JP5796509B2 - Flow cytometer - Google Patents

Description

  The present invention relates to a flow cytometer.

  A flow cytometer is a device that causes particles to flow through a flow path in which a laminar flow is formed and analyzes individual particles in turn. It is often used in the field of molecular biology and medicine, mainly for cell analysis. Moreover, it is used also for fractionating the target particle | grains from the analyzed particle | grains.

  In Non-Patent Document 1, by irradiating individual particles with laser light, detecting a plurality of types of light such as scattered light and fluorescence, and statistically analyzing these light detection data, A device for classifying is shown. Non-Patent Document 2 discloses an apparatus for photographing individual particles and classifying the particles according to the difference in the form of each particle analyzed from the photographed image.

  For example, in the medical field, there is a demand for detecting whether or not cancer stem cells are contained in the collected blood for early detection of cancer. However, even if cancer stem cells are contained in the blood, they are very small, and are detected only at a ratio of several in 1 billion.

  When the apparatus of Non-Patent Document 1 is used, tens of thousands to hundreds of thousands of cells are measured per second, and are classified according to their optical characteristics. However, it is difficult to specify only cancer stem cells, and the classified cells include a large number of cells having similar optical properties other than cancer stem cells. In order to isolate cancer stem cells from these, for example, a method of adhering a magnetic material to a protein that easily binds to cancer stem cells and mixing with a cell group, and collecting the cancer stem cells bound to the protein with a magnet Is used, but it is expensive and requires extra effort and time.

  On the other hand, in the apparatus of Non-Patent Document 2, only cancer stem cells can be identified from the form obtained by analyzing the captured image, but there is a problem that measurement at high speed is difficult due to the limitation of the imaging speed. For example, Non-Patent Document 2 describes that a CCD camera can take a picture of cells at a rate of 1000 per second. At this rate, it takes about 12 days to inspect 1 billion cells. Is required.

International Publication WO2009 / 031301

"Introduction to Principles of FCM IV. Principles of Flow Cytometry", [online], Beckman Coulter, [Searched on December 9, 2011], Internet <URL: http: //www.bc-cytometry. com / FCM / fcmprinciple_4.html> “BM Equipment Co., Ltd. Flow Cytometry ImageStream”, [online], BM Equipment Co., Ltd. [searched on December 9, 2011], Internet <URL: http://www.bmbio.com/product_catalog /imagestream.html>

  In response to these problems, the present applicant has proposed a new flow cytometer in Japanese Patent Application No. 2011-147108 (hereinafter referred to as “prior patent application”). In this flow cytometer, an optical detection system including a laser light source and a photodetector is provided on the upstream side of a flow path (flow cell) through which a test particle flows, and an imaging system including a high-speed camera is provided on the downstream side. It has been. In the optical detection system, transmitted light, reflected light, scattered light, or fluorescence generated by irradiating the test particle flowing in the flow path with laser light is measured, and the optical result of the test target particle to be measured is obtained from the result. It is determined whether the characteristic is similar to the optical characteristic of the target particle. If the optical characteristics of the test particles are similar to the target particles, the test particles are determined as candidate particles, and the imaging system is instructed to shoot the candidate particles. The imaging system that has received the imaging instruction continuously captures a plurality of images over a certain period of time. Then, it is determined whether the candidate particle is a target particle based on the photographed image. On the other hand, when the optical properties of the test particles are not similar to the target particles, the test particles are determined not to be candidate particles and pass through without being imaged by the imaging system.

  For example, when the target particles are to be detected within a few minutes from among 1 billion test particles, it is necessary to perform measurement at a speed of several millions per second. For this reason, a high-speed camera for imaging the test particles also requires a very high imaging speed of several million frames per second. However, in a high-speed camera using a conventional general image sensor (solid-state imaging device), it is necessary to read out the signal charge generated in each pixel to the outside of the imaging device every time one image is taken. The shooting speed is limited by the speed of the readout circuit. For this reason, it has been difficult for the conventional high-speed camera to perform super-high-speed shooting as described above.

  Therefore, in the above-mentioned prior patent application, as a high-speed camera for photographing a test particle, a burst-type CCD (Charge Coupled Device) image sensor or a CMOS (Complementary Metal) as described in Patent Document 1 is used. Oxide Semiconductor) using an image sensor is proposed.

  The burst-type image sensor (solid-state image sensor) includes an image recording memory (storage unit) inside the image sensor, and signals obtained from each pixel are stored in the memory arranged around the pixel area. Stored sequentially. For this reason, the photographing speed is not limited by the speed of the readout circuit, and the above-described super-high-speed photographing can be realized.

  The signals stored in the memory need to be read out to the outside of the image sensor after taking a predetermined number of images. For this reason, the burst-type image sensor as described above is not suitable for continuous shooting for a long time, but for the purpose of intermittent shooting such as the flow cytometer described in the prior patent application, It can be used very favorably because of its high imaging speed.

  As described above, the flow cytometer described in the aforementioned prior patent application has a two-stage configuration in which candidate particles are first narrowed down from test particles by an optical detection system, and then the candidate particles are photographed by an imaging system. In addition, by using a high-speed camera equipped with a burst-type image sensor for photographing candidate particles, it is possible to measure a minute amount of particles such as the above cancer stem cells in a shorter time than before. it can.

  However, in the flow cytometer described in the prior patent application, candidate particles may not be accurately detected in the optical detection system, and as a result, the target particle passes through the flow path, but the imaging system does not. There was a possibility of overlooking without taking a picture of.

  The present invention has been made in view of the above points, and the object of the present invention is that measurement can be performed in a short time, and even if the target particle is a very small amount of particles such as cancer stem cells. An object of the present invention is to provide a flow cytometer that can be detected.

The flow cytometer according to the present invention made to solve the above problems is as follows.
a) a flow path for flowing test particles;
b) a solid-state imaging device having a plurality of pixels, and imaging means for continuously imaging an imaging target area in the flow path;
c) a flow rate adjusting means for adjusting the flow rate of the test particles flowing in the flow path;
d) a determination unit that determines whether or not a test particle similar to a target particle has entered the imaging target region based on an image captured by the imaging unit ;
Have
A first photographing mode in which the photographing means continuously captures images of a plurality of frames and holds a signal charge obtained by each pixel in a storage unit provided on the solid-state image sensor; and the first photographing In the mode, the signal charge held in the storage unit is output to the outside of the solid-state imaging device, and continuous shooting is performed at a lower speed than in the first shooting mode, and the signal charge obtained in each pixel by the continuous shooting is 1 A shooting mode in which frames are output to the outside of the solid-state imaging device, and the second shooting mode in which the number of pixels per frame is smaller than the number of pixels per frame in the first shooting mode is alternately executed. Is what
The flow rate adjusting means, wherein the flow rate becomes relatively large at the time of execution of the first imaging mode, the at runtime of the second imaging mode have rows adjusted so that the flow rate is relatively small,
During the execution of the second imaging mode, when it is determined by the determination means that a test particle similar to the target particle has entered the imaging target region, the imaging means then performs a certain period of time per frame. The number of pixels is increased .

  As the solid-state imaging device as described above, for example, a burst type CCD image sensor or a CMOS image sensor as described in Patent Document 1 can be suitably used. Such a burst-type image sensor includes a plurality of pixels each including a photoelectric conversion element and a plurality of storage units corresponding to the pixels, and a signal output from each pixel is input to the storage unit in a predetermined manner. It is possible to increase the shooting speed by storing only the number of frames and reading them together. Further, in the apparatus described in the above-mentioned prior patent application, imaging of the test particle is intermittently performed, whereas in the flow cytometer according to the present invention, two types of imaging modes having different signal output methods are used. In other words, the test particles are continuously imaged while alternately repeating the first imaging mode and the second imaging mode. Here, the first shooting mode is a mode in which continuous shooting is performed while recording the signal charge obtained in each pixel of the solid-state image sensor in a storage unit provided on the image sensor, In this mode, continuous shooting is performed while the charges are sequentially output to the outside of the solid-state imaging device without being stored in the storage unit.

  In the flow cytometer according to the present invention, since these two imaging modes are executed alternately, imaging is continued in the second imaging mode even while the signal charge obtained in the first imaging mode is read from the storage unit. The Rukoto. Therefore, it becomes possible to photograph the test particles flowing in the flow path without interruption. In the second imaging mode, since the signal charges are sequentially read out, the imaging speed (number of images taken per unit time) is lower than when the first imaging mode is executed. However, in the flow cytometer according to the present invention, imaging is performed. Since the flow velocity of the test particles is adjusted according to the change in the imaging speed due to the mode switching, an almost constant number of images can be obtained for each test particle.

In addition, since the time required for sequential readout of signal charges in the second imaging mode can be shortened, the imaging speed in the second imaging mode can be increased and the time required for sample measurement can be further reduced.

Further, among the test particles that pass through the imaging target region, an image with a large amount of information can be obtained for those that are similar to the target particle, so that more accurate analysis is possible.

  As described above, according to the flow cytometer according to the present invention, a large number of test particles can be imaged in a short time and can be reliably detected without missing the target particle.

1 is a schematic configuration diagram of a flow cytometer according to an embodiment of the present invention. The wave form diagram which shows the time change of the imaging speed of the high-speed camera in the said flow cytometer, and the flow velocity of test particle. The wave form diagram which shows another example of the said time change. The wave form diagram which shows the time change of the imaging speed of the high-speed camera in the said flow cytometer, the flow velocity of test particle | grains, and the number of pixels per frame. It is the figure which showed typically the pixel pattern in a high-speed camera, (a) shows the case where all the pixels are used, (b) shows the case where only the column near the center is used. It is the figure which showed another example of the pixel pattern in a high speed camera, (a) is a case where an imaging range is widened on the downstream side, (b) is a case where an imaging range is widened on the upstream side, (c) Shows a case where the photographing range is widened in the center, and (d) shows a case where the photographing range is widened on the upstream side and the downstream side. The wave form diagram which shows another example of the said time change. The wave form diagram which shows another example of the said time change.

  An embodiment of a flow cytometer according to the present invention will be described with reference to the accompanying drawings. FIG. 1 is a schematic configuration diagram of a flow cytometer according to the present embodiment.

  In this flow cytometer, the sheath fluid is introduced from a sheath fluid introduction part 21 provided in the introduction system 20, and the flow of the sheath fluid is such that a laminar flow maintained at a predetermined flow velocity is formed in the flow cell 10. It is controlled. Further, the sample liquid is introduced into the flow cell 10 from the sample introduction part 22 provided in the introduction system 20, and each test particle in the sample liquid flows in sequence in the flow cell 10 in which the laminar flow is formed. Go.

  An imaging system 30 including a strobe lamp 31 and a high-speed camera 33 is disposed in the middle of the flow cell 10, and each test particle is illuminated by the strobe lamp 31 when passing through the imaging region 32 in the flow cell 10. Photographed by the high-speed camera 33.

  In the flow cytometer of the present embodiment, a high-speed camera 33 including a burst type CCD image sensor or a CMOS image sensor (hereinafter referred to as “burst type image sensor”) described in Patent Document 1 is used.

  The image data captured by the high-speed camera 33 is sent to the image analysis unit 53 of the data processing unit 50. In the image analysis unit 53, after image processing such as binarization is performed on each image data, the similarity with the image data of the target particle photographed in advance is calculated. If the image data whose similarity is equal to or greater than a predetermined threshold is included, it is determined that the captured test particle is the target particle.

  The data processing unit 50 is constituted by, for example, a personal computer in which a predetermined data processing program is installed. In addition to the image analysis unit 53 described above, the flow rate control unit 52 (which controls the operation of the introduction system 20). This corresponds to a flow rate adjusting means in the present invention, a photographing control unit 51 that controls the operation of the imaging system 30, and a sorting control unit 54 that controls the operation of the cell sorter 40 described later as functional blocks.

  A cell sorter 40 for sorting target particles is disposed at the outlet end of the flow cell 10, and the test particles that have reached the sorting area 41 of the cell sorter 40 are classified according to their type (whether they are target particles or other particles). Accordingly, the container 42 or the container 43 is distributed.

  When the image analysis unit 53 determines that the captured test particle is a target particle, the sorting control unit 54 is configured to perform a predetermined delay time after the imaging system 30 performs the imaging. A sorting trigger signal is output to the cell sorter 40, and the test particles (target particles) coming to the sorting area 41 of the cell sorter 40 are sorted into the container. This delay time is determined by the flow path length between the imaging region 32 and the sorting region 41 of the flow cell 10 and the flow velocity set by the flow velocity controller 52.

  For example, as described in Non-Patent Document 1, the cell sorter 40 charges a droplet including target particles dropped from the outlet end of the flow cell 10 and applies a specific electric field to the droplet while the droplet falls. A method of controlling the falling direction to the container 42 can be used.

  If the image analysis unit 53 determines that the captured test particle is not the target particle, the droplet containing the test particle falls into the container 43 as it is without being applied with an electric field in the cell sorter 40.

  Hereinafter, operation control of the imaging system 30 and the introduction system 20, which is a feature of the flow cytometer according to the present embodiment, will be described. In the flow cytometer according to the present embodiment, a test particle flowing through the flow cell 10 is detected by a high-speed camera 33 (corresponding to the imaging means in the present invention) provided with a burst type image sensor (corresponding to the solid-state imaging device in the present invention). Shoot everything. In the burst type image sensor, a storage unit 36 is provided in the sensor chip 34, and a plurality of frames of signal charges obtained from each pixel in the pixel region 35 are temporarily held in the storage unit 36, thereby speeding up photographing. It is designed for ultra-high-speed shooting of up to 10 million frames per second.

  In such a burst type image sensor, it is necessary to collectively read out the signal charges accumulated in the storage unit 36 in the sensor chip 34 after taking images for a predetermined number of frames (for example, 128 frames). Such ultra-high-speed shooting cannot be performed continuously over a long period of time. However, while signals are being collectively read from the storage unit 36 on the sensor chip 34, new signal recording is not performed in the storage unit 36, and the image signals obtained in the pixel area 35 are sequentially transmitted to the sensor chip 34. It is possible to shoot while reading out.

  Therefore, in the flow cytometer of the present embodiment, the imaging mode (referred to as “first imaging mode”) that involves signal recording in the storage unit 36 on the sensor chip 34 and the signal recording in the storage unit 36 are not involved. The high-speed camera 33 is controlled so as to alternately execute the shooting mode (referred to as “second shooting mode”). First, the high-speed camera 33 stores an image signal (signal charge) obtained while continuously shooting the shooting region 32 of the flow cell 10 in the storage unit 36 on the sensor chip 34 in the first shooting mode. Then, after shooting a predetermined number of images, the mode shifts to the second shooting mode, and the output signal from each pixel in the pixel area 35 is output for one frame as in the case of using a normal (non-burst type) image sensor. Continuous shooting is continued while reading out from the sensor chip 34 one by one. At this time, in parallel with the continuous shooting, the signal charge (acquired in the immediately preceding first shooting mode) held in the storage unit 36 is read out to the outside of the sensor chip 34. Note that in the second imaging mode, signal charges are sequentially read out, so the imaging speed is lower than in the first imaging mode. For this reason, the photographing speed of the high-speed camera 33 is alternately changed as time passes, as shown in the upper graph of FIG. Therefore, at this time, the flashing speed of the strobe lamp 31 is controlled so as to change accordingly.

  Furthermore, in the flow cytometer of the present embodiment, the operation of the introduction system 20 is performed so that the flow velocity of the test particles flowing in the flow cell 10 changes in synchronization with the change in the imaging speed as described above (upper stage in FIG. 2). It is controlled (lower part of the figure). Specifically, for example, the flow rate control unit 52 controls the operation of a pump (not shown) provided in the sheath liquid introduction unit 21 to adjust the pressure of the sheath liquid, thereby allowing the sample liquid ( And the flow rate of the test particles in the sample liquid is changed. It is also possible to adjust the flow rate of the test particles by controlling the operation of a pump (not shown) provided in the sample introduction unit 22.

  At this time, the rate of change in the flow rate of the test particles is made to be the same as the rate of change in the imaging speed by the high-speed camera 33. For example, when the shooting speed in the first shooting mode is 1 million frames / second and the shooting speed in the second shooting mode is 40,000 frames / second, shooting is performed by switching from the first shooting mode to the second shooting mode. Since the speed is 1/25, the flow rate of the test particle is controlled to be 1/25. As a result, the number of images captured by the high-speed camera 33 while one test particle passes through the imaging region 32 can be kept substantially constant regardless of the change in the imaging mode. Note that the flow velocity of the test particles in each imaging mode is desirably set so that a plurality of (for example, 10) images are obtained for each test particle. As a result, an optimal image can be used for analysis in the image analysis unit 53 when the test particles are rotating while passing through the imaging region 32.

From the viewpoint of preventing the sample liquid from being disturbed and backflowing, it is desirable to change the flow velocity of the test particles gently as shown in the lower part of FIG. Further, at this time, the imaging speed at the boundary between the first imaging mode and the second imaging mode also changes gradually in accordance with the change in the flow rate as described above, from the viewpoint of making the number of imaging per particle to be measured constant. It is desirable to make it. Specifically, as shown in FIG. 3, _first , continuous shooting is performed at the shooting speed I ₁ in the first shooting mode, and then a predetermined number of images (for example, 14 shots) before the end of the first shooting mode is shot. In the meantime, the photographing speed is gradually decreased from I ₁ to I ₂ . At this time, the flow velocity of the test particles is gradually lowered from F ₁ to F ₂ in accordance with the change in the imaging speed. Thereafter, while the shooting speed F ₂ is switched to the second imaging mode after the imaging of a predetermined number of sheets (or a predetermined time), switch to the first imaging mode, performs photographing of a predetermined number of sheets (e.g. 14 sheets) The shooting speed is gradually increased from I ₂ to I ₁ . At this time, the flow rate of the test particles is gradually increased from F ₂ to F ₁ in accordance with the change in the imaging speed.

In addition to the change in the flow velocity of the test particles as described above, the number of pixels per frame in the high-speed camera 33 may be changed with time. FIG. 4 shows an example of temporal changes in the imaging speed, the flow velocity of the test particles, and the number of pixels in this case. At this time, in the first shooting mode, all the pixels provided in the pixel area 35 on the sensor chip 34 are used for shooting, and only some of the pixels are used in the second shooting mode. The number of pixels (P ₂ ) in the second shooting mode is set to be smaller than the number of pixels (P ₁ ) (see the lower part of FIG. 4). As a result, the time required for sequential readout of signal charges can be shortened compared to the case where all pixels are used, so that the imaging speed in the second imaging mode can be increased (see the upper part of FIG. 4). As a result, the flow rate of the test particles in the second imaging mode can be increased (see the middle part of FIG. 4), and therefore the time required for sample measurement can be further shortened.

  The arrangement of the pixels in the pixel region 35 on the sensor chip 34 is shown in FIGS. In these drawings, the left-right direction corresponds to the width direction of the flow path (flow cell 10), and the up-down direction corresponds to the length direction. In addition, one square in the figure represents one pixel, a shaded area represents a pixel that is not used for photographing (that is, signal charge is not read), and the other areas are photographed. The pixel used for is shown.

  When the number of pixels per frame is reduced as described above, the pixels used for photographing may be thinned out uniformly from the entire pixel area 35, but as shown in FIG. It is desirable not to use a plurality of rows on both the left and right sides for shooting. In this case, the left and right edges of the flow path cannot be photographed, but normally, the test particles flow near the center of the flow path, so almost all the test particles can be captured if only the vicinity of the center can be photographed. It is.

  Further, as shown in FIGS. 6A to 6D, the number of pixels used for photographing may be changed depending on the position of the pixel region 35 in the length direction. In the example of FIG. 6A, in a plurality of rows near the lower end of the pixel region 35, a relatively large number of pixels near the center in the width direction (all pixels in the width direction in the drawing) are used for shooting, and the others In this row, a relatively small number of pixels near the center in the width direction are used for photographing. As a result, a wide range in the width direction of the flow path is photographed at the downstream end of the photographing region 32 of the flow cell 10, and a narrow range in the width direction is photographed in other regions. By adopting such a configuration, it is possible to obtain an image capable of measuring the length and width of the test particle while suppressing the number of pixels used for photographing as much as possible. Note that, as shown in FIGS. 6B and 6C, the width of the region used for photographing may be widened near the upper end or near the center of the pixel region 35. Further, as shown in FIG. 6D, the width of the region used for photographing may be widened both near the upper end and near the lower end of the pixel region 35. Thereby, even when the test particles are rotated while passing through the imaging region 32 of the flow cell 10, the length and width of the test particles can be accurately captured.

  In addition, as described above, the image obtained by the photographing is analyzed by the image analysis unit 53 while photographing with a reduced number of pixels in the second photographing mode, and as a result, the photographing target region is similar to the target particle. When it is determined that the detected particle (candidate particle) has entered, the number of pixels per frame may be immediately increased (in this case, the image analysis unit 53 corresponds to the determination means in the present invention). ). At this time, the number of pixels may be increased and simultaneously the first shooting mode may be switched, or the shooting may be continued in the second shooting mode.

First, a case where shooting is continued in the second shooting mode will be described. FIG. 7 shows an example of temporal changes in the imaging speed, the flow rate of the test particles, and the number of pixels in this case. In this example, shooting is performed at the shooting speed I ₁ , the flow velocity F ₁ , and the number of pixels P ₁ in the first shooting mode, and when no candidate particle is detected in the second shooting mode, the shooting speed I ₂ and the flow velocity F ₂ are detected. , And the number of pixels P ₂ (where I ₁ > I ₂ , F ₁ > F ₂ , P ₁ > P ₂ ). If candidate particles are detected during execution of the second imaging mode (time t ₀ in the figure), the number of pixels is increased to P ₁ while the imaging mode remains in the second imaging mode. As a result, the time required to sequentially read out the signal charges becomes longer, and the shooting speed of the high-speed camera 33 is reduced (I ₃ in the figure). Accordingly, the flow rate of the test particles is lowered accordingly (F ₃ in the figure), so that the number of shots per test particle is kept constant. After that, when a predetermined number of images (for example, 10 images) are taken (time t ₁ in the figure), the number of pixels is lowered again to P ₂ , and accordingly, the photographing speed is set to I ₂ and the flow speed is set to F ₂ . Then, the shooting in the second shooting mode is continued. Other points are the same as the example shown in FIG.

Next, a case where the shooting mode is switched when candidate particles are detected will be described. FIG. 8 shows an example of temporal changes in the imaging speed, the flow velocity of the test particles, and the number of pixels in this case. In this example, shooting is performed at the shooting speed I ₁ , the flow velocity F ₁ , and the number of pixels P ₁ in the first shooting mode, and shooting is performed at the shooting speed I ₂ , the flow velocity F ₂ , and the number of pixels P ₂ in the second shooting mode. performed (where _{I 1> I 2, F 1} > F 2, P 1> P 2). When candidate particles are detected during execution of the second shooting mode (time t ₀ in the figure), the shooting mode is switched to the first shooting mode, and the number of images that can be shot in the first shooting mode is shot. Switching to the second photographing mode is performed again at (time t ₂ in the figure). Other points are the same as the example shown in FIG. As described above, when switching to the first imaging mode is performed during the execution of the second imaging mode, new data is stored in the storage unit 36 before the reading of the data held in the storage unit 36 on the sensor chip 34 is completed. Therefore, a part of the image signal obtained in the immediately preceding first photographing mode is overwritten and lost. However, if the target particles are trace amounts of particles such as cancer stem cells, it is unlikely that the target particles have been captured in the immediately preceding first imaging mode, and this is unlikely to be a problem.

  The embodiment for carrying out the present invention has been described with reference to the embodiments. However, the present invention is not limited to the above embodiments, and modifications can be appropriately made within the scope of the present invention. It is. For example, although the cell sorter 40 is provided at the outlet end of the flow cell 10 in the above example, the cell sorter 40 may not be provided. In this case, all the test particles that have reached the outlet end of the flow cell 10 are accommodated in the same container regardless of the analysis result in the image analysis unit 53.

DESCRIPTION OF SYMBOLS 10 ... Flow cell 20 ... Introduction system 21 ... Sheath liquid introduction part 22 ... Sample introduction part 30 ... Imaging system 31 ... Strobe lamp 32 ... Imaging area 33 ... High speed camera 34 ... Sensor chip 35 ... Pixel area 36 ... Memory | storage part 40 ... Cell sorter 41 ... Sorting area 42, 43 ... Container 50 ... Data processing unit 51 ... Shooting control unit 52 ... Flow rate control unit 53 ... Image analysis unit 54 ... Sorting control unit

Claims (1)

a) a flow path for flowing test particles;
b) a solid-state imaging device having a plurality of pixels, and imaging means for continuously imaging an imaging target area in the flow path;
c) a flow rate adjusting means for adjusting the flow rate of the test particles flowing in the flow path;
d) a determination unit that determines whether or not a test particle similar to a target particle has entered the imaging target region based on an image captured by the imaging unit ;
Have
A first photographing mode in which the photographing means continuously captures images of a plurality of frames and holds a signal charge obtained by each pixel in a storage unit provided on the solid-state image sensor; and the first photographing In the mode, the signal charge held in the storage unit is output to the outside of the solid-state imaging device, and continuous shooting is performed at a lower speed than in the first shooting mode, and the signal charge obtained in each pixel by the continuous shooting is 1 A shooting mode in which frames are output to the outside of the solid-state imaging device, and the second shooting mode in which the number of pixels per frame is smaller than the number of pixels per frame in the first shooting mode is alternately executed. Is what
The flow rate adjusting means, wherein the flow rate becomes relatively large at the time of execution of the first imaging mode, the at runtime of the second imaging mode have rows adjusted so that the flow rate is relatively small,
During the execution of the second imaging mode, when it is determined by the determination means that a test particle similar to the target particle has entered the imaging target region, the imaging means then performs a certain period of time per frame. A flow cytometer characterized by increasing the number of pixels .

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