KR101794961B1

KR101794961B1 - Device for blood sample analysis using an in-line holographic image analysis

Info

Publication number: KR101794961B1
Application number: KR1020160021459A
Authority: KR
Inventors: 문상준; 문현민
Original assignee: 재단법인대구경북과학기술원
Priority date: 2016-02-23
Filing date: 2016-02-23
Publication date: 2017-12-04
Also published as: KR20170099465A

Abstract

A blood sample analyzer according to the present invention includes: a light source unit for emitting light; A scanner unit for scanning the blood sample with light emitted from the light source unit; A translucent plate provided with a blood sample and through which light irradiated from the scanner unit is transmitted; And an image sensor that acquires a contrasted image of the blood sample as the light is transmitted through the plate to obtain an image of the blood sample in an in-line holography manner and analyze the blood sample based on the acquired image .
According to the present invention, the diagnosis of a blood sample is performed by optical scanning. In this case, since the disease is diagnosed from the contrast image of the blood sample formed by the transmitted light, various diseases such as cancer, AIDS, and tuberculosis that can be diagnosed by the shape or number of blood cells can be diagnosed as a single test.

Description

BACKGROUND OF THE INVENTION 1. Field of the Invention [0001] The present invention relates to a blood sample analyzing apparatus using an in-line holography image analyzer,

The present invention relates to an in vitro diagnostic device that is compact and portable, and is capable of performing cell counting through cell shape, Localized Surface Plasmon Resonance (LSPR), Enzyme-Linked Immunospatial Assay (ELISA), and Surface-Enhanced Raman Scattering And is capable of diagnosing AIDS, malaria, tuberculosis, etc. from a blood sample.

Since diseases such as AIDS, tuberculosis, and malaria can not be diagnosed on their own, they should be screened at the hospital. Observing the outbreak symptom at every cycle or by self-diagnosing the outbreak symptom at each hospital can cause troublesome and unnecessary diagnostic cost in the patient's viewpoint.

In the past, a diagnosis kit using a marker of each disease was diagnosed in a hospital to identify any pathogenic bacteria. In this case, a urine test and a serum test may be performed in parallel. In the urine test, after centrifugation, the number of white blood cells can be checked to confirm the infection. Serum tests can detect the type of the disease by using the antigen antibody reaction for each pathogen. Since the diagnostic equipment used in this diagnostic process is expensive equipment costing several million won, it could be included only in public health centers, hospitals, and so on. Therefore, as described above, there is a problem that the time for early diagnosis is missed due to a large loss in terms of time and cost in the case of a patient who is required to visit.

In addition, there has not been provided a device capable of performing both a complex diagnosis of various infectious diseases such as tuberculosis, AIDS and malaria, and a function of detecting antigen antibody reaction such as LSPR, ELISA and SERS. Therefore, the hospital has to include all of the large-sized equipments, so there is a large cost loss, and there is a problem that the diagnosis is accompanied by the duplicated work or the inspection time becomes long.

If the patient can easily confirm the infection of the main disease, it will be possible to diagnose the disease early and reduce unnecessary time and cost. In this background, various in vitro diagnostic devices are being developed. As a related art, Korean Patent Laid-Open Publication No. 2003-0032809 discloses an apparatus for diagnosing a disease using physical characteristics of red blood cells.

According to the prior art, when a red blood cell is moved, it is detected that the light is partially blocked according to the length, shape, and deformation degree, thereby diagnosing various diseases. In this case, when the viscosity of blood of diabetes mellitus or malaria is changed and the mechanical characteristics of erythrocytes are changed as indicated in the column of the above-mentioned invention, there is a problem that it is difficult to distinguish the erythrocytes from cancer. In addition, there is a problem that an expensive detector is needed to detect a change in brightness of minute light that changes due to dynamic characteristics of erythrocytes. In addition, since the range of diseases that can be diagnosed by the degree of reflection of light is limited, there is a problem that it is difficult to add a function of measuring various diseases at one time.

Korean Patent Publication No. 2003-0032809

The present invention provides a blood sample analyzer including a plurality of functions capable of diagnosing various diseases such as cancer, AIDS, tuberculosis, cell counting, LSPR, ELISA, and SERS.

In addition, the present invention is intended to provide a blood sample analyzer that can be carried by a patient by being provided in a small size.

The present invention also provides a blood sample analyzer capable of being manufactured at a low cost.

The present invention also provides a blood sample analyzer capable of diagnosing a disease by interlocking with a portable mobile terminal such as a smart phone.

According to an aspect of the present invention, there is provided a blood sample analyzer comprising: a light source for emitting light; A scanner unit for scanning the blood sample with light emitted from the light source unit; A translucent plate provided with a blood sample and through which light irradiated from the scanner unit is transmitted; And an image sensor that acquires a contrasted image of the blood sample as the light is transmitted through the plate to obtain an image of the blood sample in an in-line holography manner and analyze the blood sample based on the acquired image .

Preferably, the light source unit according to the present invention may include a Red light source, a Green light source, and a Blue light source.

Preferably, the scanner unit according to the present invention includes: a mirror through which light emitted from the light source unit is transmitted; And a scanning control module for adjusting the angle of the mirror to vary the angle of irradiation of the light transmitted through the mirror.

Preferably, the scanner unit according to the present invention may include a plurality of mirrors such that light emitted from a Red light source, a Green light source, and a Blue light source are respectively incident on the scanner unit.

Preferably, the plate according to the present invention is applied with a metal thin film which is in contact with a sample on an upper portion of the substrate, and the metal thin film may be provided to have a dielectric constant different from that of the substrate.

Preferably, the apparatus for analyzing a blood sample according to the present invention may further comprise a reflector disposed on the top of the plate, for reflecting the light reflected from the plate to the image sensor. In this case, the image sensor according to the present invention can detect the surface plasmon phenomenon formed in the metal thin film.

Preferably, the image sensor according to the present invention may be provided as a complementary metal-oxide semiconductor (CMOS) sensor.

Preferably, the apparatus for analyzing a blood sample according to the present invention includes an image processing module for extracting a dot image of a blood cell in a contrasted image of a blood sample, and performing a morphology analysis by comparing the dot image with a previously stored abnormal blood cell image, As shown in FIG.

Preferably, the image processing module according to the present invention may include a counter for counting the number of dot images.

The present invention also provides a blood sample analyzer for analyzing a blood sample by being combined with a portable terminal having a light source unit for emitting light, an image sensor for acquiring an image, and an image processing module for performing morphology analysis of an image, A scanner unit which is arranged to be opposite to the light source unit and scans the blood sample with the light emitted from the light source unit;

A translucent plate provided with the blood sample and through which the light irradiated from the scanner unit is transmitted; And a reflector disposed behind the plate and adapted to direct light reflected from the plate to the image sensor, wherein the image sensor displays an image in which the blood sample is imaged by the light transmitted through the plate, in an in-line holography And the image processing module enables the blood sample to analyze the contrasted image.

According to the present invention, the diagnosis of a blood sample is performed by optical scanning. In this case, since the disease is diagnosed from the contrast image of the blood sample formed by the transmitted light, various diseases such as cancer, AIDS, and tuberculosis that can be diagnosed using the shape or number of blood cells can be diagnosed as a single test .

In addition, the present invention is capable of LSPR sensing because metal thin films or nanoparticles having different dielectric constants are applied to the plate to induce surface plasmon phenomenon. In addition, since the light reflected from the sample is input to the image sensor by the reflection plate, the reflected light can be analyzed. Therefore, the ELISA and SERS functions can be performed in a complex manner.

In addition, since the present invention analyzes a scanned in-line holography image, it can be implemented as a small optical system and a sensor. Accordingly, the present invention is advantageous in that it is possible to provide a small-sized in vitro diagnostic device that can be carried by a patient.

In addition, the present invention can replace a relatively expensive CCD (Charge Coupled Device) sensor with a CMOS sensor used in a webcam, and use a MEMS mirror used in a mini projector as a scanner, thereby remarkably reducing manufacturing and development costs .

Further, the present invention can be implemented such that an optical system that can be scanned is interlocked with a smart phone that includes a CMOS sensor or a light source and is popularly used. Thus, there is an advantage that it can be easily analyzed with a blood sample in combination with a smartphone already supplied.

1 shows an apparatus for analyzing a blood sample according to an embodiment of the present invention.
2 shows a light source unit and a scanner unit according to an embodiment of the present invention.
3 shows a plate and a reflector according to an embodiment of the present invention.
FIG. 4 shows a state in which surface plasmon resonance occurs in a plate according to an embodiment of the present invention.
5 shows an image obtained from an image sensor according to an embodiment of the present invention.
FIG. 6 shows a dot image of blood cells extracted from an image processing module according to an embodiment of the present invention.
7 shows an apparatus for analyzing a blood sample according to another embodiment of the present invention.

Hereinafter, the present invention will be described in detail with reference to the accompanying drawings. However, the present invention is not limited to or limited by the exemplary embodiments. Like reference numerals in the drawings denote members performing substantially the same function.

The objects and effects of the present invention can be understood or clarified naturally by the following description, and the purpose and effect of the present invention are not limited by the following description. In the following description, well-known functions or constructions are not described in detail since they would obscure the invention in unnecessary detail.

1 shows a blood sample analyzer 1 according to an embodiment of the present invention.

1, the blood sample analyzer 1 may include a light source 10, a scanner unit 30, a plate 50, an image sensor 50, and an image processing module 90. Each constitution of the blood sample analyzer 1 according to the present embodiment can be provided in a small portable housing 3 and can be provided and the blood sample 501 (Fig. 3) The plate 50 can be replaced or housed. The shape of the housing 3 and the arrangement of each constitution are not limited to the embodiment of Fig. The blood sample apparatus 1 according to the present embodiment acquires an image of the blood sample 501 (FIG. 3) in an in-line holography manner and extracts a blood sample 501 (FIG. 3) . Hereinafter, each configuration of the blood sample apparatus 1 will be described in detail.

2 shows a light source unit 10 and a scanner unit 30 according to an embodiment of the present invention.

Referring to FIGS. 1 and 2, the light source unit 10 can emit light in the direction of the scanner unit 30. The light source unit 10 can generate a spectral light source for a whole band of UV / VIS / IR as well as a coherent light source.

In this embodiment, the light source unit 10 may include a Red light source 101, a Green light source 103, and a Blue light source 105. The image obtained by the image sensor 70 to be described later is an image of a shade in which light does not pass through the blood cells. Therefore, the light source unit 10 should emit a wavelength absorbed by the blood cells. It is preferable that the light source unit 10 use RGB three-color light sources 101, 103, and 105 capable of absorbing the degree of absorption for each disease when analyzing a blood sample.

The scanner unit 30 can scan the blood sample 501 (Fig. 3) with the light emitted from the light source unit 10. Fig. As described above at the beginning, the blood sample analyzer 1 according to the present embodiment analyzes a blood sample using an in-line holographic image. An in-line holography image is a method of recording a hologram image with one beam. The progressing beam becomes a reference beam, and a beam scattered or diffracted by the object is recorded as an object beam. This method is particularly suitable for recording hologram images such as small particles.

Therefore, the blood sample apparatus 1 is implemented so that the light from the light source unit 10 is not directly transmitted to the blood sample 501 (FIG. 3) but can be simultaneously transmitted and scanned through the blood sample 501 . The scanner unit 30 can scan a desired area of the blood sample 501 (FIG. 3) by adjusting the path of light emitted from the light source unit 10.

In this embodiment, the scanner unit 30 may include a mirror 301 and a scanning control module 303. [ The mirror 301 can transmit the light emitted from the light source unit 10. As the mirror 301, a MEMS mirror which can be compactly and precisely adjusted and can be purchased at a low price can be used. The mirror 301 may be rotatably included in the scanning control module 303 at a predetermined angle. The light incident on the mirror 301 due to the rotation of the mirror 301 can be changed in path when it passes through the mirror 301. [

The scanning control module 303 can vary the angle of irradiation of the light transmitted through the mirror 301 by adjusting the angle of the mirror 301. [ As the scanning control module 303 rotates the mirror 301, the light emitted from the light source unit 10 can be scanned by the front surface or desired area of the blood sample 501 (FIG. 3).

In the present embodiment, the scanner unit 30 may include a plurality of mirrors 301 so that light emitted from the Red light source 101, the Green light source 103, and the Blue light source 105 is respectively incident. Each of the mirrors 301 is disposed below the Red light source 101, the Green light source 103 and the Blue light source 105 such that the red light source 101, the Green light source 103, As shown in Fig.

3 shows a plate 50 and a reflector 60 according to an embodiment of the present invention.

1 and 3, the plate 50 may be provided with a substrate 505 with a translucent material through which a blood sample 501 is provided and light irradiated from the scanner unit 30 is transmitted. The substrate 505 may be provided with a microchip formed with a microfluidic channel so that a blood sample can flow. In this embodiment, the material of the substrate 505 may be a translucent composite polymer.

In another embodiment, the plate 50 may be coated with a metal thin film 503, which is in contact with the upper portion of the substrate 505. In this case, it is preferable that the metal thin film 503 has a dielectric constant different from that of the substrate 501. In this specification, the dielectric layer on the substrate 501 is represented by the metal thin film 503, but the metal nanoparticles 503 may be coated on the surface of the substrate 501 in consideration of light transmittance. .

The blood sample analyzer 1 may be provided so that the plate 50 can be detached and the plate 50 in which the metal thin film 503 according to the present embodiment is stacked can be used for LSPR detection will be. LSPR means local surface plasmon resonance, which can detect the binding of a specific antigen-antibody. This will be described later with reference to FIG.

Although not shown in FIG. 1, the blood sample analyzer 1 may further include a reflection plate 60. The reflector 60 may be disposed on the top of the plate 50 to allow light reflected from the plate 50 to enter the image sensor 70. Accordingly, the image sensor 70 can sense a cell response such as LSPR, ELISA, etc. formed in the metal thin film 503. [

4 shows a state in which surface plasmon resonance occurs in the plate 50 according to the embodiment of the present invention. Surface Plasmon Resonance (SPR) refers to Collective Charge Density Oscillation of electrons generated from the surface of a metal thin film. The optical signal incident at a specific angle loses its energy, proceeds along the interface between the metal thin film and the sample to be measured, and the surface plasmon resonance angle can be obtained by measuring the intensity of the reflected optical signal energy. To induce surface plasmons, two layers with different dielectric constants must be stacked. In this case, the periodicity in the optical bandgap structure is broken. Therefore, a defect mode that transmits only a specific frequency band occurs, and only light of a specific wavelength is transmitted.

4, when incident light 11 incident on the plate 50 meets a substrate 505 and a metal thin film 503 having mutually different dielectric constants, surface plasmon resonance occurs on the surface of the substrate 503, And the reflected light 13 may be emitted from a specific sample such as a cell in which an antigen-antibody reaction has occurred. By using this, the state of the sample can be indirectly grasped by detecting the reflected light 13.

The image sensor 70 can acquire an image in which the blood sample 501 is imaged as the light is transmitted through the plate 50. The light transmitted through the blood sample 501 by the scanner unit 30 produces a shadow of blood cells on the image sensor 70. The shadow image on which the blood sample 501 is imaged is called an in-line holographic image.

The image sensor 70 can acquire an inline holographic image with the light transmitted through the plate 50 and obtain the reflected light 13 by the reflector 60 as described in the embodiment of FIG. The transmitted light is subjected to a shape analysis by the image processing module 90, which will be described later, to diagnose the disease, and the reflected light can be used for LSPR and ELISA detection.

The image sensor 70 may be provided as a 2D image sensor, more preferably a CMOS (complementary metal-oxide semiconductor) sensor. The CMOS sensor is mainly used in webcam, and it is advantageous in comparison with the CCD sensor used in the existing field diagnostic apparatus.

5 shows an image obtained in the image sensor 70 according to the embodiment of the present invention. FIG. 6 shows a dot image of blood cells extracted from the image processing module 90 according to the embodiment of the present invention.

5 and 6, the image processing module 90 extracts a dot image of a blood cell from an image formed by the blood sample 501, and compares the dot image with a previously stored abnormal blood cell image to obtain a morphology, Analysis can be performed. The image processing module 90 may include a separate database, and the abnormal blood cell image may be stored in the database. Abnormal blood cell images may refer to 2D images of blood cells that appear in diseases such as AIDS, malaria, and tuberculosis. In the database, morphological images of medically identified blood cells can be continuously updated.

The image processing module 90 compares the image of the abnormal blood cells inputted into the database with the image of the blood of the blood obtained from the blood sample 501 to determine the matching degree of the shape of the blood, Diagnosis is possible by disease.

Using the in-line holographic image of blood cells as in the present embodiment, there is an advantage that the diagnosis of the disease can be confirmed by software. In other words, diagnosis of diseases and the like can be performed by image processing techniques. As a result, the scope of diagnosis can be easily extended by changing, installing, and updating software.

As an example, although not shown in the figure, the image processing module 90 may include a counter for counting the number of dot images. As shown in FIG. 6, when the dot images of the blood cells are extracted, the number of blood cells can be counted by simple coding. Therefore, it is possible to automate the cell counting that was performed by the researcher.

The display 7 is provided on one side of the housing 3 and can display the result of the image processing module 90 so that the user can confirm the result.

Fig. 7 shows an apparatus 1 'for analyzing a blood sample according to another embodiment of the present invention. 7, the blood sample analyzer 1 'includes a light source 10 for emitting light, an image sensor 70 for acquiring an image, and an image processing module 90 for performing morphology analysis of the image May be provided to analyze the blood sample 501 in combination with the portable terminal device. The image sensor 70 incorporated in the portable terminal may be a CMOS sensor. The image processing module 90 built in the portable terminal can be provided in the form of an application.

In this embodiment, the blood sample analyzer 1 'may include a scanner unit 30, a plate 50, and a reflector 60.

The scanner unit 30 is arranged to face the light source unit 10 and can scan the blood sample 501 with the light emitted from the light source unit 10. That is, the scanner unit 30 may be disposed to face the light source unit 10 of the portable terminal device. The plate 50 is disposed behind the scanner unit 30 so that the light source unit 10, the scanner unit 30, and the plate 50 are positioned on a straight line. The reflector 60 may be disposed behind the plate 50 to allow the light reflected from the plate 50 to enter the image sensor 70.

In the present embodiment, the detailed functions of the respective constituent elements are omitted from the duplicated description as described in Figs. 1 to 6.

While the present invention has been particularly shown and described with reference to exemplary embodiments thereof, it is to be understood that the invention is not limited to the disclosed exemplary embodiments. will be. Therefore, the scope of the present invention should not be limited to the above-described embodiments, but should be determined by all changes or modifications derived from the scope of the appended claims and equivalents of the following claims.

1, 1 ': blood sample analyzer 3: housing
5: detachment means 7: display
10: light source part 11: incident light
13: Reflected light 101: Red light source
103: Greed light source 105: Blue light source
30: scanner unit 301: mirror
303: scanning control module 50: plate
501: blood sample 503: metal thin film
505: substrate 60: reflector
70: image sensor 90: image processing module

Claims

A light source for emitting light;
A scanner unit for scanning the blood sample with light emitted from the light source unit;
A translucent plate provided with a blood sample and through which the light irradiated from the scanner unit is transmitted; And
And an image sensor for acquiring a contrasted image of the blood sample as light is transmitted through the plate,
Obtaining an image of the blood sample in an in-line holography manner, analyzing the blood sample based on the acquired image,
The plate may comprise:
A metal thin film to which a sample is contacted is applied to an upper portion of the substrate,
Wherein the metal thin film has a dielectric constant different from that of the substrate.

The method according to claim 1,
The light source unit includes:
A red light source, a Green light source, and a blue light source.

3. The method of claim 2,
The scanner unit includes:
A mirror through which light emitted from the light source unit is transmitted; And
And a scanning control module for adjusting an angle of the mirror to vary an angle of irradiation of light transmitted through the mirror.

The method of claim 3,
The scanner unit includes:
Wherein the three mirrors are included so that the red light source, the Green light source, and the light emitted from the Blue light source are respectively incident on the mirror.

delete

The method according to claim 1,
Further comprising a reflector disposed on the plate to reflect light reflected from the plate to the image sensor,
Wherein the image sensor is capable of detecting a surface plasmon phenomenon formed in the metal thin film.

The method according to claim 1,
Wherein the image sensor comprises:
Wherein the sensor is a complementary metal-oxide semiconductor (CMOS) sensor.

The method according to claim 1,
Further comprising an image processing module for extracting a dot image of blood cells from the image of the blood sample and performing a morphology analysis against the previously stored abnormal blood image of the blood sample, .

9. The method of claim 8,
The image processing module includes:
And a counter for counting the number of the dot images.

A blood sample analyzer for analyzing a blood sample combined with a portable terminal having a light source unit for emitting light, an image sensor for acquiring an image, and an image processing module for performing morphology analysis of the image,
A scanner unit arranged to face the light source unit and scanning the blood sample with light emitted from the light source unit;
A translucent plate provided with the blood sample and through which the light irradiated from the scanner unit is transmitted; And
And a reflector disposed behind the plate and adapted to reflect light reflected from the plate to the image sensor,
Wherein the image sensor acquires an image of the blood sample through an in-line holography method by light transmitted through the plate so that the image processing module can analyze the image imaged by the blood sample And the blood sample analyzing apparatus.