Biological sample measuring device

Abstract

To provide a technique which enables accurate identification of a target portion of a biological sample to be measured when measuring the biological sample that is stored in a labeled container and separated into multiple regions without using a large imaging mechanism.SOLUTION: A biological sample measurement device disclosed herein has a mirror disposed in a light path from a surface light source to an area camera so as to refract and guide light passing through a biological sample to the area camera, and a light absorbing material disposed at a position to block reflected light reflected and returning toward the biological sample.SELECTED DRAWING: Figure 1

Description

Technical Field

[0001] The present disclosure relates to an apparatus for measuring a biological sample separated into a plurality of component regions.

Background Art

[0002] For the purpose of improving the efficiency of clinical tests such as blood tests, there is a need for a technique to automate the operation of confirming the volume of a biological specimen before unsealing (before dispensing), which has been conventionally performed by visual confirmation. In particular, a biological sample such as a blood specimen before dispensing has a structure separated into a plurality of layers by centrifugation or the like, and a technique for measuring only the volume of the sample to be analyzed is required. In addition, since a biological sample before dispensing may have a barcode label for identification or a pre-label attached to a blood collection tube and shipped, a technique that can measure in a state where these labels are attached is required.

[0003] As such a biological sample measuring apparatus, for example, Patent Document 1 discloses a technique for detecting the height of a predetermined region of a sample separated into a plurality of layers by irradiating the sample separated into a plurality of layers with pulsed light of two wavelengths by time-division switching and measuring the transmitted light while scanning the sample in the vertical direction.

[0004] Patent Document 2 discloses a liquid detection apparatus that irradiates a specimen with infrared light, detects the transmitted light with a line sensor, obtains the boundary of a label based on the first derivative value thereof, and measures the serum volume of the specimen. Further, in Patent Document 2, by changing the amount of light and acquiring the signal of the transmitted light, it is made possible to analyze regardless of the presence or absence of attenuation of the transmitted light by the label.

Prior Art Documents

Patent Documents

[0005]

Patent Document 1

Patent Document 2

Summary of the Invention

[0006] The technology disclosed in Patent Document 1 relates to a liquid volume measurement technique for a biological sample composed of multiple components, which accurately identifies the boundary of the measurement target area and measures the liquid volume from the transmitted light signals of two wavelengths with different absorption rates relative to the measurement target. However, Patent Document 1 requires measurement while vertically scanning the sample (blood collection tube) along its long axis, which presents a challenge in miniaturizing the device due to the scanning mechanism.

[0007] The technology described in Patent Document 2 measures serum volume by detecting the upper and lower surfaces of the serum through signal processing based on differentiation from the infrared transmitted light signal. However, when infrared light is absorbed or scattered by characters printed on the blood collection tube, blood cell components in the separation agent, or colored characters on the label, and the transmitted light is attenuated, it becomes difficult to separate this noise from the serum boundary, resulting in a problem of reduced accuracy in identifying the serum boundary and measuring liquid volume.

[0008] This disclosure has been made in view of the above-mentioned problems, and aims to provide a technology that can accurately identify the target portion to be measured when measuring a biological sample separated into multiple component regions, which is stored in a labeled container, without using a large imaging mechanism. [Means for solving the problem]

[0009] The biological sample measuring device according to this disclosure places mirrors in the optical path from the surface light source to the area camera, thereby refracting the light that has passed through the biological sample and guiding it to the area camera, and places an absorbent material at a position that blocks the reflected light that reflects back towards the biological sample. [Effects of the Invention]

[0010] According to the biological sample measuring device described herein, when measuring a biological sample separated into multiple component regions and stored in a labeled container, the target portion to be measured can be accurately identified without using a large imaging mechanism. [Brief explanation of the drawing]

[0011] [Figure 1] This is a plan view showing the configuration of the biological sample measuring device 100 according to Embodiment 1. [Figure 2A] This diagram explains the principle for identifying the measurement target area. [Figure 2B] This diagram explains the principle for identifying the measurement target area. [Figure 3A] The configuration of the image processing unit 108 is shown. [Figure 3B] This flowchart illustrates an example of a process in which the image processing unit 108 identifies a measurement target area 109 from a transmission image and calculates its liquid volume. [Figure 4] This diagram illustrates the working distance of area camera 103. [Figure 5A] This shows an example where label 107 is attached to the container of biological sample 101. [Figure 5B] This shows an example where label 107 is attached to the container of biological sample 101. [Figure 6A] This diagram illustrates the challenges related to re-illumination. [Figure 6B] This diagram illustrates the challenges related to re-illumination. [Figure 7A] This diagram shows the re-illumination light from the second mirror 105. [Figure 7B] This diagram illustrates a method for preventing re-illumination light from the second mirror 105. [Figure 8] A modified example of absorber 106 is shown. [Figure 9] This figure shows that scattered light from label 107 is reflected from area camera 103 to re-illuminate the biological sample 101. [Figure 10]It is a diagram showing that illumination light from the surface illumination light source 102 is reflected by the area camera 103 to re-illuminate the biological sample 101. [Figure 11A] It is a diagram showing that the surface illumination light source 102 directly illuminates the location where the transmitted light exits. [Figure 11B] It is a diagram for explaining a method of preventing the surface illumination light source 102 from directly illuminating the imaging range. [Figure 12] It is a plan view showing the configuration of the biological sample measuring device 100 according to Embodiment 2. [Figure 13] It is a plan view showing the configuration of the biological sample measuring device 100 according to Embodiment 3.

Mode for Carrying Out the Invention

[0012] <Embodiment 1> In Embodiment 1 of the present disclosure, the biological sample to be measured is a specimen with a label attached before unsealing (before analysis), and it is assumed that it is separated into a plurality of component layers (typically 1 to 3 layers) depending on whether or not centrifugation is performed. What is to be measured is a part of the specimen separated into a plurality of layers, such as plasma or serum, which is an analysis target (dispensing target) by a biochemical analyzer or the like.

[0013] FIG. 1 is a plan view showing the configuration of the biological sample measuring device 100 according to Embodiment 1 of the present disclosure. The biological sample measuring device 100 is a device for measuring the biological sample 101. The biological sample 101 is a sample configured as described above. The biological sample measuring device 100 identifies the measurement target area of the biological sample 101 and measures its liquid volume. The biological sample measuring device 100 includes a surface illumination light source 102, an area camera 103, a first mirror 104, a second mirror 105, an absorber 106, and an image processing unit 108.

[0014] The surface illumination light source 102 is configured to switch the wavelength of the emitted light between two wavelengths, and uses this light to illuminate the biological sample 101. The light emitted by the surface illumination light source 102 can simultaneously illuminate two or more component layers constituting the biological sample 101 (i.e., across two or more component layers). Furthermore, it can illuminate the upper surface of the topmost layer (the boundary between the sample and the air layer), regardless of the component layer. Switching the wavelength of light does not necessarily require emitting light with only a single wavelength; it is sufficient to switch the wavelength component with the strongest intensity (e.g., wavelength λ1 = 1550 ± 100 nm, wavelength λ2 = 970 ± 100 nm). In the case of a biological sample 101 with one or three component layers, if the number of component layers is known before measurement, it is sufficient to use either of the two wavelengths, and there is no need to switch wavelengths. The reason and method of wavelength selection will be explained later in the measurement principle section.

[0015] The area camera 103 generates a two-dimensional image of the biological sample 101 by imaging the surface illumination light that has passed through the biological sample 101. The area camera 103 has sensitivity characteristics that allow it to detect light in the wavelength range emitted by the surface illumination light source 102. The area camera 103 can be constructed using, for example, an InGaAs camera.

[0016] The first mirror 104 reflects the transmitted light that has passed through the biological sample 101 toward the second mirror 105. The second mirror 105 reflects the transmitted light that has been reflected from the first mirror 104 toward the area camera 103. As a result, the transmitted light is reflected twice from the time it passes through the biological sample 101 until it reaches the area camera 103, and the optical path is refracted twice as a result of these reflections.

[0017] The absorber 106 has the property of attenuating the amount of light transmitted through the biological sample 101 by absorbing at least partially the transmitted light. The size and arrangement of the absorber 106 will be described later.

[0018] The image processing unit 108 extracts the measurement target area (image area of ​​the sample) from the image captured by the area camera 103. The extraction principle will be described later.

[0019] Figures 2A and 2B illustrate the principle of identifying the measurement target area. In the configuration shown in Figure 1, the area camera 103 captures a two-dimensional transmission image of the biological sample 101, as shown in Figures 2A and 2B.

[0020] Figure 2A shows an example where the biological sample 101 is separated into three layers. Figure 2B shows an example where the biological sample 101 is separated into two layers. The blood clot 202 is formed in the lower layer when the biological sample 101 is centrifuged. The separating agent 201 is added to separate the blood clot 202 from the measurement target area 109.

[0021] Comparing the first wavelength (wavelength 1) and the second wavelength (wavelength 2) emitted by the surface illumination light source 102, the transmittance when wavelength 1 passes through the blood clot 202 is approximately the same as the transmittance when wavelength 2 passes through the blood clot 202. Therefore, the difference between the image of the blood clot 202 acquired using wavelength 1 and the image of the blood clot 202 acquired using wavelength 2 is very small. Similarly, for the separating agent 201, the transmittance of wavelength 1 and the transmittance of wavelength 2 are approximately the same, so the difference between the two images is very small.

[0022] In contrast, the transmittance when wavelength 1 passes through the measurement target region 109 is significantly different from the transmittance when wavelength 2 passes through the measurement target region 109. Therefore, the difference between the image of the measurement target region 109 acquired using wavelength 1 and the image of the measurement target region 109 acquired using wavelength 2 is significant. By identifying this difference, the measurement target region 109 can be extracted from the image.

[0023] The wavelength bands to be used as wavelength 1 and wavelength 2 must be selected in advance so that, as illustrated in Figures 2A and 2B, a significant difference occurs between the wavelengths in the measurement target region 109, but almost no difference occurs in other areas. As long as this condition is met, the specific numerical values ​​of the wavelengths can be arbitrary. That is, at a minimum, the difference between the transmittance when wavelength 1 passes through the measurement target region 109 and the transmittance when wavelength 2 passes through the measurement target region 109 must be greater than the difference between the transmittance when wavelength 1 passes through areas other than the measurement target region 109 and the transmittance when wavelength 2 passes through areas other than the measurement target region 109.

[0024] By using the above measurement principle, the measurement target region 109 can be identified even when the biological sample 101 is separated into multiple component layers. The image processing unit 108 identifies the measurement target region 109 according to this principle. The number of component layers does not matter, but typical biological samples such as plasma and serum are separated into 1 to 3 layers. In either case, the measurement target region 109 can be identified with high accuracy.

[0025] For biological samples 101 with one component layer and biological samples 101 with three component layers, if the number of component layers is known in advance before measurement, measurement is possible using a transmission image of only one wavelength. In the case of three layers as shown in Figure 2A, a wavelength should be selected that has a difference in absorption rate between the separation agent 201 or air layer located above and below the measurement target region 109 and the measurement target region 109. In the case of one layer, a wavelength should be selected that has a difference in absorption rate between the air layer above the measurement target region 109 and the measurement target region 109 itself.

[0026] Figure 3A shows the configuration of the image processing unit 108. The image processing unit 108 analyzes the images captured by the area camera 103 at each wavelength. The image processing unit 108 comprises an image acquisition unit 1081, a measurement target area identification unit 1082, and a liquid volume calculation unit 1083. The image acquisition unit 1081 acquires each of the two wavelength transmission images captured by the area camera 103. The measurement target area identification unit 1082 identifies the measurement target area 109 by comparing the images captured at each wavelength. The liquid volume calculation unit 1083 calculates the liquid volume in the measurement target area 109.

[0027] Figure 3B is a flowchart illustrating an example of the process by which the image processing unit 108 identifies the measurement target area 109 from the transmission image and calculates its liquid volume. The steps in Figure 3B are described below.

[0028] (Figure 3B: Step S301) The measurement target area identification unit 1082 acquires image data for wavelength 1 and wavelength 2. In this flowchart, it is sufficient to identify the measurement target area 109 according to the procedure described in Figures 2A and 2B, so the exposure time can be set to a predetermined value, for example.

[0029] (Figure 3B: Step S302) The measurement target area identification unit 1082 calculates a difference image between the image captured at wavelength 1 and the image captured at wavelength 2. This step calculates the difference image as described in Figures 2A and 2B, and the difference image can be obtained by calculating the difference in pixel values ​​of each image. For example, the calculation procedure is as follows: (a) Wavelength 1 image - Wavelength 2 image; (b) Wavelength 2 image - Wavelength 1 image; (c) (Wavelength 1 image - Wavelength 2 image) / (Wavelength 1 image + Wavelength 2 image).

[0030] (Figure 3B: Step S302: Supplement) When the biological sample 101 has one or three component layers, and the transmission image at one wavelength is to be analyzed without switching wavelengths, this step can be omitted, and the boundaries of each layer can be identified using processing such as edge detection in S305.

[0031] (Figure 3B: Step S303) The measurement target area identification unit 1082 sets a threshold for detecting the measurement target area 109. The threshold can be, for example, set to a pixel value of 0, or an appropriate threshold can be set for each sample.

[0032] (Figure 3B: Step S304) The measurement target area identification unit 1082 extracts the portion of the difference image where the pixel value is equal to or greater than a threshold, as the measurement target area 109.

[0033] (Figure 3B: Step S305: Part 1) The measurement target area identification unit 1082 detects the edges (height) of the measurement target area 109. For example, the following edge detection methods can be used: (a) an edge detection algorithm based on the vertical brightness gradient (slope) or derivative value; (b) the extracted pixel values ​​of the measurement target area 109 are accumulated horizontally to create a one-dimensional model, and the vertical edges are identified using the slope, derivative value, and variance value of the signal in the vertical direction. The identification results can be saved as coordinate values ​​on the captured image. That is, the statistics of the pixel values ​​in the horizontal direction are calculated as horizontal feature quantities, and by comparing these feature quantities along the vertical direction, the upper and lower edges of the measurement target area 109 can be identified.

[0034] (Figure 3B: Step S305: Part 2) The liquid volume calculation unit 1083 can use the results of this step to calculate the liquid volume of the measurement target area 109. For example, after identifying the boundaries of each layer, it calculates the liquid volume of the corresponding area using information on the pixel pitch, the number of extracted pixels, and the inner diameter of the container of the biological sample 101.

[0035] Figure 4 illustrates the working distance of the area camera 103. In order to measure the liquid volume from the transmission image of the biological sample 101 as shown in Figure 2, it is necessary to secure a field of view in the long axis direction that can image the boundaries of each layer of the biological sample 101. To achieve this, it is necessary to ensure a sufficient working distance (the distance from the biological sample 101 to the lens of the area camera 103).

[0036] The required working distance can be determined using the lens's focal length, the required field of view, and the sensor size. If the required field of view is 100 mm, which is the length of the blood collection tube (sample container), the focal length is 8 mm, and the sensor size is 6.4 mm (long side), then the working distance will be 125 m. In other words, to image the entire biological sample, the biological sample 101 and the area camera 103 must be placed 125 mm apart.

[0037] In Figure 1, two mirrors are used to refract the optical path of the transmitted light. By refracting the optical path in this way, it is possible to suppress the area size of the biological sample measurement device 100 while ensuring sufficient working distance. Furthermore, the size of the biological sample measurement device 100 can be changed according to the application by changing the arrangement of the mirrors.

[0038] The surface illumination light source 102 should preferably have a size that is enclosed by the line connecting the outermost shape of the biological sample 101 and the center of the area camera 103. Therefore, the size of the surface illumination light source 102 in the vertical direction of Figure 4 should preferably ensure that it is within the size of the area enclosed by the line connecting the outermost shapes shown in Figure 4. For example, if the working distance is 125 mm, the length of the blood collection tube is 100 mm, and the distance from the illumination to the area camera is 150 mm, then, due to the similarity of the triangles, the height of the surface illumination light source 102 (size in the vertical direction of Figure 4) should preferably be 120 mm.

[0039] Figures 5A and 5B show examples of containers for biological samples 101 with labels 107 attached. Figure 5A is a side view of the container, and Figure 5B is a top view. Containers for biological samples 101 (e.g., blood collection tubes) may have barcode labels or pre-labels attached. Even in such cases, it is necessary to accurately identify the measurement target area 109.

[0040] If there is no mechanism to control the orientation of the biological sample 101, the label may be on the illumination side (Figure 5B(1)) or on the opposite side of the illumination (Figure 5B(2)). In both cases, it is required to identify the measurement target area with the same accuracy.

[0041] Figures 6A and 6B illustrate the challenges related to re-illumination. Under labeling conditions as shown in Figure 5, challenges arise regarding the re-illumination of transmitted light. When miniaturization is achieved by using two mirrors as shown in Figure 1, light scattered and transmitted from the biological sample 101 is reflected from the second mirror 105, and re-illumination light is generated that illuminates the sample surface on the opposite side of the surface illumination light source 102 via an optical path as shown by the solid line in Figure 6A.

[0042] In this case, as shown in Figure 5B(1), when the label 107 is on the illumination side and not on the first mirror 104 side, a transmission image like that shown in Figure 6B(1) is obtained. Under these conditions, sufficient boundary contrast is obtained to identify the measurement target area. On the other hand, as shown in Figure 5B(2), when the label 107 is on the first mirror 104 side, the re-illumination light is reflected by the label 107, and both the transmitted light from the biological sample 101 and the reflected light from the label 107 are imaged. In the case of a label 107 with high reflectivity, such as white, if there is light reflected from the label 107, a label image like that shown in Figure 6B(2) is obtained. Such reflected light from the label 107 reduces the contrast of the transmitted light necessary to identify the measurement target area 109.

[0043] Similar re-illumination issues also arise when the surface illumination light source 102 directly illuminates the area camera 103 (arrows pointing from the surface illumination light source 102 to the area camera 103 in Figure 6A), and the light reflected from the area camera 103 illuminates the biological sample 101 (arrows pointing from the area camera 103 to the biological sample 101 in Figure 6A).

[0044] Thus, even with the same biological sample 101, the image obtained differs depending on the orientation of the biological sample 101 (the orientation of the label 107). Furthermore, if the decrease in contrast due to re-illumination light is significant, the accuracy of identifying the measurement target area 109 decreases. In other words, the accuracy of the analysis decreases depending on the orientation of the biological sample 101. To solve these problems, in this embodiment 1, the size and arrangement of the absorber 106 are configured as follows.

[0045] Figure 7A shows the re-illumination light from the second mirror 105. The dotted line indicates the optical path of the effective light beam required for the area camera 103 to acquire an image of the biological sample 101. The dashed line indicates the line where the normal of the second mirror 105 coincides with the biological sample 101. When the dashed line path is valid (i.e., transmitted light can reach the biological sample 101 through this path), re-illumination light is generated when light scattered at the label 107 is reflected from the second mirror 105 to re-illuminate the label 107.

[0046] Figure 7B illustrates a method for preventing re-illumination from the second mirror 105. As mentioned above, the working distance is determined by the field of view required for analysis, the sensor size of the area camera 103, and the focal length of the lens. Therefore, it is not possible to prevent re-illumination by changing the distance between the area camera 103 and the biological sample 101. To achieve this, the first mirror 104 and the second mirror 105 are moved away from the biological sample 101 while maintaining the working distance, and the distance between the area camera 103 and the second mirror 105 is shortened. This results in the arrangement shown in Figure 7B while maintaining the working distance.

[0047] In Figure 7B, the absorber 106 is positioned along the dashed-dotted optical path, thereby blocking the re-illumination light. Specifically, the size and position of the absorber 106 are configured to block the transmitted light reflected from the second mirror 105 from re-illuminating the biological sample 101 (more specifically, the label 107). This resolves the re-illumination problem described in Figure 6A.

[0048] It is desirable that the absorber 106 be positioned so as not to obstruct the transmitted light reflected from the first mirror 104 toward the second mirror 105. In Figure 7B, the absorber 106 is positioned such that its right end does not coincide with the straight line connecting the left end of the first mirror 104 and the left end of the second mirror 105. This allows the absorber 106 to block only the dashed-dotted path of the re-illumination light without obstructing the dotted-dotted path of the effective light beam.

[0049] The arrangement in Figure 7B also has the following advantages. In the conventional arrangement of the surface illumination light source 102 and area camera 103 as shown in Figure 4, the wiring supplying power to the surface illumination light source 102 extends to the left of the drawing, and the wiring supplying power to the area camera 103 extends to the right of the drawing, thus increasing the space required to accommodate them. In contrast, in the arrangement in Figure 7B, both wirings extend to the left of the drawing, thus reducing the space required to accommodate them. In other words, it is desirable to arrange the surface illumination light source 102 and area camera 103 so that the direction in which the surface illumination light source 102 emits light and the direction in which the area camera 103 receives light are parallel to each other and facing the same direction.

[0050] Figure 8 shows a modified example of the absorber 106. The shape of the absorber 106 does not necessarily have to be planar; for example, as shown in Figure 8, it may be bent by refraction at one or more points (i.e., it may have two or more parts that block the optical path of the dashed line). When the absorber 106 is bent, it becomes easier to create a gap between the dotted line path of the effective luminous flux and the absorber 106. Even with a gap, it is sufficient if at least one of the bent parts blocks the dashed line. This has the effect of making product design easier, taking into account misalignment of parts, etc.

[0051] Figure 9 shows how scattered light from label 107 is reflected from area camera 103 to re-illuminate the biological sample 101. The dashed line shows the path connecting the outermost shape of the biological sample 101 and the outermost shape of area camera 103. If this path is effective (i.e., scattered light from label 107 is reflected by area camera 103 and can reach the biological sample 101 via this path), the light scattered by label 107 re-illuminates the biological sample 101. The absorber 106 may be positioned to obstruct this path.

[0052] Specifically, the absorber 106 should be positioned so as to block the region between (a) the tangent line (dotted-dotted line on the left) that touches both the left side surface (first side) of the biological sample 101 (sample container) and the left side surface (second side) of the area camera 103, and (b) the tangent line (dotted-dotted line on the right) that touches both the right side surface (third side) of the biological sample 101 and the right side surface (fourth side) of the area camera 103.

[0053] Figure 10 shows how illumination light from the surface illumination light source 102 is reflected from the area camera 103 to re-illuminate the biological sample 101. The dashed line shows the path connecting both ends of the light-emitting surface of the surface illumination light source 102 and the outermost shape of the area camera 103. If this path is effective (i.e., illumination light from the surface illumination light source 102 can directly enter the area camera 103), the illumination light reflected from the area camera 103 may re-illuminate the biological sample 101.

[0054] Since this reflected light is stronger than the light scattered by the absorber 106, it is desirable to also place the absorber 106 in this path. If the dashed-dotted path in Figure 9 is blocked, the biological sample 101 will not be re-illuminated by the illumination light in Figure 10, but there is a possibility that the label 107 will be re-illuminated by the light due to multiple reflections by the mechanical components that hold the optical components. By completely eliminating the dashed-dotted path in Figure 10, such paths that involve multiple reflections can also be prevented.

[0055] Specifically, the absorber 106 should be positioned so as to block the region between (a) a tangent line (the dashed line on the left) that touches both one end of the light-emitting surface of the surface illumination light source 102 and the left side surface (fifth side) of the area camera 103, and (b) a tangent line (the dashed line on the right) that touches both the other end of the light-emitting surface of the surface illumination light source 102 and the right side surface (sixth side) of the area camera 103.

[0056] Figure 11A shows how the surface illumination light source 102 directly illuminates the area from which transmitted light is emitted. When the light-emitting surface of the surface illumination light source 102 is large, the area on the biological sample 101 captured by the area camera 103 is directly illuminated by the surface illumination light source 102. In other words, the surface illumination light source 102 directly illuminates the area from which transmitted light from the biological sample 101 is emitted. The dashed line indicates such a direct illumination path. This path, like the re-illumination light, is a factor that reduces the contrast of the measurement target area 109.

[0057] Figure 11B illustrates a method for preventing the surface illumination light source 102 from directly illuminating the imaging area. When the light-emitting surface of the surface illumination light source 102 is the same size as the biological sample 101, it is possible to prevent the area on the biological sample 101 being directly illuminated by the area camera 103. Therefore, it is desirable to form the light-emitting surface of the surface illumination light source 102 to be the same size as the biological sample 101.

[0058] However, to account for the misalignment of the components, the light-emitting surface of the surface illumination light source 102 may be made larger than that of the biological sample 101 by the amount of the misalignment. In this case, the light-emitting surface will be slightly larger than that of the biological sample 101, as shown in Figure 11B, resulting in the occurrence of direct illumination paths similar to the dashed line in Figure 11A. Therefore, it is desirable to take measures such as making the size of the light-emitting surface slightly larger than that of the biological sample 101 to account for the misalignment of the components, and having the image processing unit 108 analyze the captured image only in the area where direct illumination light does not enter.

[0059] On the other hand, the planar size of the light-emitting surface of the surface illumination light source 102 (size in the vertical direction in Figure 11A or size in the depth direction in Figure 4) needs to be of a certain size. Specifically, as explained in Figure 4, it is desirable that the size be the area enclosed by the line connecting the outermost shape of the biological sample 101 and the center of the area camera 103. For example, if the working distance is 1 mm, the width of the sample container is 16 mm, and the distance from the surface illumination light source 102 to the area camera 103 is 150 mm, then, due to the similarity of the triangles, the planar size of the light-emitting surface will be 19.2 mm.

[0060] As shown in Figure 11A, if the light-emitting surface is larger than the sample container, the illumination light will directly hit the edge of the sample container, so that part is excluded from the analysis range of the image processing unit 108. This allows the width of the light-emitting surface to be set to 19.2 mm as calculated above. Therefore, it is possible to achieve both the prevention of direct illumination light and the necessary light-emitting surface size from the standpoint of working distance. As mentioned above, assuming an area camera 103 with a working distance of 125 mm, it can be said that the best outer dimensions of the light-emitting surface are set to approximately 120 × 19.2 mm.

[0061] <Embodiment 1: Summary> The biological sample measuring device 100 according to this embodiment 1 captures transmitted light that has passed through the biological sample 101 with an area camera 103 (a camera that takes a two-dimensional image of the biological sample 101), and further includes a first mirror 104 and a second mirror 105 that refract the transmitted light and guide it to the area camera 103. The optical system using the area camera 103 eliminates the need for large mechanisms such as vertical scanning of the biological sample 101. Furthermore, the optical system using two mirrors improves the design flexibility of the size and wiring direction of the biological sample measuring device 100 while maintaining the working distance. This makes it possible to miniaturize the biological sample measuring device 100. For example, the biological sample measuring device 100 can be added as an option to existing products such as centrifuges. The biological sample measuring device 100 can, of course, be used not only as an option but also as a standalone device.

[0062] The biological sample measuring device 100 according to this embodiment 1 blocks (a) light reflected from the second mirror 105 toward the biological sample 101, (b) light scattered from the biological sample 101, incident on the area camera 103, and further reflected from the area camera 103 toward the biological sample 101, and (c) light that the surface illumination light source 102 directly illuminates the area camera 103 and further reflected from the area camera 103 toward the biological sample 101, etc., with the absorber 106. This prevents the image contrast of the measurement target area 109 from decreasing due to re-illumination. This preventive effect is particularly pronounced in biological samples 101 to which a label 107 is attached.

[0063] <Embodiment 2> Figure 12 is a plan view showing the configuration of a biological sample measuring device 100 according to Embodiment 2 of this disclosure. By adopting the configuration described in Embodiment 1, the biological sample measuring device 100 can be made sufficiently compact, and the biological sample measuring device 100 can be mounted as an additional option to existing devices such as centrifuges. That is, each component of the biological sample measuring device 100 can be mounted inside a relatively small housing 1202. Furthermore, by adjusting the arrangement of the first mirror 104 and the second mirror 105, the arrangement and size of each component of the biological sample measuring device 100 can also be adjusted so that it can be mounted inside the housing 1202.

[0064] The biological sample measuring device 100 may be equipped with an entrance 1201 for introducing the biological sample 101. The arrangement of the first mirror 104 and the second mirror 105 may be changed depending on the route through which the biological sample 101 is introduced.

[0065] As for the loading route, there are methods such as providing an loading entrance (opening) on ​​the side of the device for loading and unloading the sample, as shown in Figure 12, or providing an opening on the top of the device for loading and unloading the sample from above. As for the method of grasping and moving the biological sample 101, there are methods such as grasping and moving it using a grasping mechanism that grasps the cap area of ​​the container, or placing the container on a holder and moving it using a belt conveyor system.

[0066] <Embodiment 3> Figure 13 is a plan view showing the configuration of a biological sample measuring device 100 according to Embodiment 3 of this disclosure. The biological sample measuring device 100 according to Embodiment 3 does not have a second mirror 105. Therefore, the first mirror 104 directly reflects transmitted light toward the area camera 103. The method for identifying the measurement target area 109 is the same as in Embodiments 1 and 2. In Embodiment 3 as well, it is desirable to block re-illumination light and the like with an absorber 106.

[0067] The single-dotted line shows the path through which light scattered from the biological sample 101 illuminates the area camera 103. The double-dotted line shows the path through which the surface illumination light source 102 directly illuminates the area camera 103. In both paths, the light is scattered and reflected by the area camera 103, re-illuminating the biological sample 101. For the single-dotted line, the re-illumination light can be blocked by arranging the absorber 106 as explained in Figure 9. For the double-dotted line, the reflected light can be blocked by arranging the absorber 106 as explained in Figure 10.

[0068] In this third embodiment, it is desirable to position the absorber 106 such that it does not obstruct the effective light beam reflected from the first mirror 104 and directed toward the area camera 103. Therefore, the right end of the absorber 106 in Figure 13 is positioned so as not to overlap with the straight line connecting the left end of the first mirror 104 and the left end of the imaging surface of the area camera 103.

[0069] The biological sample measuring device 100 according to this third embodiment can have a simpler configuration compared to the case with two mirrors described in the first embodiment. By using only one mirror, the size of the biological sample measuring device 100 becomes larger compared to the case with two mirrors, but the configuration of this third embodiment is also useful if there is sufficient space.

[0070] <Regarding variations of this disclosure> The biological sample measuring device 100 according to this disclosure can be installed in an existing device as an additional option, as described in Embodiment 2, or it can be used as a standalone biological sample measuring device 100. [Explanation of symbols]

[0071] 100: Biological sample measuring device 101: Biological sample 102: Area lighting light source 103: Area Camera 104: First Mirror 105: Second Mirror 106: Absorbent material 107: Label 108: Image Processing Unit 109: Measurement target area 201: Separating agent 202: Blood clot

Claims

1. A biological sample measuring device for measuring a biological sample separated into multiple component regions, A surface light source that irradiates the aforementioned biological sample with light, An imaging device that generates a two-dimensional image of the biological sample using the light that has passed through the biological sample. A first mirror that reflects the light that has passed through the biological sample, A second mirror that reflects the light reflected from the first mirror toward the imager, The light absorber mentioned above, Equipped with, The absorber is positioned to block the light on the reflection path through which the light reflected by the second mirror returns to the biological sample. The absorber has a shape that is bent at least at one point, and comprises a first portion that blocks the light and a second portion that blocks the light. A biological sample measuring device characterized by the following features.

2. The absorber is positioned so as not to obstruct the light reflected from the first mirror toward the second mirror in the path of the light between the first mirror and the second mirror. The biological sample measuring device according to claim 1, characterized in that it is a biological sample measuring device.

3. The absorber is positioned to block the light in at least a first range of the space between the biological sample and the imager. The first range is, A first tangent line is in contact with the first side surface of the container containing the biological sample and the second side surface of the imager. A second tangent line is in contact with the third side of the container opposite to the first side and with the fourth side of the imager opposite to the second side. It is a region enclosed by The biological sample measuring device according to claim 1, characterized in that it is a biological sample measuring device.

4. The absorber is positioned to block the light in at least a second range of the space between the surface light source and the imager. The second range is, A third tangent line is in contact with one end of the light-emitting surface of the surface light source and with the fifth side surface of the imager. A fourth tangent line is in contact with the other end of the light-emitting surface and the sixth side of the imager that is opposite to the fifth side. It is a region enclosed by The biological sample measuring device according to claim 1, characterized in that it is a biological sample measuring device.

5. The biological sample measuring device further includes an image processing unit that identifies the target portion to be measured from the component region from the captured image, The surface light source has a surface size that allows it to directly illuminate at least a portion of the area from which the light transmitted through the biological sample is emitted. The image processing unit identifies the target portion of the captured image without using the portion generated from the light that has been transmitted through a portion of the image. The biological sample measuring device according to claim 1, characterized in that it is a biological sample measuring device.

6. The biological sample measuring device further includes an image processing unit that identifies the target portion to be measured from the component region from the captured image, The imaging device generates a first image of the biological sample using the first wavelength component of the light transmitted through the biological sample. The imaging device generates a second image of the biological sample using the second wavelength component of the light transmitted through the biological sample. The image processing unit calculates the difference between the portion generated using the first wavelength component in the first captured image and the portion generated using the second wavelength component in the second captured image. The image processing unit identifies the range of the target portion by identifying the portion where the difference exceeds a threshold. The biological sample measuring device according to claim 1, characterized in that it is a biological sample measuring device.

7. The biological sample measuring device further includes an entrance for introducing the biological sample into the biological sample measuring device. The biological sample measuring device according to claim 1, characterized in that it is a biological sample measuring device.

8. The light emission direction of the surface light source and the light receiving direction of the imager are parallel to each other. The direction in which the surface light source emits the light and the direction in which the imager receives the light are opposite to each other. The biological sample measuring device according to claim 1, characterized in that it is a biological sample measuring device.

9. The biological sample measuring device according to claim 1, characterized in that it measures the biological sample contained in a labeled container.

10. A method for measuring a biological sample that is contained in a labeled container and separated into multiple component regions, The steps include irradiating the biological sample with light from a surface illumination light source, A step of generating a two-dimensional image of the biological sample using an imager with light that has passed through the biological sample. A step of reflecting the light that has passed through the biological sample with a first mirror, The step of reflecting the light reflected from the first mirror toward the imager by the second mirror, A step of absorbing the light with an absorber that absorbs the light, It has, The absorber is positioned to block the light on the reflection path through which the light reflected by the second mirror returns to the biological sample. The absorber has a shape that is bent at least at one point, and comprises a first portion that blocks the light and a second portion that blocks the light. A method for measuring biological samples characterized by the following features.

11. A biological sample measuring device for measuring a biological sample separated into multiple component regions, A surface light source that irradiates the aforementioned biological sample with light, An imaging device that generates a two-dimensional image of the biological sample using the light that has passed through the biological sample. A mirror that reflects the light that has passed through the biological sample toward the imaging device. The light absorber mentioned above, Equipped with, The absorber is positioned to block the light on the reflection path through which the light scattered or transmitted from the biological sample is reflected back from the imager towards the biological sample. The absorber has a shape that is bent at least at one point, and comprises a first portion that blocks the light and a second portion that blocks the light. A biological sample measuring device characterized by the following features.

12. The absorber is positioned so as not to obstruct the light reflected from the mirror toward the imager in the path of the light between the mirror and the imager. The biological sample measuring device according to claim 11, characterized in that it is a biological sample measuring device.

13. The absorber is positioned to block the light in at least a first range of the space between the biological sample and the imager. The first range is, A first tangent line is in contact with the first side surface of the container containing the biological sample and the second side surface of the imager. A second tangent line is in contact with the third side of the container opposite to the first side and with the fourth side of the imager opposite to the second side. It is a region enclosed by The biological sample measuring device according to claim 11, characterized in that it is a biological sample measuring device.

14. The absorber is positioned to block the light in at least a second range of the space between the surface light source and the imager. The second range is, A third tangent line is in contact with one end of the light-emitting surface of the surface light source and with the fifth side surface of the imager. A fourth tangent line is in contact with the other end of the light-emitting surface and the sixth side of the imager that is opposite to the fifth side. It is a region enclosed by The biological sample measuring device according to claim 11, characterized in that it is a biological sample measuring device.

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