WO2018029882A1 - Buffer suction device and cancer analysis system - Google Patents

Abstract

To simply remove a buffer including nematodes in cancer inspection using the nematodes, the present invention is characterized by being provided with: a plate placement part (501) for placing a plate on which the nematodes are plotted together with the buffer; an inclination part (502) for inclining the plate placement part (501); and a suction part (505) for sucking the buffer that accumulates in the lower part of the plate (P) placed on the plate placement part (501) inclined by the inclination part (502). Further, the invention has an analysis device (1) for using a brightness center of gravity or DR value to carry out taxis analysis of a plate (P) for which buffer suction has been completed and a urine sample and sodium azide have been plotted.

Description

Buffer suction device and cancer analysis system

The present invention relates to a buffer suction device and a cancer analysis system used for cancer testing using nematodes.

A cancer test has been proposed that uses nematodes to attract cancer patients' urine and to show repellent behavior to healthy people's urine.
Patent Document 1 describes a cancer detection method using the olfactory sense of nematodes.

International Publication No. 2015/088039

Currently, the following procedures are used in cancer tests using nematodes.
(1) The examiner plots the urine specimen on the plate and plots sodium azide as an anesthetic agent for nematodes.
(2) The examiner plots the nematode on the plate. Here, nematodes are stored with the buffer in the tube, and when plotted, the nematodes are plotted together with the buffer.
(3) The inspector sucks out the buffer with a commercially available paper waste. This is because if the nematode remains in the buffer, the movement of the nematode slows down and the inspection accuracy decreases.
(4) Nematodes are chemotaxis for a predetermined time. If the urine sample is from a cancer patient, the nematode performs an attracting action on the urine sample, and if the urine sample is not from a cancer patient, the nematode performs a repellent action on the urine sample.
(5) After a predetermined time, the number of nematodes that have performed attracting behavior and the number of nematodes that have performed repelling behavior are counted, and a chemotaxis index is calculated based on each counted number.
(6) Based on the calculated chemotaxis index, positive / negative of cancer is determined.

Here, when the buffer is sucked with a paper waste (step (3)), if the paper waste touches the nematode, the nematode is damaged or stress is applied to the nematode. As a result, the behavior of the nematode may slow down and the inspection accuracy may be lowered.
In particular, in order to introduce a large amount of inspections, if it is attempted to introduce automation by a machine, it is difficult to perform delicate operations such as the procedure of (3) with a machine.
However, such an operation of sucking out the buffer with a paper waste is generally performed in a cancer test using a nematode.

The present invention has been made in view of such a background, and an object of the present invention is to easily remove a buffer containing nematodes in a cancer test using nematodes.

In order to solve the above-mentioned problems, the present invention provides a mounting part for mounting a plate on which nematodes are plotted together with a buffer, an inclined part for inclining the mounting part, and an inclination part that is inclined by the inclined part. And a sucking portion for sucking out the buffer accumulated in the lower portion of the plate placed on the placing portion.
Other solutions are described in the embodiments.

According to the present invention, in a cancer test using a nematode, a buffer containing the nematode can be easily removed.

It is a figure which shows the external shape of the buffer suction apparatus which concerns on this embodiment. It is a figure which shows the buffer suction apparatus of the state in which the plate mounting part is not inclined. It is a figure which shows the buffer suction apparatus of the state in which the plate mounting part inclines. It is a figure which shows the motion of the buffer by inclination. It is a functional block diagram which shows the structure of the cancer analysis system which concerns on this embodiment. It is a functional block diagram which shows the structure of the analyzer used by this embodiment. It is an external appearance perspective view of the imaging device used by this embodiment. It is an external appearance side view of the imaging device used by this embodiment. It is a section schematic diagram of an imaging device used by this embodiment. It is a figure which shows an example of the detailed procedure for the cancer test | inspection in this embodiment. It is a flowchart which shows the procedure of the process which the cancer-analysis system concerning 2nd-1 embodiment performs. It is a schematic diagram of the image imaged with the camera. It is a figure which shows the pixel combination process used in 2nd-1 embodiment. It is a figure which shows the result of a pixel combination process. It is a figure (just after a plot) which shows the change of luminance distribution at the time of making a nematode chemotaxis with the plate which sucked up the buffer with the buffer sucking device concerning this embodiment. It is a figure (after the plot predetermined time) which shows the change of luminance distribution at the time of making a nematode chemotaxis with the plate which sucked up the buffer with the buffer sucking device concerning this embodiment. It is a figure which shows the time conversion of the brightness | luminance gravity center in the plate which sucked up the buffer with the buffer suction apparatus which concerns on this embodiment. It is a figure which shows the time change of the brightness | luminance gravity center in the plate which sucked up the buffer with the conventional method. It is a schematic diagram which shows selection of a nematode. It is a functional block diagram which shows the structure of the analyzer used by 2-2 embodiment. It is a flowchart which shows the procedure of the process which the analyzer used in 2nd-2 embodiment performs. It is a figure for demonstrating the method of the pixel exclusion process used in 2-2 embodiment. It is a schematic diagram of the pixel after combination before pixel exclusion processing is performed (unprocessed). It is a schematic diagram of the pixel after a combination after a pixel exclusion process was performed. It is a functional block diagram which shows the structure of the analyzer used by 2-3 embodiment. It is a flowchart which shows the procedure of the process which the analyzer used in 2-3 embodiment performs. It is a functional block diagram which shows the structure of the analyzer used by 2nd-4 embodiment. It is a flowchart (the 1) which shows the procedure of the process which the analyzer used in 2-4 embodiment performs. It is a flowchart (the 2) which shows the procedure of the process which the analyzer used in 2-4 embodiment performs. It is a typical explanatory view of the plate exclusion process used in the 2-4 embodiment. It is a functional block diagram which shows the structure of the analyzer used by 3rd Embodiment. It is a figure for demonstrating DR value used by 3rd Embodiment. It is a flowchart which shows the procedure of the process which the analyzer used in 3rd Embodiment performs. It is a figure (healthy person) which shows the time change of DR value. It is a figure (cancer patient) which shows the time change of DR value.

Next, modes for carrying out the present invention (referred to as “embodiments”) will be described in detail with reference to the drawings as appropriate. In addition, in each drawing, about the same component, the same code | symbol is attached | subjected and description is abbreviate | omitted.

<First Embodiment: System>
First, as a first embodiment of the present invention, a cancer test system including a buffer suction device will be described.
[Buffer suction device]
FIG. 1 is a view showing the outer shape of the buffer suction device according to the present embodiment.
The buffer suction device 5 includes a plate placement part (placement part) 501, an inclined part 502, a drive part 503, a pedestal part 504, and a suction part 505.
A plate P on which nematodes are plotted is placed on the plate placement unit 501. The inclined part 502 inclines the plate mounting part 501 by a predetermined angle. The pedestal portion 504 supports the plate placement portion 501, the inclined portion 502, and the like. The suction part 505 sucks the buffer accumulated in the lower part of the plate P inclined by the inclined part 502. The buffer absorption will be described later. The plate mounting portion 501 is provided with a recess or hole having the size of the plate P, and the plate P is installed and held in the recess or hole.

FIG. 2 is a diagram illustrating the buffer suction device in a state where the plate mounting portion is not inclined, and FIG. 3 is a diagram illustrating the buffer suction device in a state where the plate mounting portion is tilted.
2 and 3, the same components as those in FIG. 1 are denoted by the same reference numerals and description thereof is omitted. 2 and 3, the suction part 505 is not shown.
First, as shown in FIG. 2, the plate P is placed on the plate placement unit 501 while the plate placement unit 501 is horizontal. An agar medium is previously set on the plate P.

Thereafter, nematodes are plotted together with the buffer on the agar medium of plate P. Although the center of the plate P is generally plotted, the present invention is not limited to this.
And as shown in FIG. 3, the drive part 503 and the inclination part 502 incline the plate mounting part 501. As shown in FIG. As a result, as shown in FIG. 4, the buffer flows from the nematode plot point 601 toward the lower part of the plate P (in the direction of the arrow) and accumulates at the lower part of the plate P. At this time, most nematodes are stuck to the agar medium, do not flow with the buffer, and remain at the plot point 601. The inclination angle is preferably about 60 °. Reference numeral 602 indicates plotting points of the urine sample and sodium azide.
Then, as shown in FIG. 1, the suction part 505 sucks the buffer accumulated in the lower part of the inclined plate P.

By using such a buffer sucking device 5, the buffer can be sucked without fear of touching or damaging the nematode.
Then, by tilting the plate mounting portion 501 and sucking out the buffer accumulated in the lower part of the plate P, it becomes possible to mechanize the buffer sucking.
If an attempt is made to cause the machine to absorb the buffer with the paper waste that has been used so far, a complicated process is required, for example, it is necessary to recognize the image where the nematode is plotted. According to the buffer suction device 5 according to the present embodiment, since the plate P is merely tilted, complicated processing such as image recognition is not required, and the buffer can be sucked with a very simple configuration.

When the sucking of the buffer by the sucking unit 505 is completed, the inclined unit 502 returns the plate placing unit 501 to the horizontal. The urine specimen and sodium azide are then plotted on the plate P medium. Then, the plate P is moved to the imaging device 2 (FIG. 5) and set.

[System configuration]
FIG. 5 is a functional block diagram showing the configuration of the cancer analysis system according to this embodiment. In FIG. 5, broken line arrows indicate movements of plates, nematodes, urine samples, sodium azide, and the like, and solid line arrows indicate the flow of information.
The cancer analysis system Z includes an analysis device (analysis unit) 1, an imaging device (imaging unit) 2, a dispensing device 3, a transport device 4, and a buffer suction device 5.
The imaging device 2 images a plate on which nematodes and urine specimens are plotted, and transmits the captured image to the analysis device 1.
The analysis device 1 acquires luminance information based on the image sent from the imaging device 2. And the analysis apparatus 1 calculates the chemotaxis index of a nematode from the acquired brightness | luminance information, and determines positive / negative of cancer based on the calculated chemotaxis index.
The dispensing device 3 plots nematodes, urine samples, and sodium azide on the plate.
The transport device 4 sets a plate in the buffer suction device 5 or sets a plate from the buffer suction device 5 to the imaging device 2.
As described with reference to FIGS. 1 to 4, the buffer sucking device 5 tilts the plate, causes the buffer to flow downward, and sucks the buffer accumulated below the plate.

[Analyzer]
FIG. 6 is a functional block diagram showing the configuration of the analysis device used in the present embodiment.
The analysis apparatus 1 is configured by a PC (Personal Computer) or the like. The analysis device 1 includes a memory 11, a CPU (Central Processing Unit) 12, a storage device 13, an input device 14, an output device 15, and a transmission / reception device 16.
The memory 11 is loaded with a program stored in the storage device 13. Then, the loaded program is executed by the CPU 12. As a result, the processing unit 100 and the image acquisition unit 101, the pixel combination unit 102, the luminance information acquisition unit 103, the luminance center-of-gravity calculation unit 104, the runnability index calculation unit 105, and the examination determination unit 106 that constitute the processing unit 100 are realized. ing.

The image acquisition unit 101 acquires an image from the imaging device 2.
The pixel combining unit 102 combines pixels of an image acquired from the imaging device 2. The pixel combination will be described later.
The luminance information acquisition unit 103 acquires luminance information in each combined pixel from the pixels combined by the pixel combining unit 102 (referred to as a combined pixel).
The luminance center of gravity calculation unit 104 calculates the luminance center of gravity based on the luminance information acquired by the luminance information acquisition unit 103. The luminance center of gravity will be described later.
The chemotaxis index calculation unit 105 calculates a nematode chemotaxis index based on the luminance centroid calculated by the luminance centroid calculation unit 104. The chemotaxis index will be described later.

The test determination unit 106 determines whether the cancer is positive or negative based on the chemotaxis index calculated by the chemotaxis index calculation unit 105.

The input device 14 is a keyboard, a mouse, or the like.
The output device 15 is a display, a printer, or the like.
The transmission / reception device 16 is a NIC (Network Interface Card) or the like.

[Imaging device]
7 is an external perspective view of an imaging device used in the present embodiment, FIG. 8 is an external side view of the imaging device used in the present embodiment, and FIG. 9 is an imaging device used in the present embodiment. FIG.
As shown in FIGS. 7 and 8, the imaging apparatus 2 includes a light source unit 202 on a base 201. The light source unit 202 is a ring LED (Light Emission Diode) light source 221 with a diffusion plate. The ring LED light source 221 with a diffuser plate is a ring-shaped LED light source, and a diffuser plate 241 is provided inside the ring as shown in FIG.

Therefore, in the imaging apparatus 2 of the present embodiment, as shown in FIGS. 7 and 8, a pedestal 203 for setting the plate P is provided on the light source unit 202. The pedestal 203 is provided with a hole for setting the plate P, and the plate P is set in the imaging device 2 by fitting the plate P into the hole.

As shown in FIGS. 7 and 8, the base 201 is provided with a rod-shaped first support portion 204, and the first support portion 204 is vertically moved along the first support portion 204 (Z direction). A second support portion 205 is provided that is movable.
A camera (imaging unit) 206 for imaging the plate P is provided at the tip of the second support unit 205.
Further, as shown in FIG. 8, a shielding plate 222 for shielding room illumination such as a fluorescent lamp is provided above the camera 206 (the shielding plate 222 is not shown in FIG. 7).
In FIG. 8, the shielding plate 222 is provided in the first support portion 204, but is not limited thereto. For example, the shielding plate 222 may be configured so that the room is not illuminated on the plate P, and may be provided in the room, for example.

When the light from the light source unit 202 is directly applied to the plate P, there is a problem that the S / N (Signal / Noise) ratio of the image is deteriorated. This is because when the light is directly applied to the plate P, it is too bright, or a specific part of the plate P such as an edge of the plate P is lit.
As shown in FIGS. 7 to 9, by providing a ring LED light source 221 with a diffusion plate as the light source unit 202, light emitted from the LED light source can be diffused, and appropriate light is irradiated onto the plate P. . Thereby, the S / N ratio of the imaged image can be improved, and it is possible to prevent difficulty in image analysis described later.
Further, by providing the shielding plate 222 above the camera 206, it is possible to block room illumination such as a fluorescent lamp, and it is possible to prevent the medium surface of the plate P from being lit by room illumination.

Next, with reference to FIG. 9, a condition for preventing an image captured by the camera 206 from being affected by the light source unit 202, that is, a condition for reducing illuminance unevenness on the image plane will be described.
When there is an illumination distance Z2 in which the illuminance distribution of the light irradiated to the plate P is good due to the characteristics of the light source unit 202 (ring LED light source 221 with a diffuser), the following first condition and second condition are satisfied. The illuminance distribution is good. Here, as shown in FIG. 9, the illumination distance Z2 is a distance between the illumination surface and the imaging symmetry plane (here, the medium surface of the plate P).

The first condition is that f1 and Z1 satisfy the condition of the following expression (1). f1 and Z1 will be described later. The second condition is that the inner radius R of the ring LED light source 221 with a diffuser is larger than the field angle radius Y2 at the light source position. When the first condition and the second condition are satisfied, the image captured by the camera 206 is not affected by the light source unit 202. This facilitates acquisition of luminance information described later.

Y1 = (Z1 × Y0) / f1 (1)

Incidentally, in Expression (1), f1 is a front focal length that is a distance between the imaging lens 231 and the front focal point 233. Z1 is the distance between the front focal point 233 and the imaging target surface (here, the surface of the medium on the plate P). Y0 is the size of the image sensor 232 in the camera 206. Furthermore, Y1 is the size of the imaging target.
By satisfying the first condition and the second condition, the illuminance unevenness in the image can be reduced, and the S / N ratio of the image can be improved.

[Inspection process]
FIG. 10 is a diagram illustrating an example of a detailed procedure for a cancer test in the present embodiment. Steps S101 to S141 are diagrams showing a culture process, and steps S201 to S215 are diagrams showing a cancer test process. Reference is made to FIGS. 1 and 5 as appropriate.
As shown in FIG. 10, first, the plate creator creates a culture plate (S101). Then, if necessary, the plate creator performs a nematode transplanting operation (S111) to create a new culture plate (S112). Further, the plate creator creates a new culture plate (S122) by performing nematode transplantation work based on the culture plate created in step S112 (S121).

Then, after nematodes are cultured on the culture plates created in steps S101, S112, and S122, the examiner performs a cancer test using the cultured nematodes (S141 to S143).

Steps S201 to S215 show details of the processing of steps S141 to S143. Steps S201 to S215 are performed in steps S141 to S143, respectively.
As shown in FIG. 10, in a cancer test, first, a plate creator creates a plate for analysis (S201).
Subsequently, the dispensing device 3 plots nematodes on the analysis plate (S203). Specifically, the dispensing device 3 sucks the nematode together with the buffer from the tube that has been left stationary for a predetermined time, and plots it at a predetermined position (for example, the center) on the plate. The amount of inhalation is, for example, 4 μL. When the nematode plotting by the dispensing device 3 is completed, the transport device 4 places the plate on the plate placement portion 501 of the buffer suction device 5. Here, after the nematode is plotted on the plate, the nematode is set in the buffer suction device 5, but the nematode may be plotted after the plate is set in the buffer suction device 5.

And the inclination part 502 of the buffer suction apparatus 5 inclines the plate | board mounting part 501 (S204). At this time, the buffer suction device 5 inclines the 60 ° plate mounting portion 501 over 30 seconds, for example. This ensures that only the buffer flows down the plate, as described above, and many of the nematodes remain plotted.
And the suction part 505 of the buffer suction device 5 sucks the buffer accumulated under the plate (buffer suction: S205).

Thereafter, when the buffer suction device 5 returns the plate placement unit 501 to the horizontal position, the dispensing device 3 plots the urine sample (for example, 2 μL) and sodium azide at predetermined positions on the plate (S206). The urine sample and sodium azide are preferably plotted at the same place. Since sodium azide is odorless to nematodes, there is no problem if the urine sample and sodium azide are plotted in the same place.

Subsequently, the transport device 4 sets the plate on the imaging device 2 (FIG. 5) (S211).
Here, the urine sample and sodium azide are plotted on the plate set in the buffer suction device 5. However, the urine sample and sodium azide may be plotted after the plate is set in the imaging device 2. Thus, a plate on which nematodes, urine detection, and sodium azide are plotted is appropriately referred to as an analysis plate.

Then, the imaging device 2 images the analysis plate (S212).
The image captured by the imaging device 2 is sent to the analysis device 1 (FIG. 5). The analysis apparatus 1 performs a chemotaxis analysis process based on the sent image (S213). In some cases, the imaging is performed again (S212), and the chemotaxis analysis is repeated on the image obtained by the imaging (S213).
And the analyzer 1 performs the test | inspection determination process which determines positive / negative of cancer based on the result of the chemotaxis analysis of step S213 (S214).

Then, the analysis device 1 stores the result of the process in step S215 in the storage device 13 (FIG. 6) (S215).

<Second Embodiment: Luminous Center of Gravity>
Next, a runnability analysis based on a luminance center of gravity will be described as a second embodiment.
<< 2-1 embodiment >>
[flowchart]
FIG. 11 is a flowchart showing a procedure of processes performed by the cancer analysis system according to the 2-1 embodiment. Reference is made to FIGS. 5 to 7 as appropriate.
First, the camera 206 of the imaging device 2 captures the plate P (S301).
And the image acquisition part 101 of the analyzer 2 performs the image acquisition process which acquires an image from the imaging device 2 (S302).
Next, the pixel combination unit 102 performs pixel combination processing (S303). The pixel combination process will be described later.
Then, the luminance information acquisition unit 103 performs luminance information acquisition processing for acquiring luminance information from the pixels combined in step S303 (post-combination pixels) (S304).
Thereafter, the luminance centroid calculation unit 104 performs luminance centroid calculation processing for calculating the luminance centroid based on the luminance information acquired in step S304 (S305). The luminance center of gravity will be described later.

Next, the processing unit 100 determines whether or not the processing of steps S301 to S305 has been performed twice (S311).
If the result of step S311 indicates that the processes of steps S301 to S305 have not been performed twice (S311 → No), has the processing unit 100 passed a predetermined time (for example, 15 minutes) after the process of step S305 is completed? It is determined whether or not (S312).
As a result of step S312, when the predetermined time has not elapsed since the process of step S305 was completed (S312 → No), the processing unit 100 returns the process to step S312.
As a result of step S312, when a predetermined time has passed since the process of step S305 is completed (S312 → Yes), the processing unit 100 returns the process to step S301 and instructs the imaging device 2 to image the plate P.

As a result of step S311, when the processes of steps S301 to S305 are performed twice (S311 → Yes), the chemotaxis index calculation unit 105 calculates the chemotaxis index based on the luminance center of gravity calculated in step S305. The calculated chemotaxis index calculation process is performed (S321).
Subsequently, the test determination unit 106 performs a test determination process for determining whether the cancer is positive or negative based on the chemotaxis index calculated in step S321 (S322).

Incidentally, step S301 in FIG. 11 corresponds to step S212 in FIG. 10, and steps S302 to S321 in FIG. 11 correspond to step S213 in FIG. Step S322 in FIG. 11 corresponds to step S214 in FIG.

[Running analysis by luminance center of gravity]
Next, with reference to FIG. 12 to FIG. 14, a description will be given of the nematode chemotaxis analysis by the luminance center of gravity according to the 2-1 embodiment.
(image)
FIG. 12 is a schematic diagram of an image captured by the camera. This image is the image acquired in step S302 in FIG.
In FIG. 12, the medium is white and the nematode E is black for easy viewing of the drawing. However, in practice, the medium appears black and the nematode E appears white.

(Pixel merge processing)
FIG. 13 is a diagram illustrating a pixel combining process used in the 2-1 embodiment. This process corresponds to step S303 in FIG.
The pixel combination unit 102 forms a predetermined number of pixels in the captured image, thereby collecting the pixels into about 13 × 13 pixels as illustrated in FIG. 13. Note that grouping into 13 × 13 pixels is an example, and the number of pixels may be other than this.

(Luminance information acquisition processing)
FIG. 14 is a diagram illustrating a result of pixel combination processing.
As shown in FIG. 14, as a result of combining pixels, as the number of nematodes increases in the combined pixels (post-combination pixels), the pixel becomes white, and as the number of nematodes decreases, the pixel becomes closer to black. That is, in the combined pixels, the luminance increases as the number of nematodes increases. In FIG. 14, the number of nematodes in the combined pixel is indicated by five levels of dots, but in actuality, for example, it is indicated by 256 levels of luminance.
In step S304 in FIG. 11, the luminance information acquisition unit 103 acquires luminance information in the combined pixels as shown in FIG. The x axis and y axis will be described later.

(Luminance center of gravity calculation processing)
In step S305 in FIG. 11, the luminance center of gravity calculation unit 104 calculates the luminance center of gravity from the luminance in the combined pixels shown in FIG. The luminance centroid is a centroid of luminance in an image after pixel combination processing, calculated by the following equation (2).

 
 

In Expression (2), the x coordinate of the i-th combined pixel from the left in FIG. 14 is x _i, and the luminance at that pixel is Bx _i . Similarly, in FIG. 14, the y coordinate at the j-th combined pixel from the bottom is y _j and the luminance at that pixel is By _j . Here, the x-coordinate and the y-coordinate are based on the x-axis and the y-axis in FIG. In Expression (2), n and m are the numbers of the combined pixels in the x-axis direction and the y-axis direction. In the example of FIG. 14, n = 13 and m = 13.
Here, Bx _i is a value obtained by accumulating the luminance of the combined pixel belonging to x _i in the y-axis direction, and By _j is a value obtained by accumulating the luminance of the combined pixel belonging to y _j in the x-axis direction. .
That is, assuming that the luminance of the combined pixel at the position (i, j) (that is, i-th from the left and j-th from the bottom in FIG. 14) is Bij, Bxi and Byj in Equation (2) are It is defined by the following formulas (3) and (4).

 
 

_Let (C _x , C _y ) be the luminance centroid of the combined pixel at the calculated position (x, y) (that is, the xth from the left and the yth from the bottom in FIG. 14). Also, _let the luminance center of gravity at time t be (C _xt , C _yt ).

(Taxis index calculation process)
In step S321 in FIG. 11, the chemotaxis index calculation unit 105 calculates the chemotaxis index CI using the luminance center of gravity by the following method. There are two methods for calculating the chemotaxis index CI: a method according to the following equation (5) and a method according to the equation (6). Note that (C _x0 , C _y0 ) indicates the luminance center of gravity immediately after plotting at time t = 0.

CI = C _x0 -C _xt (5)

 
 

Equation (5) calculates the temporal change of the luminance center of gravity in the x-axis direction, and Equation (6) calculates the temporal change of the luminance center of gravity in the x-axis direction and the y-axis direction. Note that t is, for example, 15 minutes, but is not limited thereto.

And the test | inspection determination part 106 determines the positive / negative of the cancer in a subject based on the calculated chemotaxis index CI.

FIG. 15 and FIG. 16 are diagrams showing changes in luminance distribution when nematodes are chemotaxised by a plate that has sucked a buffer by the buffer sucking device according to the present embodiment.
15 and 16, the x axis and the y axis indicate images sent from the imaging device 2 (FIG. 5). 15 and 16, the vertical axis indicates the luminance. 15 and 16, the luminance center of gravity immediately after plotting is used as the origin. This is because the plate is inclined by the buffer suction device 5 (FIG. 1), so that the nematode spreads within a predetermined range, and the plot point of the nematode on the culture medium differs for each examination. The coordinate displacement is calculated from the luminance centroid immediately after plotting and the luminance centroid after a predetermined time. That is, the luminance center of gravity immediately after plotting is used as a starting point. Thereby, the fluctuation of the plot point due to the inclination of the plate can be eliminated.

FIG. 15 shows the luminance distribution immediately after plotting the urine sample, and FIG. 16 shows the luminance distribution when the nematode chemotaxis was performed for 15 minutes after plotting the urine sample. 15 and 16, the urine sample of the cancer patient is plotted on the left side of the paper on the x-axis, and the nematode shows the attracting action with respect to the urine sample.
As shown in FIGS. 15 and 16, the chemotaxis behavior of the nematode on the plate sucked up by the buffer sucking device 5 according to the present embodiment seems to have no problem.

Next, with reference to FIG.17 and FIG.18, the chemotaxis behavior of the nematode in the plate which sucked up the buffer by the buffer sucking device 5 according to this embodiment, and the nematode in the plate which sucked up the buffer by the conventional method Compared with the chemotaxis behavior.
The conventional method is a method in which the buffer is manually sucked with a commercially available paper waste while the plate is in a horizontal state.
FIG. 17 is a diagram illustrating time conversion of the luminance center of gravity in the plate that has absorbed the buffer by the buffer suction device according to the present embodiment. FIG. 18 is a diagram (comparative example) showing a temporal change in luminance center of gravity in a plate that has absorbed a buffer by the conventional method.
17 and 18, the horizontal axis indicates time, and the vertical axis indicates the x-coordinate value of the luminance centroid (luminance centroid x-coordinate).

Lines 611 to 615 in FIG. 17 indicate time conversion of the luminance center of gravity for each plate. Among these, the line 615 shows the time change of the luminance center of gravity when the urine sample (repellent substance) of a healthy person is plotted. The other lines 611 to 614 show the time change of the luminance center of gravity when the urine specimen (attracting substance) of the cancer patient is plotted.
In addition, lines 621 to 623 in FIG. 18 indicate changes over time in the luminance center of gravity when urine specimens (attracting substances) of cancer patients are plotted.

The line 614 in FIG. 17 and the line 623 in FIG. 18 do not show a clear attracting action, but it is clear when the other lines 611 to 613 (FIG. 17) are compared with the lines 621 to 622 (FIG. 18). Lines 611 to 613 indicate that the chemotactic behavior of the nematode is more active. Further, as indicated by a line 615, the plate using the buffer suction device 5 according to the present embodiment is also active in repelling behavior.

This is because, in the conventional method, when the buffer is sucked with a paper waste, the nematode is damaged or stressed by touching the nematode, but this embodiment relates to this embodiment. This is because the buffer suction device 5 can suck the buffer without touching the nematode.
Further, by sucking the buffer with the buffer sucking device 5, the nematode is not damaged or stressed, so that stable and highly reproducible data can be obtained.

Further, according to the 2-1 embodiment, by calculating the chemotaxis index based on the luminance, the chemotaxis index can be calculated by a simple algorithm without counting individual nematodes. For this reason, the analysis of the image imaged with the imaging device 2 can be performed efficiently.

Further, as shown in FIG. 19, even when the nematode E is cultured from the larval state (symbol E1) to the adult nematode E (symbol E2) with uniform culture conditions, The state cannot be made good. Therefore, it is necessary to select the nematode E (symbol E3) in good condition. Here, the nematode E3 in good condition is the nematode E that is active.

However, measuring the movements of individual nematodes E is complicated algorithmically. In the case of the cancer analysis system Z according to the 2-1 embodiment, the calculation load can be reduced by using the luminance center of gravity using the property that the portion where the nematode E is large in the image becomes bright. .

Further, as described above, the plate is inclined in the buffer suction device 5 and the buffer is sucked. For this reason, the portion where the nematode is plotted has a spread, and the plotted point is not always the exact origin. In the present embodiment, as shown in Equation (5) and Equation (6), the difference between the luminance centroid immediately after the nematode plot and the luminance centroid after a predetermined time is defined as the chemotaxis index. By doing in this way, the problem of the shift | offset | difference of a plot point is eliminated, and the problem of having a two-dimensional spread is also eliminated.
That is, the chemotaxis index can be correctly evaluated by considering the luminance center of gravity immediately after the nematode plot as the origin.

Furthermore, the number of pixels can be reduced by performing pixel combination processing. Thereby, the capacity of the image can be reduced. Accordingly, a large amount of images can be stored. For example, if an image is captured for 15 minutes with 5 million pixels, a capacity of about 1 GB is required. However, by performing pixel combination processing as in the case of the 2-1 embodiment, the image capacity can be significantly reduced. it can.
Further, by performing pixel combination processing, noise such as dust can be averaged and the influence can be eliminated.

Note that Patent Document 1 describes that a fluorescent protein gene is introduced into a nematode and the tendency intensity of the nematode is measured. The technique described in Patent Document 1 improves the S / N ratio of an image by making nematodes fluoresce. However, since individual nematodes are counted, it is impossible to solve the above-described problems. Can not. The technique according to the 2-1 embodiment is different from the technique described in Patent Document 1 in that the amount of nematodes is estimated based on the luminance in the image.

In the embodiment 2-1, the runnability index is calculated from the difference between the luminance center of gravity immediately after plotting and the luminance center of gravity after a predetermined time, but the luminance center of gravity after the predetermined time and the center position of the plate are calculated. The chemotaxis index may be calculated from the difference between.
In the 2-1 embodiment, pixels of a fine captured image are combined, but the present invention is not limited to this. For example, the pixel combination process may be omitted by taking an image with the camera 206 (FIGS. 7 to 9) having a small number of pixels. Thus, by using the camera 206 with a small number of pixels, the cost can be significantly reduced.

<< Second to Second Embodiment >>
[Analyzer]
FIG. 20 is a functional block diagram showing the configuration of the analysis apparatus used in the 2-2 embodiment.
The analysis apparatus 1a illustrated in FIG. 20 is different from the analysis apparatus 1 illustrated in FIG. 6 in that the processing unit 100a includes a pixel exclusion unit 107 that excludes pixels near the center of the combined pixels.

[flowchart]
FIG. 21 is a flowchart showing a processing procedure performed by the analysis apparatus used in the 2-2 embodiment. Reference is made to FIG. 20 as appropriate. In FIG. 21, the same steps as those in FIG. 4 are denoted by the same step numbers and description thereof is omitted.
21 is different from the flowchart shown in FIG. 11 in that the pixel excluding unit 107 performs the pixel excluding process (S331) after step S304. The pixel exclusion process will be described later.

(Pixel exclusion process)
Next, the pixel exclusion process in step S331 in FIG. 21 will be described with reference to FIGS.
FIG. 22 is a diagram for explaining a pixel exclusion processing method used in the 2-2 embodiment.
The pixels shown in FIG. 22 indicate the combined pixels.
As shown in FIG. 22, the pixel excluding unit 107 excludes a predetermined range of combined pixels (shaded area) from the center (reference numeral 301) of the combined image after a predetermined time from the start of running. This is because nematodes in poor condition do not move from the central area (ie where the nematodes are plotted). By performing the pixel exclusion process, it is possible to exclude the influence of nematodes having a poor state, and it is possible to improve the accuracy of the luminance center of gravity and the accuracy of the chemotaxis index.

The deletion area is, for example,
(A1) A post-combination pixel for a circle (dashed circle 302 in FIG. 22) whose diameter is (elapsed time since nematode plot × slow nematode speed) (A2) a post-combination pixel of the region set by the operator Etc.

FIG. 23 is a schematic diagram of the combined pixel before the pixel exclusion process is performed (unprocessed), and FIG. 24 is a schematic diagram of the combined pixel after the pixel exclusion process is performed.
In FIG. 23 and FIG. 24, the luminance of the combined pixel is indicated by five stages of dots as in FIG.
FIG. 23 is the same as that shown in FIG. 14, and a description thereof is omitted here. Then, the pixel excluding unit 107 excludes the post-combination pixels with broken line circles in FIG. 23 in the central region of the image after the pixel combination processing, thereby obtaining a post-combination image as shown in FIG. Note that the dashed circle in FIG. 23 is the same as the dashed circle 302 in FIG.

Since nematodes in good condition, that is, nematodes with active movement, move at a high speed, it is possible to select nematodes in good condition by measuring the movement of individual nematodes.
According to the 2-2 embodiment, by removing a predetermined range from the center, it is possible to exclude the influence of a nematode having a bad state (poor movement). Thereby, the accuracy of the chemotaxis index can be improved. Such pixel exclusion in the central region can be performed by a very simple process because it is only necessary to set the luminance of the combined pixels within a predetermined range to 0.

<< 2-3 embodiment >>
[Analyzer]
FIG. 25 is a functional block diagram showing a configuration of an analysis apparatus used in the second to third embodiments.
The analysis apparatus 1b shown in FIG. 25 is different from the analysis apparatus 1a shown in FIG. 20 in that the processing unit 100b stops the calculation of the luminance centroid when the time change of the luminance centroid satisfies a predetermined condition. The determination processing unit 108 is included.

[flowchart]
FIG. 26 is a flowchart illustrating a processing procedure performed by the analysis apparatus used in the second to third embodiments. 7 and 25 will be referred to as appropriate. In FIG. 26, the same processes as those in FIG. 21 are denoted by the same step numbers and description thereof is omitted.
26 differs from the processing in FIG. 21 in the following points.
In step S305, after the luminance center of gravity calculation unit 104 calculates the luminance center of gravity, the imaging stop determination processing unit 108 performs time displacement calculation processing for calculating the time displacement Dt of the luminance center of gravity (S341). The time displacement Dt of the luminance center of gravity is a difference value between the current luminance center of gravity and the previous luminance center of gravity. If the direction in which the urine sample is plotted with respect to the center of the plate P is the x-axis direction, the temporal displacement Dt of the luminance center of gravity only needs to be considered in the x-axis direction, but in addition to the x-axis direction, , The y-axis direction may be taken into account.

Then, the imaging stop determination processing unit 108 reverses the sign of the time displacement of the luminance center of gravity calculated in step S341 and the sign of the time displacement of the previous luminance center of gravity, or calculates in step S341. Whether or not the absolute value (| Dt−Dtp |) of the difference between the time displacement Dt of the (current) luminance center of gravity and the time displacement Dtp of the previous luminance center of gravity is less than a predetermined value (e) Is determined (S342). In step S342, the absolute value (| Dt−Dtp |) of the difference between the temporal displacement Dt of the luminance center of gravity calculated in step S341 and the temporal displacement Dtp of the previous luminance center of gravity is a predetermined value (e The condition of whether or not it is less than may be omitted.

Here, whether the sign of the time displacement of the luminance center of gravity and the sign of the time displacement of the previous luminance center of gravity is reversed is determined whether or not the nematode has started moving in the opposite direction. is doing. Whether or not the absolute value (| Dt−Dtp |) of the difference between the time displacement Dt of the luminance center of gravity and the time displacement Dtp of the previous luminance center of gravity is less than a predetermined value (e) is: It is determined whether or not the movement of the nematode is slowing down.

As a result of step S342, the sign of the temporal displacement of the luminance center of gravity calculated in step S341 and the sign of the temporal displacement of the previous luminance center of gravity is reversed, or the luminance center of gravity calculated in step S341 If the absolute value (| Dt−Dtp |) of the time displacement Dt and the time displacement Dtp of the previous luminance center of gravity is less than the predetermined value (e) (S342 → Yes), the processing unit 100b performs the step The process proceeds to S345.

As a result of step S342, the sign of the temporal displacement of the luminance center of gravity calculated in step S341 and the sign of the temporal displacement of the previous luminance center of gravity are not reversed, and the luminance center of gravity calculated in step S341 When the absolute value (| Dt−Dtp |) of the difference between the time displacement Dt of the previous time and the time displacement Dtp of the previous luminance center of gravity is equal to or greater than the predetermined value (e) (S342 → No), the processing unit 100b Determines whether or not a predetermined time (for example, 15 minutes) has elapsed since the start of chemotaxis (S343).

As a result of step S343, when the predetermined time has not elapsed since the start of running (S343 → No), the imaging stop determination processing unit 108 determines whether the imaging interval time (for example, 1 minute) has elapsed since the previous imaging. (S344).
As a result of step S344, when the imaging interval time has not elapsed (S344 → No), the imaging stop determination processing unit 108 returns the process to step S344.
As a result of step S344, when the imaging interval time has elapsed (S344 → Yes), the processing unit 100b returns the process to step S301 and instructs the imaging device 2 to image the plate P.

On the other hand, as a result of step S343, when a predetermined time has elapsed from the start of running (S343 → Yes), the imaging stop determination processing unit 108 instructs the imaging device 2 to stop imaging (S345). The imaging device 2 instructed to stop imaging stops imaging.
Then, the chemotaxis index calculation unit 105 performs a chemotaxis index calculation process for calculating the chemotaxis index based on the luminance center of gravity calculated most recently (S321a).

If the movement of the nematode slows down or if the nematode begins to advance in the direction of determination, it can be said that it is not meaningful to make the nematode run more.
Therefore, the imaging stop determination processing unit 108 monitors the luminance center of gravity at a predetermined time, and when the movement of the nematode becomes slow or the luminance center of gravity returns to the origin side (the nematode plot point), the imaging is stopped there. abort.

Then, the chemotaxis index calculation unit 105 calculates the chemotaxis index using the luminance center of gravity immediately before the time when the imaging is stopped.

According to the second to third embodiments, since the imaging is discontinued when it can be said that there is not much meaning even if the nematode is chemotaxis, the inspection time can be shortened.
In addition, according to the second to third embodiments, since the chemotaxis index is calculated based on the luminance center of gravity when the nematode is chemotaxis to the most + side or − side, the accuracy of the chemotaxis index is improved. be able to.

In the second to third embodiments, the pixel exclusion process in step S331 in FIG. 26 may be omitted.
In the second to third embodiments, the temporal change of the luminance center of gravity is monitored for each inspection, and the runnability index is calculated by the luminance center of gravity when the luminance center of gravity returns to the origin side. However, the present invention is not limited to this. . For example, an average value or the like of the time for the luminance change to return to the origin side may be calculated in advance by experiment, and the nematode chemotaxis may be performed for this time. That is, the predetermined time in the 2-1 embodiment and the 2-2 embodiment may be an average value of the time for which the luminance change calculated by the experiment returns to the origin side. By doing so, the inspection time can be shortened.

Even if the odor substance of the urine sample evaporates and the nematode returns to the origin side, according to the second to third embodiments, the luminance before the odor substance of the urine sample evaporates. The chemotaxis index can be calculated based on the target center of gravity. Thereby, the accuracy of the chemotaxis index can be improved.

<Second to Fourth Embodiment>
[Analyzer]
FIG. 27 is a functional block diagram showing the configuration of the analysis apparatus used in the second to fourth embodiments.
The analysis apparatus 1c shown in FIG. 27 is different from the analysis apparatus 1b shown in FIG. 25 in that the processing unit 100c selects a plate P (FIG. 7) in which the temporal change in luminance center of gravity is not seen as an exclusion plate. The processing unit 109 is included.

[flowchart]
FIG. 28 and FIG. 29 are flowcharts showing a procedure of processing performed by the analysis apparatus according to the second to fourth embodiments. 7 and 27 will be referred to as appropriate. 28 and 29, processes similar to those in FIG. 26 are denoted by the same step numbers and description thereof is omitted.
28 and 29 are different from the processing shown in FIG. 26 in the following points.
That is, in step S305, after the luminance center of gravity calculation unit 104 calculates the luminance center of gravity, the plate exclusion processing unit 109 determines whether or not a first time (for example, 2 minutes) has elapsed from the start of running ( S351 in FIG. 28).
As a result of step S351, when the first time has not elapsed since the start of running (S351 → No), the processing unit 100c determines whether or not an imaging interval time (for example, 1 minute) has elapsed since the previous imaging ( S352).
As a result of step S352, when the imaging interval time has not elapsed (S352 → No), the processing unit 100c returns the process to step S352.
As a result of step S352, when the imaging interval time has elapsed (S352 → Yes), the processing unit 100c returns the process to step S301 and instructs the imaging device 2 to image the plate P.

As a result of step S351, when the first time has elapsed since the start of chemotaxis (S351 → Yes), after the plate exclusion processing unit 109 performs the plate exclusion processing (S353), the processing unit 100c advances the process to step S361. .
In step S353, the plate exclusion processing unit 109 instructs to exclude the plate P whose displacement from the luminance center of gravity immediately after the nematode plot is equal to or less than a predetermined value from the inspection target even after the first time has elapsed. The instruction to exclude the plate P may be output from the output device 15 of the analysis device 1c, or a display device (not shown) may be installed in the vicinity of the imaging device 2 and displayed on the display device. Alternatively, the transport device 4 (FIG. 5) may exclude based on the exclusion instruction.

Steps S361 to S366 are the same processing as steps S301 to S305, and thus description thereof is omitted here. After step S366, the processing unit 100c advances the process to step S341 in FIG. The processes in steps S341 and S342 are the same as the processes in steps S341 and S342 shown in FIG. 26, and thus the description thereof is omitted here.
If “No” is determined in the process of step S342, the imaging stop determination processing unit 108 determines whether or not a second time (for example, 13 minutes) has elapsed after the first time has elapsed (for example, 13 minutes). S371 in FIG. 29).
If the second time has elapsed as a result of step S371 (S371 → Yes), the imaging stop determination processing unit 108 advances the process to step S345.

As a result of step S371, when the second time has not elapsed since the start of chemotaxis (S371 → No), the processing unit 100c determines whether an imaging interval time (for example, 1 minute) has elapsed since the previous imaging ( S372).
As a result of step S372, when the imaging interval time has not elapsed (S372 → No), the processing unit 100c returns the process to step S372.
As a result of step S372, when the imaging interval time has elapsed (S372 → Yes), the processing unit 100c returns the process to step S361 in FIG. 28 and instructs the imaging device 2 to image the plate P.

FIG. 30 is a schematic explanatory diagram of the plate exclusion process used in the second to fourth embodiments.
FIG. 30 shows an example in which four analysis plates Pa to Pd are generated from one culture plate Pz. Here, the culture plate Pz is a plate P (FIG. 7) on which nematodes are cultured. The analysis plates Pa to Pd are plates P on which urine specimens and nematodes are placed and set in the imaging device 2 (FIG. 5).
As shown in FIG. 30, nematodes cultured in the same culture plate Pz are dispensed into four analysis plates Pa to Pd.

The four plates for analysis Pa to Pd are set in the imaging device 2, imaged, analyzed, and discarded. Here, the analysis is the calculation of the luminance center of gravity and the calculation of the chemotaxis index.
Among these, the analysis plate Pc in which the distance between the luminance centroid immediately after the nematode plot and the position of the luminance centroid after a predetermined time is a predetermined value or less may cause the nematode to be weak, It is excluded because it is not suitable for inspection.

According to the second to fourth embodiments, it is possible to improve the accuracy of inspection determination by excluding a plate with a small change in luminance center of gravity even after a predetermined time.

In the second to fourth embodiments, a plate exclusion process is added to the second to third embodiments. That is, in the second to fourth embodiments, the luminance center of gravity is obtained every predetermined interval (for example, 1 minute), but is not limited thereto. For example, as in the 2-1 embodiment and the 2-2 embodiment, imaging is performed immediately after the nematode plotting and after a predetermined time (for example, 15 minutes), and immediately after the plotting and after the predetermined time. Plates having a difference in luminance center of gravity at a predetermined value or less may be excluded.

In the first to fourth embodiments, the runnability index is obtained based on the luminance center of gravity. However, the information is not limited to the luminance center of gravity as long as the information is related to the luminance in the image captured by the camera 206. For example, in the post-combination pixel, the chemotaxis index is calculated based on the distance between the post-combination pixel with the highest luminance immediately after the nematode plot and the post-combination pixel with the highest luminance after a predetermined time after the start of chemotaxis May be.

Also, graphs, tables, and graphs showing the time transition of the luminance center of gravity as shown in FIGS. 15 to 17 may be output (displayed) to the output device 15.

<Third Embodiment>
Next, with reference to FIG. 31 to FIG. 34, a description will be given of the chemotaxis analysis based on the DR (Density Ratio) value.
The DR method is a running analysis method used instead of the luminance center of gravity.
[Analyzer]
FIG. 31 is a functional block diagram showing the configuration of the analysis device used in the third embodiment. In FIG. 31, the same components as those in FIG.
The analysis device 1d shown in FIG. 31 is different from the analysis device 1 shown in FIG. 6 in that the luminance center-of-gravity calculation unit 104 and the runnability index calculation unit 105 in the processing unit 100 in FIG. This is a point that is part 110.

[DR value]
FIG. 32 is a diagram for explaining DR values used in the third embodiment.
FIG. 32 shows an image captured by the imaging device. As indicated by reference numeral 631, a nematode is plotted at the center of the plate P, and a urine sample is plotted at a point indicated by reference numeral 632.
Then, as shown in FIG. 32, the image is divided into sections having a predetermined size. In the example of FIG. 32, it is divided into 12 × 12. These partitions are post-combined pixels that have been combined.
Among these sections, a predetermined range around the plot point 632 of the urine sample is selected. In the example of FIG. 32, a 3 × 4 range 641 around the urine sample is selected.

Then, the chemotaxis index calculation unit 105 calculates the DR value based on the sum of the luminance values of the sections in the range 641.
Assuming that the sum of the luminance values of the sections in the range 641 is S1, and the sum of the brightness values of the sections other than the range 641 is S2, the DR value is calculated by a method represented by the following formula (11): There are two ways with the method represented by 12).

DR = S1 (11)
DR = S1 / S2 (12)

[flowchart]
FIG. 33 is a flowchart illustrating a processing procedure performed by the analysis apparatus used in the third embodiment. Reference is made to FIG. 31 as appropriate. Also, FIG. 33 will be described with a focus on processing different from FIG. In FIG. 33, processes similar to those in FIG. 11 are denoted by the same step numbers and description thereof is omitted.
First, the processing unit 100d determines whether or not a predetermined time has elapsed from the start of the nematode chemotaxis (S381).
As a result of step S381, when the predetermined time has not elapsed (S381 → No), the processing unit 100d returns the process to step S381.
As a result of step S381, when the predetermined time has passed (S381 → Yes), the camera 206 (FIG. 7), the image acquisition unit 101, and the pixel combination unit 102 perform the processes of steps S301 to S303.

Thereafter, the luminance information acquisition unit 103 performs luminance information acquisition processing for acquiring luminance information from the pixels (post-combination pixels) combined in step S303 (S304a).
At this time, when the DR value is calculated by Expression (11), the luminance information acquisition unit 103 acquires luminance information of each combined pixel (section) in the range 641 in FIG.
Further, when calculating the DR value by Expression (12), the luminance information acquisition unit 103 obtains the luminance information of each combined pixel in the range 641 in FIG. 32 and the luminance information of each combined pixel other than the range 641 in FIG. get.

Then, the DR value calculation unit 110 calculates the DR value according to the equation (11) or the equation (12) (S382).
Subsequently, the test determination unit 106 performs test determination processing for determining whether the cancer is positive or negative based on the DR value calculated in step S382 (S322a).
At this time, the test determination unit 106 determines positive if the calculated DR value is equal to or greater than a preset threshold value, and determines negative if the calculated DR value is less than the threshold value.

Incidentally, step S301 in FIG. 33 corresponds to step S212 in FIG. Also, steps S302 to S382 in FIG. 33 correspond to step S213 in FIG. Step S322a in FIG. 33 corresponds to step S214 in FIG.

34 and 35 are diagrams showing temporal changes in the DR value. FIG. 34 shows a case where a urine sample (repellent substance) of a healthy person is plotted, and FIG. 35 shows a case where a urine sample (attractant) of a cancer patient is plotted. The DR value used is according to the equation (12).
34 and 35, the horizontal axis indicates time, and the vertical axis indicates DR value.
In FIG. 34, since repellent substances are plotted, there is no nematode in the range 641 of FIG. Therefore, as indicated by a line 651 in FIG. 34, the DR value is almost zero.

On the other hand, in FIG. 35, since attracting substances are plotted, there are many nematodes in the range 641 in FIG. Therefore, as indicated by a line 652 in FIG. 35, the DR value is a large value.
Thus, when the repellent substance (a healthy subject's urine sample) is plotted, the DR value is almost zero. Since it is only necessary to know whether nematodes are attracted to the urine sample in the actual examination, there is no problem even if the DR value becomes 0 when the repellent substance (a urine sample of a healthy person) is plotted.
In the analysis using such a DR value, a predetermined threshold is provided, and if the DR value exceeds this threshold, it is determined as positive.
The analysis using the DR value can be applied to other than the cancer analysis system including the buffer suction device 5.

As described above, since the technique using the DR value can be calculated simply from the luminance center of gravity, the processing load can be reduced. For this reason, efficient analysis becomes possible. In particular, with the calculation method according to Equation (11), it is only necessary to image only the periphery of the urine sample, so that the camera 206 can be easily set.
Such a DR value can be calculated by imaging the plate P with the imaging device 2 shown in FIGS.

In addition, this invention is not limited to above-described embodiment, Various modifications are included. For example, the above-described embodiment has been described in detail for easy understanding of the present invention, and is not necessarily limited to having all the configurations described. In addition, a part of the configuration of a certain embodiment can be replaced with the configuration of another embodiment, and the configuration of another embodiment can be added to the configuration of a certain embodiment. In addition, it is possible to add, delete, and replace other configurations for a part of the configuration of each embodiment.

Each of the above-described configurations, functions, units 100 to 110, storage device unit 13 and the like may be realized by hardware by designing a part or all of them, for example, with an integrated circuit. Further, as shown in FIGS. 6, 20, 25, 27, and 31, the above-described configurations, functions, and the like are obtained by interpreting and executing a program that realizes each function by a processor such as the CPU 12. It may be realized by software. Information such as programs, tables, and files for realizing each function is stored in the HD as shown in FIG. 6, FIG. 20, FIG. 25, FIG. 27, and FIG. ) Or a recording medium such as an IC (Integrated Circuit) card, an SD (Secure Digital) card, or a DVD (Digital Versatile Disc).
In each embodiment, control lines and information lines are those that are considered necessary for explanation, and not all control lines and information lines are necessarily shown on the product. In practice, it can be considered that almost all configurations are connected to each other.

1,1a-1d Analysis device (analysis unit)
2 Imaging device (imaging unit)
3 Dispensing device 4 Conveying device 5 Buffer suction device 100, 100a to 100d Processing unit 101 Image acquisition unit 102 Pixel combination unit 103 Luminance information acquisition unit 104 Luminous centroid calculation unit 105 Running index calculation unit 106 Inspection determination unit 107 Pixel exclusion Unit 108 imaging stop determination processing unit 109 plate exclusion processing unit 110 DR value calculation unit 201 base unit 202 light source unit 203 pedestal 204 first support unit 205 second support unit 206 camera (imaging unit)
221 Ring LED light source with diffuser plate 222 Shield plate 231 Imaging lens 232 Imaging element 233 Front focus 241 Diffuser plate 301 Center of combined image 302 Broken line circle 401,411 Origin (luminance center of gravity immediately after plotting)
402, 412 Nematode movement is slow 501 Plate placement part (placement part)
502 Inclination part 503 Drive part 504 Base part 505 Suction part E, E1 to E3 Nematode P plate Pz Culture plate Pa to Pc Analysis plate Z Cancer analysis system

Claims (15)

1. A mounting section for mounting a plate on which nematodes are plotted together with a buffer;
   An inclined part for inclining the mounting part;
   A suction part for sucking out the buffer accumulated in the lower part of the plate placed on the placement part inclined by the inclined part;
   A buffer suction device characterized by comprising:
2. A mounting section for mounting a plate on which nematodes are plotted together with a buffer;
   An inclined part for inclining the mounting part;
   A suction part for sucking out the buffer accumulated in the lower part of the plate placed on the placement part inclined by the inclined part;
   An analysis unit for performing the chemotaxis analysis of the nematode;
   A cancer analysis system characterized by comprising:
3. A light source unit for irradiating the plate on which the nematode and urine specimens are plotted from below;
   An imaging unit for imaging the plate irradiated by the light source unit;
   Have
   The analysis unit
   The cancer analysis system according to claim 2, wherein the chemotaxis analysis is performed based on information on luminance in an image captured by the imaging unit.
4. The cancer analysis system according to claim 3, wherein the information on the luminance is a luminance centroid that is a centroid of a luminance distribution in the image.
5. The chemotaxis analysis is performed based on a chemotaxis index that is an evaluation value related to the chemotaxis of the nematode, and the chemotaxis index is based on the following equation (1). Cancer analysis system.
   CI = C _x0 -C _xt (1)
   Here, CI represents the chemotaxis index, C _x0 represents the x coordinate of the luminance center of gravity immediately after the plot, and C _xt represents the luminance after the elapse of time t from the start of the _chemotaxis of the nematode. Indicates the x coordinate of the center of gravity. Note that the direction in which the urine sample is plotted with respect to the center of the plate is the x-coordinate direction.
6. The chemotaxis analysis is performed based on a chemotaxis index that is an evaluation value related to the chemotaxis of the nematode, and the chemotaxis index is based on the following formula (2). Cancer analysis system.
   

   

   Here, CI represents the chemotaxis index, (C _x0 , C _y0 ) represents the x-coordinate and y-coordinate of the luminance center immediately after plotting, and (C _xt , C _yt ) represents the run of the nematode. The x-coordinate and y-coordinate of the luminance center of gravity after the elapse of time t from the start of sex. The direction in which the urine sample is plotted with respect to the center of the plate is defined as the x coordinate direction, and the direction orthogonal to the x coordinate is defined as the y coordinate direction.
7. The analysis unit
   Observe the change in position of the luminance center of gravity over time of the luminance center of gravity;
   The cancer analysis system according to claim 4, wherein the analysis is stopped when the luminance center of gravity returns.
8. The cancer analysis system according to claim 7, wherein the position change of the luminance center of gravity is calculated from the luminance center of gravity immediately after plotting the nematode and the luminance center of gravity after a predetermined time.
9. The analysis unit
   The cancer analysis system according to claim 4, wherein the plate whose change in luminance center of gravity is a certain amount or less even after a predetermined time has elapsed is excluded from the target of the chemotaxis analysis.
10. The analysis unit
    The cancer analysis system according to claim 3, wherein information relating to the luminance is calculated after combining a predetermined number of pixels of the image.
11. The analysis unit
    The cancer analysis system according to claim 3, wherein an image located at a certain distance from the center of the image is excluded from a calculation target of information on the luminance.
12. The analysis unit
    4. The cancer analysis system according to claim 3, wherein the chemotaxis analysis of the nematode is performed based on information on luminance in a predetermined range from the point where the urine specimen is plotted. 5.
13. Information about the brightness is
    It is the information regarding the brightness | luminance in the predetermined range from the point where the said urine sample is plotted. The cancer-analysis system of Claim 12 characterized by the above-mentioned.
14. Information regarding luminance in the predetermined range is:
    The cancer analysis system according to claim 13, which is a sum of luminance values in a predetermined range from the point where the urine specimen is plotted.
15. Information about the brightness is
    The cancer analysis according to claim 13, wherein the sum of luminance values in a predetermined range from the point where the urine sample is plotted is divided by the sum of luminance values outside the predetermined range. system.

Images