KR101931755B1 - Small module for in vitro breast cancer diagnosis using image screening of hair structure - Google Patents

Abstract

A small module for the screening of in vitro breast cancer screening obtained from the subject includes a light source, a condenser lens, a sample holder, an objective lens and an image sensor. The small module images the structure of the hair along the longitudinal direction, The structure can be compared with the structure of the normal hair that has already been stored to compare the corresponding element of the structure of the hair that has been imaged with the predetermined element of the structure of the normal hair and to diagnose whether or not the breast cancer is progressed according to the change of the ratio of the element .

Description

TECHNICAL FIELD [0001] The present invention relates to a small module for in vitro breast screening diagnosis through screening of a hair structure,

The present invention relates to a small module capable of in-vitro diagnosis of breast cancer. More specifically, the present invention relates to an in vitro breast cancer screening diagnostic function capable of early diagnosis of breast cancer using hair obtainable from the human body, Lt; / RTI > module.

In general, in vitro diagnostic technology is a method of diagnosing a change of a specific component using a blood, an exhalation, a secretion, and a biopsy tissue as a molecular marker of a disease. Terminal hair, including hair and conspiracy, can cause component and structural changes in association with human factors such as hormones and the onset of breast cancer. The physical, chemical, and biological methods to detect these changes are called early diagnosis of breast cancer Can be utilized.

Conventional diagnostic methods, such as U.S. Patent No. 6,718,007, PCT Publication No. WO 03/060513, and WO 2008/134800, relate to X-ray diffraction, X-ray fluorescence, infrared spectroscopy, and the like, including keratin protein structure in the hair, And a method for detecting a change in a microstructure, a change in a mineral such as calcium, a change in a component of a lipid, and the like, respectively.

However, hair such as hair is generally divided into a cuticle, a cortex, and a medulla. However, the above-mentioned conventional methods reflect an average change in the entire tissue component of the hair, It is inefficient to detect minute changes based on position, and it is difficult to apply to search for all structural changes of hair according to developmental pattern of breast cancer, so the specificity of diagnosis due to false negative is inevitably low.

In addition, the hair grows more than about 2 cm per month, and the above methods can search only a specific part of the hair strand at a time. Therefore, the search for the hair area that reflects the metabolism at the time of actual breast cancer, Therefore, it is necessary to develop a new imaging method that can localize the structural change and the site of the onset of breast cancer, and detect the change of the entire region at one time.

1 is a view for explaining a hair diagnosis method using conventional X-ray diffraction.

1, the subject to be analyzed by X-ray diffraction is a lipid of a cell membrane of a region much smaller than that of a macro fibril and a microfibril, rather than a whole hair, and keratin It is aimed at microscopic changes in proteins. Therefore, as described above, such a conventional diagnostic method has a disadvantage in that the analysis target is too narrow and limited, so that it is not possible to detect the entire structural change and it takes too much time to obtain the onset-on-period information.

U.S. Patent No. 6,718,007 PCT Published Patent WO 03/060513 PCT Publication No. WO 2008/134800

 Maryakhina V.S., Scheglova L.S., Anenkova K.A. Change of optical properties of hair cells during malignant tumor development. J of Biomedical photonics & Eng 1, 59-63 (2015).  Corino G.L. and French P.W. Int.Diagnosis of breast cancer by X-ray diffraction of hair. J. Cancer: 122, 847-856 (2008). Mistry D.A.H, Haklani J and French P.W. Identification of Breast Cancer-Associated Lipids in Scalp Hair. Breast Cancer: Basic and Clinical Research 6, 113-123 (2012) Lyman D.J. and Fay S. G, The effect of breast cancer on the Fourier transform infrared attenuated total reflection spectra of human hair ecancer 8, 405 (2014).

The present invention provides a small module for in vitro breast screening diagnosis that can diagnose breast cancer in vitro through the overall change of hair.

The present invention provides a compact module for diagnosis of in vitro breast cancer screening, which is simple and efficient in diagnosing method even for generalization of in vitro diagnosis.

The present invention provides a small module for in vitro breast screening diagnosis which can improve the specificity and sensitivity of breast cancer determination from a hair sample obtained from a test subject and can be used as a bio marker such as a prognosis determination after treatment.

According to an exemplary embodiment of the present invention, a small module for in vitro breast screening diagnosis using hair obtained from a test subject includes a light source, a condenser lens, a sample holder, an objective lens, and an image sensor Wherein the compact module images the structure of the hair longitudinally and compares the structure of the imaged hair with the structure of the already stored normal hair to compare the structure of the normal hair with a predetermined element of the structure of the normal hair, The factors can be compared and the presence or progression of breast cancer can be diagnosed according to the change of the ratio of the element.

As used herein, the term " hair " may be understood as a terminal hair including hair, pubic hair, and other hair. Unlike the X-ray diffraction method in which only the points in the micrometer range are searched, the diagnostic method according to this embodiment images the structure of a specific element in the hair and determines whether or not the breast cancer is progressed according to the increase or decrease of the imaged element .

The imaged element can be, for example, a medulla in the structure of the hair, and the imaged element can be defined as a single element or a composite element. In the case of breast cancer test subjects, it was found that the water quality in the structure of the hair was partially lost or severed compared to the normal person. Using such characteristics, the water quality of the structure of the hair was imaged and the image of the medulla structure The loss ratio can be calculated and compared with the structure of normal hair, the breast cancer can be detected early or the progress can be predicted according to the degree of loss of water quality.

The small module of the present invention can be functionally connected to a smart phone or a portable terminal in various forms. For example, the small module of the present invention can be directly embedded in a smart phone or other portable terminal, and can be connected to a portable terminal using a connection terminal such as a USB terminal or a micro 5-pin terminal, and can be connected to a WiFi, It is also possible to interwork with a portable terminal or the like using the same network.

In imaging the water quality region of the hair, the water quality structure of the hair can be imaged at regular intervals or at irregular intervals of, for example, 2 to 5 cm, from the root portion of the hair obtained from the test subject . Alternatively, the water quality region of the structure of the hair may be imaged corresponding to the root portion, the end portion and the middle portion thereof adjacent to the scalp among the hair obtained from the test subject.

In the step of imaging the structure of the hair along the longitudinal direction, the hair is exposed to a light beam generated from a predetermined light source, and the phase difference between the diffracted light diffracted by the hair exposed to the light beam and the non- The structure can be imaged. It is impossible to grasp the cross-sectional structure by the method of direct exposure by visible light alone, and a method of imaging the cross-sectional structure by using the phase difference may be considered by using infrared ray or visible light.

In comparing the medulla structure of the normal hair and the structure of the image of the hair that is imaged, it is necessary to utilize the phase contrast effect caused by the diffraction in the medulla and the water quality of the hair - However, in addition to this, it is possible to add the effect of absorption and transmission difference of the water quality-infrared ray between the hairs of the hair to image the water quality structure in the hair.

The small module for extracorporeal breast screening diagnosis of the present invention utilizes the water quality of the hair that appears in breast cancer patients and does not diagnose it through the analysis of the nano unit component as in the conventional method using the hair but also the whole change of the cortical lipid in the hair section Breast cancer can be diagnosed simply in vitro.

In addition, since it does not use excessive equipment or facilities requiring high power, it can be manufactured in a small size, and it is possible to carry, which includes possibility of being universally used as an in vitro diagnostic apparatus.

In addition, the small module for extracorporeal cancer screening diagnosis of the present invention can use a light source capable of producing low power such as infrared rays, visible rays, ultraviolet rays, etc., and a clear effect can be obtained if the cross- It is possible to miniaturize the equipment. In other words, it can be implemented as a device that can be operated on a smartphone, not a device that is not portable like a synchrotron X-ray.

In addition, the specificity and sensitivity of the breast cancer judgment can be improved from the hair sample obtained from the test subject, and it can be utilized as an indicator of the prognosis after the treatment. For example, it is possible to easily detect structural deformations such as medulla loss from the subject's hair using a high-resolution imaging method, and the breast cancer detection specificity and sensitivity can be greatly improved when compared with the hair of a normal person.

1 is a view for explaining a hair diagnosis method using conventional X-ray diffraction.
FIG. 2 is a view for explaining a small-sized module for diagnosis of an ex vivo breast cancer screening according to an embodiment of the present invention and its use.
3 is a diagram of an apparatus for explaining the internal configuration of the small module of Fig.
FIG. 4 is a view for explaining a sample holder among small-sized modules for diagnosis of extracorporeal breast cancer screening of FIG. 2;
FIG. 5 is a photograph showing a comparison of hair structure between normal hair, benign breast cancer patients and breast cancer patients according to the results of implementing the in vitro breast cancer screening diagnostic method using infrared light according to an embodiment of the present invention.
6 is a view schematically showing a hair of a normal person.
7 is a view schematically showing the hair of a breast cancer patient.
8 is a view for explaining a sample holder and a driving unit of a small module according to an embodiment of the present invention.
FIG. 9 is a view for explaining the outline of a small module for extracorporeal breast cancer screening diagnosis according to an embodiment of the present invention.
FIG. 10 is a view for explaining an infrared spectro image structure built in the small module of FIG.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS Hereinafter, preferred embodiments of the present invention will be described in detail with reference to the accompanying drawings. However, the present invention is not limited to the embodiments. For reference, the same numbers in this description refer to substantially the same elements, and the contents described in the other drawings under the above-mentioned rules can be explained by quoting, and the contents which are judged to be obvious to the person skilled in the art or repeated can be omitted.

FIG. 2 is a view for explaining a small-sized module for in vitro breast cancer screening diagnosis and its use according to an embodiment of the present invention, and FIG. 3 is a view of an apparatus for explaining an internal configuration of the small module of FIG.

2 and 3, the small module 100 according to the present embodiment may be mounted on the lower portion of the smart phone 20, and may be functionally Can be connected, and can be supplied with power.

Specifically, the small module 100 can be mounted in the outer housing 180, and the infrared light source 110, the focusing lens-ring stop 120, the focusing lens 130, the sample holder 140, A lens 150, a phase plate 160, an image sensor 170, and the like may be installed.

The condensing lens-ring diaphragm 120 has a ring-shaped opening, and the light emitted from the infrared light source 110 is previously paralleled by an optical element (not shown) such as a condenser lens before reaching the ring- Light.

The light passing through the ring-shaped aperture in the ring diaphragm 120 can be converted into a ring-shaped light beam, and the condenser lens 130 can convert the light beam converted into the ring shape by the ring diaphragm 120 into the sample holder 140, It is possible to condense it on the hair in the hair. The light beam condensed by the condenser lens 130 can be imaged on the hair of the test subject. The ring diaphragm 120 lies in front of the focal plane of the condenser lens 130 and can limit the angle of the light to be viewed.

The infrared light source 110 may use an infrared diode laser having a wavelength range of about 700 to 1000000 nm as an infrared diode, and the infrared ray of the above range is determined so as to sufficiently transmit hair. The target hair can be configured to enter the silicon capillary with low infrared absorption and the light refracted by the hair and the light passing around the sample are sufficiently transmitted. It is possible to implement the phase difference image contrast through the ring stop 120 and the phase plate 160 mechanism.

The light rays irradiated with the hair can be separated into the direct light transmitted through the inside of the hair and the diffracted light diffracted by the phase object in the hair. This diffracted light diffracts by the phase object of the hair, and at the same time, the phase can be delayed by about one fourth of the original wavelength.

The objective lens 150 can be disposed in the traveling direction of the direct light and the diffracted light separated by the hair and the phase plate 160 is disposed at the eye position of the optical system, i.e., the rear focal position of the objective lens 150, 120). ≪ / RTI >

That is, the diffracted light can change the phase by about? / 4 while reducing the intensity of the direct light passing through the sample. In the Kohler irradiation condition, the direct light is focused on the back focal plane of the objective lens 150 Can be matched. The diffracted light diffracted through the hair differs according to the size, number and refractive index of the light-scattering structure of the phase object inside the hair in the rear diffraction plane of the objective lens 150 as a D-wave, ). ≪ / RTI >

The small module 100 according to the present embodiment generates a phase contrast effect caused by the diffraction in the medulla of the hair and the refractive index difference between the water quality and the medulla-cortex, Can be detected.

In addition to this, in order to detect the structure of the phase material in the hair, that is, the structure of the medulla, various light sources other than the infrared light source can be used. For example, visible light or infrared light can be used.

FIG. 4 is a view for explaining a sample holder among small-sized modules for diagnosis of extracorporeal breast cancer screening of FIG. 2;

4, the sample holder 140 includes a cylinder 142 in which an optical window 144 is formed, and the cylinder 142 is formed in a U-shape or a straight shape so that the hair 10 can pass therethrough. .

The guide 146 may be provided inside the cylinder 142 and formed with a clip portion capable of temporarily fixing the end of the hair 10. The guide 146 may be provided by a separate slide device or a manual operation, Can be moved. As described above, in order to acquire an image of the root portion, the middle portion, and the end portion of the hair, the guide 146 fixes the end portion of the hair 10, So that it can be positioned in the optical window 144.

FIG. 5 is a photograph showing a comparison of hair structure between normal hair, benign breast cancer patients and breast cancer patients according to the results of implementing the in vitro breast cancer screening diagnostic method using infrared light according to an embodiment of the present invention.

The hair phase contrast imaging method for diagnosing extracorporeal breast cancer according to the present invention is based on generating a phase difference by separating hair, that is, light diffracted by hair of a subject and surrounding non-diffracted light. In order to realize the Zernike phase contrast contrast, the apertured aluminum film phase plate is designed so that the diffracted light in the vicinity of the rear focal plane of the concentric circular plate objective determines the thickness to produce a phase difference of pi / 2, bright filed) to make the image of the sample appear dark.

According to the present embodiment, a hair-structure imaging diagnostic apparatus uses a Zernike phase difference optical system to perform a phase contrast effect generated by diffraction in the medulla of the hair and a refractive index difference between the water quality and the sub- It is possible to diagnose breast cancer by detecting the internal structure of hair, especially the structure of water (medulla).

Referring to FIG. 5, there is shown a cross-sectional view of a sample of some (about 2 cm) of hair for comparison of normal human and breast cancer patients.

In the case of the normal person (upper), the water quality is not completely cylindrical but it is continuous and clear without breaking. In positive patients, partial disruption of the water quality structure (DML) was found in the middle, and in the case of breast cancer patients, disappeared (middle) and complete loss of water quality .

In general, complete medulla loss (CML) in the middle or end of the hair was found in the hair of terminal cancer patients, and a partially disrupted water structure was found, although not completely lost at the root of the hair . On the other hand, in patients with early stage of ductal carcinoma in situ, complete loss (CML) was found only at the end, and water quality was present at the root, but weak contrast between water quality and quality ) Were found.

Fig. 6 is a view schematically showing the hair of a normal person, and Fig. 7 is a view schematically showing the hair of a breast cancer patient.

FIGS. 6 and 7 are obtained by observing the root portion (0.5 cm), the middle portion (5.0 cm) and the end portion (8.5 cm) of the hair strands at a length of about 2 mm, and using the in vitro breast cancer diagnostic apparatus Respectively.

Referring to FIG. 6, an island-like, non-continuous, dotted water quality structure may be found for a normal person and, as shown, shows a typical continuous water quality structure for a normal person . Of course, there is a discontinuous region as the subject's age approaches older age, but a completely missing region (CML) may not be found.

However, referring to FIG. 7, a non-continuous or dashed water quality structure such as an island may be found in the case of a patient with no water quality and no-line at all. The rate of TML (trace medulla loss) in cases of cancer patients, when compared with similar age of normal people, when water quality is completely lost (CML), when discontinuous medulla loss (DML) You can see that big.

In the case of a normal person, even if the patient is older than 80 years old, the case of completely missing (CML) was not found, but the case of cancer patient was found to be completely lost (CML)

As a result, it can be found that the healthy hair of a normal person is relatively well contrasted with the quality of the water and the quality of the water. As the age increases, the diameter of the water quality decreases or the distinction between the quality and the quality becomes blurred. However, in breast cancer patients, the possibility of medulla loss increases, especially in the root area, and the location of water loss in hair seems to be related to the timing of cancer development.

8 is a view for explaining a sample holder and a driving unit of a small module according to an embodiment of the present invention.

8, the sample holder 240 includes a cylinder 242 in which an optical window 244 is formed, a driving unit 250 coupled to the hair 10 within the cylinder 242 to move the hair 10, And a sensor 260 for detecting the entry of hair 10 into cylinder 242.

The sensor 260 can detect whether the end of the hair 10 or the hair that has entered the cylinder 242 is present or can detect the opposite end of the hair 10 after passing through the driving unit 250, (10) may be detected. The driving unit 250 may further include a roller 252 disposed at a lower portion of the optical window 244 and a motor 254 for driving the roller 252. The motor 254 and the roller 252 may be connected to a reducer And may be connected by other drive transmission devices.

Accordingly, as the end of the hair 10 enters the sample holder 240, the sensor 260 can generate a signal for operating the roller 252 of the driving unit 250, and the driving unit 250 And the other end is detected by the sensor 260. When the other end is detected by the sensor 260, the operation can be stopped and the reverse rotation can be performed. In this process, the length of the hair 10 inserted through the driving unit 250 may be measured, or the root portion, the middle portion and the end portion may be automatically detected according to the entire length. In addition, image acquisition for the hair 10 can be performed during the reverse rotation.

In addition, if a step motor is used, the hair 10 can be moved by a predetermined length through the driving unit 250, and the hair 10 can be moved partially in the longitudinal direction while moving the hair 10 in a predetermined length unit. Can be obtained.

In this embodiment, the cylinder 242 is provided in a U-shape, but may be formed in various shapes, such as a straight shape, an L-shape, and a curved shape.

FIG. 9 is a view for explaining the outline of a small module for in vitro breast screening diagnosis according to an embodiment of the present invention, and FIG. 10 is a view for explaining an infrared spectro image structure built in the small module of FIG.

9 and 10, a miniature module 300 for an extracorporeal cancer screening diagnosis may be provided in a separate housing 380 and may be connected to a smart phone or other portable terminal using a network such as WiFi or Bluetooth So that they can be functionally connected. That is, they may not necessarily be integrally formed but may operate independently while maintaining a certain distance including their own batteries.

The compact module 300 according to the present embodiment includes an infrared light source 310, a visible light source 312, a first rotating mirror 320, a Schwarz-Schild condenser lens 330, a sample holder 340, A Schwartz-Schild objective 350, a second rotating mirror 360, a third rotating mirror 365, and an image sensor 370.

A visible light source 312 may be used as a light source for confirming the arrangement state of the hair, and an infrared light source 310 may be used to identify a cross-sectional structure or a spectro image. Also, in order to acquire the spectro image, the second rotating mirror 360 is emitted to the infrared light source 310, and the infrared ray passed through the sample can be guided to the infrared spectrometer 375.

The infrared light source 310 may use an infrared diode laser having a wavelength band of about 700 nm or more as an infrared ray diode and may determine an internal situation through a viewfinder 385 exposed to the outside when visible light is used.

As a sample, the hair may be inserted from one end 342 of the sample holder 340 and drawn out to the opposite side, and a cross-sectional image of a plurality of points with respect to the longitudinal direction of the hair may be obtained.

Although the present invention has been described with reference to the preferred embodiments thereof, it will be apparent to those skilled in the art that various modifications and variations can be made in the present invention without departing from the spirit and scope of the invention as defined in the following claims. It can be understood that

100: Small module 110: Light source
120: ring diaphragm 130: condenser lens
140: sample holder 150: objective lens
160: phase plate 170: image sensor

Claims (9)

A small module for in vitro breast cancer screening diagnosis using hair obtained from a test subject,
A light source, a condenser lens, a sample holder, an objective lens, and an image sensor,
The small module imaging the structure of the hair along its length and comparing the structure of the imaged hair with the structure of a normal hair that has already been stored so that the structure of the hair, Comparing the corresponding elements, and diagnosing whether or not the breast cancer is progressed according to the change of the ratio of the corresponding element. The method according to claim 1,
A small module for in vitro breast screening diagnosis, characterized by calculating the loss ratio of the medulla in the structure of the imaged hair relative to the medulla of the normal hair structure and diagnosing whether or not the breast cancer is progressing. The method according to claim 1,
And a phase plate interposed between the objective lens and the image sensor, wherein the hair is exposed to a light beam generated from the light source, and diffracted light diffracted by the hair exposed to the light beam and direct light not diffracted Wherein the water quality structure in the hair is imaged using a phase difference. The method of claim 3,
In comparing the medulla structure of the normal hair structure and the water quality structure of the image of the hair to be imaged, the phase difference contrast generated due to the diffraction in the medulla and the refractive index difference between the water quality and the hair of the hair Wherein the water quality structure in the hair is imaged by using the effect. The method according to claim 1,
Wherein the small module is connected to a portable terminal using a built-in portable terminal or a connection terminal, or is interlocked with a portable terminal using a network. The method according to claim 1,
Wherein the light source comprises an infrared diode laser having a wavelength band of 700 to 1000000 nm. The method according to claim 1,
Further comprising a spectrometer for detecting a spectroimage of light rays passing through the hair. The method according to claim 1,
Wherein the sample holder includes a cylinder in which an optical window is formed and a guide in which a clip portion capable of fixing an end portion of the hair in the cylinder is formed,
Wherein the cylinder is formed in a U-shape or a straight line so that the hair can pass therethrough, and the guide moves the fixed hair while moving inside the cylinder. The method according to claim 1,
Wherein the sample holder includes a cylinder in which an optical window is formed, a driving unit coupled to the hair in the cylinder to move the hair, and a sensor for detecting entry of the hair into the cylinder,
Wherein the cylinder is formed in a U-shape or a straight line so that the hair can pass therethrough, and the driving unit moves the hair to pass the hair through the inside of the cylinder.

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