KR101611482B1 - Apparatus for analyzing samples using substrates for arraying cells and method therefor - Google Patents

Abstract

A cell alignment substrate and a sample analyzing apparatus and method based thereon are disclosed. The sample analyzer includes a light source for emitting light, a cell alignment substrate having at least one groove on one side of the plate so that the cells contained in the sample are aligned, a cell alignment substrate on which the sample is placed, An image generating unit for acquiring an image, and an image processor for analyzing an image of the acquired cell to extract information about the cell. By using the cell alignment substrate and sample analyzer and method, it is possible to easily acquire information about the cell to be analyzed by removing the problem of degradation of image restoration algorithm caused by high density of sample in inline hologram analysis have.

Description

[0001] APPARATUS FOR ANALYZING SAMPLES USING SUBSTRATES FOR ARRAYING CELLS AND METHOD THEREFOR [0002]

The present invention relates to analysis of a sample, and more particularly, to an apparatus and method for extracting information on a cell using in-line holography.

Optical Microscopy has done a lot of work in various fields such as engineering, physics, medicine and biology. In addition, various new imaging systems have been implemented in the field of optical microscopy to improve resolution, sensitivity, signal to noise ratio, and portability.

Since the first appearance of the microscope in the 17th century, optical microscopy has greatly influenced the development of medical and life sciences. Microscope equipment has various cost and size according to its purpose. It is expected to develop micro microscope equipment which is easy to carry at present, and it can be used in various applications such as medical support in a backward country, mobile health care, military field diagnostic equipment ought.

Inline Holography is a technique to overcome the limitations of lens fabrication using electromagnets in the late 1940s when electron microscopes are conceptually emerging. It is a technique to obtain images from light sources derived from one point. Since in-line holography requires a mathematical technique to reconstruct the hologram through computation to obtain the original image, digital elements such as CCD (Charge Coupled Device) and CMOS (Complementary Metal-Oxide Semiconductor) are introduced and actively studied and applied . Inline holography does not require a lens, and its structure is much simpler than an optical microscope because it can be realized with only three components: a light source, an image sensor, and a computing device.

On the other hand, a non-lens microscope using an LED light source has been proposed instead of a laser using mainly in-line holography, so that a device can be easily manufactured and operated at a low cost.

The methods used in in-line holography for reconstruction of object images from holograms include Rayleigh-Sommerfeld Diffraction Integral and Phase Retrieval.

However, in-line holograms require a lot of mathematical operations in image processing, diluted samples are ideal so that multiple scattering does not occur, and reconstructed images reconstructed from holograms have a principle constraint Or defects, it is difficult to effectively obtain reconstructed image images when the distances of the individual cells are close to each other. Therefore, when the sample becomes complicated, analysis accuracy may be degraded or analysis may not be possible.

It is an object of the present invention to improve the accuracy of inline hologram image analysis by reducing the complexity of the sample by aligning the cells to be analyzed at specific positions on the surface.

Another object of the present invention is to provide a sample analyzer capable of obtaining information on a cell by using a sample ideal for performing in-line holography by eliminating the complexity of the sample using alignment of cells.

It is still another object of the present invention to provide a sample analysis method performed in a sample analysis apparatus.

According to one aspect of the present invention, there is provided a sample analyzer comprising: a light source that emits light; a cell array having at least one groove on one surface of the plate so that the cells included in the sample are aligned; An image generating unit for acquiring an image of the cell through the light provided to the sample placed on the cell alignment substrate, and an image processing unit for analyzing the image of the obtained cell to extract information about the cell .

Here, the cell alignment substrate may include at least one groove to align the cells contained in the sample.

The cell alignment substrate may further include at least one groove having a size, an interval, a shape, an arrangement, and a depth based on at least one of the type, size, and properties of cells to be analyzed, Can be determined.

Further, the shape of the at least one groove may be any one of a circle, a polygon, a V shape, and a C shape.

Here, the image generator may generate a hologram using a CCD (Charge-Coupled Device) or a CMOS (Complementary Metal-Oxide Semiconductor).

Here, the image generating unit may generate a hologram image of a cell based on an interference fringe generated by irradiating a light source onto a sample placed on the cell alignment substrate.

Here, the image processing unit may receive an image of a cell remotely from the image generating unit.

Here, the information on the cells may include information on the size, number, shape, and density of the target cells to be analyzed in the cells included in the sample.

According to another aspect of the present invention, there is provided a cell alignment substrate comprising at least one groove to align cells contained in a sample.

Here, the size, spacing, shape, arrangement and depth of at least one groove can be determined based on at least one of the type, size, and properties of cells to be analyzed in the cells included in the sample have.

Further, the shape of the at least one groove may be any one of a circle, a polygon, a V shape, and a C shape.

According to another aspect of the present invention, there is provided a method of analyzing a sample, comprising: aligning cells contained in a sample using a cell alignment substrate having at least one groove on one surface of a flat plate; , Obtaining an image of a cell through light provided on a sample placed on the cell alignment substrate, receiving the image of the cell, and extracting information on the cell through analysis of the image of the received cell As shown in FIG.

Here, aligning the cells contained in the sample may align the cells contained in the sample based on at least one groove on the cell alignment substrate.

Here, the step of acquiring the image of the cell may generate a hologram image of the cell based on the interference pattern generated by irradiating the light source onto the sample placed on the cell alignment substrate.

Here, the step of extracting information on the cell may extract information on the cell using the reconstructed image based on the information on the amplitude and the phase of the hologram.

By using the sample analyzing apparatus and method and the cell alignment substrate according to the present invention, it is possible to eliminate the problem of degradation of the image reconstruction algorithm caused by high density of samples in inline holographic analysis, Information can be easily acquired.

1 is a conceptual diagram for explaining the operation of a sample analyzer according to an embodiment of the present invention.
2 is a perspective view illustrating a cell alignment substrate according to an embodiment of the present invention.
3 is a cross-sectional view illustrating a cell alignment substrate according to an embodiment of the present invention.
4 is an exemplary view illustrating a cell alignment substrate for aligning cells contained in a sample according to an embodiment of the present invention.
5 is a conceptual diagram for explaining a sample analyzing apparatus and method according to an embodiment of the present invention.
6 is a flowchart for explaining a sample analysis method according to an embodiment of the present invention.

While the invention is susceptible to various modifications and alternative forms, specific embodiments thereof are shown by way of example in the drawings and will herein be described in detail. It should be understood, however, that the invention is not intended to be limited to the particular embodiments, but includes all modifications, equivalents, and alternatives falling within the spirit and scope of the invention. Like reference numerals are used for like elements in describing each drawing.

The terms first, second, A, B, etc. may be used to describe various elements, but the elements should not be limited by the terms. The terms are used only for the purpose of distinguishing one component from another. For example, without departing from the scope of the present invention, the first component may be referred to as a second component, and similarly, the second component may also be referred to as a first component. And / or < / RTI > includes any combination of a plurality of related listed items or any of a plurality of related listed items.

It is to be understood that when an element is referred to as being "connected" or "connected" to another element, it may be directly connected or connected to the other element, . On the other hand, when an element is referred to as being "directly connected" or "directly connected" to another element, it should be understood that there are no other elements in between.

The terminology used in this application is used only to describe a specific embodiment and is not intended to limit the invention. The singular expressions include plural expressions unless the context clearly dictates otherwise. In the present application, the terms "comprises" or "having" and the like are used to specify that there is a feature, a number, a step, an operation, an element, a component or a combination thereof described in the specification, But do not preclude the presence or addition of one or more other features, integers, steps, operations, elements, components, or combinations thereof.

Unless defined otherwise, all terms used herein, including technical or scientific terms, have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Terms such as those defined in commonly used dictionaries are to be interpreted as having a meaning consistent with the contextual meaning of the related art and are to be interpreted as either ideal or overly formal in the sense of the present application Do not.

First, the terms used in the present application will be briefly described as follows.

A hologram is a light wave that enters our eye after it interacts with an object and records all the information about the light wave in the form of a light interference pattern. In other words, when we shine a light on a hologram, the light restores the original light wave through diffraction. When we observe it, we can see the same image as if there is an actual object.

An inline hologram is a hologram that records an interference pattern of a wave that is not diffracted by an object to be recorded but diffracted by an object. In other words, the object to be recorded should be an object with good permeability and low scattering.

When two or more lightwaves are superimposed, strong lightwaves or weakly coherent interferences are remarkably generated in the case of a lightwave having a constant wavelength and amplitude. Such a coherent lightwavelength is called a coherent lightwavelength source, An Incoherent Light Source is a light source having various light waves whose wavelength and amplitude are not constant.

Hereinafter, preferred embodiments according to the present invention will be described in detail with reference to the accompanying drawings.

FIG. 1 is a conceptual diagram for explaining the operation of a sample analyzer 400 according to an embodiment of the present invention.

Referring to FIG. 1, the sample analyzer 400 may include a cell alignment substrate 100 and an image generator 200.

The light emitted from the light source 10 can be irradiated onto the sample 20 placed on the cell alignment substrate 100 to extract information on the cells contained in the sample 20. [ Light generated in the light source 10 can be irradiated onto the sample 20 placed on the cell alignment substrate 100 through the opening of the filter 30. [ In addition, an image of cells contained in the sample 20 can be generated by the light irradiated onto the sample 20 placed on the cell alignment substrate 100.

Here, the light source 10 may include a coherent light source, an incoherent light source, or a partially coherent light source. For example, LEDs of a predetermined color can be used as the light source 10.

Also, the sample 20 is a substance to be analyzed, and can be cultured in a culture container or extracted from an organism. The sample 20 may include various cells of an organism, for example, blood may be included.

There are blood cells and plasma in the blood, and red blood cells, white blood cells, and platelets are present in the blood cells. Plasma is mainly composed of water, which includes blood clotting factors and electrolytes that are essential for life support. For optical analysis of blood, Centrifugation, Membrane Separation Method, Peripheral Blood Smear Examination, etc. can be utilized.

In detail, the cell alignment substrate 100 may be formed of an optically transparent material. For example, the cell alignment substrate 100 may be formed of a material such as glass or plastic.

The cell alignment substrate 100 can be fabricated using COC (Cyclic Olefin Copolymer) used as a surface plasmon resonance (SPR) biosensor.

Next, the filter 30 may include an aperture through which light generated from the light source 10 can pass. In detail, the filter 30 may be installed at a predetermined distance from the upper surface of the cell alignment substrate 100.

In addition, an aperture formed to allow light generated from the light source 10 to pass therethrough may have various sizes and shapes. For example, the opening may be circular with a diameter within the range of 50 [mu] m to 100 [mu] m.

On the other hand, the cell alignment substrate 100 may be placed on the image generation unit 200. In other words, the image generating unit 200 is disposed adjacent to the lower side of the cell alignment substrate 100. The image generating unit 200 may be a Charge Coupled Device (CCD) or a Complementary Metal Oxide Semiconductor (CMOS).

In detail, the CCD and the CMOS constituting the image generating unit 200 generally have a small pixel size of less than 9 um in size. CCD and CMOS sensors with smaller pixel sizes can produce higher resolution images.

2 is an exemplary view illustrating a cell alignment substrate according to an embodiment of the present invention. 3 is a cross-sectional view illustrating a cell alignment substrate according to an embodiment of the present invention. Here, FIG. 3 is a cross-sectional view of the cell alignment substrate 100 taken along the line connecting A and A 'in FIG.

2 and 3, the cell alignment substrate 100 includes an injection unit 110 provided at one side of a flat plate for injecting a sample 20 and a sample 20 injected through the injection unit 110 And an irradiation unit 130 for aligning the cells contained in the sample 20 by providing at least one groove between the injection unit 110 and the discharge unit 130, 120).

The injection unit 110 can be made in a circular shape based on the properties of the sample in which the tension exists. The portion extending from the circular groove to the irradiation unit 120 can be formed in the shape of an oblique slant line. The sample 20 seated in the circular groove can be spread along oblique slant lines. That is, the cell alignment substrate 100 may be inclined such that the sample 20 injected into the injection unit 110 flows to the discharge unit 130 through the irradiation unit 120.

In detail, the cell alignment substrate 100 according to an embodiment of the present invention will be described with reference to a manufacturing process for the cell alignment substrate 100.

The cell alignment substrate 100 may be manufactured by a die casting method. For example, plastic or COC (Cyclic Olefin Copolymer) excellent in glass or optical properties can be used as the material of the cell alignment substrate 100.

The cell alignment substrate 100 is manufactured by forming a top surface and a bottom surface of the substrate using a micro injection molding method and bonding the two surfaces using a thermal bonding method using hot embossing Can be used.

As a method of manufacturing a mold required for micro injection molding, a semiconductor process can be referred to. For example, a photoresist material can be used. In this case, a lithography technique can be used. Here, SU-8 may be used as the photoresist material, and nickel may be used as the material of the substrate. That is, a photoresist material SU-8 may be used to make a microstructure on the disk.

3, the injection unit 110, the irradiation unit 120, and the discharge unit 130 may have a predetermined depth on the upper surface of the flat plate, so that the sample flows out of the flat plate and can be seated without overflowing. The depth of the groove can be made inclined so as to be deepened from the injection part 110 to the discharge part 130 through the irradiation part 120. [ According to this, the sample can flow from the injection part 110 toward the discharge part 130 by gravity.

In addition, the remaining sample excluding the cells aligned in at least one groove of the irradiation unit 120 may be discharged through the opening formed in the discharge unit 130.

4 is an exemplary view for explaining an irradiation unit 120 of a cell alignment substrate 100 for aligning cells contained in a sample according to an embodiment of the present invention.

Referring to FIG. 4, the cell alignment substrate 100 may have a physical microstructure such as at least one groove to align the cells contained in the sample 20.

First, the examination unit 120 measures the size, spacing, and shape of physical microstructures such as at least one groove based on at least one of the types, sizes, and properties of cells to be analyzed in the cells included in the sample 20 , Placement and depth can be determined.

For example, the shape of the at least one groove included in the irradiation unit 120 may be any one of a circle, a polygon, a V shape, and a C shape.

4A shows an irradiation unit 120 having a circular groove, FIG. 4B shows an irradiation unit 120 having a C-shaped protrusion, and FIG. 4C shows an irradiation unit 120 having V-shaped protrusions.

In detail, the grooves are formed in the shape of a depressed shape in the upper plane of the irradiation unit 120, so that cells can enter into the grooves by gravity. Alternatively, they can be fabricated in the form of embossed cubicles to allow cells to enter the grooves. In other words, the grooves can be made in the form of engraved, embossed.

The grooves may have a microwell structure in the form of a hole and the sample 20 flowing into the irradiating unit 120 may have a shape such that cells contained in the sample 20 enter the holes due to gravity Can be produced. In another embodiment, the irradiating unit 120 may be made to be capable of aligning cells by making a microfluid into a cubic structure.

5 is a conceptual diagram for explaining a sample analyzing apparatus and method according to an embodiment of the present invention.

Referring to FIG. 5A, the sample analyzer 400 may include a cell alignment substrate 100, an image generator 200, and an image processor 300.

First, when the sample 20 is injected into the injection unit 110 provided at one side of the plate, the cell alignment substrate 100 is caused to flow to the discharge unit 130 provided at the other side of the flat plate due to gravity. The irradiating unit 120 located between the injecting unit 110 and the discharging unit 130 has at least one groove so that the cells included in the sample 20 are aligned in the respective grooves.

Next, the image generating unit 200 disposed adjacent to the lower side of the cell alignment substrate 100 may be a CCD (Charge Coupled Device) or a CMOS (Complementary Metal Oxide Semiconductor) It is possible to obtain a hologram which is an image of a cell to be analyzed.

In detail, the image generating unit 200 may use a CCD or a CMOS sensor to generate a raw hologram amplitude image of the target sample 20. The lost hologram phase is then recovered and recovered phase information along with the measured amplitude information can be used to reconstruct the image of the object sample 20.

Next, the image processing unit 300 receives the hologram, which is an image of the cell, from the image generating unit 200, and analyzes the image of the cell received by the at least one processor to extract information about the cell. Information on the extracted cells may be displayed to the user on the display.

Analysis of the image of the cell in the form of a hologram can be implemented by reconstructing the image based on information about the amplitude and phase of the hologram. Here, the amplitude of the hologram may be normalized and utilized.

Two methods can be used for image reconstruction from a hologram. First, the Back-Propagate the Fourier Components method of each hologram intensity can be utilized. Second, we can take advantage of the 2D phase recovery method of each hologram amplitude.

These two approaches enable reconstruction of the object's Twin Image from the raw hologram amplitude image of the object sample 20 generated in the image generator 200. [

In both of these approaches, a Transfer Function of Rayleigh-Sommerfeld Integral may be used for Back-Propagating the field.

The Transfer Function of the Rayleigh-Sommerfeld Integral is a function of the amplitude and phase of the image hologram of the cell generated by the image generating unit 200, which is a certain distance from the light source 10, And the like.

Referring to FIG. 5B, the image processing unit 300 may receive an image of a cell remotely from the image generating unit 200. That is, the image of the cell can be transferred from the image generating unit 200 to the computer 50 including the image processing unit 300.

First, the image processing unit 300 includes at least one or more processors capable of driving software for receiving and analyzing images from the image generating unit 200. The image processing unit 300 may receive an image of a cell including a holographic amplitude or an intensity.

In this case, the image processing unit 300 may be connected to the image generating unit 200 by wire. The wired connection may include, for example, USB.

Next, as another alternative embodiment, the mobile communication device 40 including the image processing unit 300 may be connected to the image generating unit 200. [ For example, one or more processors included in the mobile communication device 40 may perform a function of receiving an image of a cell from the image generating unit 200.

In addition, the mobile communication device 40 can be interworked with a remote computer 60 including the image processing unit 300 through a communication network.

The mobile communication device 40 may be connected to a remote computer 60 that includes the image processing unit 300 via a communication network. The communication network may comprise a general wired, wireless and mobile communication network. Examples of communication networks may include broadband networks such as the Internet and may include CDMA, GSM, WCDMA, LTE, LTE-Advanced, Wi-MAX, Wireless LAN, Zigbee, Bluetooth, UWB Ultra Wideband).

On the other hand, the mobile communication device 40 can receive information processed by an external device including the image processing unit 300. [

Further, the mobile communication device 40 may be configured to include the light source 10 and the filter 30. [

Therefore, the above-described sample analyzer 400 can be manufactured as a portable device including the image processor 300. [ If the image processing unit 300 is located in the remote computer 60 to remotely receive the image generated by the image generating unit 200, the image processing unit 300 may be manufactured as a portable device including the cell alignment substrate 100 and the image generating unit 200 .

As one embodiment of the sample analyzing apparatus 400, it can be used as a health diagnostic apparatus and a field bacteria detecting apparatus linked to a smartphone. For example, it may be implemented in a form of 5 cm * 5 cm * 15 cm except for the image processing unit 300, and may be connected to a computer, a notebook, and a smart phone. Or an independent computing device and a screen output device can be implemented.

Although the respective components of the sample analyzer according to the above-described embodiments of the present invention have been described as being arranged in the respective components for convenience of explanation, at least two of the components may be combined to form one component, It is to be understood that the invention is not limited to the disclosed embodiments, but, on the contrary, is intended to cover various modifications and equivalent arrangements included within the spirit and scope of the appended claims.

6 is a flowchart for explaining a sample analysis method according to an embodiment of the present invention.

Referring to FIG. 6, a sample analyzing method according to an exemplary embodiment of the present invention includes aligning cells (S610), obtaining images of cells (S620), and extracting information about cells (S630) .

The cells included in the sample 20 can be aligned using the cell alignment substrate 100 having at least one groove on one surface of the flat plate S610.

In more detail, the step of aligning the cells (S610) includes the steps of injecting the sample 20 into the injection unit 110 provided at one side of the flat plate, and injecting the sample 20 injected into the injection unit 110 into the flat plate To the discharging part 130 provided on the other side of the discharging part 130. That is, the cells included in the sample 20 can be aligned based on at least one groove provided between the injection unit 110 and the discharge unit 130.

When the sample 20 is injected into the injection unit 110, a flow occurs to the discharge unit 130 provided on the other side of the flat plate due to gravity. The irradiating unit 120 located between the injecting unit 110 and the discharging unit 130 has at least one groove so that the cells included in the sample 20 are aligned in the respective grooves.

For example, the cell alignment substrate 100 may be manufactured in the form of a depressed shape on the upper plane of the irradiation unit 120, and cells may be formed into a groove by gravity or may be fabricated in the form of a relief partition, 20). ≪ / RTI > Here, the examination unit 120 may measure at least one of the size, spacing, shape, arrangement, and depth of at least one groove based on at least one of the type, size, and properties of cells to be analyzed in the cells included in the sample 20 Can be determined.

The image of the cell can be obtained through the light provided to the sample 20 placed on the cell alignment substrate 100 (S620). The image of the cell can be generated as a hologram based on the interference pattern generated by irradiating the non-coherent light source onto the sample 20 placed on the cell alignment substrate 100.

For example, it is possible to obtain a hologram, which is an image of a cell to be analyzed included in the sample 20, using either a CCD (Charge Coupled Device) or a CMOS (Complementary Metal Oxide Semiconductor).

The image of the cell can be received, and the information about the cell can be extracted through analysis of the image of the received cell (S630). That is, an image of a cell can be received, and information on the cell can be extracted through analysis of the image of the received cell.

Information about the cell can be extracted by analyzing the image of the cell in the form of a hologram. For example, the image can be reconstructed based on information about the amplitude and phase of the hologram to extract information about the cell. As an algorithm for analysis, it is possible to utilize a method of Back-Propagate the Fourier Components of each hologram intensity or a method of recovering the 2D phase of each hologram amplitude.

The sample analyzing method according to the embodiment of the present invention can be performed by the sample analyzing apparatus 400 described above.

The step S610 of aligning the cells may be performed by the cell alignment substrate 100 of the sample analyzer 400 and the step S620 of acquiring an image of the cells may be performed by the image generating unit 200, And extracting information about the cell (S630) may be performed by the image processing unit 300. [0053] FIG.

According to the sample analyzing apparatus 400 and method according to the present invention as described above, the problem of deterioration in performance of the image reconstruction algorithm caused by high density of samples in the in-line holographic analysis is originally eliminated, It can be easily learned.

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 or scope of the present invention as defined by the following claims It can be understood that

10: light source 20: sample
30: filter 40: mobile communication device
50: computer 60: remote computer
100: cell alignment substrate 110:
120: irradiator 130:
200: image generating unit 300:
400: sample analyzer

Claims (16)

A sample analyzer using in-line holographic image analysis,
A light source for emitting light;
A cell alignment substrate having a plurality of grooves on one surface of the flat plate transmitting the light and aligning a plurality of cells contained in the sample in the plurality of grooves;
An image generating unit for acquiring a hologram including an interference fringe of a wave that is not diffracted by the cell when the light is irradiated onto the sample placed on the cell alignment substrate but is not diffracted by the cell; And
And an image processor for extracting information on each of a plurality of cells located in the plurality of grooves using an image reconstructed based on information on the amplitude or phase of the hologram,
Wherein the cell alignment substrate comprises: an injection part provided at one side of the flat plate and to which the sample is injected; a discharge part provided at the other side of the flat plate and through which the sample is discharged; And an irradiating portion spaced apart from the flat plate by a predetermined distance and regularly arranged in the horizontal and vertical directions,
Wherein the plurality of grooves have an alignment resolution at an individual cell level and the distance between adjacent grooves of the plurality of grooves or the distance between adjacent cells aligned by the plurality of grooves is determined by overlapping of hologram information between individual cells, A sample analyzer that is determined through a balance of cell analysis accuracy. The method according to claim 1,
The size, spacing, shape, arrangement, and depth of the plurality of grooves provided in the irradiation unit are determined based on at least any of the type, size, and properties of cells to be analyzed in the cells included in the sample ,
Wherein the sample including cells not aligned in the plurality of grooves of the irradiation unit flows to the injection unit, the irradiation unit, and the discharge unit, and is discharged through the opening formed in the discharge unit. The method of claim 2,
Wherein the cell alignment substrate is inclined such that a sample injected into the injection section flows through the irradiation section to the discharge section. The method of claim 3,
Wherein the shape of each of the plurality of grooves includes one of a circle, a polygon, a V shape, and a C shape. The method of claim 3,
The image generation unit
(CCD) or a CMOS (Complementary Metal-Oxide Semiconductor). delete The method of claim 5,
Wherein the image processing unit comprises a processor and is adapted to recover from the holograms an image of the individual cells using a Back-Propagating the Fourier Components of the intensity of the hologram, or a recovery of the two-dimensional phase of the amplitude of the hologram. And reconstructs the image. A sample analyzer using in-line holographic image analysis,
A cell alignment substrate having a plurality of grooves on one surface of a flat plate through which light is transmitted and aligning a plurality of cells contained in the sample in the plurality of grooves; And
And an image generating unit for acquiring a hologram including an interference fringe of a wave transmitted through the cell without being diffracted by a wave diffracted by the cell when the sample placed on the cell alignment substrate is irradiated with light,
Wherein the cell alignment substrate is provided on one side of the flat plate and includes an injection unit into which the sample is injected, a discharge unit provided on the other side of the one side of the flat plate and through which the sample is discharged, And an irradiating portion having grooves and regularly spaced apart from each other at regular intervals so as to separate the plurality of grooves from each other on the flat plate,
The hologram is transmitted to an image processing unit located remotely and extracts information on each of the plurality of cells located in the plurality of grooves from the reconstructed image based on the information on the amplitude and phase of the hologram in the image processing unit And,
Wherein the plurality of grooves have an alignment resolution at an individual cell level and a distance between adjacent grooves of the plurality of grooves or a distance between adjacent cells aligned by the plurality of grooves is determined by overlapping of hologram information between individual cells, A sample analyzer that is determined through a balance of cell analysis accuracy. The method of claim 8,
The information on the cell includes information on the size, number, shape, and density of the target cell to be analyzed in the cells included in the sample,
Wherein the cell alignment cartridge including the cell alignment substrate and the image generation unit is connected to a computer, a notebook computer, or a portable terminal,
The computer, notebook computer or portable terminal includes an image processing unit for processing the hologram,
The image processing unit includes a processor and reconstructs the image of the individual cells from the hologram using a Back-Propagating the Fourier Components of the intensity of the hologram or a recovery of the 2D phase of the amplitude of the hologram A sample analyzer characterized by. delete delete delete A method of analyzing a sample analyzer using in-line holographic image analysis,
A cell array substrate having a plurality of grooves formed on one surface of a flat plate through which light is transmitted and spaced apart from each other by a predetermined distance so that the plurality of grooves are separated from each other on the flat plate, Aligning the plurality of grooves;
Obtaining a hologram including an interference fringe of a wave that is not diffracted by the cell when the light is irradiated onto the sample placed on the cell alignment substrate but is not diffracted by the cell; And
And extracting information on each of a plurality of cells located in the plurality of grooves using an image reconstructed based on information on amplitude or phase of the hologram,
Wherein the plurality of grooves have an alignment resolution at an individual cell level and the distance between adjacent grooves of the plurality of grooves or the distance between adjacent cells aligned by the plurality of grooves is greater than the distance between adjacent cells A method of analyzing a sample determined by balancing the overlap of hologram information and the accuracy of analysis of individual cells. 14. The method of claim 13,
Wherein the cell alignment substrate is provided on one side of the upper surface of the flat plate and includes an injection part into which the sample is injected, a discharge part provided on the other side of the upper surface of the flat plate and through which the sample is discharged, And an irradiating portion having grooves of the light-
The size, spacing, shape, arrangement, and depth of the plurality of grooves provided in the irradiation unit are determined based on at least any of the type, size, and properties of cells to be analyzed in the cells included in the sample ,
Wherein a sample including cells not aligned in a plurality of grooves of the irradiation unit flows from the injection unit to the discharge unit via the irradiation unit and is discharged through an opening formed in the discharge unit. delete 15. The method of claim 14,
Wherein the step of extracting information on each of the plurality of cells comprises:
Reconstructing the image of the individual cells from the hologram using Back-Propagating the Fourier Components of the intensity of the hologram or restoring the two-dimensional phase of the amplitude of the hologram based on the reconstructed image And extracting information on a plurality of cells located in the plurality of grooves, respectively.

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