Particle size distribution measurement device, particle size distribution measurement method, and particle size distribution measurement program

Abstract

A laser diffraction / scattering type particle size distribution measurement device 100 includes: a cell 2 in which a sample is circulated and / or accommodated; an imaging part 5 for imaging the cell 2 while the sample is circulated and / or accommodated in the cell 2; and a cell state determination part 72 for acquiring a plurality of images captured at different times by the imaging part 5 and comparing the images to determine dirt and / or scratches of the cell 2.

Description

Particle size distribution measuring device, particle size distribution measuring method, and particle size distribution measuring program

[0001] The present invention relates to a particle size distribution measuring device, a particle size distribution measuring method, and a particle size distribution measuring program.

[0002] 2. Description of the Related Art Conventionally, there are laser diffraction / scattering particle size distribution measuring devices that use the diffraction phenomenon and Mie scattering phenomenon to measure the particle size distribution of particles contained in a sample.

[0003] As disclosed in Patent Document 1, for example, this type of laser diffraction / scattering particle size distribution measuring device includes a cell through which a sample solution flows, a laser light source that irradiates laser light onto the sample flowing through the cell, and a detector that detects transmitted light and scattered light generated from the sample by the laser light irradiated from the laser light source.

[0004] Japanese Patent Application Laid-Open No. 2003-28778

[0005] However, as the sample solution flows into the cell, particles contained in the sample solution may adhere to the inner wall of the cell, causing the inner wall to become dirty. Therefore, a blank measurement is performed in which only the dispersion medium is injected into the cell instead of the sample solution, and the transmitted light emitted from the cell is measured. Based on the transmitted light obtained in the blank measurement, it is determined whether the cell needs to be cleaned.

[0006] However, in the above-mentioned laser diffraction / scattering particle size distribution device, in order to determine whether the cell has been cleaned, the liquid contained in the cell must be replaced from the sample solution to a dispersion medium, and therefore it is not possible to determine whether the cell is dirty and / or damaged while the sample solution is contained in the cell.

[0007] The present invention has been made in view of the above problems, and its main object is to determine whether a cell is dirty and / or damaged in a laser diffraction / scattering type particle size distribution device.

[0008] That is, the particle size distribution measuring device of the present invention is a laser diffraction / scattering type particle size distribution measuring device that measures the particle size distribution of particles contained in a sample based on diffracted light and / or scattered light generated by irradiating a sample with laser light, and is characterized by comprising: a cell through which the sample is circulated and / or contained; an imaging unit that images the cell in a state in which the sample is circulated and / or contained in the cell; and a cell condition determining unit that obtains a plurality of images taken by the imaging unit at different times and determines whether the cell is dirty and / or damaged by comparing the images.

[0009] With this configuration, the cell state determination unit determines whether there is any dirt and / or damage to the cell by comparing multiple images taken at different times while a sample is circulating and / or contained in the cell. Therefore, in a laser diffraction / scattering particle size distribution measuring device, it is possible to determine whether there is any dirt and / or damage to the cell while a sample is circulating and / or contained in the cell.

[0010] A specific configuration for determining cell dirt and / or scratches is one in which the cell state determination unit determines that an object shown in multiple images is dirt and / or scratches on the cell when the object remains within a specified range at different times.

[0011] With this configuration, if an object shown in multiple images remains within a predetermined range at different times, the object is judged to be dirt and / or scratches on the cell, making it easy to determine whether or not there is dirt and / or scratches on the cell.

[0012] It is preferable that the imaging unit further includes an imaging light irradiator that irradiates light onto the cell when the imaging unit images the cell.

[0013] With this configuration, the imaging light irradiation unit irradiates light onto the cell when the imaging unit images the cell, so the contrast of the image captured by the imaging unit becomes clear and it is possible to accurately determine dirt and / or scratches on the cell.

[0014] The particle size distribution measuring device preferably has a cell state determination mode in which dirt and / or scratches on the cell are determined from the image while the sample is circulating and / or contained in the cell, and an image analysis mode in which particle information, which is information indicating the state of the particles, is analyzed from the image.

[0015] With this configuration, the particle size distribution measuring device has a cell state determination mode and an image analysis mode while a sample is flowing through and / or contained in the cell, so that in addition to the particle size distribution of the particles, the user can obtain desired information depending on each mode. Specifically, in the image analysis mode, the particle size distribution of the particles and particle information indicating the state of the particles contained in the cell, such as the particle's equivalent circle diameter, aspect ratio, length, etc., can be obtained, and in the cell state determination mode, the particle size distribution of the particles and any dirt and / or scratches on the cell can be obtained.

[0016] As a specific embodiment of the particle size distribution measurement, the particle size distribution measuring device may measure the particle size distribution while the cell state determination mode and the image analysis mode are simultaneously proceeding.

[0017] The imaging unit preferably includes a first imaging unit that images the cell in the cell state determination mode, and a second imaging unit that images the cell in the image analysis mode.

[0018] With this configuration, the imaging unit used for the cell state judgment mode and the image analysis mode can be separated, so that by capturing images of the cell using an imaging unit appropriate for each mode, it is possible to appropriately determine whether the cell is dirty and / or scratched and analyze particle information.

[0019] Specifically, the first imaging unit images the cell at a magnification lower than that of the second imaging unit, and the second imaging unit images the cell at a magnification higher than that of the first imaging unit.

[0020] With this configuration, the first imaging unit images the cell at a lower magnification than the second imaging unit, making it possible to determine the contamination and / or damage of the cell over a wide area at once, and the second imaging unit images the cell at a higher magnification than the first imaging unit, making it possible to capture particle information more clearly.

[0021] The device further includes a focal depth adjustment unit that adjusts the focal depth of the first imaging unit according to the cell state judgment mode and the image analysis mode, and the focal depth adjustment unit may be configured to make the focal depth shallower in the image analysis mode than in the cell state judgment mode, and to make the focal depth deeper in the cell state judgment mode than in the image analysis mode.

[0022] With this configuration, the focal depth adjustment unit makes the focal depth shallower in the image analysis mode than in the cell state determination mode, thereby preventing the focus of the first imaging unit from being located on the cell surface. On the other hand, the focal depth adjustment unit makes the focal depth deeper in the cell state determination mode than in the image analysis mode, thereby positioning the focus of the first imaging unit on the cell surface, allowing the first imaging unit to clearly image the cell surface.

[0023] The apparatus further includes a measurement light irradiating unit that irradiates the sample with laser light when measuring the particle size distribution of the particles, and a detector that detects the diffracted light and / or scattered light generated from the sample when the measurement light irradiating unit irradiates the sample with laser light, and it is desirable that the imaging unit images at least the portion in the cell from which the diffracted light and / or scattered light toward the detector is emitted.

[0024] With this configuration, the imaging unit captures an image of the portion of the cell from which diffracted light and / or scattered light directed toward the detector is emitted, and therefore, when measuring particle size distribution by the laser diffraction / scattering method, it is possible to determine, based on the image captured by the imaging unit, whether the diffracted light and / or scattered light is affected by contamination and / or scratches on the cell, thereby improving the reliability of measurement when measuring particle size distribution by the laser diffraction / scattering method.

[0025] The imaging unit preferably images a portion of the cell that is irradiated with light from the measurement light irradiation unit.

[0026] With this configuration, when measuring particle size distribution using a laser diffraction / scattering method, it is possible to determine whether the light irradiated from the measurement light irradiator is affected by contamination and / or scratches on the cell. As a result, the reliability of measurement when measuring particle size distribution using a laser diffraction / scattering method can be further improved. In addition, since the imaging unit images the area irradiated with light from the measurement light irradiator and the area from which diffracted light and / or scattered light toward the detector is emitted, it is possible to determine at least contamination and / or scratches on the cell on both the surface facing the detector and the surface facing the measurement light irradiator.

[0027] A laser diffraction / scattering particle size distribution measurement method for measuring the particle size distribution of particles contained in a sample based on diffracted light and / or scattered light generated by irradiating the sample with laser light, the method comprising: imaging a cell in which the sample is distributed and / or contained; acquiring multiple images captured at different times by the imaging unit; and comparing the images to determine whether the cell is contaminated or damaged. Also, a particle size distribution measurement program for use with a laser diffraction / scattering particle size distribution measurement device for measuring the particle size distribution of particles contained in the sample based on diffracted light and / or scattered light generated by irradiating the sample with laser light, the particle size distribution measurement device comprising: a cell in which the sample is distributed and / or contained; and an imaging unit that images the cell while the sample is distributed and / or contained in the cell; and causing a computer to function as a cell condition determination unit that acquires multiple images captured at different times by the imaging unit and determines whether the cell is contaminated or damaged by comparing the images.

[0028] With this configuration, it is possible to obtain the same effects as those of the particle size distribution measuring device described above.

[0029] According to the present invention, contamination and / or damage to a cell in a laser diffraction / scattering particle size distribution device can be determined.

[0030] Fig. 1 is a schematic diagram of a particle size distribution measuring device according to one embodiment of the present invention; Fig. 2 is a diagram showing a portion of a cell imaged by an imaging unit according to the same embodiment; (a) a diagram showing a judgment image at time t1, (b) a diagram showing a judgment image at time t2, and (c) a diagram showing a comparison of judgment images at times t1 and t2 according to the same embodiment; (a) a diagram showing the focal depth in an image analysis mode, and (b) a diagram showing the focal depth in a cell state judgment mode according to the same embodiment; Fig. 2 is a flowchart showing a particle size distribution measuring method according to the same embodiment; Fig. 3 is a flowchart showing particle size distribution measurement according to another embodiment;

[0031] A particle size distribution measuring device according to one embodiment of the present invention will be described below with reference to the drawings. Note that in all of the drawings shown below, some parts may be omitted or exaggerated in schematic form for ease of understanding. Identical components will be assigned the same reference numerals, and their description will be omitted where appropriate.

[0032] <Device Configuration> The particle size distribution measuring device 100 of this embodiment is a laser diffraction / scattering type that measures the particle size distribution of particles contained in a sample based on diffracted light and / or scattered light generated by irradiating the sample with laser light. In this embodiment, the sample is, for example, a pharmaceutical product, food product, and / or a chemical industrial product. Here, the sample is composed of particles and a liquid dispersion medium, and the particles are the object of measurement.

[0033] 1 , the particle size distribution measuring device 100 includes a cell 2 through which a sample flows, a measurement light irradiating unit 3 that irradiates the sample with laser light when measuring the particle size distribution of particles, a detector 4 that detects diffracted light and / or scattered light generated from the sample, an imaging unit 5 that images the cell 2, an imaging light irradiating unit 6 that irradiates the cell with light when the imaging unit 5 images the cell 2, and a control device 7 that performs various controls based on detection by the detector 4 and / or the image captured by the imaging unit 5. The configuration of each unit will be described below.

[0034] The cell 2 is a circulation-type flow cell, and includes an inlet port (not shown) through which a sample is supplied, an outlet port (not shown) through which the sample is discharged, and an internal flow path connected to the inlet port and the outlet port and through which the sample flows. When the sample is flowing and / or contained within the cell 2, particles contained in the sample move within the cell 2. The cell 2 is provided on the circulation flow path through which the sample circulates, and in addition to the cell 2, the circulation flow path may be provided with a circulation pump and / or a particle agitator for dispersing the particles in the liquid. In this embodiment, the cell 2 may have any shape as long as an irradiation surface irradiated with laser light and an emission surface from which diffracted light and / or scattered light are emitted face each other, and may be, for example, a roughly rectangular parallelepiped shape.

[0035] The measurement light irradiator 3 irradiates a sample flowing through the internal flow path of the cell 2 with laser light that generates diffracted light and / or scattered light. Examples of the measurement light irradiator 3 include a semiconductor laser. The measurement light irradiator 3 may irradiate the sample with laser light via an optical member such as a lens. The measurement light irradiator 3 may further include a light source with low light intensity, such as an LED, in addition to a light source with high light intensity, such as a laser light source.

[0036] The detector 4 detects the light intensity of the diffracted light and / or scattered light generated by the irradiation of the laser light according to the divergence angle, and here, a plurality of detectors 4 are provided to detect the light intensity of the diffracted light and / or scattered light according to the divergence angle. In Fig. 1, the detector 4 is provided behind the irradiation surface of the cell 2 onto which the laser light from the measurement light irradiator 3 is irradiated, but it may also be provided in front of the irradiation surface of the cell 2.

[0037] The imaging unit 5 images the cell 2 in a state where a sample is flowing through and / or contained in the cell 2. Here, the state where a sample is flowing through and / or contained in the cell 2 refers to a state where the sample is flowing through and / or contained in the internal flow path of the cell 2. More specifically, the imaging unit 5 images the cell 2 in a state where diffracted light and / or scattered light from the sample is generated by irradiation of laser light by the measurement light irradiator 3, but the imaging unit 5 may also image the cell 2 in a state where the measurement light irradiator 3 is not irradiating laser light. In this embodiment, the cell 2 imaged by the imaging unit 5 is the same cell 2 to which the measurement light irradiator 3 irradiates laser light.

[0038] Specifically, the imaging unit 5 has a first imaging unit 51 that images the cell 2 to determine whether the cell 2 is dirty and / or damaged, and a second imaging unit 52 that images the cell 2 to analyze particle information, which is information indicating the state of the particles, from the image. Here, the particle information is information that indicates the shape of the particles, separate from the particle size distribution of the particles, and examples of the particle information include the circle-equivalent diameter, aspect ratio, and length of the particles.

[0039] The first imaging unit 51 images the cell 2 at different times t1, t2, ..., tn while the particle size distribution is being measured. In this embodiment, the first imaging unit 51 is an imaging camera with a lower magnification than the second imaging unit 52. The first imaging unit 51 is configured with an adjustable aperture. Note that the first imaging unit 51 only needs to image the cell 2 at at least two different times, and may also image the cell 2 at three or more different times.

[0040] 1 and 2 , the first image capturing unit 51 is provided at a position that does not overlap with the optical path of the diffracted light and / or scattered light traveling from the cell 2 toward the detector 4. In this embodiment, the first image capturing unit 51 is provided behind the irradiation surface of the cell 2 onto which the laser light from the measurement light irradiator 3 is irradiated. However, the first image capturing unit 51 may be provided in front of the irradiation surface of the cell 2.

[0041] 2, the first imaging unit 51 images the portion of the cell 2 from which the diffracted light and / or scattered light toward the detector 4 is emitted. Specifically, the first imaging unit 51 images the exit surface of the cell 2 from which the diffracted light and / or scattered light is emitted. The exit surface of the cell 2 referred to here includes at least the opposing surface that faces the irradiation surface of the cell 2 that is irradiated with the laser light, and may also include a side surface interposed between the irradiation surface and the opposing surface if the diffracted light and / or scattered light is emitted from that side surface. Furthermore, if the diffracted light and / or scattered light is emitted from the irradiation surface, the first imaging unit 51 may image the irradiation surface as the exit surface.

[0042] In this embodiment, the first imaging unit 51 images a portion of the cell 2 irradiated with the laser light from the measurement light irradiation unit 3. Specifically, the first imaging unit 51 images the irradiation surface of the cell 2 irradiated with the laser light. As a result, the image captured by the first imaging unit 51 shows both the irradiation surface of the cell 2 irradiated with the laser light and the emission surface of the cell 2 from which the diffracted light and / or scattered light is emitted.

[0043] In this embodiment, the second imaging unit 52 is a camera with a higher magnification than the first imaging unit 51. The number of times that the second imaging unit 52 images the cell 2 is not particularly limited, and the cell 2 may be imaged at a plurality of different times, or the cell 2 may be imaged only at a certain predetermined time.

[0044] 1 , the second image capturing unit 52 is provided at a position that does not overlap with the optical path of the diffracted light and / or scattered light traveling from the cell 2 toward the detector 4. The second image capturing unit 52 is provided behind the irradiation surface of the cell 2 that is irradiated with the laser light from the measurement light irradiator 3, but may be provided in front of the irradiation surface of the cell 2.

[0045] 1 , the imaging light irradiating unit 6 is provided on the opposite side of the cell 2 from the imaging unit 5, and in this embodiment, is provided on the same side of the cell 2 as the measurement light irradiating unit 3. The imaging light irradiating unit 6 is, for example, an LED. In this embodiment, two imaging light irradiating units 6 are provided corresponding to each of the first imaging unit 51 and the second imaging unit 52, but a common irradiating unit may be used for the first imaging unit 51 and the second imaging unit 52.

[0046] The control device 7 is a general-purpose or dedicated computer equipped with a CPU, a memory, an input / output interface, etc., and performs at least the functions of a particle size distribution calculation unit 71, a cell state determination unit 72, a mode acceptance unit 73, and a focal depth adjustment unit 74, as shown in FIG. 1 , by causing the CPU and peripheral devices to cooperate with each other in accordance with a predetermined program stored in a predetermined area of ​​the memory.

[0047] The particle size distribution calculation unit 71 calculates the particle size distribution of particles contained in the sample based on the light intensity signals output from the detectors 4. Specifically, the particle size distribution corresponding to the scattering pattern is calculated based on a scattering pattern indicated by the light intensity signals output from each detector 4, the scattering pattern being composed of the scattering angle and the intensity of the scattered light at that scattering angle, and a theoretical calculation formula such as the Mie scattering theory. The particle size distribution data indicating the particle size distribution calculated by the particle size distribution calculation unit 71 is stored in a predetermined memory and is also displayed on a display unit D, such as a display.

[0048] The cell state determination unit 72 acquires a plurality of images taken by the first imaging unit 51 at different times t1, t2, ..., tn and compares these images to determine the dirt and / or scratches on the cell 2. The dirt and / or scratches on the cell 2 referred to here are formed on the wall surface of the cell 2 and obstruct the diffracted light and / or scattered light emitted from the cell 2, such as deposits adhering to the wall surface of the cell 2, defects formed on the wall surface of the cell 2, etc.

[0049] Specifically, the cell state determination unit 72 determines that an object shown in multiple images is a stain and / or scratch on the cell 2 if the object remains within a predetermined range at two different times, e.g., t1 and t2. As shown in FIGS. 3( a) and 3(b), the multiple images captured by the first image capture unit 51 at different times t1 and t2 show an object with a predetermined shape through which light from the imaging light irradiator 6 is less likely to transmit than the dispersion medium liquid, because light from the imaging light irradiator 6 passes through the dispersion medium liquid. In FIGS. 3( a) and 3(b), the object shown in each image is indicated by a solid black dot. Here, examples of objects through which light from the imaging light irradiator 6 is less likely to transmit than the dispersion medium liquid include particles contained in the sample, stains and / or scratches on the cell 2, etc.

[0050] Then, as shown in FIG. 3(c), the cell state determination unit 72 acquires an image captured at time t1 and an image captured at time t2 and compares the objects captured in these images. In FIG. 3(c), the object shown in dashed lines indicates the object at time t1, and the object shown in black indicates the object at time t2. As shown in FIG. 3(c), if an object moves between time t1 and time t2, the object is determined to be a particle rather than a stain and / or scratch on cell 2. Here, an example of an object moving between time t1 and time t2 is when the object at time t2 moves outside the frame line indicated by the object at time t1. Note that, depending on the setting of the predetermined range, even if a portion of the object at time t2 overlaps with the frame line indicated by the object at time t1, the object may be determined to have moved between time t1 and time t2.

[0051] On the other hand, as shown in Figure 3(c), if an object remains within the predetermined range between time t1 and time t2, the object is determined to be a stain and / or scratch on cell 2. Here, cases in which an object remains within the predetermined range between time t1 and time t2 include, for example, (1) when the amount of movement of the object between time t1 and time t2 is zero (symbol A in Figure 3), (2) when the object moves between time t1 and time t2, but the amount of movement is extremely small compared to other objects and is equal to or less than a predetermined number of pixels, such as when a part of the object at time t2 overlaps with the object at time t1 (symbol B in Figure 3(c)), and (3) when the object at time t2 has shrunk and remains within the frame line indicated by the object at time t1 (symbol C in Figure 3).

[0052] In this embodiment, the particle size distribution measuring device 100 is configured to be switchable between a cell state determination mode in which contamination and / or damage to the cell 2 is determined from an image, and an image analysis mode in which particle information is analyzed from an image, while a sample is circulating and / or contained in the cell 2. Specifically, the cell state determination mode and the image analysis mode are selected, for example, according to a user input or a preset program, and the selected mode is received by the mode receiving unit 73.

[0053] The focal depth adjustment unit 74 adjusts the focal depth of the first imaging unit 51 in accordance with the cell state determination mode and the image analysis mode. Specifically, the focal depth adjustment unit 74 acquires the selected mode from the mode reception unit 73 and adjusts the focal depth of the first imaging unit 51 by controlling the aperture of the first imaging unit 51 in accordance with the selected mode.

[0054] More specifically, in the image analysis mode, the focal depth adjustment unit 74 makes the focal depth of the first imaging unit 51 shallower than in the cell state determination mode. As shown in FIG. 4A, within the range of the cell 2 imaged by the first imaging unit 51, the focal depth of the first imaging unit 51 is located inside the cell 2 rather than the irradiation surface and the emission surface of the cell 2.

[0055] 4(b), the focal depth adjustment unit 74 deepens the focal depth of the first imaging unit 51 in the cell state determination mode compared to the image analysis mode. As shown in FIG. 4(b), in the range of the cell 2 imaged by the first imaging unit 51, the focal depth of the first imaging unit 51 is positioned so as to include the irradiation surface and the emission surface of the cell 2.

[0056] <Particle Size Distribution Measuring Method> Next, a particle size distribution measuring method using the particle size distribution measuring device 100 of this embodiment will be described with reference to FIG.

[0057] First, a sample is introduced into the cell 2, and the sample flows through the internal flow path of the cell 2 (S1).

[0058] When the sample flows through the internal flow path of the cell 2, the imaging unit 5 to be used is determined depending on whether the particle size distribution measuring device 100 is in the cell state determination mode or the image analysis mode (S2). Specifically, the focal depth adjusting unit 74 adjusts the focal depth of the first imaging unit 51 depending on the mode of the particle size distribution measuring device 100 accepted by the mode accepting unit 73. Note that the mode of the particle size distribution measuring device 100 may be selected either before or after the start of measurement of the particle size distribution of particles.

[0059] When the particle size distribution measuring device 100 is in the image analysis mode, the focal depth adjusting unit 74 makes the focal depth of the first imaging unit 51 shallower than in the cell state determination mode.

[0060] Then, the measurement light irradiator 3 irradiates the sample with laser light. This generates diffracted light and / or scattered light from the sample, and measurement of the particle size distribution of the particles begins (S3). While the particle size distribution of the particles is being measured, the detector 4 detects the diffracted light and / or scattered light from the sample, and the particle size distribution calculator 71 calculates the particle size distribution of the particles based on the light intensity signal output by the detector 4.

[0061] When the measurement of particle size distribution of particles is started, the first image capturing unit 51 and the second image capturing unit 52 capture images of the cell 2 (S4). Then, particle information is analyzed based on the captured images (S5), and the analyzed particle information and the captured images are displayed on the display unit D. After the particle information is analyzed, if the measurement of particle size distribution is to be continued, the process returns to S4. If the measurement of particle size distribution is to be ended, the irradiation of laser light by the measurement light irradiating unit 3 is ended.

[0062] When the particle size distribution measuring device 100 is in the cell state determination mode, the focal depth adjusting unit 74 makes the focal depth of the first imaging unit 51 deeper than in the image analysis mode.

[0063] Then, the measurement light irradiator 3 irradiates the sample with laser light. This generates diffracted light and / or scattered light from the sample, and measurement of the particle size distribution of the particles begins (S6). While the particle size distribution of the particles is being measured, the detector 4 detects the diffracted light and / or scattered light from the sample, and the particle size distribution calculator 71 calculates the particle size distribution of the particles based on the light intensity signal output by the detector 4.

[0064] When the measurement of particle size distribution of particles is started, the first image capturing unit 51 captures images of the cell 2 at different times t1, t2, . . . , tn (S7).

[0065] When the first imaging unit 51 captures images of the cell 2 at different times t1, t2, ..., tn, the cell state determination unit 72 acquires these images. Then, by comparing these images, the cell state determination unit 72 determines whether an object shown in the multiple images remains within a predetermined range at, for example, times t1 and t2 (S8). Note that the images used by the cell state determination unit 72 are not limited to the images captured at time t1 and time t2, but may be images captured at multiple times from among the images captured at different times t1 to tn.

[0066] If an object shown in multiple images is located outside the predetermined range at different times t1 and t2, the cell state determination unit 72 determines that the object is not dirt and / or a scratch on the cell 2. Thereafter, if the measurement of the particle size distribution is to be continued, the process returns to S7, and if the measurement of the particle size distribution is to be ended, the irradiation of the laser light by the measurement light irradiation unit 3 is ended.

[0067] If an object shown in multiple images remains within a predetermined range at different times t1 and t2, the cell state determination unit 72 determines that the object is a stain and / or scratch on the cell 2 (S9). If the proportion of objects determined to be stains and / or scratches on the cell 2 in the images is equal to or greater than a predetermined value, the cell state determination unit 72 determines that cleaning of the cell 2 is necessary and outputs a signal urging the user to clean the cell 2. Examples of the signal urging the user to clean the cell 2 include characters or graphics displayed on the display unit D and a warning sound output by an audio device such as a speaker (not shown). In addition to the signal urging the user to clean the cell 2, the cell state determination unit 72 may also output a signal to stop measuring the particle size distribution of particles.

[0068] <Effects of this embodiment> According to the particle size distribution measuring device 100 of this embodiment, the cell state determining unit 72 determines the contamination and / or damage of the cell 2 by comparing multiple images captured at different times t1 and t2, and therefore, in the laser diffraction / scattering particle size distribution measuring device 100, it is possible to determine the contamination and / or damage of the cell 2 while a sample is contained in the cell 2. Furthermore, when determining the contamination and / or damage of the cell 2, it is not necessary to replace the sample contained in the cell 2 with another fluid, and therefore it is not necessary to interrupt the measurement of the particle size distribution of the particles contained in the sample.

[0069] Other Embodiments The present invention is not limited to the above-described embodiments.

[0070] In the above embodiment, the particle size distribution measuring device 100 switches between either the cell state determination mode or the image analysis mode during a single particle size distribution measurement. However, it may also be configured to perform both the cell state determination mode and the image analysis mode during a particle size distribution measurement. Specifically, as shown in FIG. 6 , the particle size distribution measuring device 100 may perform particle size distribution measurement while simultaneously running the cell state determination mode and the image analysis mode. In other words, the particle size distribution measuring device 100 may simultaneously determine whether the cell 2 is contaminated and / or damaged using the first imaging unit 51 and perform image analysis of particle information using the second imaging unit 52. A method for measuring particle size distribution in both the cell state determination mode and the image analysis mode will be described below.

[0071] A sample is introduced into the cell 2, and the sample flows through the internal flow path of the cell 2 (S21).

[0072] When measuring the particle size distribution of particles in both the cell state determination mode and the image analysis mode, the focal depth adjustment unit 74 sets the focal depth of the second imaging unit 52 shallower than in the cell state determination mode. In this case, the focal depth of the first imaging unit 51 is set to a predetermined value, and the focal depth adjustment unit 74 does not adjust the focal depth of the first imaging unit 51. Note that the focal depth of the first imaging unit 51 is configured to be adjustable, and the focal depth adjustment unit 74 may adjust the focal depth of the first imaging unit 51.

[0073] Then, similarly to the above embodiment, measurement of particle size distribution of particles is started (S22).

[0074] When the measurement of particle size distribution of particles is started, the first imaging unit 51 and the second imaging unit 52 capture images of the cell 2 (S23), and particle information is analyzed based on the captured images (S24), as in the image analysis mode in the above embodiment. Here, the first imaging unit 51 captures images of the cell 2 at different times t1, t2, ..., tn.

[0075] Once the particle information has been analyzed, the cell state determination unit 72 determines whether the object shown in the multiple images remains within a predetermined range at time t1 and time t2, for example, as in the cell state determination mode in the above embodiment (S25). Note that the images used by the cell state determination unit 72 are not limited to the images captured at time t1 and time t2, but may be images captured at multiple times among images captured at different times t1 to tn.

[0076] As in the cell state determination mode in the above embodiment, if the cell state determination unit 72 determines that the object is not dirt and / or a scratch on the cell 2, it returns to S23 if it wants to continue measuring the particle size distribution, or it ends the irradiation of laser light by the measurement light irradiation unit 3 if it wants to end the measurement of the particle size distribution.

[0077] As in the cell state determination mode in the above embodiment, when the cell state determination unit 72 determines that the object is a stain and / or a scratch on the cell 2 (S26), if the proportion of objects in the image that are determined to be a stain and / or a scratch on the cell 2 is equal to or greater than a predetermined value, the cell state determination unit 72 determines that cleaning of the cell 2 is necessary and outputs a signal urging the user to clean the cell 2. In addition to the signal urging the user to clean the cell 2, the cell state determination unit 72 may also output a signal urging the user to stop measuring the particle size distribution of particles.

[0078] In the above embodiment, the particle size distribution measuring device 100 is a wet type that measures the particle size distribution of particles in a sample composed of particles and a liquid dispersion medium, but it may also be a dry type that measures the particle size distribution of particles in a sample composed of particles and a gaseous dispersion medium.

[0079] In the above embodiment, the cell 2 is a flow cell in which a sample flows through an internal flow path, but it may also be a batch-type cell having an internal space in which a sample is accommodated. When a sample is accommodated in the cell 2, particles move within the cell 2. Specifically, when a sample is accommodated in the cell 2, particles move within the cell 2 due to natural settling, stirring by, for example, a magnetic stirrer, and / or Brownian motion of the particles. Note that, because the movement of particles due to natural settling is slower than that in the case of a flow cell, the interval at which the first image capturing unit 51 captures images of the cell 2 may be adjusted.

[0080] In the above embodiment, the first imaging unit 51 is a low-magnification camera and the second imaging unit 52 is a high-magnification camera, but this is not limiting. For example, the first imaging unit 51 may be a high-magnification camera and the second imaging unit 52 a low-magnification camera, or both the first imaging unit 51 and the second imaging unit 52 may be low-magnification cameras, or both the first imaging unit 51 and the second imaging unit 52 may be high-magnification cameras.

[0081] In the above embodiment, the imaging unit used can be switched depending on the cell state determination mode and the image analysis mode, but a common imaging unit may capture images of the cells 2 for both the cell state determination mode and the image analysis mode without switching the imaging unit 5. In this case, by adjusting the focal depth of the common imaging unit depending on the cell state determination mode and the image analysis mode, it is possible to analyze particle information and determine dirt and / or scratches on the cells 2 without switching the imaging unit 5.

[0082] In the above embodiment, the imaging light irradiation unit 6 is provided on the opposite side of the cell 2 to the imaging unit 5 , but it may be provided on the same side of the cell 2 as the imaging unit 5 .

[0083] In the above embodiment, the particle size distribution measuring device 100 is configured to be switchable between two modes, the cell state determination mode and the image analysis mode, but in order to determine contamination and / or damage to the cell 2, it is sufficient to have at least the cell state determination mode, and it does not have to have the image analysis mode. Furthermore, if the particle size distribution measuring device 100 does not have the image analysis mode, the particle size distribution measuring device 100 does not have to have the second imaging unit 52 and / or the focal depth adjustment unit 74.

[0084] In the above embodiment, the first image capturing unit 51 captures images of both the irradiation surface and the emission surface of the cell 2, but it may capture images of either one of the surfaces. Furthermore, the first image capturing unit 51 may capture images of a portion of the cell 2 from which diffracted light and / or scattered light generated by the sample is not emitted.

[0085] In the above embodiment, the focal depth of the first imaging unit 51 is adjusted according to the cell state determination mode and the image analysis mode, but it may also be turned on or off according to the cell state determination mode and the image analysis mode. Even in this case, the first imaging unit 51 can prevent interference with imaging by the second imaging unit 52 in the image analysis mode. Note that turning on or off the first imaging unit 51 here refers to, for example, turning on or off a trigger for starting the camera, turning on or off the power supply for the camera, and / or turning on or off the startup of the camera circuitry.

[0086] In the above embodiment, the cell state determination unit 72 uses two images, one captured at time t1 and one captured at time t2, but the number of images is not limited to this. For example, the cell state determination unit 72 may use three or more images captured consecutively between times t1 and tn, or may extract and use two or more images from the multiple images captured between times t1 and tn.

[0087] In the above embodiment, the particle size distribution measuring device 100 uses the first imaging unit 51 in the cell state determination mode. However, if it is determined that the cell 2 is free from dirt and / or scratches, the first imaging unit 51 may be used to perform particle analysis.

[0088] In the previous embodiment, the particle size distribution measuring device 100 includes the focal depth adjustment unit 74 that adjusts the focal depth, but the particle size distribution measuring device 100 may include a focal position adjustment unit that adjusts the focal position of the imaging unit 5. Specifically, the focal position adjustment unit adjusts the focal position by adjusting the position and / or angle of the imaging unit 5. More specifically, the focal position adjustment unit adjusts the focal position by adjusting the position and / or angle of at least one of the first imaging unit 51 and the second imaging unit 52.

[0089] In addition, the present invention can be modified in various ways without departing from the spirit of the invention.

[0090] According to the present invention, in a laser diffraction / scattering particle size distribution device, contamination and / or damage to a cell can be determined without interrupting particle size distribution measurement.

[0091] REFERENCE SIGNS LIST 100 Particle size distribution measuring device 2 Cell 3 Measurement light irradiating section 4 Detector 5 Imaging section 51 First imaging section 52 Second imaging section 6 Imaging light irradiating section 7 Control device 71 Particle size distribution calculating section 72 Cell state determining section 73 Mode receiving section 74 Focal depth adjusting section

Claims

1. A laser diffraction / scattering particle size distribution measuring device that measures the particle size distribution of particles contained in a sample based on diffracted light and / or scattered light generated by irradiating the sample with a laser beam, comprising: a cell through which the sample is circulated and / or contained; an imaging unit that images the cell while the sample is circulating and / or contained in the cell; and a cell condition determining unit that obtains multiple images taken by the imaging unit at different times and compares the images to determine whether the cell is dirty or damaged.

2. The particle size distribution measuring device of claim 1, wherein the cell state determination unit determines that an object shown in a plurality of the images remains within a predetermined range at different times as a stain and / or scratch on the cell.

3. A particle size distribution measuring device according to claim 1 or 2, further comprising an imaging light irradiating unit that irradiates light onto the cell when the imaging unit images the cell.

4. The particle size distribution measuring device according to any one of claims 1 to 3, having a cell state determination mode for determining whether the cell is dirty and / or damaged from the image while the sample is circulating and / or contained in the cell, and an image analysis mode for analyzing particle information, which is information indicating the state of the particles, from the image.

5. The particle size distribution measuring device according to claim 4, wherein the particle size distribution measuring device measures particle size distribution while the cell state determination mode and the image analysis mode are simultaneously proceeding.

6. A particle size distribution measuring device according to claim 4 or 5, wherein the imaging unit has a first imaging unit that images the cell in the cell state determination mode, and a second imaging unit that images the cell in the image analysis mode.

7. A particle size distribution measuring device according to claim 6, wherein the first imaging unit images the cell at a magnification lower than that of the second imaging unit, and the second imaging unit images the cell at a magnification higher than that of the first imaging unit.

8. A particle size distribution measuring device according to any one of claims 4 to 7, further comprising a focal depth adjustment unit that adjusts the focal depth of the imaging unit in accordance with the cell state judgment mode and the image analysis mode, wherein the focal depth adjustment unit makes the focal depth shallower in the image analysis mode than in the cell state judgment mode, and makes the focal depth deeper in the cell state judgment mode than in the image analysis mode.

9. A particle size distribution measuring device according to any one of claims 1 to 8, further comprising: a measurement light irradiating unit that irradiates the sample with laser light when measuring the particle size distribution of the particles; and a detector that detects the diffracted light and / or scattered light generated from the sample as a result of the light irradiation by the measurement light irradiating unit, wherein the imaging unit images at least a portion of the cell from which the diffracted light and / or scattered light directed toward the detector is emitted.

10. The particle size distribution measuring device according to claim 9, wherein the imaging unit images a portion of the cell that is irradiated with laser light from the measurement light irradiation unit.

11. A laser diffraction / scattering particle size distribution measurement method for measuring the particle size distribution of particles contained in a sample based on diffracted light and / or scattered light generated by irradiating the sample with laser light, the method comprising: capturing an image of a cell in which the sample is distributed and / or contained; acquiring multiple images captured at different times by the imaging unit; and comparing the images to determine whether the cell is dirty or damaged.

12. A particle size distribution measurement program used in a laser diffraction / scattering particle size distribution measurement device that measures the particle size distribution of particles contained in a sample based on diffracted light and / or scattered light generated by irradiating the sample with laser light, wherein the particle size distribution measurement device comprises a cell through which the sample is circulated and / or contained, and an imaging unit that images the cell while the sample is circulating and / or contained in the cell, and the particle size distribution measurement program causes a computer to function as a cell condition determination unit that acquires multiple images taken by the imaging unit at different times and compares the images to determine whether the cell is dirty or damaged.

Images