JP7515879B2 - Blood product inspection device and blood product inspection method - Google Patents

Description

The patent law, Article 30, Paragraph 2, applies. The data was made available to the relevant personnel at the Japanese Red Cross Kinki Block Blood Center.

The present invention relates to a blood product testing device and method for testing swirling.

As shown in Non-Patent Document 1, a unique phenomenon called swirling is observed in platelet concentrates (PC). Swirling is a phenomenon in which a vortex pattern is observed when a bag containing PC is held up to light and slowly stirred. It is said that this is because unstimulated platelets have a disk-like shape, and when stirred, the disk-like platelets cause a light scattering phenomenon (swirling) in which light is uniformly refracted. When the platelet shape changes, uniform refraction does not occur, and swirling decreases and disappears. This shows that the presence or absence of the light scattering phenomenon in PC is closely related to the platelet shape and reflects the state of the platelets. It is said that the proportion of disk-shaped platelets in PC correlates with the lifespan in the body.

In the swirling test in daily work, the purpose is to reliably exclude PCs with negative swirling, so the test is performed by two people and graded on a two-level scale: pass or fail. Two graders hold the PC bag under a white light source (50-100 W) and gently shake it, and observe the swirling pattern inside the bag from a distance of 30-70 cm. If the two graders disagree on their judgment, the other observer retests and the result is used. The PC swirling test is a useful method for easily and quickly determining the quality of PC without taking samples, because it allows the morphology of platelets in PC to be confirmed by external observation. Since the swirling test is judged visually, it is important for graders with little experience to be trained, and differences in proficiency may affect variability between facilities.

Currently, donated blood is collected at 11 blood centers across the country and manufactured into red blood cell products, plasma products, and platelet products. These blood products are inspected at the blood centers, including a visual inspection process, which is carried out by dedicated inspectors at a rate of approximately 2,000 to 4,000 bags per day.

In order to improve the efficiency of visual inspection by humans as described above, the invention of Patent Document 1 captures an image of a blood product bag that includes a white area in the center due to light passing through from the back side when illuminated with LED white parallel light transmitted illumination, and a black spiral pattern within that area. This image is then binarized by making only the area where swirling occurs white and the rest black. The inspection image shows a specified inspection area, and the area of white pixels (swirling area) is found by performing the binarization process described above in this inspection area. The proportion of the swirling area found in this way is then calculated. Naturally, if there is little swirling, this proportion will be smaller.

Although not related to the above swirling, an invention for inspecting the shape parameters of platelets is disclosed in Patent Document 2.

Although not related to the above swirling, Patent Document 3 discloses an invention for testing fibrin contained in the supernatant of gravity-separated blood.

Patent No. 4929422 JP 2000-46723 A JP 2000-88844 A

Journal of the Japan Society of Blood Transfusion, Vol. 49, No. 3, 49(3): 432-438, 2003

However, the correlation between the assessment results (ratio of swirling area) of the invention in Patent Document 1 and the evaluation results of platelet morphology was not stable, and the assessment results were not yet sufficient to be used as an objective numerical value for swirling.

The invention in Patent Document 1 compares actual swirling inspections with images, and attempts to determine differences in swirling from the results of analyzing the actual images, but since no image is ever the same, it has been difficult to put into practical use. Up until now, various studies have been conducted on mechanizing swirling inspections, but no established device has yet been developed. Patent Document 2 has also not led to the development of a mechanized swirling inspection.

Patent Document 3 is used to separate blood into red blood cells, plasma, and platelets for analysis of the target blood, and is used in a significantly different context in terms of managing the quality of the preparation after separation. When the difference between blood cells (red blood cells) and fibrin is examined using RGB colors, the difference between objects with significantly different colors is detected, making it difficult to apply to swirling.

Ideally, such tests would be carried out at the distribution center where the blood products are delivered (or even within the hospital in some cases), but currently there is a shortage of personnel. Furthermore, with the COVID-19 pandemic, it is difficult to manage these tests even in hospitals with a large number of COVID-19 patients.

Therefore, the present invention aims to establish a system for mechanizing swirling inspection.

In view of the above problems, the present invention provides a blood product testing device that includes a color distribution generation unit that captures a first image of the blood product by a colorimeter before swirling occurs, generates a first color distribution of the acquired first image, captures a second image of the blood product by the colorimeter after swirling occurs, and generates a second color distribution of the acquired second image, and a swirling testing unit that compares the first color distribution with the second color distribution and performs a swirling test based on the degree of agreement between the first color distribution and the second color distribution. This makes it possible to mechanize the swirling test device by comparing the color distributions of the swirling test images.

"Swirling" is a swirling or striped pattern that appears when a blood product bag is shaken. "Blood products before swirling occurs" is the standard, and is a blood product in which swirling has disappeared. "Blood products after swirling occurs" is the subject of swirling testing, and is the state of the blood product after the blood product bag containing the blood product is shaken. In most cases, swirling occurs when a blood product bag is shaken, but there are also blood product bags that do not result in swirling.

The present invention is fundamentally different in that it does not involve image processing of the color distribution in the real space, but rather judges based on the color distribution mapped to a color space. In the present invention, since the swirling color distribution (three-dimensional distribution) is measured, even if the swirling pattern of the real image changes, the swirling color distribution remains almost the same, allowing for stable evaluation (quantification, graphing, etc.).

A "color distribution" is the distribution of independent quantities of color in a color space. A "color space" is a space in which color can be specified by three independent quantities, and when the magnitude of each quantity is expressed as the distance from the origin along the three axes, color can be specified as the coordinates of a point in the space.

Any suitable color system can be used for the "color distribution". For example, the "XYZ color system" was defined by the CIE in 1931 at the same time as the RGB color system so that negative values would not appear in a simple linear conversion of the RGB color system. The "XYZ color system" includes CIE color systems such as xyY, Yxy, XYZ, Lab, and Luv, and is a concept that includes two-dimensional color distribution or three-dimensional color space. In the XYZ color system, normalization as x=X/(X+Y+Z), y=Y/(X+Y+Z) and definition as Yxy are commonly used.

The "XYZ color system" includes color spaces defined by two-dimensional coordinates and three-dimensional coordinates. Representative examples of color spaces include the XYZ color space and the Lab color space. In the case of two-dimensional color spaces, for example, the Yxy color space and the Luv color space, examples of the configuration include the xy chromaticity diagram (xy chromaticity values (plane) normalized in the Yxy color space), the uv chromaticity diagram, and the u'v' chromaticity diagram, which are two-dimensional planes. Corresponding examples include the xy chromaticity histogram distribution or the Luv chromaticity histogram distribution, which are expressed as the density of pixel count values of the two-dimensional chromaticity diagram on a plane. The XYZ color system with three spectral sensitivities (S1(λ), S2(λ), S3(λ)) that are linearly converted to be equivalent to the CIE XYZ color matching functions is also included. In the case of three-dimensional color spaces, for example, the XYZ color space and the Lab color space are included. A color distribution is obtained by mapping pixel color information onto a three-dimensional color space.

The L ^* a ^* b ^* color system is CIE L ^* a ^* b ^* , which was derived from the XYZ color system to measure color differences due to differences in perception and devices. In Japan, JIS
This color system is specified in International Standard Z 8729. This color system was established to correct the uneven color discrimination sensitivity of the human eye in the color space of the previous XYZ color system, and the color difference measured in this space is widely used. Generally, Lab values are considered to be L ^* a ^* b ^* values.

The L ^* u ^* v ^* color system is one of the uniform color spaces established by the CIE in 1976. CIE L ^* u ^* v ^* is based on the wavelength of light and improves the uniformity of the wavelength intervals of the xy chromaticity diagram of the XYZ color system. In Japan, it is called JIS
It is specified in Z8518.

A colorimeter is a measuring instrument that measures the light from the object to be measured and outputs it as coordinates in color space.

"Color difference (ΔE)" is the difference between two colors expressed as the distance in color space. Colors are expressed by coordinates in color space. The greater the difference in colors, the greater the distance between the two points in color space. Currently, the definition of ΔE2000 is widely used.

The color distribution is based on the L ^* a ^* b ^* color system or the L ^* u ^* v ^* color system, thereby making it possible to improve the accuracy of the swirling inspection.

The present invention relates to a blood product comprising: a housing having an internal space; a computer unit having the color distribution generating unit and the swirling inspection unit; a light emitting unit that illuminates the blood product;
and a swirling generating unit that sets the blood product bag in a predetermined position by opening and closing a lid and shakes the blood product bag by sliding the lid in a predetermined direction. This makes it possible to efficiently perform swirling tests.

The swirling generating unit is provided in the upper part of the housing, and the colorimeter is provided in the lower part of the housing, and the blood product bag illuminated from above is imaged from below. This improves the work efficiency of the swirling inspection.

The swirling generating unit sets the blood product bag in a predetermined position by opening and closing the lid, and then slides it in a predetermined direction to agitate the blood product bag. This makes it possible to agitate the blood product bag simply by sliding the slider, improving the work efficiency of the swirling test.

The swirling generating section has a slider that slides in a predetermined direction and a stopper that holds the slider. When the slider moves from the predetermined position to the holding position, the stopper holds the slider, and when the stopper is released, the slider returns to the predetermined position, thereby applying agitation to the blood product bag. This makes it possible to agitate the blood product bag simply by moving the slider, thereby improving the work efficiency of the swirling test.

The light-emitting unit includes an oblique light-emitting unit and a surface light-emitting unit, and switches between them depending on the red blood cells, plasma, or platelets being measured, or on one of them. This makes the lighting more efficient.

The difference between the degree of consistency of the color distribution of the blood product at the first point and the degree of consistency of the color distribution of the blood product at the second point is calculated. This makes it possible to eliminate blood products with reduced swirling while transporting the blood product from the first point to the second point.

Another aspect of the present invention is a blood product testing method comprising a color distribution generation step of imaging a blood product before swirling occurs with a colorimeter, generating a first color distribution of the acquired first image, imaging a blood product after swirling occurs with the colorimeter, and generating a second color distribution of the acquired second image, and a swirling detection step of comparing the first color distribution with the second color distribution, detecting the degree of agreement between the first color distribution and the second color distribution, and detecting swirling based on the degree of agreement. This makes it possible to mechanize a swirling testing device by comparing the color distributions of images from swirling testing.

The data on the degree of agreement is stored on a server and shared among the blood product center, hospital/transport center, and hospital. This makes it easier to track swirling test results.

Yet another invention of the present invention is a blood product testing program for a blood product testing device that tests blood products, the blood product testing device being equipped with a monitor and a computer, the computer having a memory unit, a calculation unit, a judgment unit, and an instruction unit, and causing the computer to execute a color distribution generation step of capturing an image of a blood product before swirling occurs using a colorimeter, generating a first color distribution of the acquired first image, capturing an image of a blood product after swirling occurs using the colorimeter, generating a second color distribution of the acquired second image, and a swirling detection step of comparing the first color distribution with the second color distribution, detecting the degree of agreement between the first color distribution and the second color distribution, and detecting swirling based on the degree of agreement, and causing the monitor to display the first color distribution, the second color distribution, and the swirling detection result.

This allows for mechanization of swirling inspection equipment by comparing the color distribution of swirling inspection images. By downloading or uploading programs between multiple locations, swirling inspection programs can be improved.

The present invention makes it possible to mechanize swirling inspection equipment by comparing the color distribution of swirling inspection images.

1A to 1D are a perspective view, a left side view, and a right side view of a blood product testing device according to an embodiment of the present invention. 13A and 13B are perspective views of the blood product testing device before and after the door is opened and closed. 13A and 13B are perspective views showing the unlocking of the blood product testing device. 13A and 13B are perspective views showing the movement of a slider of the blood product testing device. 13A and 13B are perspective views showing the position of a side switch of the blood product testing device. 13 is a side view showing a state in which the slider of the swirling generating unit of the blood product testing apparatus has moved and is held by a stopper. FIG. 1 is a diagram showing the internal structure of a blood product testing device according to an embodiment of the present invention; FIG. 2 is an internal structure diagram of the blood product testing device according to the embodiment of the present invention. FIG. 3 is an internal structure diagram of the blood product testing device according to the embodiment of the present invention. 4 is a function showing the spectral sensitivity of a colorimeter 9 which is an XYZ color system camera in the embodiment of the present invention. 1 shows a specific example of a method for acquiring image information according to three spectral sensitivities (S1(λ), S2(λ), S3(λ)) in an embodiment of the present invention. (a) is an explanatory diagram of the case where a dichroic mirror is used. (b) is an explanatory diagram of the case where a filter turret is used. (c) is an explanatory diagram of the case where optical filters 92a, 92b, and 92c are microscopically attached to an image sensor 93. FIG. 2 is a block diagram of a computer unit according to an embodiment of the present invention. 13 is a screenshot of illumination aging of a blood product testing device according to an embodiment of the present invention. 1 is a screenshot showing screen 1 of the white calibration. 13 is a screenshot showing screen 2 of the white calibration. 13A and 13B are screenshots showing screen 3 of the white calibration. This is a screenshot showing screen 1 of the blood product test. This is a screenshot showing screen 2 of the same blood product test. This is a screenshot showing screen 3 of the same blood product test. (a) and (b) are screenshots showing screen 4 of the same blood product test. This is a screenshot showing screen 5 of the same blood product test. This is a screenshot showing screen 6 of the same blood product test. This is a screenshot showing screen 7 of the blood product test. This is a screenshot showing screen 7 of the blood product test. 1A and 1B are explanatory diagrams showing examples 1 and 2 of color distribution obtained by the same blood product testing method. This is an explanatory diagram showing the flow of transportation and photography to ensure the quality of blood products using this blood product testing method.

A blood product testing device 1 (hereinafter referred to as BIS1) according to a preferred embodiment of the present invention will be described with reference to Figures 1 to 25.

As shown in Figs. 1 to 9, the BIS 1 includes a housing 2 having an internal space 2a, a swirling generator 3 provided on the top of the housing 2 and in which a blood product bag B (hereinafter referred to as bag B) with an IC tag is set, an opening 4 opening to the top and sides of the swirling generator 3, a lid 5 having a handle 5a and a lever 5b that can open and close the opening 4 of the swirling generator 3 and assists in opening and closing, a stopper 6 that holds the blood product bag B in a slid state and returns it to its original position when a return switch 6a is turned ON, a touch panel monitor 7 attached to the housing 2, a computer unit 8 (hereinafter referred to as PC unit 8) that performs calculations for the swirling test, a colorimeter 9 that captures an image of the bag B set in the swirling generator 3, oblique light LEDs 10a and 10b, a surface-emitting LED 10c, and a power supply unit 11.

The housing 2 is equipped with a power switch 12 which turns the colorimeter 9 on/off and lights a lamp when the switch is on, a main power switch 13 which supplies power to each section, a power cable connection section 14 which connects the power supply to each section, a power switch 15 for the PC section 8, and a program start switch 16. The power to the colorimeter 9 should always be kept on. Immediately after start-up, the lights should be turned on and no photographs should be taken, allowing the device to age for about 30 minutes. Only when there is a problem with the colorimeter 9 should the power to the colorimeter 9 be turned off to deal with the problem. This is because the values are not stable in the initial state. Before operation, make sure the power to the colorimeter 9 is turned on. Each element is explained below.

As shown in Figures 2 to 4 and 6, the swirling generating unit 3 has a space for housing the bag B, and is equipped with a slider 32 having a glass plate 31 on the bottom surface that forms an imaging surface so that an image can be captured from below by the colorimeter 9, and a support unit 34 having a slide mechanism 33 including a spring that slides the slider 32. The bag B is slid while housed in the slider 32, and swirling is generated in the bag B by the vibration caused by the impact of the slider 32 colliding with the wall of the support unit 34.

The bag B can be set or removed by opening and closing the lid 5.

As shown in FIG. 6, the stopper 6 holds the slider 32 in the slid position, and the return switch 6a releases the hold. In response to this release, the swirling generator 3 applies agitation to the bag B. In response to the detection of this agitation, the colorimeter 9 automatically captures an image of the bag B.

Monitor 7 is used to operate the main unit and display results, etc.

The input means of the computer unit 8 are a keyboard, a mouse, a touch panel provided on the monitor 7, etc.

The PC unit 8, which controls the swirling inspection, will be described with reference to FIG. 12. The PC unit 8 is made up of a CPU 81, RAM 82, ROM 83, counter 84, timer 85, audio control unit 86, storage unit 87, and input/output interface 89, all connected to one another via a bus 90. The input/output interface 89 is connected to a monitor 7, colorimeter 9, oblique light LEDs 10a and 10b, surface light LED 10c, power switch 12, main power switch 13, power cable connection unit 14, power switch 15, start switch 16, and the like. The CPU 81 performs initial settings or performs a predetermined calculation upon receiving an input signal, and control signals are sent to these components.

The CPU 81 generates control signals to be output to each unit, and executes swirling detection and the like by outputting the control signals through program control. The RAM 82 temporarily reads and writes data for swirling detection and the like. Programs for swirling detection and the like are stored in the ROM 83 in read-only mode. The CPU 81 generates control signals to be output to each unit, and executes swirling detection by outputting the control signals. Instead of program control, it is also possible to implement this through hardware control such as LSI logic.

The counter 84 functions as a counting unit or the like that indicates a count value _N1 of pixels, etc., and a cumulative value _N2 of pixels, etc., and after power is turned on, the initial values of the count value _N1 and cumulative value _N2 of the counter 84 are set to "0", and the counter 84 counts and increments by referring to various input signals.

Timer 85 performs time calculations related to swirling inspections, etc.

The audio control unit 86 is composed of a sound source IC and an amplifier, etc., and is responsible for driving and controlling the speakers, etc.

The memory unit 87 stores image data captured by the colorimeter 9, calculation data such as swirling inspection and color distribution, etc. The memory unit 87 is a hard disk, etc.

The colorimeter 9 has three spectral sensitivities (S1(λ), S2(λ), S3(λ)) that are linearly transformed to be equivalent to the CIE XYZ color matching functions, and generates three-band visual sensitivity images S1i, S2i, S3i.

The spectral sensitivities of the colorimeter 9 satisfy the Luther condition, and the spectral sensitivities (S1(λ), S2(λ), S3(λ)) are equivalently converted from the XYZ color matching functions under the conditions that they have no negative values, are mountain-shaped with a single peak, the peak values of the respective spectral sensitivity curves are equal, and overlap of the spectral sensitivity curves is minimized as much as possible, as shown in Figure 10. Specifically, the spectral sensitivities (S1(λ), S2(λ), S3(λ)) have the following characteristics:
Peak wavelength Half width 1/10 width S1 582 nm 523-629 nm 491-663 nm
S2 543 nm 506-589 nm 464-632 nm
S3 446 nm 423-478 nm 409-508 nm

The spectral sensitivities (S1(λ), S2(λ), S3(λ)) of the colorimeter 9 are mountain-shaped with a single peak that does not have negative values from the CIE XYZ spectral characteristics, as shown in FIG. 10, and are equivalently converted under the conditions that the peak values of the respective spectral sensitivity curves are equal and the overlap of the spectral sensitivity curves is minimized. The curve of the spectral characteristics S1 has a peak wavelength of 582 nm, a half width of 523 to 629 nm, and a 1/10 width of 491 to 663 nm. The curve of the spectral characteristics S2 has a peak wavelength of 543 nm, a half width of 506 to 589 nm, and a 1/10 width of 464 to 632 nm. The curve of the spectral characteristics S3 has a peak wavelength of 446 nm, a half width of 423 to 478 nm, and a 1/10 width of 409 to 508 nm.

The peak wavelength of the above spectral characteristic S1 can also be treated as 580±4 nm, the peak wavelength of the spectral characteristic S2 as 543±3 nm, and the peak wavelength of the spectral characteristic S3 as 446±7 nm.

The relationship between the three spectral sensitivities (S1(λ), S2(λ), S3(λ)) and normalized xyz is defined by the following formula 1. For details about the spectral characteristics themselves, see JP-A-2005-257827.

The specifications of the Colorimeter 9 are, for example, an effective frequency value of approximately 2 to 3 million pixels, an effective area of 5.12 mm x 3.84 mm, an image size of 2.5 μm x 2.45 μm, a video output of 10 bits, a camera interface of Camera Link, a shutter speed of 1/10,000 sec to 1/15 sec, an accumulation time of 30 frames, an S/N ratio of 56 dB or higher, and a lens mount of C mount %.

As shown in Figs. 11(a) to (c), the colorimeter 9 includes a photographing lens 91, three optical filters 92a, 92b, and 92c arranged behind the photographing lens 91, and an image sensor 93 (CCD, CMOS, etc.) arranged behind the optical filters 92a, 92b, and 92c. The three spectral sensitivities (S1(λ), S2(λ), and S3(λ)) of the colorimeter 9 are given by the product of the spectral transmittances of the optical filters 92a, 92b, and 92c and the spectral sensitivity of the image sensor 93. The arrangement relationship between the optical filters 92a, 92b, and 92c and the image sensor 93 in Fig. 9 is merely a schematic diagram. Specific examples of methods for acquiring image information according to the three spectral sensitivities (S1(λ), S2(λ), and S3(λ)) are given below, but any of these may be used in this embodiment, and other methods may also be used.

Figure 11 (a) shows a method using a dichroic mirror. This is a method in which light of a specific wavelength is reflected by a dichroic mirror 92c', and the remaining light that passes through is further split by reflecting light of another specific wavelength by another dichroic mirror 92a', and the three image pickup elements 93a, 93b, and 93c are arranged in parallel to read out. Here, the dichroic mirror 92a' corresponds to the optical filters 92a and 92b, and the dichroic mirror 92c' corresponds to the optical filter 92c. Of the light that enters from the photographing lens 91, light according to the spectral sensitivity S3 is reflected by the dichroic mirror 92c', and the remaining light passes through. The light reflected by the dichroic mirror 92c' is reflected by a reflecting mirror 96, and the spectral sensitivity S3 is obtained by the image pickup element 23c. On the other hand, of the light that passes through dichroic mirror 92c', light according to spectral sensitivity S1 is reflected by dichroic mirror 92a', and the remaining light according to spectral sensitivity S2 passes through. The light that passes through dichroic mirror 92a' is imaged by image sensor 93b to obtain spectral sensitivity S2. The light reflected by dichroic mirror 92a' is reflected by reflector 95 and image sensor 93a obtains spectral sensitivity S1. Instead of the dichroic mirror, a dichroic prism with similar characteristics may be used to split the light into three, and image sensors 93a, 93b, and 93c may be attached at the positions where the respective lights pass through.

Figure 11(b) shows a method that uses a filter turret 97. Optical filters 92a, 92b, and 92c are mounted on a filter turret 97, which has an axis of rotation in the same direction as the incident light from the photographing lens 91, and are mechanically rotated, and three spectral sensitivities S1, S2, and S3 are obtained by the image sensor 93 for the light that passes through in sequence.

Figure 11 (c) shows a method of attaching optical filters 92a, 92b, and 92c to an image sensor 93 microscopically. The optical filters 92a, 92b, and 92c on the image sensor 93 are arranged in a Bayer array. In this arrangement, the optical filter 92b is provided in half of the area on the image sensor 93 divided into a lattice shape, and the optical filters 92a and 92c are evenly arranged in the remaining half of the area. In other words, the arrangement amount is optical filter 92a:optical filter 92b:optical filter 92c=1:2:1. In this embodiment, it is not particularly prevented that the optical filters 92a, 92b, and 92c are arranged in an array other than the Bayer array. Since each optical filter 92a, 92b, and 92c is very fine, it is attached to the image sensor 93 by printing. However, the significance of this invention is not in this arrangement, but in attaching filters with the characteristics of spectral sensitivity (S1(λ), S2(λ), S3(λ)) to the imaging element.

The oblique light LEDs 10a and 10b emit light toward the internal space 2a at an angle to the imaging direction of the colorimeter 9.

The surface-emitting LED 10c is provided on the back surface of the lid 5 and emits light toward the top surface of the bag B.

The power supply unit 11 supplies power to the monitor 7, PC unit 8, colorimeter 9, etc.

The swirling inspection method of this embodiment will be explained. After pressing the main power switch 13, the monitor 7 and PC unit 8 start up a few seconds later.

1. Explain the process before starting measurement.

1-1 Lighting Aging As shown in Figure 13, there is an icon for the blood product testing software "Blood Inspector" on the desktop of monitor 7 of PC unit 8, so double-click it to launch it. When the software launches, a screen will be displayed. Once displayed, click the "Start" button in the upper right corner of the screen. A live image from the colorimeter 9 will be displayed as shown above. Make sure that both the "Surface emission" and "Oblique light" checkboxes for the lighting are checked, and wait 30 minutes with both lights on.

1-2 White calibration As shown in FIG. 14, when the aging of the lighting is completed, proceed to white calibration. White calibration cannot be performed when the surface emitting lighting is on, so click the "Surface Emission" check box to uncheck it. When only the oblique lighting LEDs 10a and 10b are on, perform the Blood
Close the Inspector. Place a piece of white paper for white calibration in the space of the swirling generator 3 of the equipment.

Then, double-click the "RCView" icon on the desktop. The software will start and the following screen will be displayed.

After launching, select the "ROI" tab from the operation tabs at the bottom right. Click the "Load" button in the tab to load the data for the white frame for white calibration (this frame is called the ROI).

As shown in Figure 15, a dialog box will appear. Open the folders "PC" → "Windows (C;)" → "DATA" → "Settings" and select the "White Calibration" FRM file from there. A white frame will appear on the screen as shown below. Move the cursor inside this frame and right-click to display a menu. Select "Reset" from the menu.
This will reset the white calibration once.

Click the capture button (labeled "Live") in the top right of the software screen to apply the reset.

Once applied, the shooting button will change from "Live" to "Freeze," so click "Freeze." The shooting button will then revert to "Live."

In this state, place the cursor within the ROI again and right-click. Click "Set Calibration Value" in the menu to set the white calibration. After setting it, click the capture button that shows "Live" to apply it. When white calibration is applied, the colors on the screen will change, as shown in Figure 16 (a) before application and (b) after application.

There is a histogram on the right side of the screen, and below it the values for "S123" (3-band visual sensitivity image S1i, S2i, S3i) are displayed. It is set to "Freeze." When you press the capture button, the "ROI" value is displayed there. There is no problem as long as the value is within the range of around 13,000 (±100).

If the value is not within the range of the "ROI" values, right-click within the ROI again, click "Reset Calibration Value" in the menu, reset it, and redo the white calibration.

When white calibration is complete, close the software. From then on, do not launch "RCview" for any purpose other than white calibration operations. It is recommended that you perform white calibration once a day before starting measurements.

2-2 Setting bag B Hold the handle 5a and open the lid 5. When the lid 5 is opened to the end, it is held in that position by the lever 5b. Set the bag B and close the lid 5. The lid 5 is designed so that it will not close unless the stopper 6 is released.

2-3 Platelet Measurement After setting the bag B, slide the slider 32 in a specified direction, for example, in the direction of the arrow. When pulled all the way out, the slider 32 is held in that position. When the return switch 6a on the side of the housing 2 is pressed, the slider 32 returns to its original position and collides with the wall of the support part 34, causing the bag B to vibrate.

2. Measure blood products
2-0 Operations common to all blood products Double-click the "Blood Inspector" icon on the desktop of Monitor 7 to start the software and open the "Settings" tab.

As shown in Figure 17, first press the "Start" button in the upper right corner to display a real-time image of the colorimeter 9. When the screen enters real-time mode, switch the lighting to match the blood product being measured. For red blood cells, select only the oblique light LEDs 10a and 10b. For plasma and platelets, select only the surface light LED 10c.

Under the lighting settings, use the shutter speed to apply the exposure time set for each blood product. Select the blood product to be measured.

When you click the "Start" button, it will change to "Stop." You can stop the video by pressing "Stop."

It is possible to set the measurement range while the image of the colorimeter 9 is stopped. By placing the cursor inside the image and dragging it, a white frame indicating the is formed, as shown in Figure 18.

Once you have determined the size and position of the white frame, click the "Save" button. A dialog will appear, so select the save destination and save.

If the measurement range you want to use has already been saved, press the "Load" button to load the data.

If you want to delete the measurement range on the screen, place the cursor inside the white frame, right-click, and select "Remove ROI". Setting, saving, and loading the measurement range can only be done when the image of the colorimeter 9 is stopped. If the measurement range has not been set, measurements cannot be performed, so set the measurement range.

2-1 Red blood cells and plasma After setting bag B and completing the measurement range settings, open the "Red blood cells" and "Plasma" tabs from the tabs in the upper right corner of the screen as shown in Figure 19.

Enter the ID of the blood product to be measured in the ID bar on the screen.

When you press the "Start" button on the right side of the bar, if a blood product with the same ID has been photographed in the past, the oldest image data among them will be displayed on the "Reference" side. If there is no photographed data for a blood product with an ID, the "Reference" screen will change to a check pattern. As shown in Figures 20 (a) and (b), it will display whether there is any past photographed data or not.

The "reference" side refers to the location in Figure 25 where measurements are taken first. In this case, this refers to the test at the blood product center.

By pressing the "Measure" button at the bottom right of the screen, an image of the colorimeter 9 will be displayed and the button label will change to "Stop." Pressing this "Stop" button will execute an image capture, and the absolute value will be displayed below the captured image, and the comparison results of the two image data will be displayed in the "Measurement Results" column as shown in Figure 21. The size of the image displayed on the screen will change depending on the size of the measurement range that has been set.

Image data and measurement results can be saved by pressing the "Save" button. Saved data is stored in the "Red Blood Cells", "Plasma", and "Platelets" folders in the "PC" → "Windows (C;)" → "DATA" folder, which are folders corresponding to each blood product. There is also a shortcut to the "DATA" folder on the desktop.

If you want to change the image to be measured from already saved data, you can select it by clicking the "Load reference data" or "Load test data" button below each image.

2-2 Platelets Place bag B in the swirling generator 3, and once the measurement range has been set, open the "Platelets" tab from the tabs in the upper right corner of the screen. Enter the ID of bag B to be measured, etc., in the ID bar on the screen.

When the "Start" button on the right side of the bar is pressed, if a photograph of bag B with the same ID has been taken in the past, the oldest image data among them will be displayed on the "Reference" side. If there is no photographed data for bag B with an ID, the "Reference" screen will change to a checkered pattern (see Figure 22). Up to this point, it is the same as for red blood cells and plasma. When the "Photograph" button on the bottom right is pressed, real-time video from the colorimeter 9 will be displayed on the "Before generation" screen on the "Test" side. The button label will change to "Stop." When the "Stop" button is pressed, the L ^* , a ^* , and b ^* values will be displayed for the "Before generation" image on the "Test" side, as shown in Figure 22.

The "testing" side refers to the location where measurements are taken later in time as shown in Figure 25. In this case, this refers to testing at hospitals and distribution centers.

After that, a real-time image is displayed on the screen of "after occurrence" of swirling, so press the "Start measurement" button. As shown in FIG. 6, when the slider 32 is slid to a predetermined position by the operation of the slide mechanism 33, the stopper 6 is operated and the position of the slider 33 is maintained. When the return switch 6a is operated, the stopper 6 is released and the slider 33 moves, and the bag B is shaken by the impact when it returns to the original position and stops. Two seconds after the slider 33 returns to the original position, an image is automatically taken and the "after occurrence" image is stopped. As soon as the image of "after occurrence" is taken, a comparison is made between "before occurrence" of swirling and "after occurrence". As shown in FIG. 23, the degree of agreement, ΔE, L ^* , a ^* , and b ^* calculated on the "reference" side and the "test" side are displayed on the right side of the screen.

The first color distribution of the blood product before swirling occurs, which serves as a comparison standard, may be prepared in advance, or may be photographed on the spot and the first color distribution created. The blood product before swirling occurs is preferably the same blood product, but may be another blood product.

When Bag B containing platelets in good condition is shaken, swirling occurs. When Bag B containing platelets in poor condition is shaken, swirling does not occur or is insufficient. When blood products are in a stationary state, whether in good or poor condition, no swirling occurs. The timing for swirling to stop occurring is before shaking the blood product after swirling has occurred, or after about 20 seconds have passed since shaking or after shaking has been applied.

The above-mentioned color distribution coincidence will be described in detail. The blood product before swirling occurs is the reference blood product from which swirling has disappeared. The blood product after swirling occurs is the subject of swirling inspection, and is the blood product with swirling or the blood product that has disappeared. A colorimeter 9 having spectral sensitivity ( _S1 (λ), _S2 (λ), _S3 (λ)) converts and calculates the tristimulus values X, Y, and Z in the CIE XYZ color system in the measurement range of the three-band visual sensitivity images S1i, S2i, and S3i corresponding to the reference blood product before swirling has occurred from which swirling has disappeared, and calculates the L ^* a ^* b ^* value and ΔE according to Equation 2, and stores the data in the memory unit 87.

In the measurement range of the three-band visual sensitivity images S1i, S2i, and S3i corresponding to the blood product after swirling has occurred, conversion calculations are performed to convert them into tristimulus values X, Y, and Z in the CIE XYZ color system, and the L ^* a ^* b ^* values and ΔE are calculated according to Equation 2, and these data are stored in the memory unit 87.

As shown in Figure 25, a first color distribution in Lab color space for the blood product before swirling occurs as a reference, and a second color distribution in Lab color space for the blood product after swirling occurs are created, and the two are compared to calculate, for example, the percentage of overlap in the volume of the color distributions, thereby calculating the degree of color distribution agreement regarding swirling.

The example in FIG. 22 is a screenshot of the first test, for example, at the blood product center shown in FIG. 26. In FIG. 22, the degree of match is 86.31%, so it is judged to be a non-conforming product and is not transported to the hospital/distribution center. The appearance of swirling is correlated with the shape of the platelets, and when the platelets become spherical, light is no longer refracted and swirling does not occur. FIG. 23 is a screenshot of the test at the next destination, for example, at the hospital/transport center. The "reference" side is the test at the blood product center, and the degree of match is 76.30%, so it is judged to be a conforming product and is transported to the hospital/distribution center. The degree of match of the test there is 84.96%, the difference in the degree of match is 8.66%, and the swirling deteriorates over time, making it a non-conforming product, and it is not sent to the next destination. As shown in FIG. 24, if the degree of match is below a certain percentage, for example, 70% or less, on both the reference side and the test side, it is judged to be a conforming product and is transported to the hospital, where it is examined. This allows inspections to be carried out at each destination, ensuring that non-conforming products are removed.

The Lab color space is a type of complementary color space, with a dimension L ^* representing lightness and complementary color dimensions a ^* and b ^* , and is based on a nonlinear compression of the coordinates of the CIEXYZ color space. In the Lab color space, a match is obtained that also takes into account the brightness direction.

When calculating the color distribution in the Lab space corresponding to the measurement range, the degree of match is calculated based on the distribution in the three-dimensional space of the L axis, a axis, and b axis. The degree of match of the Lab color distribution is calculated based on the three-dimensional distribution.

The sensitivity of the match can be set in multiple stages. For example, ultra-high sensitivity match (LLab(H)) is the value that matches when the color information for each pixel in the measurement range is plotted in Lab space and the color distribution in Lab space of the reference product and the product to be inspected are compared. It compares colors and textures including brightness information. High sensitivity match (Lab(L)) has a relaxed sensitivity to make it easier to set a threshold value indicating the presence or absence of swirling, as ultra-high sensitivity match (Lab(H)) is a task in which the detection sensitivity is too high. The sensitivity can be set by the size of the squares in the 3D lattice.

When using ultra-high sensitivity matching (Lab(H)), as shown in Figure 25, Example 1 indicates that the blood product after swirling occurs is a conforming product, and there is a gap in the L-axis direction between the first color distribution as the comparison standard and the second color distribution of the test subject, so there is no overlap in the color distributions. Example 2 indicates that the blood product after swirling occurs is a conforming product, and there is a deviation in the L-axis direction between the first color distribution as the comparison standard and the second color distribution of the test subject, but there is a certain amount of overlap in the color distributions. If there is a large amount of overlap in Example 2, it is determined that the product matches a non-conforming product.

As shown in Figure 26, donated blood is sealed in a bag, an IC tag is attached, and a swirling test is performed. This bag is transported to a blood center (manufacturing plant), where blood products are manufactured into blood product bags, and a swirling test is performed. This blood product bag is transported to a hospital/distribution center, where a swirling test is performed. Bag B is then transported to a hospital, where a swirling test is performed. Data from the swirling tests performed at these points is sent to a server and managed.

2-3 Message Display The following messages may be displayed while operating the “Blood Inspector” software.

(1) "Please set the measurement range."
This will be displayed when you press the "Start", "Measure" or "Photograph" button on each Bag B tab when the measurement range has not been set. Set the measurement range on the "Settings" tab before moving on to measuring each Bag B.

(2) "Please close lid 5."
This message is displayed if you attempt to perform a measurement with the lid 5 open. Always keep the lid 5 closed when taking photographs.

(3) "Please close slider 33."
This is displayed when measurement is attempted while the slider 33 is moving. Images are taken without moving the slider 33 except when measuring platelets.

3. Operations after measurement is completed After measurement is completed, close the Blood Inspector window. If necessary, save and then close. Shut down the PC unit 8. Turn off only the main power switch 13 of the BIS 1. The oblique light LEDs 10a, 10b and the surface light LED 10c are turned off by turning off the main power switch 13.

As described above, the BIS1 stabilizes the correlation with the platelet swirling results, and the degree of agreement of swirling can be used as an objective numerical value of swirling, so that mechanization of swirling testing can be established. This is because the difference in swirling is not obtained from the analysis result on the actual image, but from the color distribution based on the image captured by the colorimeter 9. It is possible to detect slight differences such as those in already separated red blood cell preparations, plasma, and platelets, and the accuracy of the detection can be obtained, and the color detection accuracy of L ^* a ^* b ^* can be obtained with extremely high accuracy. This contributes greatly to the speed and accuracy improvement of swirling testing.

Bag B is urgently needed to treat blood clots that have developed in blood vessels due to the new coronavirus. This is because "drugs that suppress the action of clotting factors are used to treat and prevent blood clots, and when there is an urgent need to neutralize the action of these drugs, it may become necessary to replenish clotting factors."

Bag B is essential not only for treating blood clots developed by COVID-19 patients, but also for regular surgical procedures for cancer, etc., and its supply is supported by blood donations, etc. Blood collected through blood donations is used to manufacture blood products at blood centers around the country, which manage supply and demand and provide them.

The quality control of bag B is carried out not only by the blood product manufacturer (blood center) where it is manufactured, but also at the medical site where it is supplied (hospital, etc.), and this method is carried out using the blood product testing device of the embodiment of the present invention.

With no end to the coronavirus in sight, and with no choice but to coexist with the virus, it is expected that blood products will be needed more than ever in the future. BIS1 will resolve the chronic shortage of personnel in medical facilities and in the supply chains of blood products amid the COVID-19 pandemic, improve the current situation in which the quality of blood products is maintained by people's experience and knowledge, and prevent the risk of testing errors caused by distraction or poor health, ensuring the safety of medical care.

By quantifying the color and color distribution of blood products using the Colorimeter 9, we can provide a device that can cover everything from in-line testing at blood centers to checks at delivery destinations and checks at hospitals, and we can provide a device for confirming the effectiveness of blood products, with the goal of deploying it in medical facilities in the post-COVID era.

Bag B, which contains blood products for transfusion, has a short shelf life, such as platelet products (4 days), so it is necessary to supply the products quickly after blood collection. Since the quality of blood products changes from moment to moment, checking their effectiveness during the transportation process ensures quality, and ultimately medical safety.

The BIS1 is a device that can assess the skills of blood testers in a similar manner to the way blood testers currently work at blood centers, and has the advantage of being as easy to use as a copy machine.

The BIS1 can be equipped with an IC tag reader function, allowing a system to be established where blood products shipped from blood centers can be inspected at gates set up at distribution centers or hospitals. This uploads data on the product in its shipped state to the cloud, and the color and swirling of this shipped state can be compared with the current state in the image, allowing for quality verification.

The embodiments of the present invention are not limited to the above-mentioned embodiments, and modifications can be made without departing from the technical concept of the present invention. These modifications and equivalents are also included in the technical scope of the present invention, and it goes without saying that various forms can be adopted as long as they fall within the technical scope. For example, the method of acquiring image information according to three spectral sensitivities (S1(λ), S2(λ), S3(λ)) is merely a specific example, and is not limited to these, and the technical concept of the present invention can be implemented by other methods as well.

The blood product testing device of the present invention can mechanize platelet swirling testing, which was previously performed manually and visually, and can therefore be used in blood donation centers, blood product centers (manufacturers and distributors), hospital distribution centers, hospitals, etc., and therefore has great potential for use in the medical industry.

1: Blood product testing device B: Blood product bag 2: Housing 3: Blood product setting section 31: Glass plate 32: Slider 33: Slide mechanism 34: Support section 4: Opening 5: Lid 5a: Handle 5b: Lever 6: Stopper 6a: Return switch 7: Monitor 8: Computer section (PC section)
9: Colorimeter 10a, 10b: Oblique light LED
10c... Surface-emitting LED
11: Power supply unit 12: Power switch 13: Main power switch 14: Power cable connection unit 15: Power switch 16: Start switch

Claims (11)

a color distribution generating unit that captures a first image of the blood product by a colorimeter before the occurrence of swirling, generates a first color distribution of the acquired first image, captures a second image of the blood product by the colorimeter after the occurrence of swirling, and generates a second color distribution of the acquired second image;
a swirling inspection unit that compares the first color distribution with the second color distribution and performs a swirling inspection based on a degree of coincidence between the first color distribution and the second color distribution;
A blood product testing device comprising: 2. The blood product testing device according to claim 1, wherein the color distribution is based on the L ^* a ^* b ^* color system or the L ^* u ^* v ^* color system. A housing having an internal space;
a computer unit having the color distribution generating unit and the swirling inspection unit;
A light emitting unit that illuminates the blood product;
3. The blood product testing device of claim 1 or 2, further comprising: a swirling generating unit that sets the blood product bag in a predetermined position by opening and closing a lid and shakes the blood product bag by sliding it in a predetermined direction. The blood product inspection device of claim 3, in which the swirling generating unit is provided in the upper part of the housing, the colorimeter is provided in the lower part of the housing, and the blood product bag illuminated from above is imaged from below. The blood product testing device of claim 3 or 4, wherein the swirling generating unit sets the blood product bag in a predetermined position by opening and closing the lid, and shakes the blood product bag by sliding it in a predetermined direction. A blood product testing device according to any one of claims 3 to 5, in which the swirling generating section has a slider that slides in a predetermined direction and a stopper that holds the slider, and when the slider moves from the predetermined position to a holding position, the stopper holds the slider, and when the stopper is released, the slider returns to the predetermined position, thereby applying agitation to the blood product bag. A blood product testing device according to any one of claims 3 to 6, wherein the light emitting unit has an oblique light emitting unit and a surface light emitting unit, and switches between them depending on red blood cells, plasma, or platelets to be measured. A blood product testing device according to any one of claims 1 to 7, which calculates the difference between the degree of coincidence of the color distribution of the blood product at a first point and the degree of coincidence of the color distribution of the blood product at a second point. a color distribution generating step of capturing an image of the blood product before swirling occurs using a colorimeter, generating a first color distribution of the acquired first image, capturing an image of the blood product after swirling occurs using the colorimeter, and generating a second color distribution of the acquired second image;
a swirling detection step of comparing the first color distribution with the second color distribution, detecting a degree of agreement between the first color distribution and the second color distribution, and detecting swirling based on the degree of agreement;
A blood product testing method comprising: The blood product testing method of claim 9, in which the data on the degree of match is stored in a server and shared between the blood product center, the hospital/transport center, and the electronic computer departments of the hospital. A blood product testing program for a blood product testing device that performs blood product testing,
The blood product testing device includes a monitor and a computer,
The computer unit has a storage unit, a calculation unit, a determination unit, and an instruction unit,
a color distribution generating step of capturing an image of the blood product before swirling occurs using a colorimeter, generating a first color distribution of the acquired first image, capturing an image of the blood product after swirling occurs using the colorimeter, and generating a second color distribution of the acquired second image;
a swirling detection step of comparing the first color distribution with the second color distribution, detecting a degree of agreement between the first color distribution and the second color distribution, and detecting swirling based on the degree of agreement;
causing the computer to execute
A blood product testing program that causes the monitor to display the first color distribution, the second color distribution, and the detection results of the swirling.

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