KR101793568B1 - Particle Analyzer Microscope having mounting module for the sample capilary - Google Patents

Particle Analyzer Microscope having mounting module for the sample capilary Download PDF

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KR101793568B1
KR101793568B1 KR1020160009387A KR20160009387A KR101793568B1 KR 101793568 B1 KR101793568 B1 KR 101793568B1 KR 1020160009387 A KR1020160009387 A KR 1020160009387A KR 20160009387 A KR20160009387 A KR 20160009387A KR 101793568 B1 KR101793568 B1 KR 101793568B1
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particle
sample capillary
sample
mounting module
light
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KR20170089236A (en
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조재형
김명수
김남일
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윈포시스(주)
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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
    • G01N15/02—Investigating particle size or size distribution
    • G01N15/0205—Investigating particle size or size distribution by optical means
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
    • G01N15/10—Investigating individual particles
    • G01N15/1012—Calibrating particle analysers; References therefor
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
    • G01N2015/0038—Investigating nanoparticles
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
    • G01N2015/03—Electro-optical investigation of a plurality of particles, the analyser being characterised by the optical arrangement
    • G01N2015/035—Electro-optical investigation of a plurality of particles, the analyser being characterised by the optical arrangement the optical arrangement forming an integrated apparatus with the sample container
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N2035/00178—Special arrangements of analysers
    • G01N2035/00237—Handling microquantities of analyte, e.g. microvalves, capillary networks

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Abstract

The present invention relates to a sample capillary mounting module and a particle analyzer having the same, and more particularly, to an apparatus for analyzing particle characteristics such as particle size and shape based on an image of a particle captured by a camera, A sample capillary mounting module to be mounted and a particle analyzer having the same are provided.
To this end, the present invention provides a sample capillary mounting module on which a sample capillary into which a particle to be analyzed is mounted is mounted, and a sample capillary is mounted on the upper surface of the sample capillary mounting module in a longitudinal direction thereof Wherein the sample capillary mounting module is mounted on a floor, and the sample capillary mounting module is mounted on a side surface of the sample capillary mounting module, Is made incident on one side of the side surface of the through-hole, passes through the sample capillary, and is emitted to the other side of the side surface.

Description

[0001] The present invention relates to a particle analyzer having a sample capillary mounting module,

The present invention relates to a sample capillary mounting module and a particle analyzer having the same, and more particularly, to an apparatus for analyzing particle characteristics such as particle size and shape based on an image of a particle captured by a camera, A sample capillary mounting module to be mounted, and a particle analyzer having the same.

The particle analyzer is a device for analyzing the characteristics of particles such as particle size and shape. Accurate measurement of particle size is essential to deal with polymerization kinetics (particle formation, growth and aggregation), and particle size analysis is used as analytical information to determine the physical, chemical and mechanical properties of the final material.

Dynamic light scattering (DLS) is a method of measuring nanoscale particles, which shoots light onto nanoparticles using a laser and measures the size of the particles by measuring how much the light is scattered. This method has the disadvantage of lowering the reliability of the measured nanoparticle size, since the emitted light may affect the nanoparticles in addition to the laboriousness to be measured at various angles.

Further, the DLS device has a problem that the configuration, alignment, and preservation of the laser optical system are difficult and the maintenance cost is high. In addition, the scattering angle and the measurement angle are fixed in the DLS device, and it is difficult to ensure the reliability of the measurement result and the verification is also impossible. Some of the materials have a low dependency on the theoretical basis, scattering angle and measurement angle of the DLS, but there are more substances that should never be relied on at a specific angle, and therefore only the particle size The reliability of the measurement result can be assured.

In addition, the DLS device is fundamentally limited in understanding the phenomenon because it is impossible to observe the actual change of the sample during the particle size measurement, and it is difficult to understand the phenomenon that the sample affected by the laser light source (for example, And the like), there is a limit in that analysis is impossible.

SUMMARY OF THE INVENTION Accordingly, the present invention has been made to solve the above problems and to solve the above-mentioned problems, and an object of the present invention is to provide a device for analyzing particle characteristics such as particle size, shape, And a particle analyzer having the sample capillary mounting module.

Other objects and advantages of the present invention will become apparent to those skilled in the art from the following description. Will be more clearly understood by means of the embodiments of the present invention. It will also be readily apparent that the objects and advantages of the invention may be realized and attained by means of the instrumentalities and combinations particularly pointed out in the appended claims.

According to an aspect of the present invention for achieving the above object, there is provided a sample capillary mounting module on which a sample capillary to which analysis target particles are injected is mounted, and on an upper surface of the sample capillary mounting module, Wherein the sample capillary mounting module is formed with a through groove from one side to the other side of the sample capillary mounting module, and the sample capillary mounting module is mounted on the table, The light irradiated toward the side surface of the capillary mount module is incident on one side of the side surface of the through-hole, passes through the sample capillary, and is emitted to the other side of the side surface.

According to another embodiment of the present invention, there is provided a sample capillary mounting module in which a sample capillary into which particles to be analyzed are injected is mounted; A platform on which the sample capillary mounting module is mounted; A laser light source for irradiating light to a side surface of the sample capillary that is seated on the sample capillary mounting module; An optical system for scattering light on particles of the sample capillary through which the light passes by irradiating the sample capillary with the laser light source and guiding the particle image by the scattered light to the camera; A camera for photographing a scattered light particle image pathway guided from the optical system for a specific time; And a computer for tracking particle movement and analyzing particle characteristics using the input information about the particle to be analyzed and the result of signal processing of scattered light particle image frames for a specific time taken by the camera, Wherein the sample capillary mounting module has a mounting groove formed on an upper surface of the sample capillary mounting module so that the sample capillary is seated in a longitudinal direction of the mounting capillary mounting module, The light irradiated toward the side surface of the sample capillary mounting module is incident on one side of the side surface of the through-hole, and passes through the sample capillary so as to be emitted to the other side of the side surface.

According to another aspect of the present invention, there is provided a sample capillary mounting module including: a sample capillary mounting module on which a sample capillary to which analysis target particles are injected is mounted; A platform on which the sample capillary mounting module is mounted; A lower light source for irradiating light to a bottom surface of the sample capillary that is seated on the sample capillary mounting module; An optical system for scattering light on the sample capillary through which the light is transmitted as the sample capillary is irradiated with the lower light source and guiding the image by the scattered light to the camera; A camera for photographing a scattered light image guided by the optical system for a predetermined time; And a computer for analyzing particle characteristics using the information about the particle to be analyzed and the result of signal processing of scattered light image frames for a specific time taken by the camera, And a bottom groove having a specific size is formed on a lower surface of the sample capillary mounting module so that a bottom surface of the sample capillary mounting module So that the sample capillary is transmitted through the sample.

The particle tracking analyzing apparatus of the present invention can analyze nanoparticle characteristics such as nanoparticle size measurement by a dark field imaging method and analyze the particle size and number of each nanoparticle widely dispersed in a liquid state It is possible to visualize the number of particles per particle size and display them to the user in a graph. The user can directly observe the distribution state of each particle by real-time image and use a sample having low density (concentration) It is economical by lowering the product unit price. It has the effect of counting the number of particles in a low concentration environment by tracking the fluidity of the particles from the image photographed by the camera, allowing the user to visually see through the display.

In the particle tracking analyzer according to the present invention, the light irradiation is performed at a specific angle with respect to a predetermined longitudinal axis of the sample, thereby widening the area of the scattered light particle image necessary for analyzing the particle characteristics (the effect of broadening the laser spot sample measurement area ).

The imaging particle analyzer of the present invention can analyze the inverse spatial scattering information simultaneously with the real space image observation and can observe the actual change of the sample occurring during the particle size measurement. In addition, since no complicated laser optical system is used, the configuration, alignment, and maintenance of the laser optical system are not required, and there is no damage to the sample by the light source. Do. It is also possible to measure at low angles, which could not be measured with conventional DLS particle size measurement equipment. In addition, it is possible to acquire the information that can be obtained by the multiple measurement of the conventional DLS type particle size measuring instrument by one measurement, and it is possible to measure the particle size of several μl of the sample at the sample level for the ordinary optical microscope .

The real-time multifocal-based imaging particle analyzer according to the present invention can be used to combine real-time multifocus-based imaging particle analysis functions without changing parts of the imaging particle analyzer (without adding specifications) And can broaden the particle characterization area such as the type of particles to be analyzed, meet the market needs such as the particle shape measurement with the imaging-based camera image, and overcome the short lens focus area of the conventional microscope It is possible to analyze particle characteristics of various kinds and sizes, and to see the size and shape of actual particles.

The composite apparatus according to the present invention can share components according to the analysis mode and can perform its function, so that the manufacturing cost can be lowered compared with the case where the particle tracking analyzing apparatus, the imaging particle analyzing apparatus and the real time multifocal particle analyzing apparatus are separately made Specification, function, and processing of the particle-tracking analyzer, the imaging particle analyzer, and the real-time multifocal particle analyzer, and the particle-tracking analyzing mode, the imaging particle analyzing mode, In real-time multifocal particle analysis mode, there is no interference between parts and processing, and particle characteristics can be analyzed without degrading performance.

The sample capillary mounting module of the present invention can easily mount the sample capillary having a small size of 1 mm X 1 mm X 80 mm in the analyzer, thereby making it easy for the user to operate and easy handling, Since the sample capillary injected with the sample is only required to be raised to the capillary mounting module, it is possible to perform the preliminary working of the sample preparation such as washing at the time of replacing the sample easily and conveniently. Through the sample capillary mounting module, The laser beam can be irradiated at various desired angles with respect to the laser light irradiation axis and the sample capillary side axis, and the particle tracking analysis mode It is a sample capillary mounting module that can be commonly used in the imaging particle analysis mode. It can reduce the number of parts and reduce manufacturing cost. have.

BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a block diagram of an embodiment of a particle tracking analyzer according to the present invention; FIG.
FIG. 2 is a perspective view showing the particle tracking analyzing apparatus of FIG. 1. FIG.
FIG. 3 is an explanatory view showing images acquired and processed by the particle tracking analyzing apparatus of FIG. 1; FIG.
4 is a view showing another embodiment of a particle tracking analyzing apparatus according to the present invention.
FIG. 5 is a view showing another embodiment of a particle tracking analyzing apparatus according to the present invention. FIG.
6 is a block diagram of an embodiment of an imaging particle analyzer according to the present invention.
FIG. 7 is a perspective view showing the imaging particle analyzer of FIG. 6;
8 is an explanatory view showing an imaging particle analysis method according to the present invention.
FIG. 9 is an explanatory view showing a real-time multifocus imaging and synthesis process of the imaging particle analyzer of FIG. 6;
10 is a perspective view of a composite apparatus having a particle tracking analysis mode and an imaging particle analysis mode according to the present invention.
11 is a perspective view of an embodiment of a sample capillary mounting module according to the present invention.
12A to 12C are perspective views of another embodiment of a sample capillary mounting module according to the present invention.
13 is a perspective view of a composite apparatus having a sample capillary mounting module according to an embodiment of the present invention.

It should be understood that the specific details of the invention are set forth in the following description to provide a more thorough understanding of the present invention and that the present invention may be readily practiced without these specific details, It will be clear to those who have knowledge. In the following description, well-known functions or constructions are not described in detail since they would obscure the invention in unnecessary detail.

Hereinafter, preferred embodiments according to the present invention will be described in detail with reference to the accompanying drawings, with reference to the parts necessary for understanding the operation and operation according to the present invention.

FIG. 2 is a perspective view showing the particle tracking analyzing apparatus of FIG. 1, and FIG. 3 is a sectional view of the particle tracking analyzing apparatus according to the present invention, It is an explanatory diagram showing the image.

1, the particle tracking analyzing apparatus according to the present invention includes a laser light source 11, a platform 12, a sample capillary 13, an optical system 14, a camera 15, and a computer 16, And the like.

The particle tracking analyzing apparatus of the present invention further includes a microscope oculars so that the user can directly observe the sample with eyes.

Although not shown in the drawings, the computer 16 further includes an image capture board, a signal processor, a display, and the like. Here, the image capturing board and the signal processing unit may be provided in the camera 15.

The particle tracking analyzing apparatus of the present invention injects a solution (suspension) in which sample particles (sample) are dissolved (dissolved) in a sample capillary 13, and transfers the sample capillary 13 to a stage 12 (Laser beam) of the laser light source 11 is irradiated so as to pass through the sample capillary 13 while being placed on the sample capillary 13 and the Brownian motion causes particles to scatter the light, and the particle by the scattered light is guided to the optical system 14, and the scattered light particle image is photographed by the camera 15 for a predetermined time (image frame capture of the particle moving by the Brownian motion , Eg 30 to 60 seconds]. The scattered light particle image frames for a predetermined time taken by the camera 15 are processed by the computer 16 to track individual particle movements and the particle characteristics such as size, shape, concentration and number of particles are analyzed ) To visually present to the user via the display of the computer 16.

The analyte particles of the present invention can be nanoparticles, and the particle size can be any kind of particles from several nanometers to several thousand nanometers (e.g., 1 nm to 2000 nm). Illustratively, the particles to be analyzed may be bio-nanoparticles that are applied to drug delivery system development, virus vaccines, nanotoxicology and biomarkers, protein aggregation, extracellular vesicles (exosomes and microcysts), and the like.

The particle tracking analyzing apparatus of the present invention applies light scattering and brownian motion to a microscope. This will be described in detail as follows.

The particle position, preferably the center of gravity, of the particles moving with the Brownian motion is tracked by the image capturing method from the scattered light particle image frames captured by the camera 15 for a predetermined period of time. Then, the moving distance of the particle is calculated from the moving position of the tracked particle. The Stokes-Einstein relation is used to calculate the diffusion coefficient based on the Mean Squared Displacement (MSD) of the moving distance of the particles over time, and the hydrodynamic diameter ) Is measured and the particle size is measured. Then, based on the measured particle size, a particle size distribution profile is created in real time and visually presented to a user through a display.

The Stokes-Einstein relation is used to calculate the diffusion coefficient based on the Mean Squared Displacement (MSD) for the particle travel distance per hour of the present invention to determine the hydrodynamic diameter ), And the particle size is measured will be described in more detail as follows.

The Stokes-Einstein relation is expressed by the following equation (1).

Figure 112016008547724-pat00001

Where D m is the diffusion co-efficient, K B is the Boltzman constant, T is the temperature, η is the viscocity, d h is the particle size (hydrodynamic diameter, sphere) equivalent hydrodynamic diameter particle size).

The random movement of particles in solution, Brownian motion, is related to the mean square displacement of the particles. In addition, the particles spread in solution in a Gaussian distribution spatially with time, and the value that characterizes the Gaussian distribution form by diffusion at each time is a mean squared displacement, .

Figure 112016008547724-pat00002

Where <MSD 2 > is the mean square displacement, D m is the diffusion coefficient, and t is the time.

As described above, the mean square displacement of the particles moving in the solution in the solution can be obtained from the scattered light particle image frames photographed by the camera 15, and the mean square displacement of [Equation 2] The particle size can be measured by substituting into the Stokes-Einstein formula.

As mentioned earlier, the diffusion coefficient is calculated from the scattered light particle image frames using the average moving distance [x, y] of the two-dimensional image. In practice, the particles in the solution are three-dimensionally subjected to Brownian motion. Therefore, in consideration of the fact that the scattered light particle image frames photographed by the camera 15 are two-dimensional images, the particle size measurement formula is derived by modifying the Stokes-Einstein formula by applying a two-dimensional variable as shown in the following [Equation 3] can do.

Figure 112016008547724-pat00003

Here, t may be expressed as '1 / FPS (frame per second)'.

The laser light source 11 may be implemented by a laser diode having a wavelength band of 642 nm (red), 532 nm (green), 488 nm (blue), or 405 nm (violet).

The optical system 14 may be implemented as an objective lens having a magnification of 20 (x20) or the like.

The camera 15 may be implemented as a CCD camera, an Electron Multiplied Charged Coupled Device (EMCCD) camera, a CMOS camera, or the like. For example, a typical camera that shoots 30 frames per second (30 fps), or a high-speed camera that shoots 1,000 frames per second to 3,000 frames per second may be used.

The sample capillary 13 may be realized as a capillary having a rectangular parallelepiped shape, and a sample may be injected into an inner space surrounded by the outer glass layer, and both ends thereof may be sealed. The external size of the sample capillary 13 may be 1 mm X 1 mm X 80 mm, for example, and the length 80 mm may be changed depending on the type of sample to be analyzed. In addition, the thickness of the outer glass layer of the sample capillary 13 suffices as long as it is at a commercial level used in a well-known microscope. As described above, the sample capillary 13 of the present invention has a size of 1 mm X 1 mm X 80 mm, which is 0.08 cm 3 , that is, 0.08 ml when converted into a volume. Even if the volume of the internal space into which the sample is injected is equal to the apparent volume A maximum of 0.08 ml sample can be used to analyze the particle characteristics, requiring only a small sample volume for the user. In addition, the sample capillary 13 of the present invention has a capillary structure and can easily inject a sample by sucking the sample by capillary phenomenon. The sample capillary 13 has a small size of 1 mm X 1 mm X 80 mm, It is possible to make the particle movement by the Brownian motion without being influenced by the convection phenomenon, and to analyze the particle characteristics such as the more accurate particle size measurement.

The ground station 12 is connected to a motor (not shown in the figure), and can be moved up and down by the motor drive control of the computer 16, ), Side-to-side movement, and side-tilting (eg horizontal alignment when the horizontal is tilted).

2, a hole is formed in a specific portion of the platform 12 on which the sample capillary 13 is mounted. This is illustrated in FIG. 10, It is an additional component to the particle tracking analyzer for common use. That is, in the particle tracking analyzer, the irradiation light of the laser light source 11 passes through the side surface of the sample capillary 13, and in the imaging particle analysis mode of FIG. 10, It is preferable that grooves are formed in the platform 12 because the capillary 105 should be permeated from the lower side to the upper side.

The advantages of the particle tracking apparatus of the present invention as described above are as follows.

The Dark Field imaging method can analyze the characteristics of nanoparticles such as nanoparticle size measurement, analyze the particle size and number of each nanoparticle widely dispersed in liquid state, visualize the number of particles per particle size The user can observe the distribution status of each particle directly by the real-time image, and it is possible to use the sample of low dilution type and density (low concentration) The fluidity can be traced from the image captured by the camera, visually displayed to the user through the display, and the number of particles can be counted in a low concentration environment.

Next, another principal feature of the present invention will be described.

As shown in the drawing, the sample capillary 13 is placed on the platform 12 so that the laser beam (light) of the laser light source 11 is irradiated to the side surface in the longitudinal direction of the sample capillary 13 , The laser beam is irradiated at a predetermined angle (by turning the horizontal axis) about the light source axis of the laser light source 11 and the side axis of the sample capillary 13. In other words, in irradiating light to a sample with a light source, light irradiation is performed at an angle with respect to a predetermined longitudinal axis of the sample.

That is, although the light source axis of the laser light source 11 and the side axis of the sample capillary 13 may be irradiated horizontally at an angle of 90 °, in this case, a small size of 1 mm × 1 mm × 80 mm The field of view of the scattered light particle image due to the light passing through the sample capillary 13 having a small scattered light particle image can be reduced and the scattered light particle image to be acquired by the camera 15 can be reduced.

Therefore, in the present invention, in order to widen the area of the scattered light particle image necessary for analyzing the particle characteristics, that is, to widen the laser spot sample measurement area, light irradiation is performed at a specific angle with respect to a predetermined longitudinal axis of the sample.

The side surface in the longitudinal direction of the sample capillary 13 on the basis of the shape of the sample is arranged in such a manner that light irradiation is performed at a specific angle (for example, 10 ° to 80 °, preferably 20 °) Or the laser beam irradiation direction of the laser light source 11 can be switched in comparison with the side direction of the sample capillary 13 in the direction opposite to the direction of the laser beam irradiation of the laser light source 11. [

The laser beam is irradiated at a predetermined angle to the light source axis of the laser light source 11 of the present invention and the side axis of the sample capillary 13 (by turning the horizontal axis) The FOV (field of view) of the optical system 14 and the camera 15 with respect to the sample capillary 13 having a size of 30 mu m x 50 mu m x 80 mu m, for example, .

3A shows a scattered light particle image taken by a camera 15, that is, a laser beam is irradiated to the light source axis of the laser light source 11 and the side axis of the sample capillary 13 at a predetermined angle Obtained scattered light particle images are shown. In FIG. 3A, particles are seen in the diagonal direction of the camera image, and the diagonal angle means the light irradiation angle.

Next, in the present invention, as shown in FIG. 3B, an algorithm for distinguishing and tracking each particle is presented. FIG. 3B shows an image obtained by applying the particle-based classification tracking algorithm of the present invention to the scattered light particle image photographed by the camera 15. The image is provided to the user through the display of the computer 16. FIG.

The red line in the image of FIG. 3b shows the movement trajectory by the Brownian motion of the individual particles, and the left red line in the image represents the movement trajectory of the first particle and the right red line in the image represents the movement trajectory of the second particle . Through these images, the user can intuitively receive the analysis results of the particle behavior.

According to the particle classification tracking algorithm of the present invention, particle labeling is performed by image pattern matching, for example, identification information is given to particles to separate each particle to derive movement trajectories of individual particles.

As an example of the particle-by-particle classification tracking algorithm, particles having a change in the near-field motion between neighboring image frames according to time changes on the scattered light particle image frames acquired for a predetermined time are discriminated as the same particles, And generates a movement locus by plotting the position coordinates of the particle given the same identification information for each of the image frames.

As another example of the particle classification tracking algorithm, particles having the same shape among neighboring image frames according to time changes on the scattered light particle image frames acquired for a predetermined time are discriminated as the same particles, and individual identification And generates a movement locus by plotting the position coordinates of the particle given the same identification information for each of the image frames.

Next, in the present invention, a plurality of laser light sources can be used to irradiate the sample capillary 13 with light. Illustratively, a laser beam synthesizer is provided between the two laser light sources and the side surfaces of the sample capillary 13 so that the laser beam emitted from each laser light source is input to the laser beam synthesizer, The laser beam can be irradiated so as to be directed toward the side surface of the sample capillary 13. As another example, in a state where two laser light sources are provided on the side surface of the sample capillary 13, the laser beam irradiated from each laser light source is focused so as to pass through the same area of the inner space of the sample capillary 13 Light irradiation can be performed.

As described above, the use of a plurality of laser light sources in the present invention is intended to increase the amount of light received by the sample capillary 13. For example, when the 30 mW laser is used, the amount of light received by the sample capillary 13 is low, and the scattered light particle image obtainable by the camera 15 has a maximum of 33 frames per second. Therefore, in the present invention, the amount of light received by the sample capillary 13 is increased by using a plurality of laser light sources, and the frame of the scattered light particle image acquired by the camera 15 is increased to 33 frames per second or more, It is possible to shorten the total measurement time required for the measurement.

Next, the particle tracking analysis method of the present invention will be described.

The information about the solution (suspension) containing (dissolved) the analysis target particles (sample) injected into the sample capillary 13 and parameters relating to the measurement conditions are input to the computer 16. [ Here, the sample information and measurement condition parameters may be temperature, number of frames per second, number of images to be analyzed, camera setting information, image intensity, and sample information (e.g., water, alcohol, toluene, etc.). It is preferable that the light irradiation control, the image capturing control, and the image frame signal processing control be set differently according to the inputted sample information and the measurement condition parameters.

The sample capillary 13 placed on the table 12 is rotated at a predetermined angle with respect to the light source axis of the laser light source 11 and the side axis of the sample capillary 13 And the laser beam is irradiated. As a result, particles which are in the inner space of the sample capillary 13 through which the laser beam passes pass a brownian motion and scatter light.

Then, as described above, the particles of the scattered light are guided to the optical system 14 and the scattered light particle image is photographed by the camera 15 for a predetermined time (image frame capture of particles moving by the Brownian motion, for example, 30 to 60 second].

The computer 16 processes the scattered light particle image frames for a predetermined time taken by the camera to track individual particle movements and analyzes (measures) particle characteristics such as particle size, shape, concentration, Lt; RTI ID = 0.0 &gt; 16 &lt; / RTI &gt; At this time, the diffusion coefficient is calculated using a Stokes-Einstein relation based on Mean Squared Displacement (MSD) of the particle moving distance per time as described above, and the hydrodynamic diameter (hydrodynamic diameter) is measured and the particle size is measured.

Next, another embodiment of the particle tracking analyzing apparatus according to the present invention will be described with reference to FIG.

4 is a block diagram of another embodiment of a particle tracking analyzing apparatus according to the present invention.

4, the particle tracking analyzing apparatus according to another embodiment of the present invention includes the laser light source 11, the platform 12, the sample capillary 13, the optical system 14, A camera 15 and a computer 16 and is provided with a scattered light filtering unit 17 between the optical system 14 and the camera 15. [

Scattering light is generated by irradiating the sample capillary 13 with the laser beam of the laser light source 11. At this time, multiple scattering interference can be generated by a large number of particles of the sample capillary 13. This multiple scattering interference has an effect of impairing accuracy, reliability, and reproducibility in analyzing particle characteristics based on scattered light particle images acquired by camera 15. [

As shown in the drawing, in the present invention, when the scattered light filtering unit 17 is disposed between the optical system 14 and the camera 15, the output focusing point (also referred to as imaging plane) of the optical system 14, And the camera 15 is positioned at a predetermined position on the rear end of the scattered light filtering unit 17. [

The scattered light filtering unit 17 selectively passes the scattered light by the particles of the sample capillary 13 input from the optical system 14, that is, the scattered light which is subjected to the multiple scattering interference is blocked, thereby preventing the influence by the multiple scattering interference do. The scattered light filtering unit 17 may be implemented as a pinhole having a size of several nanometers to several nanometers. The optical system 14 can be implemented as an objective lens.

Next, another embodiment of the particle tracking analyzing apparatus according to the present invention will be described with reference to FIG.

5 is a block diagram of another embodiment of a particle tracking analyzing apparatus according to the present invention.

5, the particle tracking analyzing apparatus according to another embodiment of the present invention includes the laser light source 11, the ground 12, the sample capillary 13, the optical system 14 A camera 15 and a computer 16, and includes a light reflection prevention unit 18 and a leveling system 19. [

In the particle tracking analysis of the present invention, the laser beam of the laser light source 11 is irradiated to pass through the sample capillary 13 in a state where the sample capillary 13 is placed on the ground 12, The light having passed through the sample capillary 13 may be reflected to an external object or internal parts of the particle tracking analyzer and may be re-incident on the sample capillary 13. As the reflected light enters the sample capillary 13 again, the scattered light particle image due to the reflected light is mixed with the scattered light particle image due to the light of the laser light source 11, which causes the accuracy of measurement of the particle characteristics to deteriorate.

Therefore, in the present invention, the light reflection preventing portion 18 is provided at the rear end of the sample capillary 13 on the table 12, and the light (laser beam) passing through the sample capillary 13 is prevented from being reflected To be absorbed by the portion (18). The light reflection preventing portion 18 may be formed of any material having a material, a material and a characteristic for absorbing light (laser beam), for example, a sheet having a black cloth attached thereto.

As shown in the figure, a horizontal system 19 is provided on the platform 12 of the particle tracking apparatus of the present invention to grasp the horizontal state of the platform 12, and when the platform 12 is in a horizontal state The horizontal axis can be adjusted by adjusting the axis of the platform 12. For example, when the leveling instrument 19 is electronically implemented, the computer 16 may determine the horizontal state of the leveling instrument 19 to automatically control the motor to adjust the axis of the grounding stand 12, The user can grasp the horizontal state of the leveling instrument 19 and directly control the motor by the computer 16 to adjust the axis of the grounding platform 12. [

As described above, according to the present invention, the horizontal position of the platform 12 is corrected by the leveling system 19 to prevent the sample capillary 13 placed on the platform 12 from being biased to one side, and the sample capillary 13, It is possible to prevent a convection phenomenon from occurring inside the reed 13. By doing so, the light (laser beam) emitted from the laser light source 11 can be properly focused on the sample capillary 13, and the convection phenomenon can be prevented and the particle characteristic measurement performance can be enhanced.

Next, an imaging particle analyzer of the present invention will be described with reference to Figs. 6 to 8. Fig.

6 is a perspective view of an imaging particle analyzing apparatus according to an embodiment of the present invention, FIG. 7 is a perspective view showing the imaging particle analyzing apparatus of FIG. 6, and FIG. 8 is an explanatory view showing an imaging particle analyzing method according to the present invention And FIG. 9 is an explanatory view showing a real-time multifocus imaging and synthesis process of the imaging particle analyzer of FIG.

6, an imaging particle analyzer according to the present invention includes a lower light source 61, a platform 62, a sample capillary 63, an optical system 64, a camera 65, and a computer 66, And the like. The imaging particle analyzer may further include an upper light source 67.

The imaging particle analyzing apparatus of the present invention may further include a microscope oculars so that the user can directly observe the sample with eyes.

Although not shown in the figure, the computer 66 further includes an image capture board, a signal processor, a display, and the like. Here, the image capturing board and the signal processing unit may be provided in the camera 65.

The analyzing particle analyzing apparatus of the present invention injects a solution (suspension) containing (dissolving) analytes (sample) into the sample capillary 63 and transfers the sample capillary 63 to the stage 62, The particles of the brownian motion located in the inner space of the sample capillary 63 are scattered by the scattered light so that the light of the lower light source 61 is transmitted through the sample capillary 63, And the scattered light is guided to the optical system 64, and the camera 65 photographs the scattered light for a predetermined time (scattered light image frame capture, for example, 30 to 60 seconds). The computer 66 processes the scattered light image frames for a predetermined time taken by the camera 65 to analyze (measure) the particle characteristics such as size, shape, concentration, and number of particles to display the display of the computer 66 To the user.

The analyte particles of the present invention can be nanoparticles, and the particle size can be any kind of particles from several nanometers to several thousand nanometers (e.g., 1 nm to 2000 nm). Illustratively, the particles to be analyzed may be bio-nanoparticles that are applied to drug delivery system development, virus vaccines, nanotoxicology and biomarkers, protein aggregation, extracellular vesicles (exosomes and microcysts), and the like.

The lower light source 61 may be implemented as a 300 W halogen lamp as a general-purpose white light source.

The upper light source 67 may be implemented as a general-purpose white light source or a laser diode or the like. The upper light source 67 is used for analyzing the particle characteristics of the sample which can not measure the flow due to the transmitted light. For example, the upper light source 67 may include a phase separation analysis according to the temperature change of the metal solid solution, a melting point analysis of the solder, Or phase separation analysis of a block copolymeric polymer film. That is, the upper light source 67 is used in analyzing the particle characteristics of the impermeable material including the metal and the polymer.

The optical system 64 may be implemented as an objective lens having a magnification of 20 (x20) or the like.

The camera 65 may be implemented as a CCD camera, an Electron Multiplied Charged Coupled Device (EMCCD) camera, a CMOS camera, or the like. For example, a typical camera that shoots 30 frames per second (30 fps), or a high-speed camera that shoots 1,000 frames per second to 3,000 frames per second may be used.

The sample capillary 63 may be realized as a capillary having a rectangular parallelepiped shape, and a sample may be injected into an inner space surrounded by the outer glass layer, and both ends thereof may be sealed. The outer size of the sample capillary 63 may be, for example, 1 mm X 1 mm X 80 mm, and the length 80 mm may be changed depending on the kind of sample to be analyzed. In addition, the thickness of the outer glass layer of the sample capillary 63 may be sufficient for a commercial level used in a well-known microscope. As described above, the sample capillary 63 of the present invention has a size of 1 mm X 1 mm X 80 mm, which is 0.08 cm 3 , that is, 0.08 ml when converted into a volume. Even if the volume of the inner space into which the sample is injected is equal to the apparent volume A maximum of 0.08 ml sample can be used to analyze the particle characteristics, requiring only a small sample volume for the user. In addition, the sample capillary 63 of the present invention has a capillary structure and can easily inject a sample by sucking the sample by capillary phenomenon. The sample capillary 63 has a small size of 1 mm X 1 mm X 80 mm, It is possible to make the particle movement by the Brownian motion without being influenced by the convection phenomenon, and to analyze the particle characteristics such as the more accurate particle size measurement.

The floor platform 62 is connected to a motor (not shown in the figure) and can be moved up and down by the motor drive control of the computer 66 or by direct manipulation of the user (e.g., the focus variable of the optical system 64 and the camera 65) ), Side-to-side movement, and side-tilting (eg horizontal alignment when the horizontal is tilted).

The imaging particle analyzer of the present invention applies light scattering and brownian motion to a microscope. This will be described in detail as follows.

The light of the lower light source 61 is transmitted to the sample capillary 63 so that the particles of Brownian motion located in the inner space of the sample capillary 63 scatter the transmitted light.

Accordingly, the camera 65 obtains the scattered light changes due to the time-varying particles generated by the Brownian motion, processes the scattered light image frames by Fourier analysis to decompose the temporal / spatial information of the scattered light, To measure the size of the nanoparticles.

That is, a difference image between the scattered light image frames obtained by the camera 65 is obtained (for example, 5,999 difference images are obtained for 2 seconds at 3,000 frames per second), and two-dimensional Fourier transformation is performed on the difference images . This difference image can be used to detect the change of scattered light intensity in each pixel. Spatial distribution of scattered light is obtained by Fourier transform on the difference image, and spatial / temporal information of scattered light according to time is analyzed by interpreting scattered light spatial distribution. .

Then, an azimuthal scan is performed to obtain the average of the values at the same pixel distance from the origin of the center of the Fourier transform result. 8A is a conceptual diagram showing an azimuthal scan of a two-dimensional Fourier transform value, and the right side (b) of FIG. 8 is a graph showing an absolute value change of an azimuth scan value according to a time change. From the center of the Fourier transform values on the left side (a) of FIG. 8, q 1 , q 2 , and q 3 correspond to scattering angles, respectively. As described above, the Fourier transform value obtained from the difference image includes the multiple scattering information, and when the mean value of the sum value obtained by adding the Fourier transform value along the concentric circle is plotted according to the time change, .

The azimuth scan value thus obtained is measured using a numerical analysis technique. In this case, the following equation (4) is used.

Figure 112016008547724-pat00004

here,

Figure 112016008547724-pat00005
Is the absolute value of the azimuth scan value along the distance q from the center in the inverse space, A (q) is related to the characteristics of the particle, B (q) is the noise due to the camera itself,
Figure 112016008547724-pat00006
Represents a relaxation time.

The dwell time of Equation (4)

Figure 112016008547724-pat00007
(5) with respect to the diffusion coefficient D m (diffusion co-efficient) and the inverse spatial position value (q).

Figure 112016008547724-pat00008

The diffusion coefficient D m of Equation (5) has the same relationship as the Stokes-Einstein relation of Equation (1).

Based on the above equations (4), (5) and (1), nonlinear curve fitting is performed on Equation (4) (Unknown), that is, A (q), B (q)

Figure 112016008547724-pat00009
, And the estimated
Figure 112016008547724-pat00010
Is substituted into the equation (5), and the particle size d h is measured from the equation (1).

On the other hand, in the imaging particle analysis of the present invention, it is desirable to input the sample information and the measurement condition parameters to the computer 66. [ That is, the information about the solution (suspension) containing (dissolved) the analysis target particles (sample) injected into the sample capillary 63 and parameters relating to the measurement conditions are input to the computer 66. Here, the sample information and measurement condition parameters may be an image number, an average number, an image interval, a radius interval, a temperature value input, a light source displacement sensor, a background dust imaging elimination, and the like. It is preferable that the light irradiation control, the image capturing control, and the image frame signal processing control be set differently according to the inputted sample information and the measurement condition parameters.

The advantages of the imaging particle analyzer of the present invention as described above are as follows.

It is possible to analyze the inverse spatial scattering information simultaneously with the real space image observation and to observe the actual change of the sample during the particle size measurement. In addition, since no complicated laser optical system is used, the configuration, alignment, and maintenance of the laser optical system are not required, and there is no damage to the sample by the light source. Do. It is also possible to measure at low angles, which could not be measured with conventional DLS particle size measurement equipment. In addition, information obtained from multiple DLS particle size measuring devices can be acquired with a single measurement, and particle size measurement is possible for several μL samples at the sample level for a conventional optical microscope.

Next, another principal feature of the present invention will be described.

FIG. 9 is an explanatory view showing a real-time multifocus imaging and synthesis process of the imaging particle analyzer of FIG.

The imaging particle analyzer of the present invention is equipped with a real-time multi-focal-based imaging particle analysis function as well as a particle characteristic analysis function such as particle size measurement by applying light scattering and Brownian motion as described above.

As shown in Fig. 9, the height of the platform 62 in the direction of the optical system 64 is elevated by a motor control or the like by the computer 66 to change the focusing in real time, And photographs the particle of the sample 91 by the camera 65 at real time and at high speed. Then, the computer 66 synthesizes the focused particle images taken by the camera 65 to analyze the characteristics of the particles.

That is, in the real-time multifocal particle analysis mode of the present invention, the focus is varied in real time so that each focus is aligned with a sharp portion (i.e., surface boundary, edge) of the particle, Take pictures at real time high speed. Then, a single particle image is synthesized based on the respective particle surface boundaries of the focused particle images captured by the camera 65, and the particle characteristics are analyzed.

The particle characteristics may be particle size, area, major axis, minor axis, sphericity, circumference, shape, and the like. The particles to be analyzed may be particles of several nanometers or solid powders ranging from several micrometers to several millimeters, or flow cells of several micrometers, and the like, and may be applied to the detection of foreign substances in metal powders and panels.

In the above-described real-time focusing (variable focusing) method, the platform 62 can be elevated or lowered by a predetermined distance in the direction of the optical system 64 by motor control by the computer 66 or the like. In another example, The optical system 64 can be raised or lowered by a predetermined distance in the direction of the platform 62. Of course, the user can manually adjust the platform 62 or the optical system 64 to vary the real-time focus (focusing).

In the real-time multifocal particle analysis mode of the present invention, the camera 65 may be a high-speed camera that captures more than 1,000 frames per second.

In addition, a light source for irradiating the sample according to the kind of particles to be analyzed may be selectively used as transmitted light by the lower light source 61 or reflected light by the upper light source 67.

Advantages of the real-time multifocal-based imaging particle analyzer of the present invention as described above are as follows.

The imaging particle analyzing apparatus described with reference to FIG. 6 can be equipped with a real-time multifocus-based imaging particle analyzing function in a complex manner without changing parts (without adding specifications), and the sharp part (surface boundary) It is possible to broaden the analysis area of particle characteristics such as the type of particles to be analyzed and to meet the market needs such as particle shape measurement with an imaging based camera shot image and to overcome the short lens focus area of the conventional microscope, Can be analyzed, and there is an advantage that the size and shape of the actual particles can be seen.

On the other hand, the real-time multifocal particle analyzer according to the present invention described with reference to Fig. 6 or described with reference to Fig. 9 of the present invention described with reference to Fig. 6 differs from the optical particle analyzer shown in Fig. As shown in Fig. A detailed description of the scattered light filtering unit will be omitted.

The real-time multifocal particle analyzer of the present invention described with reference to Fig. 6 or described with reference to Fig. 9 of the present invention can be provided with a leveling system described with reference to Fig. 5 on the ground 62 have. A detailed description of such a leveling system will be omitted.

10 is a perspective view of a composite apparatus having a particle tracking analysis mode and an imaging particle analysis mode according to an embodiment of the present invention.

10, a composite apparatus having a particle tracking analysis mode and an imaging particle analysis mode according to the present invention includes a laser light source 101, a lower light source 102, an upper light source 103, a platform 104, A sample capillary 105, an optical system 106, a camera 107, and a computer not shown in the figure.

The composite apparatus of FIG. 10 may further include the scattered light filtering unit described with reference to FIG. 4, the light reflection preventing unit described with reference to FIG. 5, and a leveling system.

The composite apparatus of the present invention performs the functions of the particle tracking analyzing apparatus described with reference to Figs. 1 to 5 and the functions of the imaging particle analyzing apparatus described with reference to Figs. 6 to 8 in one apparatus, And the imaging particle analysis mode.

Of course, the composite apparatus of the present invention can perform the functions of the particle tracking analyzing apparatus described with reference to FIGS. 1 to 5 and the real-time multifocus particle analyzing function described with reference to FIG.

In addition, the composite apparatus of the present invention has the function of the particle tracking analyzing apparatus described with reference to Figs. 1 to 5, the functions of the imaging particle analyzing apparatus described with reference to Figs. 6 to 8, Analysis function can be performed.

That is, in performing the particle tracking analysis mode and the imaging particle analysis mode, the composite apparatus of the present invention may include a laser light source 101, a bed material 104, a sample capillary 105, An optical system 106 and a camera 107 are used in the imaging particle analysis mode using the optical system 106 and the camera 107 and the lower light source 102, the platform 104, the sample capillary 105, Lt; / RTI &gt;

As described above, the composite apparatus according to the present invention can perform the functions by sharing components according to the analysis mode, so that the manufacturing cost can be lowered compared with the case where the particle tracking analyzing apparatus, the imaging particle analyzing apparatus and the real- And can be implemented without any modification to the structure, specification, function, and process of the particle tracking analyzer, the imaging particle analyzer and the real time multifocal particle analyzer, and the particle tracking analysis mode and the imaging particle analysis mode And the real-time multifocal particle analysis mode, there is no interference between parts and processes, and there is an advantage that the particle characteristics can be analyzed without degrading performance.

Next, the sample capillary mounting module of the present invention will be described in detail.

FIG. 11 is a perspective view of an embodiment of a sample capillary mounting module according to the present invention, FIGS. 12A to 12C are perspective views of another embodiment of a sample capillary mounting module according to the present invention, FIG. 2 is a perspective view of a composite apparatus equipped with a sample capillary mounting module according to an embodiment of the present invention; FIG.

The sample capillary mounting module according to the present invention includes the particle tracking analyzing apparatus described with reference to Figs. 1 to 5, the imaging particle analyzing apparatus described with reference to Figs. 6 to 9, the particle tracking analyzing mode described with reference to Fig. 10 The sample capillary (13, 63, 105) is mounted on the sample capillary mounting module as it is mounted on the platform (12, 62, 104) of the composite apparatus having the imaging particle analysis mode.

11, the upper surface of the sample capillary mounting module 200 according to the first embodiment of the present invention is provided with a seating groove 201 in which the sample capillary 13 is seated in its longitudinal direction, A through hole 202 is formed from one side of the side of the sample capillary mounting module 200 to the other side of the side and the light irradiated toward the side of the sample capillary mounting module 200 is incident, Through the pillar (13).

12A, the upper surface of the sample capillary mounting module 300 according to the second embodiment of the present invention is provided with a seating groove 301 in which the sample capillary 13 is seated in its longitudinal direction, A through hole 302 is formed from one side of the sample capillary mounting module 300 to the other side of the sample capillary mounting module 300 and the other side of the sample capillary mounting module 300 is closed, Reflection preventing portion 303 described with reference to FIG. 5 is formed on the other side. 12A, when the light reflection preventing part 303 is formed on the other side of the sample capillary mounting module 300, the particle tracking analyzing device does not need to include the light reflection preventing part 18.

12B, on the upper surface of the sample capillary mounting module 400 according to the third embodiment of the present invention, there is formed a seating portion for allowing the sample capillary (13, 63, 105) A through hole 402 is formed from one side of the side of the sample capillary mounting module 400 to the other side of the side surface and a bottom surface of the sample capillary mounting module 400 is formed with a predetermined size The lower groove 403 is formed.

That is, the lower groove 403 of the sample capillary mounting module 400 is in contact with the hole of the platform 62 of the imaging particle analyzer of Fig. 7 or the hole of the platform 104 of the composite device of Fig. 10, The light irradiated from the light sources 61 and 102 passes through the holes of the ground rod 104 and the lower grooves 403 of the sample capillary mounting module 400 to be transmitted to the sample capillaries 63 and 105. The sample capillary mounting module 400 of FIG. 12B can be commonly used in a particle tracking analysis mode and an imaging particle analysis mode.

The sample capillary mounting module 400 of FIG. 12B has a structure in which the other side of the sample capillary mounting module 400 is clogged as shown in FIG. 12A, and a light reflection preventing portion may be formed on the other side of the side.

12C, on the upper surface of the sample capillary mounting module 500 according to the fourth embodiment of the present invention, there are formed seats for allowing the sample capillaries 13, 63 and 105 to be seated in the longitudinal direction thereof A groove 501 is formed in the sample capillary mounting module 500 and a through hole 502 is formed from one side of the side of the sample capillary mounting module 500 to the other side of the side, And an upper groove 504 having a specific size is formed in the lid 503.

That is, the sample capillary mounting module 500 of FIG. 12C is provided with a cover 503 to prevent foreign substances such as dust from penetrating the outside of the sample capillaries (13, 63, 105) , The scattered light from the sample capillaries (13, 63, 105) goes out in the upward direction, so that the upper groove (504) is formed in the lid (503) by the scattered light exit path.

The lid 503 of the sample capillary mounting module 500 of FIG. 12C is formed by fastening the side of the sample capillary mounting module 500 and one side of the lid 503 with a hinge to open / close the lid 503 Structure. For example, the measurement can be started after the cover cap 503 is closed by raising the sample capillary 13, 63, 105 while the cover 503 is opened.

In addition, both ends of the seating groove 501 of the sample capillary mounting module 500 of FIG. 12C may have a clogged structure to block foreign substances such as dust that may enter through the both ends of the seating groove 501.

In addition, a lower groove having a specific size may be formed on the lower surface of the sample capillary mounting module 500 of FIG. 12C, and the other side of the sample capillary mounting module 500 may be closed. A light reflection preventing portion may be formed.

On the other hand, may be a matte anodizing surface treatment, such as 11 to sample capillary mounted module (200, 300, 400 and 500) of Figure 12c is Al 2 O 3 in order to prevent light reflection.

As shown in FIG. 13, the sample capillary mounting modules 200, 300, 400, and 500 of FIGS. 11 to 12C are fixedly mounted on the platform 12, 62, 104 by the fastening member.

In another example, the upper capillary mounting modules 200, 300, 400 and 500 may have uneven grooves formed in the longitudinal direction on the lower outer surface of the sample capillary mounting modules 200, 300, 400, And concave and convex grooves corresponding to the concave and convex grooves of the sample capillary mounting modules 200, 300, 400, The concavo-convex grooves of the sample capillary mounting modules 200, 300, 400, and 500 and the concave-convex grooves of the platforms 12, 62, and 104 can be fixed and fixed. This uneven groove allows the stopper and guide fastening function.

On the other hand, as shown in Fig. 13, it can be mounted on the fixing member 901 to fix the light irradiation direction of the laser light sources 11 and 101. The laser light source fixing member 901 is disposed at an arbitrary position capable of irradiating light to the side surfaces of the sample capillaries 13, 63, and 105 mounted on the sample capillary mounting modules 200, 300, For example, on the upper side of the platform 12, 62, 104, or the like.

In the present invention, the light irradiation directions of the sample capillary mounting modules 200, 300, 400, 500 and the laser light sources 11, 101 in which the sample capillaries 13, 63, The convenience and accuracy of the structure of the apparatus can be improved by irradiating the laser beam with a fixed angle with respect to the laser beam irradiation axis and the sample capillary side axis using a fixed fixing member 901 (by turning the horizontal axis). That is, when setting the angle between the laser beam irradiation axis and the side cap axis of the sample capillary to a certain value, the mounting direction of the laser beam source fixing member 901 is changed according to the angle, or the sample capillary mounting modules 200, 300, 400, and 500 may be different.

The advantages of the above-described sample capillary mounting module of the present invention are as follows.

The sample capillary having a small size of 1 mm X 1 mm X 80 mm can be easily mounted on the analyzer so that the user's convenience of operation and ease of handling can be reduced and the sample to which the sample is injected into the sample capillary mounting module Since it is only necessary to raise the capillary, it is possible to perform the preliminary work of sample preparation such as washing at the time of sample change easily and conveniently, and the sample capillary mounting module can accurately focus the irradiation light onto the sample capillary, And a laser beam irradiation can be performed at various desired angles with respect to the laser beam irradiation axis and the side cap axis of the sample capillary and a sample which can be commonly used in the particle tracking analysis mode and the imaging particle analysis mode The capillary mounting module has the advantage of reducing the manufacturing cost by reducing the number of parts.

Meanwhile, the method of the present invention as described above can be written in a computer program. And the code and code segments constituting the program can be easily deduced by a computer programmer in the field. In addition, the created program is stored in a computer-readable recording medium (information storage medium), and is read and executed by a computer to implement the method of the present invention. And the recording medium includes all types of recording media readable by a computer.

While the present invention has been described in connection with what is presently considered to be the most practical and preferred embodiment, it is to be understood that the invention is not limited to the disclosed embodiments, but is capable of various modifications within the scope of the invention. Therefore, the scope of the present invention should not be limited by the illustrated embodiments, but should be determined by the scope of the appended claims and equivalents thereof.

11: laser light source 12:
13: sample capillary 14: optical system
15: camera 16: computer

Claims (12)

delete delete delete delete delete delete delete delete delete delete A sample capillary mounting module on which the sample capillary into which the particles to be analyzed are placed is mounted;
A platform on which the sample capillary mounting module is mounted;
A laser light source for irradiating light to a side surface of the sample capillary that is seated on the sample capillary mounting module;
A white light source for irradiating a lower surface of the sample capillary seated on the sample capillary mounting module with light;
An optical system in which particles on the sample capillary passing through the light scatter the light by irradiating the sample capillary with the laser light source or the white light source and guiding the particle image by the scattered light to the camera;
A camera for photographing a scattered light particle image pathway guided from the optical system for a specific time; And
And a computer for tracking the particle movement and analyzing the particle characteristics using the information about the particle to be analyzed and the result of signal processing of scattered light particle image frames for a specific time taken by the camera,
Wherein the sample capillary mounting module has a mounting groove formed on an upper surface thereof for allowing a sample capillary to be seated in the longitudinal direction thereof,
A through hole is formed from one side of the side of the sample capillary mounting module to the other side of the side,
The laser beam irradiated toward the side surface of the sample capillary mounting module is incident on one side of the side surface of the through-hole and is emitted to the other side of the side surface through the sample capillary so that particle tracking analysis using the laser beam is possible,
A lower groove having a specific size is formed on the lower surface of the sample capillary mounting module so that white light irradiated toward the lower surface of the sample capillary mounting module is transmitted through the sample capillary to analyze imaging particles using white light Yes,
Wherein an upper groove having a specific size is formed in the lid to allow scattered light from the sample capillary to pass through the upper groove,
And a cover is opened and closed by fastening a side of the sample capillary mounting module and one side of the cover with a hinge,
Moving the lifting bar or the optical system in the height direction so that the focal point of the particles is varied so that each focus is aligned with the surface boundary of the particles, We synthesized a single particle image based on each particle surface boundary of the focused particle images taken by the camera, and analyzed the particle characteristics
Particle analyzer. delete
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JP2010249760A (en) 2009-04-20 2010-11-04 Bridgestone Corp Sample holder
KR101472454B1 (en) * 2013-04-29 2014-12-16 전자부품연구원 Light scattering analyzer based on real space image

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JP2010249760A (en) 2009-04-20 2010-11-04 Bridgestone Corp Sample holder
KR101472454B1 (en) * 2013-04-29 2014-12-16 전자부품연구원 Light scattering analyzer based on real space image

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