JP2008261737A - Particle size measuring device - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To measure a particle size accurately by a simple constitution. <P>SOLUTION: Particles A<SB>1</SB>, A<SB>2</SB>, A<SB>3</SB>flowing along a fine channel 2a are photographed by a camera 60, and the particle size is calculated from the image. If a particle is deviated to the front or rear side relative to a focal plane 60a of the camera 60 (refer to signs A<SB>1</SB>, A<SB>3</SB>), the particle is photographed dimly and larger than the actual state, and therefore the calculated particle size is enlarged. In this invention, the position in the z-direction of each particle is determined, and deviation amounts Δz<SB>1</SB>, Δz<SB>3</SB>are calculated, to thereby correct the particle size. Consequently, the position in the z-direction of each particle can be determined only by a simple constitution having one camera, and the particle size can be measured accurately. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

    The present invention relates to a particle size measuring device for measuring the particle size of particles mixed in a fluid.

Conventionally, a method is known in which a particle size is calculated by photographing a fluid mixed with particles and analyzing the image (see, for example, Patent Document 1).
JP-A-8-136439

    Such an apparatus can be used in various technical fields, and an apparatus having a simple configuration and high measurement accuracy is desired.

    An object of the present invention is to provide a particle size measuring device that can obtain a particle size with high accuracy while having a simple configuration.

The invention according to claim 1 is illustrated in FIG. 1 and FIG. 2, and in the particle size measuring device (1) for measuring the particle size of particles mixed in the fluid,
A micro-channel (2a) for causing the fluid mixed with particles to flow down in the first axial direction (x);
An imaging means (6) arranged to image a third axis direction (z) substantially perpendicular to the first axis direction and imaging particles flowing down the microchannel (2a);
A flow rate measuring means (4) for measuring a flow rate of the fluid flowing down the microchannel (2a);
First particle diameter calculating means (70) for calculating an apparent particle diameter (d _e ') on the image based on image data (GD) photographed by the photographing means (6);
A flow velocity calculating means (71) for calculating a flow velocity (u) of particles based on the image data (GD);
A second axial position measuring means (72) for measuring a position of the particle with respect to the second axial direction (y) substantially orthogonal to the first axial direction and the third axial direction from the image data (GD);
The calculation results of the flow rate measuring means (4), the flow velocity calculating means (71) and the second axial position measuring means (72), and the Navier-Stokes equations for the fluid flowing through the microchannel (2a), A third axial position calculating means (73) for calculating the third axial position of the particles,
Based on the calculation result of the third axial position calculation means (73), the deviation of the particle in the third axial direction (z) with reference to the focal plane (see reference numeral 60a in FIG. 5) of the imaging means (6). A deviation amount calculating means (74) for calculating the amount (Δz);
A blur degree predicting means (75) for predicting the blur degree of the image of the particle based on the calculation result of the deviation amount calculating means (74);
And second particle size calculation means (76) for correcting the apparent particle diameter (d _e ') based on the prediction result of the blur degree prediction means (75).

The invention according to claim 2 is illustrated in FIG. 2 and FIG. 11, and in the particle size measuring device (1) for measuring the particle size of particles mixed in the fluid,
A micro-channel (2a) for causing the fluid mixed with particles to flow down in the first axial direction (x);
An imaging means (6) arranged to image a third axis direction (z) substantially perpendicular to the first axis direction and imaging particles flowing down the microchannel (2a);
A flow rate measuring means (4) for measuring a flow rate of the fluid flowing down the microchannel (2a);
First particle diameter calculating means (70) for calculating an apparent particle diameter (d _e ') on the image based on image data (GD) photographed by the photographing means (6);
A flow velocity calculating means (71) for calculating a flow velocity (u) of particles based on the image data (GD);
A second axial position measuring means (72) for measuring a position of the particle with respect to the second axial direction (y) substantially orthogonal to the first axial direction and the third axial direction from the image data (GD);
The calculation results of the flow rate measuring means (4), the flow velocity calculating means (71) and the second axial position measuring means (72), and the Navier-Stokes equations for the fluid flowing through the microchannel (2a), A third axial position calculating means (73) for calculating the third axial position of the particles,
Based on the calculation result of the third axial position calculation means (73), the deviation of the particle in the third axial direction (z) with reference to the focal plane (see reference numeral 60a in FIG. 5) of the imaging means (6). A deviation amount calculating means (74) for calculating the amount (Δz);
And third particle size calculation means (77) for calculating the particle size (d _p ) from the apparent particle size (d _e ′), the deviation amount (Δz), and the following formula: .

The invention according to claim 3 is the invention according to claim 2, wherein the formula is the following formula.

According to a fourth aspect of the present invention, in the first aspect of the invention according to any one of the first to third aspects, the first particle size calculation means (70) calculates the area (S) of the particles based on the image data (GD). Area calculation unit (701) to calculate, particle size calculation unit (702) to calculate the apparent particle size (d _e ′) based on the area (S) calculated by the area calculation unit (701) and the following formula It is characterized by comprising.

    The invention according to claim 5 is the invention according to any one of claims 1 to 4, characterized in that the microchannel (2a) has a shape in which the fluid flows down in a laminar flow state. .

    The invention according to claim 6 is the storage container according to any one of claims 1 to 5, wherein the flow rate measuring means (4) stores the fluid that has flowed out of the microchannel (2a). 40), a weight measurement unit (41) for measuring the weight of the fluid stored in the storage container (40), and a flow rate calculation for calculating a flow rate based on the measurement result and time data by the weight measurement unit (41) Part (42).

    The invention according to claim 7 is the invention according to any one of claims 1 to 6, further comprising: a fourth particle size calculation unit that corrects an error associated with a light diffraction phenomenon by performing a deconvolution process. It is characterized by having.

    The invention according to claim 8 is the invention according to any one of claims 1 to 7, wherein the fluid is a liquid, a gas, a liquid-gas mixed phase fluid, a liquid-solid mixed phase fluid, or a gas-solid. It is a multiphase fluid or a liquid-gas-solid multiphase fluid.

    The numbers in parentheses are for the sake of convenience indicating the corresponding elements in the drawings, and therefore the present description is not limited to the descriptions on the drawings.

    According to the first to eighth aspects of the invention, the particle diameter can be accurately measured with a simple configuration.

The best mode for carrying out the present invention will be described below with reference to FIGS. Here, FIG. 1 is a block diagram showing an example of the configuration of the main part (data processing device) of the particle size measuring apparatus according to the present invention, and FIG. 2 shows the overall configuration of the particle size measuring apparatus according to the present invention. is a schematic diagram showing an example, FIG. 3 is a schematic view for explaining the shape of the fine channel, FIG. 4 is a schematic view for explaining conditions for calculating the apparent particle diameter d _{e '} It is. FIG. 5 is a schematic view of the flow of particles as seen from the second axial direction side, FIG. 6 is a drawing schematically showing an image of three particles, and FIG. It is drawing which shows the relationship between a flow velocity and a 3rd axial direction position. Further, FIG. 8 (a) is a diagram showing an analysis result when the correction by the second particle size calculation means or the like is not performed, and FIG. 8 (b) shows the correction by the second particle size calculation means or the like. It is a figure which shows the analysis result at the time of performing. Further, FIG. 9 is a view for explaining the effects of the present invention, FIG 10 is a diagram showing the relationship between the actual particle size d _X value d _Y of the measured particle size.

    The particle diameter measuring apparatus according to the present invention is an apparatus for measuring the particle diameter of particles mixed in a fluid, and a preferred embodiment thereof is shown in FIGS. 1 and 2.

    Reference numeral 2 in FIG. 2 indicates a microchemical chip having a microchannel 2a. The upstream side of the microchannel 2a communicates with a container (referred to as a “sample container” in this specification) 3, and a fluid mixed with particles is placed in the sample container 3. Further, a flow rate measuring means 4 for measuring the flow rate of the fluid flowing down the micro flow channel 2a is disposed on the downstream side of the micro flow channel 2a. A micropump 5 is arranged on the downstream side of the flow rate measuring means 4. By driving the micropump 5, the fluid in the sample container 3 flows down through the microchannel 2 a and the flow rate is measured by the flow rate measuring means 4. In this device, the micropump 5 is arranged on the downstream side of the flow rate measuring means 4, but it is of course not limited to this, and may be arranged at other positions.

Here, the fluid in this specification is
Liquid,
Gas,
Liquid-gas mixed phase fluid,
Liquid-solid multiphase fluids,
A gas-solid mixed phase fluid or a liquid-gas-solid mixed phase fluid. The present invention can be used, for example, to measure the particle size of platelets in blood. The blood contains plasma, platelets, red blood cells, and white blood cells. In this case, plasma corresponds to the liquid, platelets correspond to the particles, red blood cells correspond to the solid, and the blood itself. Corresponds to a liquid-gas-solid mixed phase fluid.

    The flow rate measuring means 4 shown in FIG. 2 includes a storage container 40 that stores the fluid that has flowed out of the microchannel 2a, and a weight measurement unit (electronic balance) 41 that measures the weight of the fluid stored in the storage container 40. The flow rate calculation unit 42 calculates a flow rate (for example, a flow rate in units of μl / s) based on the measurement result (data of the weight of the sample) and time data. The container 40 in FIG. 2 is a sealed container, and the sample flows from the sample container 3 → the microchannel 2a → the container 40 by sucking the air in the container by the pump 5 described above. Become. The flow rate measuring means used in the present invention may have a different configuration, and may be arranged at a position other than the downstream side of the microchannel 2a. Furthermore, the flow rate calculation unit 42 may be incorporated in data processing devices 7 and 17 described later.

    FIG. 3 is a perspective view schematically showing the micro flow channel (a perspective view in a state where the micro flow channel 2a is looked down obliquely from above in FIG. 2). The direction in which the particles (mixed with particles) flow down (see symbol x) is referred to as “first axis direction”, and the direction substantially perpendicular to the first axis direction (see symbol y) is referred to as “second axis direction”. A direction (refer to reference numeral z) substantially orthogonal to the first axis direction and the second axis direction is referred to as a “third axis direction”. The micro flow path 2a may have any shape as long as the fluid flows down in a laminar flow state. For example, the width W in the second axial direction is 200 μm, the depth (2D) in the third axial direction is 50 μm, The length in the first axis direction is preferably 30 mm.

    Furthermore, the particle size measuring apparatus 1 according to the present invention is provided with an imaging unit 6 for imaging the third axial direction z, and the imaging unit 6 can image the particles flowing down the minute channel 2a. It is like that. The photographing means 6 is preferably composed of a camera 60 for photographing a moving image, a light source 61 for illuminating the minute flow path 2a, and lenses 62 and 63. Here, as the camera 60, a known camera such as a CCD camera, a high-speed CCD camera, an EMCCD camera, an IICCD camera, or a CMOS camera may be used. The light source 61 may be a known light source such as a halogen lamp, a xenon lamp, or a white LED.

    The image data GD photographed by the photographing means 6 is transmitted to a data processing device (personal computer) 7, and the particle size and the like are calculated in the processing device. The captured image may be transmitted via a USB 2.0 interface or a video capture board.

In this data processing device 7, as illustrated in FIG.
- a first particle diameter calculation means 70 for calculating a particle size d _{e 'apparent} in the image based on the image data GD which the imaging means 6 is taken,
A flow velocity calculating means 71 for calculating a flow velocity u of particles based on the image data GD;
A second axial position measuring means 72 for measuring the position of the particle in the second axial direction y from the image data GD;
It is good to have.

Among these, the first particle size calculation means 70 is an area calculation unit 701 that calculates the area S of the particles based on the image data GD, an apparent particle based on the area S calculated by the area calculation unit 701 and the following equation. It may be configured by a particle size calculator 702 that calculates the diameter d _e ′. That is, in the first particle size calculation means 70, it is assumed that the particles have a flat shape as illustrated by the solid line A in FIG. and it calculates the particle diameter d _{e '.} The first particle size calculating means 70 calculates the diameter d _e ′, but the configuration for calculating the radius is not excluded from the scope of the right of the present invention.

Incidentally, the calculation result d _e ′ according to the above equation may include an error depending on the position of the particle in the third axis direction. Hereinafter, this point will be described with reference to FIGS.

In FIG. 5, reference numeral 60 indicates a camera, and reference numeral 60 a indicates a focal plane of the camera 60. Now, the particles _{A 2} middle flows the focal surface 60a, particles _{A 1} shown upward flow side far from the camera 60 than the focal surface 60a, particles _{A 3} shown below is the side close to the camera 60 from the focal plane 60a Suppose it flows. FIG. 6 is a drawing schematically showing an image obtained by photographing these three particles. 5 and 6 are similar drawings, but the viewing direction is different, and FIG. 5 is a view seen from the second axial direction side (+ side of the y-axis), and FIG. It is the figure (figure of the image | photographed image) seen from the negative | minus side of the axis | shaft (z axis). In the photographed image, although the particle A ₂ flowing through the focal plane 60a appears to be minimal (see FIG. 6), the other two particles (that is, the particle A ₁ flowing on the side farther from the focal plane 60a and the focal plane) The particle A ₃ ) flowing on the side closer to 60 is blurred and appears larger than the middle particle A ₂ (see FIG. 6). Therefore, the two particles A _1, A ₃ of the apparent particle size d _{e 'becomes} that would be calculated larger than the actual one. To eliminate this error, it is necessary to correct the particle size d _{e 'depending} on the amount of deviation from the focal plane 60a (see reference numeral Delta] z ₁ and Delta] z ₃ of FIG. 5).

Therefore, in this embodiment,
Based on the calculation results of the flow rate measuring unit 4, the flow velocity calculating unit 71, and the second axial position measuring unit 72, and the Navier-Stokes equation for the fluid flowing through the microchannel 2a. A third axial position calculating means 73 (see FIG. 1; details will be described later) for calculating the third axial position z of the particles;
A deviation amount calculation means 74 for calculating a deviation amount Δz of the particle in the third axis direction with reference to the focal plane 60a of the imaging means 6 based on the calculation result of the third axis direction position calculation means 73;
· A blur degree predicting means 75 for predicting the blur of the image of the particles based on the calculation result (relative proportions of the actual particle diameter and apparent grain size d _{e ')} of the deviation amount calculation unit 74,
A second particle size calculation unit 76 that corrects the apparent particle size d _e ′ based on the prediction result of the blur degree prediction unit 75;
By providing the correction, the correction according to the deviation amount Δz of the particles from the focal plane 60A is performed. For convenience of explanation, the particle diameter d _p corrected by the second particle diameter calculating means 76 is referred to as “corrected particle diameter”.

    Here, the third axial position calculating means 73, the Navier-Stokes equation, and the like will be described.

The analytical solution for the flow velocity of the Navier-Stokes equation when the microchannel 2a has a rectangular cross section is as follows.

    Here, the values of D and W are known because they are each half the height of the flow path and the flow path width, the flow velocity u is calculated by the flow velocity calculation means 71 described above, and the flow rate Q is the flow rate. Calculated by the measuring means 4, the second axial position of the relevant particle is measured by the second axial position measuring means 72, and both are known values. Accordingly, the third axial position z of the corresponding particle is obtained from the above equation.

From the above, the relationship between the flow velocity u and the third axial position z is obtained. Here,
Then, the flow velocity u and the third axial position z (however,
7), the third axial position z is calculated based on the calculation result u of the flow velocity calculation means 71.

Incidentally, the data processing device 17 shown in FIG. 11 may be used instead of the data processing device 7 shown in FIG. The data processing device 17 is different only in that a third particle size calculation unit 77 is used instead of the blur degree prediction unit 75 and the second particle size calculation unit 76. The third particle size calculating means 77 calculates the particle size d _p from the apparent particle size d _e ′, the deviation amount Δz, and the following equation.

Furthermore, d _p may be calculated by the following equation.

Alternatively, d _p may be calculated using the following equation.

In the above formula A, the second term on the right side is about the influence of diffraction on the blur of the image, and the third term on the right side is about the effect of the deviation amount on the particle size. Thus, a value (particle diameter d _p ) that eliminates the influence of diffraction and the amount of deviation can be calculated.

The air disk diameter ds can be obtained by the following equation.

    According to the present invention, the particle position in the depth direction (third axis direction) can be obtained based on image data obtained by capturing particles from one direction with one camera, and the particle size can be corrected. And according to this invention, although it is a simple structure, a particle size can be measured accurately.

    The inventors of the present invention have confirmed the measurement accuracy of this apparatus by experiments.

<Experiment 1>
A sample mixed with commercially available particles (particles having a diameter of 2 μm) was measured by the particle size measuring apparatus 1. The particle size distribution should be consistent with the Gaussian distribution, but the analysis result when the correction by the second particle size calculating means 76 or the like is not performed is as shown in the bar graph of FIG. It did not agree with the distribution (dashed line). On the other hand, the analysis result when the correction by the second particle size calculation means 76 is performed is shown in FIG.
It became like the bar graph of, and it agreed with the Gaussian distribution (broken line), and the high measurement accuracy was confirmed.

<Experiment 2>
Four types of samples:
・ Polystyrene with 2 μm diameter ・ Latex particles mixed with fluid ・ Polystyrene with 5 μm diameter ・ Latex particles mixed with fluid ・ Polystyrene with 10 μm diameter ・ Latex particles mixed with fluid ・ 20 μm diameter A material in which polystyrene latex particles were mixed in a fluid was prepared, and the particle size of each sample was measured by the particle size measuring device 1 described above. The result was as shown in FIG. 9, and it was found that the measurement accuracy of this apparatus was high.

Figure 10 is a diagram showing the measured actual particle size value d _Y particle size (nominal value by the maker) relationship between d _X. Of course, the relationship between the d _Y and d _X is _(as the origin, the slope is a straight line right up 45 degrees) d _{Y =} d X be a relationship such as it is ideal. When the result of FIG. 9 is plotted, d _Y = 0.985 d _X +0.550 (this d _Y corresponds to d _p described above), and the relationship is almost close to d _Y = d _X , and the measurement accuracy of this apparatus is high. I found out. In the case where the correction with the deviation amount Δz is not performed, d _Y = 0.827 d _X +4.240 (this d _Y corresponds to the above d _e ′), which is larger than the straight line of d _Y = d _X. This also confirmed the effectiveness of the particle size correction according to the present invention.

Meanwhile, the apparent particle diameter d _{e ',} the diffraction phenomenon of light becomes larger than it actually caused. Now, the particle size of the image and then d _e, the actual particle diameter d _p, the Airy disk diameter due to diffraction and d _s, the magnification of the imaging optical system is M, and the wavelength of the illumination light lambda, opening When the number is NA, the following formula is established. For example, M = 5, λ = visible light (400 to 700 nm), the case of NA = 0.18, even the particle size of the apparent a _{d e} ≒ _19~30μm as the actual particle diameter d _p was 2μm End up. That is, the apparent particle size is a convolution of the actual particle size and the PSF, and the particle size calculated from the image data GD by the first particle size calculating means 70 is much larger than the actual particle size d _p. End up.

    Therefore, it is preferable to provide a fourth particle size calculation means (not shown) in the data processing device 7 described above and correct the error associated with the light diffraction phenomenon by performing a deconvolution process.

FIG. 1 is a block diagram showing an example of a configuration of a main part (data processing apparatus) of a particle size measuring apparatus according to the present invention. FIG. 2 is a schematic diagram showing an example of the overall configuration of the particle size measuring apparatus according to the present invention. FIG. 3 is a schematic diagram for explaining the shape and the like of the microchannel. Figure 4 is a schematic view for explaining conditions for calculating the apparent particle diameter d _{e '.} FIG. 5 is a schematic view of particles flowing from the second axial direction side. FIG. 6 is a drawing schematically showing an image obtained by photographing three particles. FIG. 7 is a drawing showing the relationship between the flow velocity and the position in the third axial direction. FIG. 8 (a) is a diagram showing an analysis result when correction by the second particle size calculation means or the like is not performed, and FIG. 8 (b) is a correction made by the second particle size calculation means or the like. It is a figure which shows the analysis result in a case. FIG. 9 is a diagram for explaining the effect of the present invention. Figure 10 is a diagram showing the relationship between the actual particle size d _X value d _Y of the measured particle size. FIG. 11 is a block diagram showing another example of the configuration of the main part (data processing apparatus) of the particle size measuring apparatus according to the present invention.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Particle size measuring device 2a Micro flow path 4 Flow rate measuring means 6 Imaging means 60a Focal plane 70 First particle diameter calculating means 71 Flow velocity calculating means 72 Second axial direction position measuring means 73 Third axial direction position calculating means 74 Deviation amount calculation It means 75 blur degree prediction means 76 second particle diameter calculating unit 77 third grain diameter calculation means 701 of the area calculation unit 702 particle size computing unit d _e 'apparent particle diameter d _p corrected particle diameter GD image data u velocity x first Axial direction y Second axial direction z Third axial direction Δz Deviation

Claims (8)

In the particle size measuring device that measures the particle size of particles mixed in the fluid,
A microchannel that causes the fluid mixed with particles to flow down in the first axial direction;
An imaging means arranged to image a third axis direction substantially perpendicular to the first axis direction and imaging particles flowing down the microchannel;
A flow rate measuring means for measuring a flow rate of the fluid flowing down the microchannel;
First particle size calculating means for calculating an apparent particle size on the image based on image data taken by the photographing means;
A flow velocity calculating means for calculating a flow velocity of particles based on the image data;
A second axial position measuring means for measuring a position of the particle in the second axial direction substantially orthogonal to the first axial direction and the third axial direction from the image data;
Based on the calculation results of the flow rate measuring means, the flow velocity calculating means, and the second axial position measuring means, and the Navier-Stokes equation for the fluid flowing through the microchannel, the third axial position of the particle is calculated. A third axial direction position calculating means,
A deviation amount calculating means for calculating a deviation amount of the particles in the third axis direction with reference to the focal plane of the imaging means based on the calculation result of the third axis direction position calculating means;
A degree-of-blurring prediction means for predicting the degree of blurring of the particle image based on the calculation result of the deviation amount calculation means;
Second particle size calculation means for correcting the apparent particle size based on the prediction result of the blur degree prediction means;
A particle size measuring apparatus comprising: In the particle size measuring device that measures the particle size of particles mixed in the fluid,
A microchannel that causes the fluid mixed with particles to flow down in the first axial direction;
An imaging means arranged to image a third axis direction substantially perpendicular to the first axis direction and imaging particles flowing down the microchannel;
A flow rate measuring means for measuring a flow rate of the fluid flowing down the microchannel;
First particle size calculating means for calculating an apparent particle size on the image based on image data taken by the photographing means;
A flow velocity calculating means for calculating a flow velocity of particles based on the image data;
A second axial position measuring means for measuring a position of the particle in the second axial direction substantially orthogonal to the first axial direction and the third axial direction from the image data;
Based on the calculation results of the flow rate measuring means, the flow velocity calculating means, and the second axial position measuring means, and the Navier-Stokes equation for the fluid flowing through the microchannel, the third axial position of the particle is calculated. A third axial direction position calculating means,
A deviation amount calculating means for calculating a deviation amount of the particles in the third axis direction with reference to the focal plane of the imaging means based on the calculation result of the third axis direction position calculating means;
A third particle diameter calculating means for calculating a particle diameter d _p from the apparent particle diameter, the deviation amount, and the following equation:
A particle size measuring apparatus comprising:
The above formula is:
The particle size measuring apparatus according to claim 2, wherein
Wherein the first particle diameter calculating means, and the area calculation unit for calculating the area S of the particles based on the image data, the particle size d _{e 'of} the apparent based on the said area calculating section area S and the following equation was calculated A particle size calculation unit for calculating,
The particle size measuring apparatus according to any one of claims 1 to 3, wherein The microchannel has a shape in which the fluid flows down in a laminar flow state.
The particle size measuring device according to any one of claims 1 to 4, wherein The flow rate measuring means includes a storage container that stores the fluid that has flowed out of the microchannel, a weight measurement unit that measures the weight of the fluid stored in the storage container, a measurement result and time data by the weight measurement unit, A flow rate calculation unit for calculating a flow rate based on
The particle size measuring device according to any one of claims 1 to 5, wherein A fourth particle size calculating means for correcting an error associated with a light diffraction phenomenon by performing a deconvolution process;
The particle size measuring apparatus according to any one of claims 1 to 6, further comprising: The fluid is a liquid, a gas, a liquid-gas mixed phase fluid, a liquid-solid mixed phase fluid, a gas-solid mixed phase fluid, or a liquid-gas-solid mixed phase fluid.
The particle size measuring device according to any one of claims 1 to 7, wherein