] The above-described first antibody AB and/or second antibody
AB may be provided by a patch PA. In this case, an immunoassay
method may be applied in accordance with the above-described direct
technique or indirect technique.
[0532] After the providing the sample SA on the plate PL and/or the
providing the antibodies AB on the plate PL which have been
described above, a washing patch PA may be used as necessary to
remove antibodies AB that have been provided by the patch PA but
have not bound to the sample SA.
[0533] 6.3 Culture
[0534] FIG. 45 is a view for describing performance of culture of
cells CE in cancer diagnosis according to an embodiment of the
present application.
[0535] A process of culturing cells CE according to an embodiment
of the present application may include providing a sample SA on a
plate PL (S3100), providing a nutrient substance NT on the plate
(S3200), and acquiring an image of the sample SA (S3300). This may
be intended to detect circulating tumor cell CE included in the
sample SA.
[0536] The providing the sample SA on the plate PL (S3100) may be
performed similarly to the above-described Step S1100.
[0537] The nutrient substance NT may be provided to the sample SA
located on the plate PL (S3200). The nutrient substance NT may be
provided by a patch PA that contains at least some reagents that
are used in culturing tumor cells CE.
[0538] As described above, the patch PA may contain amino acids,
vitamins, trace elements, and the like. Alternatively, as another
example, the patch PA may contain proteins, peptides, hormones,
minerals, and the like.
[0539] Due to contact between the patch PA and the plate PL, the
nutrient substance NT contained in the patch PA may move to the
plate PL. When the nutrient substance NT is provided, cells CE
included in the sample SA which is located on the plate PL may
proliferate.
[0540] In the present step, a washing process may be performed on
the plate PL as necessary. This may be a procedure performed by the
above-described washing patch PA.
[0541] For analysis of the proliferated cells CE, an image of the
sample SA may be acquired (S3300). As described above, an image of
the sample SA on which culturing of cells CE has been completed or
an image of the sample SA on which culturing of cells CE is in
progress may be acquired.
[0542] A plurality of images of the cells CE may be acquired. An
image of the sample SA may be acquired once prior to the start of
culturing of cells CE and may be acquired at least one or more
times at a desired point in time. In image analysis, the reason for
acquiring an image prior to the start of culturing of cells CE may
be to estimate a proliferation rate of cells CE using the image
prior to cell culturing.
[0543] FIGS. 46 and 47 are views for describing a process in which
cells CE included in a sample proliferate in cancer diagnosis
according to an embodiment of the present application.
[0544] Referring to FIG. 46, in culturing of cells CE according to
an embodiment of the present application, a sample SA may be
applied on a plate PL. Some cells CE may be included in the applied
sample SA. Due to contact between the nutrient patch PA and the
plate PL, the nutrient substance NT that has been contained in the
nutrient patch PA may move to the plate PL.
[0545] When the nutrient substance NT that has been contained in
the nutrient patch PA is provided to the sample SA applied on the
plate PL, the cells CE included in the sample SA may
proliferate.
[0546] As illustrated in FIG. 47, proliferation speeds of some
cells CE may be different. A speed of cell division of tumor cells
CE may be higher than that of normal cells CE. On the basis of such
a comparison, the tumor cells CE included in the sample SA may be
detected. This may be a means in which cells which are dividing
more are presumed to be tumor cells CE.
[0547] 6.4 PCR
[0548] FIG. 48 is a view for describing performance of a PCR
process in cancer diagnosis according to an embodiment of the
present application. The PCR process according to an embodiment of
the present disclosure may include providing a sample SA on a plate
PL (S4100), providing reagents on the plate PL (S4200), adjusting a
temperature of the sample SA (S4300), and analyzing the sample SA
(S4400). This may be intended to detect DNA of circulating tumor
cell CE included in the sample SA.
[0549] The providing the sample SA on the plate PL (S4100) may be
performed similarly to the above-described Step S1100. However, a
sample SA on which a pre-processing process for extracting DNA from
the blood has been completed may be used.
[0550] Reagents may be provided on the plate PL on which the sample
SA has been provided (S4200). The reagents may be provided by a
patch PA that contains at least some of a plurality of reagents
used in the PCR process.
[0551] The patch PA may be a patch PA that contains a dNTP, a patch
PA that contains a primer, or a patch PA that contains a DNA
polymerase. Also, the patch PA may be a patch PA that contains a
buffer solution or a patch PA that contains a coenzyme.
Alternatively, the patch PA may be a patch PA that contains two or
more of the above-mentioned dNTP, primer, DNA polymerase, buffer
solution, and coenzyme.
[0552] The patch PA and the plate PL may be contacted so that the
reagents included in the patch PA are provided on the plate PL. Due
to the contact between the patch PA and the plate PL, the reagents
contained in the patch PA may move to the plate PL.
[0553] When a plurality of patches PA are used to provide reagents
on the plate PL, the plurality of patches PA may sequentially be
brought into contact with the plate PL, or one patch PA from among
the plurality of patches PA may be brought into contact with the
plate PL and then a patch PA different from the one patch PA may be
contacted with the one patch PA.
[0554] When reagents are provided on the plate PL, the temperature
of the sample SA may be adjusted (S4300). The temperature of the
sample SA may be adjusted by increasing or decreasing the
temperature of the plate PL or maintaining the temperature of the
plate PL at a desired temperature. The temperature of the sample SA
may be adjusted by increasing or decreasing the temperature of the
patch PA or maintaining the temperature of the patch PA at the
desired temperature. The temperature of the sample SA may be
adjusted by increasing or decreasing the temperatures of the patch
PA and the plate PL or maintaining the temperatures of the patch PA
and the plate PL at desired temperatures.
[0555] The temperature of the sample SA may be adjusted to the
above-described denaturation temperature, annealing temperature,
and extension temperature. Due to adjustment of the temperature of
the sample SA, the double helix structure of the DNA included in
the sample SA may be separated, a primer may bind to the separated
DNA, and a dNTP may bind to the DNA bound with the primer so that
the DNA may extend.
[0556] When the temperature of the sample SA is adjusted (S4300),
the sample SA may be analyzed (S4400). Here, the analyzing of the
sample SA may include detecting a fluorescent substance attached to
the primer. Alternatively, the analyzing of the sample SA may
include acquiring an image of the sample SA.
[0557] The analysis may be performed after the PCR process on the
sample SA is completed. Due to performing analysis in a state in
which DNA amplification on the sample SA has been completed, more
accurate data may be acquired.
[0558] The analysis may be performed in the middle of the PCR
process on the sample SA. More specifically, the analysis on the
sample SA may be continuously performed while the PCR process is
performed, or, on the basis of one cycle of the PCR process (for
example, the denaturation step, the annealing step, and the
extension step are sequentially performed), the analysis may be
repeatedly performed every cycle at an arbitrary point in time.
This form of analysis compares the amounts of amplified DNA with
the amount of time that has passed and enables quantitative
analysis on target DNA in real time.
[0559] FIG. 49 is a view for describing a method of using a patch
PA to decompose a cell membrane of cells CE included in a sample SA
when a PCR process is performed in cancer diagnosis according to an
embodiment of the present application.
[0560] In a modified example of the above-described embodiment,
providing reagents on the plate PL (S4120) and fixating the sample
SA located on the plate PL (S4140) may be additionally performed
after the providing the sample SA on the plate PL (S4100) described
above.
[0561] After the sample SA is provided on the plate PL (S4100),
reagents may be provided on the plate PL (S4120). The sample SA may
be blood that has not gone through pre-processing. The reagent may
be a substance for breaking down cell membrane of circulating tumor
cell that float in the blood. For example, the reagent may be a
lysozyme for destroying the cell membrane of the cells CE. The
reagent may be provided by the patch PA. The reagent may be
contained in the patch PA.
[0562] After the reagents are provided on the plate PL (S4120), the
sample SA located on the plate PL may be fixated (S4140). The
sample SA located on the plate PL may be the blood and DNA of cells
CE included in the blood. The sample SA may be in a state in which
a portion of a cell membrane of the cells CE is floating.
[0563] After the sample SA is fixated on the plate PL (S4140), the
PCR process may be performed on the sample SA. The PCR process to
be performed afterwards may be performed using any method of PCR
process such as the method disclosed herein and a method generally
performed by those of ordinary skill in the art.
[0564] FIG. 50 is a view for describing performance of a PCR
process in cancer diagnosis according to an embodiment of the
present application. In the present embodiment, description will be
given which assumes that reagents are provided on the plate PL by a
plurality of patches PA.
[0565] When the sample SA is provided on the plate PL (S4100), the
temperature of the sample SA may be adjusted to the denaturation
temperature (S4310). As described above, the temperature of the
sample SA may be adjusted by adjusting a temperature of the plate
PL and/or temperature of the patch PA. When the temperature of the
sample SA is maintained at the denaturation temperature for a
predetermined amount of time, the double helix structure of the DNA
included in the sample SA may be separated.
[0566] Annealing reagents may be provided on the plate PL (S4310).
Here, the annealing reagents may refer to at least some of reagents
used in the annealing step. For example, the annealing reagents may
be primers.
[0567] The annealing reagents may be provided by a patch PA. Due to
contact between the patch PA and the plate PL, the reagents
contained in the patch PA may be movable to the plate PL, and
accordingly, the reagents may be provided on the plate PL by the
patch PA.
[0568] The patch PA may contain annealing reagents. For example,
the patch PA may contain primers. In this case, the primers may be
produced to correspond to sequences commonly included in DNA of
cancer patients.
[0569] When the annealing reagents are provided on the plate PL
(S4310), the reagents may also be provided to the sample SA located
on the plate PL.
[0570] The temperature of the sample SA may be adjusted to the
annealing temperature (S4320). To adjust the temperature of the
sample SA to the annealing temperature, as described above, the
temperatures of the plate PL and/or the patch PA may be
adjusted.
[0571] A target that is subject to temperature adjustment to adjust
the temperature of the sample SA to the annealing temperature may
be different from a target that is subject to temperature
adjustment to adjust the temperature of the sample SA to the
extension temperature. For example, even when the plate PL has been
heated to adjust the temperature of the sample SA to the
denaturation temperature, the patch PA may be cooled and brought
into contact with the plate PL in order to adjust the temperature
of the sample SA to the annealing temperature.
[0572] When the temperature of the sample SA is adjusted to the
annealing temperature (S4320), the DNA included in the sample SA
may react with the annealing reagents. For example, the DNA
included in the sample SA may bind to the primers.
[0573] After the temperature of the sample SA has been maintained
at the annealing temperature for a predetermined amount of time,
extension reagents may be provided on the plate PL (S4220). Here,
the extension reagents may refer to some of reagents used in the
extension step. For example, the annealing reagents may be a dNTP,
a DNA polymerase, a buffer solution, and a coenzyme.
[0574] The extension reagents may be provided by the patch PA.
[0575] For example, due to contact between the patch PA and the
plate PL, the reagents contained in the patch PA may be movable to
the plate PL, and accordingly, the reagents may be provided on the
plate PL by the patch PA.
[0576] As another example, the patch PA may be brought into contact
with another patch PA that is already in contact with the plate PL
so that the reagents contained in the patch PA are movable to the
other patch PA. Accordingly, the reagents may be provided to the
plate PL in contact with the other patch PA.
[0577] The patch PA may contain the extension reagents. For
example, the patch PA may contain a dNTP, a DNA polymerase, a
buffer solution, and a coenzyme.
[0578] The temperature of the sample SA may be adjusted to the
extension temperature (S4330). The temperature of the sample SA may
be adjusted by adjusting temperatures of the patch PA and/or the
plate PL. When the temperature of the sample SA is adjusted to the
extension temperature, the sample SA may react with the extension
reagents. For example, the DNA bound to the primers may extend.
[0579] 7. Multi-Test
[0580] 7.1 Meaning
[0581] Cancer is an incurable disease of which complete treatment
has not yet been developed. Survival rates greatly differ between
early cancer, middle cancer, and terminal cancer. Therefore,
accurate diagnosis of whether cancer has developed is an important
factor in cancer diagnosis.
[0582] In relation to this, in cancer diagnosis according to the
present application, for accuracy of diagnosis, multiple diagnoses
may be performed on a single sample SA.
[0583] An embodiment in which multiple diagnostic processes are
performed on a sample SA and advantageous effects thereof will be
described in detail below.
[0584] 7.2. Embodiment of Multi-Test
[0585] 7.2.1 First Embodiment
[0586] FIG. 51 is a view for describing multiple types of
diagnostic methods for a sample SA in cancer diagnosis according to
an embodiment of the present application.
[0587] The cancer diagnosis according to an embodiment of the
present application may be performed using a method which includes
performing morphological analysis of a sample SA (S5100) and
analyzing culture progress of the sample SA (S5200).
[0588] The above-described embodiments related to morphological
analysis may be applied to the morphological analysis on the sample
SA.
[0589] The above-described embodiments related to culture progress
analysis may be applied to the culture progress analysis on the
sample SA.
[0590] The performing of the morphological analysis on the sample
SA refers to analyzing the morphology of cells CE included in the
sample SA. By analyzing the morphology of the cells CE included in
the sample SA, cells CE presumed to be tumor cells CE may be
identified.
[0591] Although staining may be performed on the sample SA as
necessary, description will be given which assumes that an image of
an unstained sample SA is acquired in the morphological analysis of
the present embodiment.
[0592] The performing of the culture progress analysis after the
morphological analysis on the sample SA refers to culturing the
sample SA on which the morphological analysis has been
performed.
[0593] In the culture analysis, cells CE suspected as tumor cells
CE may be identified by culturing the sample SA. In this case,
locations of cells CE confirmed, through the morphological analysis
of the sample SA, as cells highly likely to become tumor cells CE
may be identified, and the culture progress of the cells CE at the
corresponding locations may be identified.
[0594] The culture progress analysis on the sample SA may include
identifying whether cells CE included in the sample SA continuously
divide. In other words, on the basis of the above-mentioned
characteristic of tumor cells CE that the tumor cells CE
proliferate infinitely, cells CE which divide continuously may be
detected as tumor cells CE.
[0595] The method of cancer diagnosis according to the present
embodiment will be described in more detail below.
[0596] FIG. 52 is a view for describing multiple types of
diagnostic methods for a sample SA in cancer diagnosis according to
an embodiment of the present application.
[0597] When a sample SA is provided on the plate PL (S5110), an
image of the sample SA may be acquired (S5120).
[0598] Step S5110 may be performed similarly to the above-described
Step S1100. Step S5120 may be similar to the above-described Step
S1300.
[0599] As described above, the sample SA may be applied in a single
layer on the plate PL. The sample SA may not have been stained.
Although this is not essential, this may be intended to prevent
culturing of a sample SA on which an unnecessary specimen (e.g., a
stain) is provided in the culture progress analysis which will be
performed afterwards.
[0600] Also, as necessary, the sample SA provided on the plate may
not be fixated on the plate in the present embodiment. This may be
intended to prevent destruction of membranes of cells CE in the
fixating process.
[0601] The image of the sample SA may be analyzed. Through the
image of the sample SA, cells CE presumed to be circulating tumor
cell CE may be identified, and precise analysis may be attempted on
the corresponding cells CE.
[0602] The precise analysis may be performed using a method in
which the culture progress analysis is performed on the
corresponding cells CE.
[0603] Nutrition may be provided to the sample SA (S5210). The
nutrition may be provided due to contact between the patch PA and
the sample SA. As described above, the patch PA may be a nutrient
patch PA which contains a nutrient substance NT.
[0604] When the nutrition is provided to the sample SA, an image of
the sample SA may be acquired (S5220).
[0605] Step S5210 may be performed similarly to the above-described
Step S3200. Step S5220 may be performed similarly to the
above-described Step S3300.
[0606] The image of the sample SA may be acquired in real time
while the nutrition is being provided to the sample SA. In this
case, the image acquired in real time has an advantage of allowing
instantaneous changes of the cells CE to be observed.
[0607] Alternatively, an image of the sample SA may be acquired
after an arbitrary amount of time has elapsed after the providing
nutrition to the sample SA. The image of the sample SA may be
compared with an image for the above-described morphological
analysis. For example, by analyzing changes in sizes of specific
cells CE and a relative difference in culture speeds of the
specific cells CE and other cells CE, tumor cells CE included in
the sample SA may be detected.
[0608] 7.2.2 Second Embodiment
[0609] FIG. 53 is a view for describing multiple types of
diagnostic methods for a sample SA in cancer diagnosis according to
an embodiment of the present application.
[0610] The cancer diagnosis according to an embodiment of the
present application may be performed using a method which includes
performing an immunoassay of a sample SA (S6100) and performing
culture progress analysis of the sample SA (S6200).
[0611] The above-described embodiments related to an immunoassay
may be applied to the immunoassay on the sample SA.
[0612] The above-described embodiments related to culture progress
analysis may be applied to the culture progress analysis on the
sample SA.
[0613] The performing of the immunoassay on the sample SA refers to
analyzing an immune system of cells CE included in the sample SA.
Using antibodies AB related to proteins distributed on surfaces of
cells CE included in the sample SA, characteristics of the cells CE
(for example, whether the cells CE are tumor cells CE) may be
analyzed.
[0614] According to circumstances, the morphology of the cells CE
may also be analyzed using antibodies AB that are bound to proteins
on surfaces of cells CE due to binding between antigens and the
antibodies AB. This corresponds to a method in which schematic
external morphology of the cells CE is estimated using labels bound
to the antibodies AB.
[0615] The performing of the culture progress analysis on the
sample SA includes culturing the sample SA on which the
above-described immunoassay has been performed. Since the culture
progress analysis on the sample SA has already been described
above, detailed description thereof will be omitted.
[0616] The method of cancer diagnosis according to the present
embodiment will be described in more detail below.
[0617] FIG. 54 is a view for describing multiple types of
diagnostic methods for a sample SA in cancer diagnosis according to
an embodiment of the present application.
[0618] When a sample SA is provided on the plate PL (S6110),
antibodies AB may be provided on a plate PL (S6120). The antibodies
AB provided on the plate PL may bind specifically to antigens
included in the sample SA. The patch PA may contain the antibodies
AB. The antibodies AB may be provided on the plate PL by the patch
PA.
[0619] The providing the antibodies AB may be performed using any
of the above-described direct technique, indirect technique, and
sandwich technique.
[0620] After the antibodies AB are provided on the plate PL,
antibodies AB that have bound specifically to antigens may be
identified (S6130). For example, when a fluorescent substance is
attached to the antibodies AB, fluorescence of the sample SA may be
detected. As another example, when an enzyme is attached to the
antibodies AB, a substrate SU may be provided to the sample SA, and
color development of the sample SA may be detected. Using the
above-described methods, the presence of antibodies AB that have
bound specifically to antigens included in the sample SA may be
identified, and in this way, whether cancer has developed may be
identified.
[0621] Step S6110 may be performed similarly to the above-described
Step S2100, Step S6120 may be performed similarly to the
above-described Step S2200, and Step S6130 may be performed
similarly to the above-described Step S2300.
[0622] Since providing nutrition to the sample SA provided on the
plate PL (S6210) and acquiring an image of the sample SA (S6220)
may be performed similarly to the above-described Steps S5210 and
S5220, detailed description thereof will be omitted.
[0623] 7.2.3 Third Embodiment
[0624] FIG. 55 is a view for describing multiple types of
diagnostic methods for a sample SA in cancer diagnosis according to
an embodiment of the present application.
[0625] After culture progress analysis on the sample SA is
performed, any one of morphological analysis, immunoassay, and DNA
analysis may be performed on the sample SA.
[0626] When the culture progress analysis is performed, cells CE
included in the sample SA may proliferate. Therefore, when cancer
diagnosis using another method is performed after the culture
progress analysis is performed, a sample SA that includes
proliferated cells CE may be analyzed, and a more accurate cancer
diagnosis may be possible.
[0627] To assist in understanding the present application, a case
in which culture progress analysis on a sample SA is performed
(S7100) and then immunoassay on the sample SA is performed (S7200)
will be described below as an example.
[0628] FIG. 56 is a view for describing multiple types of
diagnostic methods for a sample SA in cancer diagnosis according to
an embodiment of the present application.
[0629] When a sample SA is provided on the plate PL (S7110), a
nutrient substance NT may be provided on the plate PL (S7120). The
providing the nutrient substance NT may be performed by the patch
PA. The patch PA may contain the nutrient substance NT.
[0630] The nutrient substance NT provided on the plate PL may also
be provided to the sample SA located on the plate PL and an
environment that allows cells CE included in the sample SA to
proliferate may be provided.
[0631] In addition, a buffer patch PA may be used to suitably
adjust the pH and/or salt concentration of the sample SA. The
buffer patch PA may be brought into contact with the plate PL or
brought into contact with the nutrient patch PA.
[0632] After the nutrient substance NT is supplied to the plate PL
for an arbitrary amount of time, an image of the sample SA may be
acquired (S7130) and analyzed.
[0633] Alternatively, an image of the sample SA may be acquired
(S7130) while the nutrient substance NT is supplied to the plate PL
so that cells CE included in the sample SA are analyzed in real
time.
[0634] Alternatively, an image of the sample SA may not be
acquired. That is, instead of being a procedure for acquiring an
image of the sample SA, the culture progress analysis on the sample
SA may be a procedure for proliferating cells CE in a sample SA to
be used in various diagnoses which will be performed afterwards. In
this way, by performing various diagnoses using the proliferated
cells CE, the efficiency of detecting circulating tumor cell CE
distributed in the blood may be increased.
[0635] Since providing antibodies AB on the plate PL (S7210) and
identifying antibodies AB that have bound specifically to antigens
(S7220) may be performed similarly to the above-described Steps
S6120 and S6130, detailed description thereof will be omitted.
[0636] 7.2.4 Fourth Embodiment
[0637] FIG. 57 is a view for describing multiple types of
diagnostic methods for a sample SA in cancer diagnosis according to
an embodiment of the present application.
[0638] The cancer diagnosis according to an embodiment of the
present application may be performed using a method in which an
immunoassay of a sample SA is performed (S8100) and morphological
analysis of the sample SA is performed (S8200).
[0639] The above-described embodiments related to an immunoassay
may be applied to the immunoassay on the sample SA.
[0640] The above-described embodiments related to morphological
analysis may be applied to the morphological analysis on the sample
SA.
[0641] The morphological analysis on the sample SA may be performed
first, and then the immunoassay on the sample SA may be performed.
Alternatively, like the present embodiment, the immunoassay on the
sample SA may be performed first, and then the morphological
analysis on the sample SA may be performed.
[0642] When staining of the sample SA is performed while the
morphological analysis on the sample SA is performed, some of the
cells CE included in the sample SA may be destroyed. This is
related to the fact that cells CE may undergo necrosis due to a
dye. Therefore, it is understood that, when staining of the sample
SA is performed during the morphological analysis, a more accurate
examination of the sample SA may be possible if the immunoassay on
the sample SA is performed first.
[0643] The immunoassay on the sample SA (S8100) may be performed
using any of the above-described direct technique, indirect
technique, and sandwich technique.
[0644] The morphological analysis on the sample SA (S8200) may be
performed using the above-described acquisition of an image of an
unstained sample SA or acquisition of an image of a sample SA that
is stained using any one of the simple staining technique, the
Romanowsky staining technique, and the DAPI staining technique.
[0645] However, staining techniques are not limited thereto, and
staining using other staining techniques not disclosed herein may
also be used in the above-described morphological analysis.
[0646] The embodiments in which multiple types of diagnoses on the
sample SA are performed in performing cancer diagnosis according to
the present application have been described above.
[0647] However, the above-described embodiments are merely a few
exemplary embodiments, and the scope of the present application is
not limited by the above-described embodiments.
[0648] Also, although, for convenience of description, embodiments
in which two types of diagnoses are sequentially performed has been
described, cases in which cancer diagnosis is performed using three
or more types of diagnoses may also be easily practiced by those of
ordinary skill in the art.
[0649] 8. Multi-Region
[0650] In cancer diagnosis according to the present application,
when multiple types of diagnostic methods are applied to a single
sample SA, the multiple types of diagnostic methods may be
simultaneously performed.
[0651] FIG. 58 is a view for describing multiple types of
diagnostic methods for a sample SA in cancer diagnosis according to
an embodiment of the present application.
[0652] A plurality of patches PA may be brought into contact with
the plate PL. The plurality of patches PA may contain different
reagents.
[0653] For example, the plurality of patches PA may include a first
patch PA, a second patch PA, and a third patch PA.
[0654] The first patch PA may contain a stain. The staining reagent
may be a specimen for staining a nucleus and/or cytoplasm of cells
CE included in the sample SA.
[0655] The second patch PA may contain antibodies AB. The
antibodies AB may be antibodies AB that react specifically with
tumor cells CE included in the sample SA.
[0656] The third patch PA may contain a nutrient substance NT. The
nutrient substance NT may be a specimen used for proliferation of
cells CE included in the sample SA through division of the cells
CE.
[0657] The first patch PA may be brought into contact with a first
region of the plate PL. The second patch PA may be brought into
contact with a second region of the plate PL. The third patch PA
may be brought into contact with a third region of the plate PL. As
a result, cells CE included in the sample SA located in the first
region may be stained, some of the antibodies AB may bind to
surfaces of cells CE included in the sample SA located in the
second patch PA, and cells CE included in the sample SA located in
the third patch PA may proliferate.
[0658] Images of the first region, the second region, and the third
region of the plate PL may be acquired. The images of the first
region, the second region, and the third region may be separately
acquired or acquired in a single frame. Alternatively, the images
of the first region, the second region, and the third region may
also be acquired in a form in which an image of each part of a
single image is acquired separately, and the acquired images are
combined into the single image.
[0659] The multiple types of diagnostic methods disclosed in
Multi-region section and the multiple types of diagnostic methods
disclosed in Multi-test section may be combined with each other.
For example, after cell CE culture analysis is performed on a
region in which the sample SA is provided, the region of the sample
SA on which the cell CE culture analysis has been performed may be
divided, and multiple types of diagnoses may be performed in
divided regions.
[0660] 9. Diagnostic Device
[0661] FIG. 59 is a block diagram of a diagnostic device according
to an embodiment of the present application.
[0662] A diagnostic device according to the present application may
include a relative position adjusting module 100, a temperature
adjusting module 200, and an image acquiring module 300. The
diagnostic device according to the present application may also
include more or less elements.
[0663] The relative position adjusting module 100 may perform a
function of relatively moving the patch PA and the plate PL to each
other. The relative position adjusting module 100 may relatively
move the patch PA and the plate PL to each other in a horizontal
direction and/or a vertical direction.
[0664] The horizontal direction may refer to a direction parallel
to a surface at which the plate PL and the patch PA come into
contact. The vertical direction may refer to a direction
perpendicular to the surface at which the plate PL and the patch PA
come into contact.
[0665] FIG. 60 is a conceptual diagram illustrating an example in
which a structure of a diagnostic device is moved due to a relative
movement operation of the relative position adjusting module 100
according to an embodiment of the present application.
[0666] Referring to FIG. 60(a), the relative position adjusting
module 100 may relatively move the patch PA and the plate PL to
each other in the horizontal direction and change a relative
position of the patch PA on the plate PL.
[0667] The relative position adjusting module 100 may relatively
move the patch PA and the plate PL to each other in the horizontal
direction and perform a function of changing a patch PA that is
disposed to be capable of coming into contact with the sample SA.
The changing of the patch PA that is disposed to be capable of
coming into contact with the sample SA may allow a liquid substance
provided from another patch PA to be delivered to the sample
SA.
[0668] Referring to FIG. 60(b), the relative position adjusting
module 100 may relatively move the patch PA and the plate PL to
each other in the vertical direction and control whether the plate
PL and the sample SA are brought into contact. The bringing of the
patch PA and the sample SA into contact may become involved in
delivery of a substance captured in the patch PA to the sample
SA.
[0669] The relative position adjusting module 100 may include a
moving power source configured to relatively move the patch PA and
the plate PL to each other in the horizontal direction and a other
moving power source configured to relatively move the patch PA and
the plate PL to each other in the vertical direction.
Alternatively, the relative position adjusting module 100 may use a
single moving power source to move the patch PA and the plate PL in
the horizontal and/or vertical directions.
[0670] The temperature adjusting module 200 may perform a function
of controlling a temperature. The temperature adjusting module 200
may perform heating or cooling of the plate PL and/or the patch PA.
Also, the temperature adjusting module 200 may perform a function
of adjusting a temperature of the sample SA and maintaining a
constant temperature.
[0671] For example, the temperature adjusting module 200 may be
used to adjust a temperature of the sample SA to the
above-described denaturation temperature, annealing temperature,
and/or extension temperature.
[0672] The temperature adjusting module 200 may perform an
exothermic reaction and an endothermic reaction. Consequently, the
temperature adjusting module 200 may include a heating element or a
thermoelectric element. The temperature adjusting module 200 is not
limited thereto, and any substance capable of heating may be used
as the temperature adjusting module 200 without limitations.
[0673] The temperature adjusting module 200 may further include a
temperature sensor as necessary. The temperature sensor may be used
to identify a current temperature of a target that is subject to
temperature adjustment.
[0674] The image acquiring module 300 may perform a function of
acquiring an image of the sample SA. For example, the image
acquisition may be performed by a method in which an image of a
portion of a plate PL or an entire plate PL is acquired, a method
in which an image of a portion of a patch PA or an entire patch PA
is acquired, or a method in which an image of the sample SA is
directly acquired.
[0675] The image acquiring module 300 may include a means for
acquiring an image. For example, the image acquiring module 300 may
include an image generator configured to generate an image, such as
an image sensor including a complementary metal oxide semiconductor
(CMOS) image sensor and a charge-coupled device (CCD) image sensor,
a predetermined light generator configured to generate light that
transmits through the sample SA, and/or an optical system
configured to form an image of light that has transmitted through
the sample SA.
[0676] The image acquiring module 300 may directly acquire an image
of a sample SA smeared on a plate PL. Here, the image acquiring
module 300 may receive light that has been irradiated from a light
source and transmitted through the plate PL on which the sample SA
is smeared, and acquire an image of the sample SA.
[0677] For example, the image acquiring module 300 may be disposed
on a surface of a slide glass on which a sample SA is smeared
(hereinafter referred to as "front surface"), and the light source
may be disposed at a surface opposite the front surface of the
slide glass, i.e., a rear surface of the slide glass. Due to such
arrangements, the image acquiring module 300 may receive light that
has been irradiated from the light source from the rear surface
side of the slide glass and has passed through the slide glass, and
acquire an image of the sample SA.
[0678] As another example, the image acquiring module 300 may be
disposed on the rear surface of the slide glass, and the light
source may be disposed on the front surface of the slide glass. Due
to such arrangements, the image acquiring module 300 may receive
light that has been irradiated from the light source from the front
surface side of the slide glass and has passed through the slide
glass, and acquire an image of the sample SA.
[0679] The image acquiring module 300 may detect fluorescence or
acquire a fluorescence image for quantitative and/or qualitative
analysis of the sample SA.
[0680] An image generated from the image acquiring module 300 may
have various magnifications. For example, the image may be an image
with a magnification that enlarges the sample SA, an image with a
fixated magnification, or may also be an image with a magnification
that reduces the sample SA as necessary.
[0681] The image acquiring module 300 may also include a power
member configured to move the plate PL on which the sample SA is
located or move an element of the image acquiring module 300,
thereby acquiring an image of the sample SA.
[0682] The diagnostic apparatus according to the present
application may perform the PCR process described above.
Description of the process in terms of a mechanical aspect will be
omitted since it is deemed that those of ordinary skill in the art
to which the present application pertains would be able to easily
understand the process without repetitive description of the
details.
[0683] The above description is merely illustrative of the
technical spirit of the present application, and those of ordinary
skill in the art to which the present application pertains should
be able to make various modifications and changes within a scope
not departing from essential characteristics of the present
application. Therefore, the above-described embodiments of the
present application may also be implemented separately or in
combination.
[0684] The embodiments disclosed herein are for describing the
technical spirit of the present application instead of limiting the
same, and the scope of the technical spirit of the present
application is not limited by such embodiments. The scope of the
present application should be interpreted on the basis of the
claims below, and all technical spirits within the equivalent scope
should be interpreted as belonging to the scope of the present
application.
* * * * *