JP7241145B2 - Reagent selection support device, method, program, recording medium, and sample measurement device - Google Patents

Description

The present invention relates to a reagent selection support device, method, program, recording medium, and sample measurement device.

Flow cytometry can detect various antigens present on the cell surface or inside cells by combining with fluorescent immunostaining, for example, as disclosed in Patent Document 1 below, and is particularly useful for cell analysis. is.

When detecting multiple types of antigens at once using flow cytometry, the number of antigens to be detected increases and the number of assays per sample also increases. metrics are useful. In multicolor flow cytometry, it is necessary to fluorescently stain the antigen to be detected in advance. A test reagent called a cocktail antibody reagent is used for fluorescent staining of an antigen. In a cocktail antibody reagent, a plurality of frequently used antibodies are combined after their cross-reactivity and the like have been prepared in advance.

However, in order to detect multiple types of antigens in a single assay, it is necessary not only to select antigens according to the cell type to be detected, but also to detect antigens other than the target antigen that are detected at the same time. It is necessary to know in advance that there is no cross-reactivity. If cross-reactivity is observed, information on antibody characteristics is required before applying immunostained cells to the flow cytometer, such as using separate assays for cross-reactive antigens. . Therefore, currently, in order to obtain reliable and reproducible results in multicolor flow cytometry, it is necessary for the operator performing multicolor flow cytometry to use all antibody types and antibody types used in flow cytometry. Cross-reactivity must be known in advance. Furthermore, since the number of fluorescent dyes that can be used varies depending on the number of light sources and the number of dichroic mirrors installed in the flow cytometer to be used, knowledge of the flow cytometer and the knowledge of the fluorescent dyes are also required for the measurer. . Against this background, current multi-color flow cytometry is a technique that can only be performed by those with highly specialized knowledge.

On the other hand, flow cytometry is a technology that has contributed significantly to disease diagnosis, disease stage determination, and treatment policy determination. The widespread use of flow cytometry has made it possible to accurately determine the cell lineage of tumor cells. Many have moved to diagnoses based on profiling of cell surface markers. Physicians who diagnose diseases also request a plurality of types of antigens to be used for diagnosis from measurers as items to be measured by flow cytometry.

When determining cell lineage, it is generally necessary to detect 10 to 30 surface markers per specimen, even just to identify, for example, a B-cell tumor. Furthermore, multiple rounds of multicolor flow cytometry using several detection antibodies per assay are required per sample to detect all target surface markers. After that, the flow cytometer operator should select the appropriate combination of detection antibodies according to the measurement items requested by the doctor or technician, and the combination of detection antibodies that can be obtained from the detection antibodies held at hand at the time of the test. must choose. Furthermore, cells used for flow cytometry must be measured within 24 hours after collection, so it is necessary to investigate combinations of detection antibodies that enable efficient measurement per sample. . Under such circumstances, it is necessary to efficiently select cocktail antibody reagents used for fluorescent staining of detection antibodies from stocks of cocktail antibody reagents held at hand.

Under these circumstances, flow cytometry is currently performed exclusively by measurement personnel who have knowledge of the characteristics of detection antibodies. The actual situation is that the measurement is performed exclusively by a person who has such specialized knowledge.

JP 2011-85587 A

At hospital testing sites, there is a need to "provide stable test results quickly and whenever necessary." However, with the increasing expertise of flow cytometry measurement personnel, flow cytometry tests are deviating significantly from the above-mentioned needs, and flow cytometry tests are becoming more and more complicated. be. Even if a person other than a dedicated measurer receives measurement items for multiple antigens from a doctor or technician, it is possible to efficiently combine cocktail antibody reagents to detect multiple antigens indicated in the measurement items. It is extremely difficult to choose It is possible to detect multiple types of antigens contained in the measurement items one by one by flow cytometry, but as described above, the cells must be subjected to measurement within 24 hours after collection. Not realistic. In hospital testing sites, there is a demand for a method of efficiently selecting a combination of cocktail antibody reagents according to the measurement items for multiple types of antigens requested by doctors.

In addition, although the method of Patent Document 1 is intended to simplify the setup of a device such as a flow cytometer, it is a method that assumes an operator who has a certain degree of specialized knowledge. Not a user-friendly way to target The method of Patent Literature 1 does not satisfy the above-described needs for examination sites in hospitals in the first place.

One aspect of the present invention is a reagent selection support device. In an embodiment, the reagent selection support device (100) is a reagent selection support device (100) that supports selection of a cocktail antibody reagent containing a plurality of antibodies, and obtains a measurement order for measuring a plurality of antigens. an acquisition unit (15, 16); and a processing unit that determines a plurality of cocktail antibody reagents to be used in a plurality of assays for detecting a plurality of antigens, based on the measurement order acquired by the acquisition unit (15, 16). (10A, 10B), and an output section (17) for outputting information of a plurality of cocktail antibody reagents to be used in a plurality of assays determined by the processing section. This makes it possible for even an examiner who does not have specialized knowledge to select an appropriate combination of antibody reagents according to the measurement order.

Storage units (12, 13) for storing information on a plurality of cocktail antibody reagents composed of combinations of different antibodies are further provided, and processing units (15, 16) store a plurality of cocktail antibody reagents read from the storage units (12, 13). It is desirable to determine a plurality of cocktail antibody reagents to be used for a plurality of assays based on the cocktail antibody reagent information and the measurement order. As a result, it is possible to select an appropriate combination of antibody reagents according to the measurement order based on information on multiple cocktail antibody reagents stored in advance in the storage unit, even if the examiner does not have specialized knowledge. becomes.

Each of the plurality of cocktail antibody reagents is desirably composed of a different combination of antibodies. As a result, the types of fluorescence that can be measured simultaneously can be increased, and the number of measurements and the measurement time can be shortened.

The processing unit (10A, 10B) determines an antibody reagent that can be used in combination with the cocktail antibody reagent in at least one of the plurality of assays, and the output unit (17) provides information on the antibody reagent that can be used in combination with the cocktail antibody reagent. Output is desirable. As a result, the types of fluorescence that can be measured simultaneously can be increased, and the number of measurements and the measurement time can be shortened.

Based on the measurement order, the processing unit (10A, 10B) selects a first candidate that is a combination of cocktail antibody reagents used in a plurality of assays, and a second candidate that is a combination of cocktail antibody reagents different from the first candidate. The candidates are determined, and the output section (17) preferably outputs the first and second candidates determined by the processing sections (10A, 10B). This enables the user to perform efficient testing using antibody reagents that are in stock at hand.

It is desirable that the output unit (17) outputs the first candidate and the second candidate so as to be distinguishable from each other. This allows the user to more reliably grasp whether or not the antibody reagents in stock at hand can be used to perform the measurement that satisfies the measurement order.

When the processing unit (10A, 10B) receives an input specifying the cocktail antibody reagent to be used in either the first candidate or the second candidate, the processing unit (10A, 10B) selects the first candidate and the second candidate, it is desirable to change the display mode of the cocktail antibody reagent corresponding to the designation. When the user inputs information on the antibody reagents that are in stock at hand to the reagent selection support device (100), the display mode of the antibody reagents that are in stock at hand is changed in the output unit (17). output. This allows the user to more reliably grasp whether or not the antibody reagents in stock at hand can be used to perform the measurement that satisfies the measurement order.

The processing units (10A, 10B) desirably present the first candidate and the second candidate according to the number of cocktail antibody reagents used and/or the number of measurements. This enables the user to perform efficient testing using antibody reagents that are in stock at hand.

When there are a plurality of results using the same number of cocktail antibody reagents, the processing unit (10A, 10B) selects the first candidate and the second candidate using the same number of cocktail antibody reagents, and the number of times of measurement is large or small. It is desirable to present the first candidate and the second candidate according to the relationship. This enables the user to perform efficient testing using antibody reagents that are in stock at hand.

It is desirable that the processing units (10A, 10B) present the first candidate and the second candidate according to the degree of matching between the multiple antibodies and multiple antigens contained in the cocktail antibody reagent. This enables the user to perform efficient testing using antibody reagents that are in stock at hand.

One aspect of the present invention is a reagent selection support method. In an embodiment, the reagent selection support method is a reagent selection support method for supporting selection of a cocktail antibody reagent containing a plurality of antibodies, the step of obtaining a measurement order for measuring a plurality of antigens (S1); Determining a plurality of cocktail antibody reagents to be used in a plurality of assays for detecting a plurality of antigens based on the obtained measurement order (S2 to S5); and determining a plurality of cocktail antibody reagents to be used in the plurality of assays. and a step (S6) of outputting the information of the reagent. This makes it possible for even an examiner who does not have specialized knowledge to select an appropriate combination of antibody reagents according to the measurement order.

Further comprising the step of reading information on a plurality of cocktail antibody reagents composed of different combinations of antibodies from the storage unit, and the determining step includes the information on the plurality of cocktail antibody reagents and the measurement order read from the storage unit in the reading step. It is desirable to determine multiple cocktail antibody reagents to be used in multiple assays based on. As a result, it is possible to select an appropriate combination of antibody reagents according to the measurement order based on information on multiple cocktail antibody reagents stored in advance in the storage unit, even if the examiner does not have specialized knowledge. becomes.

Each of the plurality of cocktail antibody reagents is desirably composed of a different combination of antibodies. As a result, the types of fluorescence that can be measured simultaneously can be increased, and the number of measurements and the measurement time can be shortened.

Preferably, the determining step determines antibody reagents that can be used in combination with the cocktail antibody reagent in at least one of the plurality of assays, and the outputting step outputs information on the antibody reagents that can be used in combination with the cocktail antibody reagent. As a result, the types of fluorescence that can be measured simultaneously can be increased, and the number of measurements and the measurement time can be shortened.

The determining step determines a first candidate that is a combination of cocktail antibody reagents used in a plurality of assays, and a second candidate that is a combination of cocktail antibody reagents different from the first candidate, based on the measurement order. and outputting preferably outputs the first candidate and the second candidate determined in the determining step. This enables the user to perform efficient testing using antibody reagents that are in stock at hand.

Preferably, the outputting step outputs the first candidate and the second candidate so as to be distinguishable from each other. This allows the user to more reliably grasp whether or not the antibody reagents in stock at hand can be used to perform the measurement that satisfies the measurement order.

Receiving an input specifying a cocktail antibody reagent to be used in one of the first candidate and the second candidate; changing the display mode. When the user inputs information on the antibody reagents that are in stock at hand to the reagent selection support device (100), the display mode of the antibody reagents that are in stock at hand is changed in the output unit (17). output. This allows the user to more reliably grasp whether or not the antibody reagents in stock at hand can be used to perform the measurement that satisfies the measurement order.

The step of determining preferably presents the first candidate and the second candidate according to the number of cocktail antibody reagents used and/or the number of measurements. This enables the user to perform efficient testing using antibody reagents that are in stock at hand.

In the step of determining, if there are multiple results with the same number of cocktail antibody reagents, among the first candidate and second candidate with the same number of cocktail antibody reagents, depending on the magnitude of the number of measurements , a first candidate and a second candidate. This enables the user to perform efficient testing using antibody reagents that are in stock at hand.

Preferably, the determining step presents a first candidate and a second candidate according to the degree of match between the multiple antibodies and multiple antigens contained in the cocktail antibody reagent. This enables the user to perform efficient testing using antibody reagents that are in stock at hand.

One aspect of the present invention is a computer program. In an embodiment, the computer program provides a computer with an acquisition function (S1) for acquiring a measurement order for measuring a plurality of antigens, and a plurality of assays for detecting a plurality of antigens based on the acquired measurement order. A determination function (S2 to S5) for determining a plurality of cocktail antibody reagents to be used in the assay, and an output function (S6) for outputting information on the plurality of cocktail antibody reagents to be used in the determined plurality of assays. program.

One aspect of the present invention is a computer-readable non-transitory tangible recording medium. In an embodiment, the computer-readable non-transitory tangible recording medium provides a computer with an acquisition function (S1) for acquiring a measurement order for measuring a plurality of antigens, and based on the acquired measurement order, A determination function (S2 to S5) for determining multiple cocktail antibody reagents to be used in multiple assays for detecting multiple antigens, and outputting information on the determined multiple cocktail antibody reagents to be used in multiple assays. A computer-readable, non-temporary, tangible recording medium recording an output function (S6) and a program for realizing the output function (S6).

One aspect of the present invention is a reagent selection support device. In an embodiment, the reagent selection support device (100) is a reagent selection support device that supports selection of a cocktail antibody reagent containing a plurality of antibodies, and includes an acquisition unit ( 15, 16), a processing unit (10) that determines a plurality of antibody reagents that can be used together in an assay for detecting a plurality of antigens, based on the measurement order acquired by the acquisition unit (15, 16); an output unit (17) for outputting information on a plurality of antibody reagents that can be used together in the assay, determined by the processing unit (10).

One aspect of the present invention is a sample measurement device. In an embodiment, the sample measuring device (1000) is a sample measuring device (1000) for measuring a sample (29) in which a cocktail antibody reagent containing a plurality of antibodies and a plurality of antigens to be measured are mixed. A reagent selection support device (100) for determining a plurality of cocktail antibody reagents to be used in a plurality of assays for detecting a plurality of antigens in (29); A suction unit (21) for sucking a sample (29) in which a plurality of cocktail antibody reagents used in the assay are mixed for each assay, and a fluid circuit (22) for conveying the sample (29) sucked by the suction unit (21). ) and a detection unit (23) for measuring the sample (29) conveyed by the fluid circuit (22).

According to the present invention, even an examiner without specialized knowledge can select an appropriate combination of antibody reagents according to a measurement order.

It is an example of a screen display of the reagent selection support device. 1 is a schematic diagram for explaining an inspection system according to a first embodiment; FIG. It is a schematic diagram showing an example of an optical system of a flow cytometer. 3 is a block diagram showing the hardware configuration of the reagent selection support device; FIG. 2 is a block diagram for explaining functions of the inspection system according to the first embodiment; FIG. Fig. 10 is a flow chart showing a procedure for determining candidate combinations of antibody reagents. Fig. 10 is a flow chart showing a procedure for determining candidate combinations of antibody reagents. Fig. 10 is a flow chart showing a procedure for determining candidate combinations of antibody reagents. Fig. 10 is a flow chart showing a procedure for determining candidate combinations of antibody reagents. Fig. 10 is a flow chart showing a procedure for determining candidate combinations of antibody reagents. FIG. 10 is a flow chart showing a procedure for grasping a combination of antibody reagents that satisfies a measurement order; FIG. It is an example of a screen display of the reagent selection support device. It is an example of a screen display of the reagent selection support device. It is an example of a screen display of the reagent selection support device. It is an example of a screen display of the reagent selection support device. It is an example of a screen display of the reagent selection support device. It is a schematic diagram for explaining the inspection system according to the second embodiment. FIG. 5 is a block diagram for explaining functions of an inspection system according to a second embodiment; FIG.

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, embodiments of the present invention will be described in detail with reference to the accompanying drawings. In the following description and drawings, the same reference numerals denote the same or similar components, and thus the description of the same or similar components is omitted.

<Definition of terms>
In the following description, an antigen is a target to be detected. Antigens are present in cells and may be present on the cell membrane, in the cell membrane, or intracellularly. A plurality of antigens means multiple types of antigens. The multiple types of antigens are the same or different biomolecules (proteins, sugar chains, lipids, glycoproteins, glycolipids, lipoproteins, nucleic acids, etc.), preferably different biomolecules.

A cocktail antibody reagent is a reagent that contains a mixture of multiple antibodies that can bind to different or the same antigen. For example, one cocktail antibody reagent can contain 2 to 5 antibodies. Here, at least one antibody of each antibody contained in one cocktail antibody reagent binds to one antigen. In addition, two or more antibodies may bind to one antigen for each antibody contained in the cocktail antibody reagent. The number of antibodies contained in one cocktail antibody reagent is called the cocktail number. A single antibody reagent is a reagent containing one type of antibody capable of binding to an antigen. Each antibody may be labeled with a fluorescent dye. Each antibody in one cocktail antibody reagent is preferably labeled with a different fluorochrome. Different fluorochromes means that the peak wavelength of the fluorescence spectrum of each fluorochrome is optically distinguishable. Moreover, the antibody contained in the single antibody reagent is preferably labeled with a fluorescent dye that is not contained in the cocktail antibody reagent used in combination.

Cocktail antibody reagents and single antibody reagents are collectively referred to as antibody reagents. The information on the antibody reagent includes the type of antibody contained in the antibody reagent, the type of antigen recognized by the antibody, the type of labeled fluorescent dye, and the like. Preferably, the antibody reagent information includes cocktail antibody reagent information and single antibody reagent information that can be used in combination with the cocktail antibody reagent.

[Summary of Invention]
FIG. 1 shows an example of screen display of the reagent selection support device 100 according to the present invention. The reagent selection support device 100 according to the present invention automatically determines antibody reagent combination candidates to be used for detecting the antigen specified in the measurement order, based on the measurement order and antibody reagent information. , the results are output in the manner illustrated in FIG. As exemplified in FIG. 1 as "first candidate" and "second candidate", the reagent selection support device 100 can determine and present a plurality of candidate combinations of antibody reagents. A method for automatically determining antibody-reagent combination candidates will be described with reference to the flow charts of FIGS.

To elaborate on the example shown in FIG. 1, "first candidate", for example, the combination of the CD3/CD4/CD8 cocktail antibody reagent and the CD25 single antibody reagent shown in row 1, in one assay, Combination of antibody reagents used. In addition, for example, in the assay shown on the second line, the CD16/CD56/CD57 cocktail antibody reagent is the antibody reagent used in one assay. The assay shown in row 2 did not use a single antibody reagent. That is, in the example shown in "first candidate", all antigens specified in the measurement order can be detected by a total of 7 measurements using 7 types of assays. On the other hand, in the example shown in "second candidate", all antigens specified in the measurement order can be detected by a total of eight measurements using eight types of assays.

Of the antibody reagent combination candidates shown in "first candidate" and "second candidate", the judgment as to which combination candidate to actually use depends on the antibody reagents that are actually in stock. It can be done interactively by contrasting with The method of comparing the automatically determined antibody reagent combination candidates and the antibody reagents actually in stock at hand in an interactive format is shown in the flow chart of FIG. 11 and an example of the screen display of FIGS. will be described with reference to

A measurement order is, for example, a test item instructed by a doctor or a technician. Preferably, it is a test item necessary for a doctor to determine whether or not a patient is suffering from a certain disease. In other words, the measurement order is the type of one or more antigens to be measured in flow cytometry. The antibody reagent information is information on antibody reagents including cocktail antibody reagents that can be used by the measurement device main body 200 for measuring a sample. As a result, the user of the sample measuring device 1000 can efficiently select an appropriate combination of antibody reagents according to the measurement order without having specialized knowledge of the measurement order and antibody reagents.

<First embodiment>
[Configuration overview]
The inspection system according to the first embodiment shown in FIG. 2 includes a sample measuring device 1000. As shown in FIG. The sample measuring device 1000 may be connected to the client terminal 300 and the network 99 with each other. A measurement order instructed by, for example, a doctor via the client terminal 300 is transmitted to the sample measuring device 1000 through the network. The client terminal 300 is composed of, for example, a general-purpose computer having a CPU and memory. A sample to be tested (for example, blood) is separately handed over to the user of the sample measuring device 1000 .

A sample measurement device 1000 includes a reagent selection support device 100 and a measurement device main body 200 that measures a sample.

The reagent selection support device 100 is composed of, for example, a general-purpose computer, and determines an appropriate combination of antibody reagents according to the measurement order based on the procedure shown in the flow chart described later. The user of the sample measuring device 1000 prepares the sample 29 by mixing the antibody reagent with the sample to be measured based on the combination of antibody reagents determined by the reagent selection support device 100, and inserts it into the measuring device main body 200 for measurement. set.

The measurement device main body 200 includes a suction section 21 , a fluid circuit 22 and a detection section 23 . The measurement device main body 200 sucks the sample 29 contained in the sample container 28 by the suction unit 21 , conveys the sucked sample 29 by the fluid circuit 22 , and measures the conveyed sample 29 by the detection unit 23 .

In this embodiment, the control of the measuring device main body 200 is also performed by the reagent selection support device 100 . That is, the optical information detected by the detection unit 23 is transmitted to the reagent selection support device 100, and the reagent selection support device 100 detects the number of cells and each antigen based on the optical information transmitted from the detection unit 23. perform the corresponding analysis. The reagent selection support device 100 stores a computer program defining a processing procedure for controlling the measuring device main body 200 and a processing procedure for measuring the measured value transmitted from the detection unit 23 in the recording unit 13 described later. recorded in advance. The reagent selection support device 100 controls the measuring device main body 200 by executing a computer program by the CPU 11, which will be described later.

The suction unit 21 is, for example, a nozzle capable of sucking and discharging a sample or the like. The fluid circuit 22 is a flow path for fluid, and the fluid is conveyed by, for example, a syringe pump. Sample measuring device 1000 is, for example, a flow cytometer. A flow cytometer optically measures a sample by flow cytometry. A flow cytometer can simultaneously measure a plurality of types of fluorescence released from a sample by using a cocktail antibody reagent as an antibody reagent, thereby shortening the measurement time.

The number of light-receiving elements (for example, photomultiplier tubes) for fluorescence detection provided in the detection unit 23 is determined according to the number of cocktails of cocktail antibody reagents that the measurement apparatus main body 200 can handle. For example, if the measuring device main body 200 can handle cocktail antibody reagents with a cocktail number of “3”, the measuring device main body 200 includes a total of four light receiving elements for fluorescence detection in the detection unit 23 . As a result, the detection unit 23 can simultaneously measure a total of four colors of fluorescence, that is, three colors of fluorescence from the cocktail antibody reagent and one color of fluorescence from the single antibody reagent, per assay. The optical system of the flow cytometer will be described below with reference to FIG. 3, taking as an example a case in which a total of four colors of fluorescence are measured simultaneously.

FIG. 3 shows an example of an optical system of a flow cytometer as an example of the detection unit 23. As shown in FIG. The flow cytometer detects a cell 27 for receiving a cell-containing liquid containing cells in a sample, light sources 201 and 224 for irradiating light on particles passing through the cell 27, and optical information of light derived from cells. light-receiving elements 200A to 200F for outputting detection signals converted into electric signals by the light receiving elements 200A to 200F. Here, the sample is a cell suspension that is aspirated into the flow cytometer. In the following description of the flow cytometer of FIG. 3, the case where the sample is a mixture of blood and antibody reagent will be described as an example.

Cells preferably emit one or more lights when irradiated with predetermined light. Light emitted from a cell when it is irradiated with predetermined light is collectively called light derived from the cell. Light derived from the cells includes scattered light and luminescence. The light derived from cells may be light of any wavelength, but preferably light having a peak wavelength in the range of 400 nm to 850 nm. More specifically, it is preferred that the light originating from the cells is fluorescence. The light derived from the cells may be light emitted by substances contained in the cells themselves. Alternatively, the light derived from the cells may be obtained by labeling the cells with a luminescent substance such as a fluorescent dye, and detecting the light emitted by this luminescent substance as the light derived from the cells. In addition, it is preferable that the light derived from cells has a different peak wavelength for each antigen. In the first embodiment, the cell-derived fluorescence is derived from the fluorochrome labeled on each antibody contained in the detection reagent.

The cell-containing liquid is a liquid containing a cell suspension aspirated from the sample into the flow cytometer, and optionally a diluent. Optical information is information contained in one or more light wavelength spectra emitted from cells. An optical wavelength spectrum includes individual optical wavelengths, optical wavelength regions, and the intensity of each optical wavelength or optical wavelength region contained in the optical wavelength spectrum. Individual light wavelengths and wavelength regions can be specified by which one of the one or two or more light-receiving elements, which will be described later, receives the light. Further, the intensity of each light wavelength or light wavelength region can be specified by an electric signal output by the light receiving element that has received the light.

A case where the light originating from cells is scattered light and fluorescence will be specifically described below as an example. Light emitted from the light source 201 passes through the collimator lens 202 , the dichroic mirror 203 and the condensing lens 204 and irradiates the cell 27 . Forward scattered light of light originating from cells passing through the cell 27 is condensed by a condensing lens 205, passes through a beam stopper 206, a pinhole plate 207, and a bandpass filter 208 and enters the light receiving element 200A.

On the other hand, side scattered light and side fluorescent light originating from cells passing through the cell 27 are collected by the collecting lens 209 . The side scattered light passes through dichroic mirrors 210, 211, 212, pinhole plate 203, and bandpass filter 214 and enters light receiving element 200B. Lateral fluorescence with a wavelength of 520 nm or more and 542 nm or less is transmitted through dichroic mirrors 210 and 211, reflected by dichroic mirror 212, passes through pinhole plate 215 and bandpass filter 216, and enters light receiving element 200C. Side fluorescence with a wavelength of 570 nm or more and 620 nm or less is transmitted through the dichroic mirror 210, reflected by the dichroic mirror 211, passes through the pinhole plate 217 and the bandpass filter 218, and enters the light receiving element 200D. Lateral fluorescence with a wavelength of 670 nm or more and 800 nm or less is reflected by the dichroic mirror 210, passes through the dichroic mirror 219, passes through the pinhole plate 220 and the bandpass filter 221, and enters the light receiving element 200E.

The light emitted from the light source 224 passes through the collimator lens 225, the dichroic mirror 203, and the condensing lens 204 and is applied to the cell 27. FIG. Lateral fluorescence of cell-derived light passing through cell 27 is collected by collection lens 209 . Lateral fluorescence of 662.5 nm or more and 687.5 nm or less is reflected by dichroic mirror 210, and after being reflected by dichroic mirror 219, passes through pinhole plate 222 and bandpass filter 223 and enters light receiving element 200F.

In the example shown in FIG. 3, light source 201 uses a laser diode with a wavelength of 488 nm, and light source 224 uses a laser diode with a wavelength of 642 nm. A sheath flow cell is used for the cell 27 . A photodiode is used for the light receiving element 200A for receiving forward scattered light, and an avalanche photodiode (APD) is used for the light receiving element 200B for receiving side scattered light. A photomultiplier tube (PMT) is used for the light receiving elements 200C to 200F that receive lateral fluorescence.

Thus, in the flow cytometer shown in FIG. 3, the number of light receiving elements 200C to 200F for receiving lateral fluorescent light is four. Therefore, the flow cytometer shown in this example is equipped with four light receiving elements for fluorescence detection, and the sum of the fluorescence of three colors from the cocktail antibody reagent and the fluorescence of one color from the single antibody reagent per assay. Four colors of fluorescence can be measured simultaneously.

Each detection signal output from each of the light receiving elements 200A to 200F is amplified by an amplifier circuit (not shown), A/D converted by an A/D converter (not shown), and converted into digital data. The detection signal converted into digital data is transmitted to the reagent selection support device 100 in this embodiment, and the cells are analyzed. The amplifier circuit is a known amplifier circuit composed of, for example, an operational amplifier.

The number of light sources may be one or two or more. The light source is selected according to the wavelength range of the light originating from the cells. If there are two or more light sources, they preferably emit light with different peak wavelengths.

The number of photodiodes, dichroic mirrors, and bandpass filters can be varied according to the number of peak wavelengths of light originating from the cells. Also, the types of photodiodes, dichroic mirrors, and bandpass filters can be selected according to the peak wavelength or wavelength range of the light originating from the cells and its intensity.

The reagent selection support device 100 selects information on detection sensitivity when the detection unit 23 detects scattered light or fluorescence, information on fluorescence correction according to the combination of detected fluorescence, and a distribution area of cells to be detected. Information about the gating for the antigen is sent to the detection unit 23, and based on this information, the detection unit 23 is controlled so that it can acquire appropriate optical information according to the antigen.

[Overview of operation]
In the first embodiment, information on antibody reagents that can be used by the measurement device main body 200 is recorded in the reagent selection support device 100 in advance. First, for example, a doctor examining a patient inputs a measurement order to the requester terminal 300 to determine whether the patient has a certain disease (eg, leukemia). Requester terminal 300 transmits the input measurement order to reagent selection support apparatus 100 . The reagent selection support device 100 detects the antigen specified in the measurement order based on the obtained measurement order and information on antibody reagents including cocktail antibody reagents that can be used by the measurement device main body 200. determine candidate combinations of antibody reagents to be used, and output the results. This allows the user of the sample measuring device 1000 to select an appropriate combination of antibody reagents according to the measurement order.

Further, the user inputs information on cocktail antibody reagents and information on single antibody reagents that are in stock at hand into the reagent selection support device 100 . As a result, the user can determine whether or not the measurement satisfying the measurement order can be performed using the antibody reagents that are in stock at hand, while referring to the result of the antibody reagent combination candidates determined by the reagent selection support device 100. , can be grasped more reliably by the interactive form described later.

After that, the user mixes the antibody reagent with the sample 29 for each combination, that is, for each assay, based on the combinations of the antibody reagents stocked at hand, which are understood to be possible for the measurement that satisfies the measurement order, and performs the measurement. It is set in the measuring device main body 200 for this purpose. The antigen specified in the measurement order is detected by the measuring device main body 200 and the test result is transmitted to the client terminal 300 .

[Hardware configuration]
The reagent selection support device 100 shown in FIG. 4 includes a processing unit 10 (10A, 10B), an input unit 16, and an output unit 17.

The processing unit 10 includes a CPU (Central Processing Unit) 11 that performs data processing, which will be described later, a memory 12 that is used as a work area for data processing, a recording unit 13 that records programs and processing data, which will be described later. It has a bus 14 for transmitting data and an interface section 15 (hereinafter referred to as "I/F section") for inputting and outputting data with an external device. The input section 16 and the output section 17 are connected to the processing section 10 . As an example, the input unit 16 and the output unit 17 can be integrated to form a touch panel type input display device.

In addition, the processing unit 10 converts the program according to the present invention into, for example, an executable format (for example, generated by converting from a programming language by a compiler) in order to perform the processing of each step described below with reference to FIGS. , and the processing unit 10 performs processing using the program recorded in the recording unit 13 .

In the following description, processing performed by the processing unit 10 actually means processing performed by the CPU 11 of the processing unit 10 based on a program stored in the recording unit 13 or the memory 12 unless otherwise specified. The CPU 11 temporarily stores necessary data (intermediate data during processing, etc.) using the memory 12 as a work area, and appropriately records data to be stored for a long time, such as calculation results, in the recording unit 13 .

[Function block]
The processing unit 10A of the reagent selection support apparatus 100 according to the first embodiment shown in FIG. . These functional blocks are realized by installing the program according to the present invention in the recording unit 13 or the memory 12 of the processing unit 10A and executing the program by the CPU 11. FIG.

In the first embodiment, the antibody reagent information database 401 (hereinafter referred to as "antibody reagent information DB 401") is recorded in advance in the recording unit 13 or memory 12 of the processing unit 10A. The antibody reagent information DB 401 is information on antibody reagents including cocktail antibody reagents that can be used by the measurement device main body 200 .

The requester terminal 300 includes an input unit 301 that receives input of a measurement order, and a data transmission/reception unit 302 that transmits the measurement order to the detection reagent selection support device 100 .

[Method for Determining Antibody Reagent Combination Candidates]
A method of determining antibody reagent combination candidates performed by the reagent selection support apparatus 100 will be described using a case where a patient is suspected to have leukemia as an example.

Tables 1-1 to 1-3 (hereinafter collectively referred to as "Table 1") show an example of antibody reagent information recorded in the antibody reagent information DB 401 used in the first embodiment.

The information on antibody reagents shown in Table 1 includes information on cocktail antibody reagents and information on single antibody reagents that can be used in combination with the cocktail antibody reagents. In the following description, the variable N is used to specify the cocktail number of cocktail antibody reagents. Variable N is a natural number (positive integer other than zero). In the example shown in Table 1, the cocktail number of cocktail antibody reagents is "3" and the value of variable N is "3". In the following description, candidate antibody reagent combinations are determined based on information on antibody reagents including cocktail antibody reagents with a cocktail number of "3", but the number of cocktail antibody reagent cocktails is limited to this. not. The number of cocktail antibody reagents to be used can be appropriately changed according to the number of cocktail antibody reagent cocktails that the measuring device main body 200 can handle in one assay. For details, refer to the <Additional remarks> column described later.

Also, in the following description, variables x and y are used to identify cocktail antibody reagents and single antibody reagents within the antibody reagent information or candidate antibody reagents shown in Table 1. Variable x and variable y are natural numbers (positive integers other than zero).

In the following description, cocktail antibody reagent (x) means the x-th cocktail antibody reagent. For example, in the antibody reagent information shown in Table 1, the cocktail antibody reagent (2) is a cocktail antibody reagent shown in "No. 2" in Table 1, in which the three antibodies CD117, CD34 and CD45 are grouped together. . Single antibody reagent (y) means the y-th single antibody reagent. For example, in the information on the antibody reagents shown in Table 1, the single antibody reagent (3) that can be used in combination with the cocktail antibody reagent (2) is seven reagents that can be used in combination with the cocktail antibody reagent shown in "No. 2" in Table 1. Of the single antibody reagents "CD56, HLA-DR, CD38, CD11b, CD33, CD7, CD34", the third "CD38" antibody.

The order of measurement, which is illustratively used in the first embodiment, is as follows.
Measurement order "HLA-DR, CD38, CD10, CD11c, CD19, CD20, CD22, CD23, CD103, Igκ, Igλ, CD2, CD3, CD4, CD8, CD5, CD7, CD25, CD16, CD56"

The processing unit 10A of the reagent selection support device 100 performs the operations shown in the flowcharts of FIGS. 6 to 10. FIG. To explain using each functional block shown in FIG. 5, the processing of step S1 is performed by the antigen information acquisition unit 101. FIG. The candidate reagent determining unit 102 performs the processing of steps S2 to S5, steps S11 to S20, steps S151 to S158, and steps S161 to S170, except for steps S1 and S6. The output control unit 103 performs the process of step S6.

Please refer to the flow chart of FIG. In step S<b>1 , the processing section 10</b>A acquires a measurement order from the client terminal 300 . The measurement order is transmitted from the data transmitter/receiver 302 in the form of text information, for example.

In step S2, the processing unit 10A sets the variable x to an initial value of "1", and first selects the first cocktail antibody reagent (1).

In step S3, the processing section 10A determines whether or not one or more antibodies contained in the x-th cocktail antibody reagent (x) are present in the measurement order. If it exists, the processing unit 10A performs the processing of step S11, which will be described later, and if it does not exist, performs the determination of step S4.

That is, through the repeated processing of steps S3 to S5, in order to present a plurality of candidate combinations of antibody reagents, the processing unit 10A first selects the first cocktail antibody reagent (1), and selects this first cocktail antibody. Determine whether reagent (1) is a reagent candidate. If it is a reagent candidate, the processing unit 10A continues to perform the processing of steps S11 to S20 described with reference to FIG. and a process of determining whether or not the combination can be used. If it is not a reagent candidate, the processing unit 10A performs steps S4 to S5, and then similarly determines whether the second cocktail antibody reagent (2) is a reagent candidate in step S3.

Specifically, through the repeated processing of steps S3 to S5, out of the 18 cocktail antibody reagents shown in Table 1, 11 cocktail antibody reagents represented by variables x = 3, 5, 10 to 18, step This is the cocktail antibody reagent first extracted from the measurement order shown in S11. That is, the process of step S3 can be said to be the process of determining the cocktail antibody reagent (x) to be extracted first from the measurement order in step S11. When the cocktail antibody reagents to be drawn first from the measurement order change, the candidates for the cocktail antibody reagents to be drawn next from the measurement order are limited, so the antibody reagent combination candidates also change. This finally presents a plurality of candidate antibody reagents.

In step S<b>4 , the processing unit 10</b>A determines whether or not the x+1th cocktail antibody reagent (x+1) exists in the antibody reagent information DB 401 . If it exists, the processing unit 10A increments the variable x by "1" in step S5, and then makes the determination in step S3. If not, the processing unit 10A performs the processing of step S6 because the judgment processing has been completed for all the cocktail antibody reagents in the antibody reagent information DB 401. FIG.

In step S6, the processing unit 10A displays candidate combinations of antibody reagents determined as reagent candidates. The display order of the antibody reagent combination candidates displayed by the processing unit 10A as the determined result is arbitrary. For example, the processing unit 10A can display a plurality of candidates for the determined combination of antibody reagents in descending order of the number of reagents used or the number of measurements. Alternatively, the processing unit 10A can display a plurality of candidates for the determined combination of antibody reagents in descending order of evaluation points, which will be described later.

Please refer to the flow chart of FIG. The processing of steps S11 to S20 shown in FIG. 7 is processing performed when one or more antibodies contained in the x-th cocktail antibody reagent (x) are present in the measurement order in step S3.

In step S11, the processing section 10A removes the antibody contained in the cocktail antibody reagent (x) from the measurement order and updates the measurement order. Antibodies excluded from the measurement order are antibodies contained in the cocktail antibody reagent (x) determined to be present in the measurement order in step S3.

In step S12, the processing section 10A adds the cocktail antibody reagent (x) to new reagent candidates.

In step S13, the processing section 10A adds the number of antibodies matching the measurement order to the new evaluation score. The number of antibodies that match the measurement order is the number of antibodies contained in the cocktail antibody reagent (x) determined to be in the measurement order in step S3.

In step S14, the processing unit 10A sets an initial value "3" to the variable N representing the number of cocktails of the cocktail antibody reagent.

In step S15, the processing section 10A performs cocktail antibody reagent search processing. The cocktail antibody reagent search process will be described later with reference to FIG. If the value of the variable N is "3", the cocktail antibody reagent search process first checks whether all three antibodies among the three antibodies possessed by the cocktail antibody reagent (x) are included in the measurement order. It is a process to decide.

In step S16, the processing unit 10A performs single antibody reagent search processing. The single antibody reagent search process is a process of determining single antibody reagents that can be used in combination with the cocktail antibody reagent (x). The single antibody reagent search process will be described later with reference to FIGS. 9 and 10. FIG.

In step S17, the processing section 10A determines whether or not the antibody still exists within the measurement order.

If there is, in step S18, the processing unit 10A records the new reagent candidate added in step S12 and the new evaluation point added in step S13, and makes the determination in step S4.

If not, the processing unit 10A determines whether or not the variable N can be subtracted in step S19, and then subtracts "1" from the variable N in step S20. After that, the processing unit 10A performs the cocktail antibody reagent search process in step S15 with the value of the variable N after the subtraction. If the value of the variable N is "2", the cocktail antibody reagent search process determines whether two of the three antibodies in the cocktail antibody reagent (x) are included in the measurement order. processing.

Please refer to the flow chart of FIG. The process of steps S151 to S158 shown in FIG. 8 is a cocktail antibody reagent search process.

In step S151, the processing unit 10A sets the variable x to the initial value "1", and first selects the first cocktail antibody reagent (1).

In step S152, the processing unit 10A searches the measurement order for the x-th cocktail antibody reagent (x), and in step S153, the processing unit 10A searches the measurement order for antibodies contained in the cocktail antibody reagent (x) is N or more. If there are N or more, the processing unit 10A performs the process of step S154, and if there are not N or more, the determination of step S157 is performed.

In step S154, the processing unit 10A removes the antibody contained in the cocktail antibody reagent (x) from the measurement order and updates the measurement order. The antibodies withdrawn from the measurement order are the N antibodies contained in the cocktail antibody reagent (x) determined to be present in the measurement order in step S153.

In step S155, the processing section 10A adds the cocktail antibody reagent (x) to the reagent candidates.

In step S156, the processing unit 10A adds the value N to the evaluation score. After the end of step S156, the process of step S15 is recursively called, and the processing unit 10A continues the process of step S15.

In step S<b>157 , the processing unit 10</b>A determines whether or not the x+1-th cocktail antibody reagent (x+1) exists in the antibody reagent information DB 401 . If it exists, the processing unit 10A increments the variable x by "1" in step S158, and then makes the determination in step S153. If not, the processing unit 10A terminates the cocktail antibody reagent search process in step S15. At the end of step S15, reagent candidate cocktail antibody reagents and the current remaining measurement orders are listed. After completing the process of step S15, the processing unit 10A performs the process of step S16 shown in FIG.

Please refer to the flow charts of FIGS. The processing of steps S161 to S170 shown in FIGS. 9 and 10 is single antibody reagent search processing.

In step S161, the processing unit 10A sets the initial value "1" to each of the variable x and the variable y. The variable x indicates the first cocktail antibody reagent of the reagent candidate, and the variable y indicates the first single antibody reagent that can be used in combination with the cocktail antibody reagent (x).

In step S162, the processing unit 10A searches the measurement order for the y-th single antibody reagent (y). determines whether it exists in If it exists, the processing unit 10A performs the processing of step S164, and if it does not exist, performs the determination of step S167.

In step S164, the processing section 10A removes the antibody indicated in the single antibody reagent (y) from the measurement order and updates the measurement order.

In step S165, the processing section 10A adds the single antibody reagent (y) to the reagent candidates.

In step S166, the processing unit 10A adds the value "1" to the evaluation score. After the end of step S166, the process of step S16 is recursively called, and the processing unit 10A continues the process of step S16.

In step S167, the processing unit 10A determines whether or not the y+1-th single antibody reagent (y+1) exists in the antibody reagent information DB 401 for the x-th cocktail antibody reagent (x). If it exists, the processing unit 10A increments the variable y by "1" in step S168, and then makes the determination in step S163. If it does not exist, the processing unit 10A makes a determination in step S169.

In step S169, the processing section 10A determines whether or not the x+1-th cocktail antibody reagent exists in the reagent candidates. If it exists, the processing unit 10A increments the variable x by "1" in step S170, and then makes a determination in step S163. If not, the processing unit 10A terminates the single antibody reagent search process in step S16. At the end of step S16, reagent candidate cocktail antibody reagents, reagent candidate single antibody reagents, and the current remaining measurement orders are listed. After finishing the process of step S16, the processing unit 10A makes the determination of step S17 shown in FIG.

After the process of step S17, the reagent candidates and evaluation points recorded in step S18 are output to the output unit 17 of the reagent selection support device as shown in FIG. 12, for example. In the example shown in FIG. 12, the processing unit 10A displays the combination of reagent candidates with the highest evaluation score on the left side of the screen as the first candidate, and displays the combination of the reagent candidates with the second highest evaluation score as the second candidate. 2 is displayed on the right side of the screen.

As described above, the user of the reagent selection support device 100 can mix the antibody reagent with the sample 29 based on the combination of antibody reagents determined by the reagent selection support device 100, and set it in the measurement device main body 200 for measurement. can. This allows the user to select an appropriate combination of antibody reagents according to the measurement order.

[Antibody reagent selection support method in interactive format]
The user can further input the information on the cocktail antibody reagents and the information on the single antibody reagents that are stocked at hand into the reagent selection support device 100 . This allows the user to interactively grasp whether or not the antibody reagents in stock at hand can be used to perform the measurement that satisfies the measurement order, while referring to the determined antibody reagent combination candidates. can be done. The following description will be made with reference to the flowchart of FIG. 11 and screen display examples of FIGS. 12 to 16 .

The processing unit 10A of the reagent selection support device 100 includes an output control unit 103 and a reagent designation reception unit 104. FIG. The reagent designation reception unit 104 acquires designation of a reagent candidate input by the user via the input unit 16 and transmits the designation to the output control unit 103 . The output control unit 103 controls the display mode of the designated reagent candidate on the output unit 17 based on the designation of the reagent candidate received from the reagent designation reception unit 104 . In addition, the reagent designation receiving unit 104 counts the number of times the input reagent candidate is designated as the number of reagents to be used, and displays the number on the screen. Specifically, the number of times the reagent candidates are specified corresponds to the number of times the check boxes are checked.

The processing unit 10A of the reagent selection support device 100 detects an input to the check box, and performs the operation shown in the flowchart of FIG. 11 each time it detects an input. 5, the processing of steps S31 and S32 is performed by the reagent designation reception unit 104, and the processing of steps S33 and S34 is performed by the output control unit 103. FIG.

FIG. 12 shows combinations of antibody reagents determined by the reagent selection support device 100 . The user confirms the information on the cocktail antibody reagents and the information on the single antibody reagents that are stocked on hand, and the antibody reagents that are on hand are displayed in the combinations of antibody reagents displayed in FIG. If so, check the check box in the corresponding column.

For example, if the user has a CD25 single antibody reagent, the user checks the checkbox 51 corresponding to the CD25 single antibody reagent in the first candidate antibody reagent combination. In step S31, the processing unit 10A obtains designation of reagent candidates for the first candidate antibody reagent combination. Determine whether the candidate is included.

If the second candidate also includes the same designated reagent candidate as the first candidate, in step S33, the processing unit 10A, as shown in FIG. The check box 52 is checked in conjunction with checking the check box of the first candidate. Check box 52 is a check box corresponding to a single antibody reagent for CD25 in the second candidate antibody reagent combination. If the second candidate does not include the same designated reagent candidate as the first candidate, the processing section 10A terminates the process. When the processing unit 10A detects an input to the check box, the processing from step S31 is performed again.

In step S34, the processing unit 10A changes the display mode of the checked check boxes 51 and 52. FIG. The display mode after the change is, for example, hatching display.

Subsequently, the user continues to check the information on the cocktail antibody reagents and the information on the single antibody reagents that are stocked on hand, and the antibody reagents that are on hand among the combinations of antibody reagents displayed in FIG. If it is displayed, check the check box in the corresponding column.

For example, if the user has a CD3/CD4/CD8 cocktail antibody reagent, the user checks the checkbox 53 corresponding to the CD3/CD4/CD8 cocktail antibody reagent in the first candidate antibody reagent combination. . This CD3/CD4/CD8 cocktail antibody reagent is also included in the second candidate. Therefore, as shown in FIG. 14, the processing unit 10A also checks the check boxes 54 of the antibody reagent candidates of the second candidate in conjunction. Check box 54 is a check box corresponding to the CD3/CD4/CD8 cocktail antibody reagent in the second candidate antibody reagent combination. Check boxes 53 and 54 are hatched.

Thereafter, similarly, the user confirms the information on the cocktail antibody reagents and the information on the single antibody reagents that are in stock for the combination of the antibody reagents of the first candidate, and inputs them to the reagent selection support device 100 .

In the state shown in FIG. 15, the measurement order to be detected is "CD38" and there is only one remaining state.

For example, if the user has a CD38 single antibody reagent, the user can check checkbox 55 . As a result, all combinations of antibody reagents shown as the first candidates are checked and displayed with hatching. All the antibody reagents shown in the first candidate are hatched, that is, the cocktail antibody reagents and single antibody reagents that the user has in stock at hand can be used to perform measurements that satisfy the measurement order. It means that there is After that, the user can detect the antibody specified in the measurement order using the measurement device main body 200 based on the antibody reagent combination shown as the first candidate.

On the other hand, if the user does not have the CD38 single antibody reagent, the user cannot check the check box 55 . In such a case, the user continues to check the cocktail antibody reagent information and the single antibody reagent information that are in stock at hand for the combination of antibody reagents shown as the second candidate. For example, if the user has a CD2/CD7/CD3 cocktail antibody reagent, the user can check the box corresponding to the CD2/CD7/CD3 cocktail antibody reagent in the second candidate antibody reagent combination. Check 56.

Thereafter, similarly, the user confirms the information on the cocktail antibody reagents and the information on the single antibody reagents that are in stock for the second candidate antibody reagent combination, and inputs them to the reagent selection support device 100 .

Continuing in the state shown in FIG. 15, for example, if the user has a CD5 single antibody reagent and a CD38/CD56/CD19 cocktail antibody reagent, the user can check check boxes 57 and 58. can. As a result, as shown in FIG. 16, all combinations of antibody reagents shown as second candidates are checked and displayed with hatching. All the antibody reagents shown in the second candidate are hatched, which means that the user can use cocktail antibody reagents and single antibody reagents in stock at hand to perform measurements that satisfy the measurement order. It means that there is After that, the user can use the measuring device main body 200 to detect the antibody specified in the measurement order based on the antibody reagent combination shown as the second candidate.

As described above, the user of the reagent selection support device 100 can further input into the reagent selection support device 100 the information on the cocktail antibody reagents and the information on the single antibody reagents that are stocked at hand. This allows the user to interactively grasp whether or not the antibody reagents in stock at hand can be used to perform the measurement that satisfies the measurement order, while referring to the determined antibody reagent combination candidates. can be done.

<Second embodiment>
In the first embodiment, information on antibody reagents that can be used by the measurement device main body 200 is recorded in the reagent selection support device 100 in advance. In the second embodiment, information on antibody reagents that can be used by the measuring device main body 200 is obtained from an external server 400 . The external server 400 is composed of, for example, a general-purpose computer having a CPU and memory.

The inspection system according to the second embodiment shown in FIG. 17 further includes a server 400 in addition to the sample measuring device 1000 and client terminal 300 . Server 400 , sample measuring device 1000 and client terminal 300 are connected to each other through network 99 .

The processing unit 10B of the reagent selection support device 100 according to the second embodiment shown in FIG. 18 further includes a reagent information acquiring unit 105 in addition to the processing unit 10A according to the first embodiment. That is, the processing unit 10B includes an antigen information acquisition unit 101, a candidate reagent determination unit 102, an output control unit 103, a reagent designation reception unit 104, and a reagent information acquisition unit 105. These functional blocks are realized by installing the program according to the present invention in the recording unit 13 or the memory 12 of the processing unit 10B and executing the program by the CPU 11. FIG.

The external server 400 has a data transmission/reception unit 402 that transmits the antibody reagent information DB 401 to the detection reagent selection support device 100 .

To explain using the functional block shown in FIG. 18, in the second embodiment, the reagent information acquisition unit 105 acquires the antibody reagent information DB 401 from the external server 400 and stores it in the recording unit 13 or the memory 12 of the processing unit 10B. Record. By updating the antibody reagent information DB 401 recorded in the external server 400 to the latest state, the detection reagent selection support device 100 can also always determine candidate combinations of antibody reagents based on the latest antibody reagent information DB 401. can be done. The second embodiment is the same as the first embodiment in terms of the method of determining antibody reagent combination candidates and the method of supporting the selection of antibody reagents in an interactive manner. The processing performed by the reagent information acquisition unit 105, which is a functional block, is actually performed by the processing unit 10B shown in FIG.

As described above, according to the inspection system according to the second embodiment, in addition to the effects of the inspection system according to the first embodiment, information on antibody reagents that can be used by the measurement device main body 200 is always updated. state can be kept.

<Additional notes>
Although the present invention has been described in terms of specific embodiments, the present invention is not limited to the above-described embodiments.

In the above-described first and second embodiments, the processing units 10A and 10B are implemented as an integrated device, but the processing units 10A and 10B do not have to be an integrated device, and the CPU 11, the memory 12, the recording unit, and the like. 13, etc. may be arranged separately and connected by a network. The processing units 10A and 10B, the input unit 16, and the output unit 17 do not necessarily need to be arranged in one place, and may be arranged in separate places and connected to each other so as to communicate with each other via a network.

In the above-described first and second embodiments, each functional block of the antigen information acquisition unit 101, the candidate reagent determination unit 102, the output control unit 103, the reagent designation reception unit 104, and the reagent information acquisition unit 105 is implemented by a single CPU 11. However, these functional blocks do not necessarily need to be executed by a single CPU 11, and may be processed by a plurality of CPUs in a distributed manner.

In the above-described first and second embodiments, the program for performing the processing of each step described in FIGS. 6 to 11 is recorded in the recording unit 13 in advance. It may be installed in the processing units 10A and 10B from a computer-readable non-transitory tangible recording medium (not shown), or the processing units 10A and 10B may be connected to the network 99, and via the network 99, for example A program may be downloaded from an external server 400 and installed.

In the first and second embodiments, the input unit 16 and the output unit 17 are integrated and implemented as a touch panel display device. The unit 17 may be composed of a liquid crystal display or the like. Alternatively, the output unit 17 may be configured by a printer or the like to print candidate combinations of antibody reagents determined by the reagent selection support device 100 .

In the above-described first and second embodiments, the measurement order is transmitted from the requester terminal 300 to the reagent selection support device 100 through the network 99, but the measurement order is input to the reagent selection support device 100 It may be input through the unit 16 . In this case, the measurement order is transmitted to the user of the reagent selection support device 100 by e-mail, telephone, or other means, and the user inputs the transmitted measurement order to the reagent selection support device 100 through the input unit 16. .

In the above first and second embodiments, when the measuring device main body 200 can identify three or more fluorescent dyes, for example, one assay is performed using a cocktail antibody reagent with a cocktail number of "3". The reagent selection support apparatus 100 can determine antibody reagent combination candidates based on information on antibody reagents including cocktail antibody reagents with the number of cocktails of “3”. The number of cocktails of cocktail antibody reagents is not limited as long as it is 2 or more. For example, when the measurement device main body 200 can identify four or more fluorescent dyes, one assay can be performed using a cocktail antibody reagent with a cocktail number of "4", and the reagent selection support device 100 Antibody reagent combination candidates may be determined based on information on antibody reagents including cocktail antibody reagents with the number of cocktails of "4". In this case, the measuring device main body 200 includes a total of five light-receiving elements for fluorescence detection in the detection unit 23, and the detection unit 23 detects four colors of fluorescence from the cocktail antibody reagent and one color of fluorescence from the single antibody reagent. A total of 5 colors of fluorescence are measured simultaneously. Further, for example, when the measurement device main body 200 can identify two or more fluorescent dyes, one assay can be performed using a cocktail antibody reagent with a cocktail number of "2", and the reagent selection support device 100 Antibody reagent combination candidates may be determined based on information on antibody reagents including cocktail antibody reagents with the number of cocktails of “2”. In this case, the measuring device main body 200 includes a total of three light-receiving elements for fluorescence detection in the detection unit 23, and the detection unit 23 detects two colors of fluorescence from the cocktail antibody reagent and one color of fluorescence from the single antibody reagent. A total of three colors of fluorescence are measured simultaneously.

In the above-described first and second embodiments, when displaying the antibody reagents stocked at hand, the display mode after inputting in the check box is hatched display, but the display mode is limited to this. not. For example, instead of hatching display, black and white may be reversed for display, and the frame of the check box may be highlighted with double lines, for example. In other words, any mode may be used as long as the change in the display mode can be visually recognized by the user.

In addition to the first and second embodiments described above, the present invention has a third embodiment described below. The detailed description of the third embodiment is similar to the first and second embodiments, except as noted below.

In a further third embodiment of the present invention, the reagent selection support device 100 is a reagent selection support device that supports selection of a cocktail antibody reagent containing a plurality of antibodies, and is a measurement order for measuring a plurality of antigens. Acquisition units 15 and 16 for acquiring, a processing unit 10 for determining a plurality of antibody reagents that can be used together in an assay for detecting a plurality of antigens, based on the measurement orders acquired by the acquisition units 15 and 16; and an output unit 17 that outputs information on a plurality of antibody reagents that can be used together in the assay, which has been determined by the processing unit 10 .

. Information on a plurality of antigens means antigen information on 2 or more, 3 or more, 4 or more, 5 or more, 6 or more, 10 or more, 15 or more. The antibody reagents are cocktail antibody reagents, combinations of cocktail antibody reagents and single antibody reagents, or combinations of different cocktail antibody reagents. Determining a plurality of antibody reagents means determining two or more antibody reagents to be used in one assay. Can be used in combination means that when one assay is performed using the first antibody reagent and the second antibody reagent, at least one fluorescent dye contained in the first antibody reagent and the second antibody reagent It means that at least one fluorescent dye can be identified and detected. The first antibody reagent can be a cocktail antibody reagent or a single antibody reagent. Preferably, if the first antibody reagent is a cocktail antibody reagent, the second antibody reagent is either a single antibody reagent or a cocktail antibody reagent. Preferably, when the second antibody reagent is a cocktail antibody reagent, the first antibody reagent is either a single antibody reagent or a cocktail antibody reagent. Both the first antibody reagent and the second antibody reagent may be cocktail antibody reagents. For example, when detecting using at least four fluorescent dyes in one assay, the first antibody reagent is a cocktail antibody reagent with a cocktail number of "2" or more, and the second antibody reagent is a cocktail number. One assay can be performed with "2" or more cocktail antibody reagents. Further, when the first antibody reagent is a single antibody reagent, the second antibody reagent may be a cocktail reagent with the number of cocktails "3". Also, even if the first antibody reagent and the second antibody reagent are combined, if the four measurement items cannot be assayed at once, the first antibody reagent and the second antibody reagent are used in the first assay. may be used in combination to assay three measurements, and a third antibody reagent may be selected to assay the remaining measurements in the second assay. The third antibody reagent can be a cocktail antibody reagent or a single antibody reagent.

10, 10A, 10B processing unit 12 memory 13 recording unit 14 bus 15 interface unit 16 input unit 17 output unit 21 suction unit 22 fluid circuit 23 detection unit 27 sheath flow cell 28 sample container 29 sample 99 network 100 reagent selection support device 101 antigen information Acquisition unit 102 Candidate reagent determination unit 103 Output control unit 104 Reagent designation reception unit 105 Reagent information acquisition unit 200 Measuring apparatus main body 300 Requester terminal 301 Input unit 302 Data transmission/reception unit 400 Server 401 Antibody reagent information database 402 Data transmission/reception unit 1000 Sample measurement Device

Claims (18)

A detection method for detecting multiple types of antigens contained in a specimen using flow cytometry,
obtaining , by a computer, a measurement order for measuring the plurality of types of antigens;
A step of selecting a cocktail antibody reagent used for detecting a plurality of antigens to be measured and a single antibody reagent that can be used in combination with the cocktail antibody reagent by the computer, based on the obtained measurement order; ,
displaying , by the computer, information of the selected cocktail antibody reagent and information of the single antibody reagent ;
and detecting multiple types of antigens contained in a sample using the cocktail antibody reagent. The detection method according to claim 1, wherein the cocktail antibody reagent is a reagent containing a mixture of multiple types of antibodies that bind to different or same antigens. The detection method according to claim 1 or 2 , wherein the single antibody reagent is a reagent containing one type of antibody that binds to an antigen. further comprising reading information of the cocktail antibody reagent;
4. The detection method according to any one of claims 1 to 3 , wherein in the selecting step, the cocktail antibody reagent is selected based on the measurement order and readout information on the cocktail antibody reagent. In the selecting step, based on the measurement order, selecting a first candidate for the cocktail antibody reagent and a second candidate different from the first candidate,
The detection method according to any one of claims 1 to 4 , wherein in the displaying step, the selected first candidate and second candidate are displayed. 6. The detection method according to claim 5 , wherein in said displaying step, said first candidate and said second candidate are displayed so as to be distinguishable from each other. receiving a designation of the cocktail antibody reagent to be used in one of the displayed first candidate and second candidate;
7. The detection method according to claim 5 , further comprising the step of changing the display mode of said cocktail antibody reagent corresponding to said designation in each of said first candidate and said second candidate. A detection method for detecting multiple types of antigens contained in a specimen using flow cytometry,
obtaining, by a computer, a measurement order for measuring the plurality of types of antigens;
a step of reading, by the computer, information on cocktail antibody reagents used to detect the plurality of types of antigens to be measured;
selecting the cocktail antibody reagent by the computer based on the obtained measurement order and the read information of the cocktail antibody reagent;
displaying, by the computer, information of the selected cocktail antibody reagent;
detecting multiple types of antigens contained in a sample using the cocktail antibody reagent;
A method of detection, including A detection method for detecting multiple types of antigens contained in a specimen using flow cytometry,
obtaining, by a computer, a measurement order for measuring the plurality of types of antigens;
A step of selecting, by the computer, a first candidate and a second candidate different from the first candidate for cocktail antibody reagents to be used for detecting the plurality of types of antigens to be measured, based on the obtained measurement order. and,
displaying information of the selected cocktail antibody reagents of the first candidate and the second candidate by the computer;
a step in which the computer accepts designation of the cocktail antibody reagent to be used in one of the displayed first candidate and second candidate;
and detecting a plurality of antigens contained in a specimen using the designated cocktail antibody reagent. A detection device for detecting multiple types of antigens contained in a specimen using flow cytometry,
an acquisition unit that acquires a measurement order that targets the plurality of types of antigens to be measured;
Based on the measurement order acquired by the acquisition unit, a process of selecting a cocktail antibody reagent used for detecting a plurality of antigens to be measured and a single antibody reagent that can be used in combination with the cocktail antibody reagent Department and
a display unit that displays information on the cocktail antibody reagent selected by the processing unit and information on the single antibody reagent ;
and a detection unit that detects multiple types of antigens contained in a specimen using the cocktail antibody reagent. 11. The detection device according to claim 10 , wherein the cocktail antibody reagent is a reagent containing a mixture of multiple antibodies that bind to different or same antigens. The detection device according to claim 10 or 11 , wherein the single antibody reagent is a reagent containing one type of antibody that binds to an antigen. The processing unit reads the information of the cocktail antibody reagent, and selects the cocktail antibody reagent based on the measurement order and the read information of the cocktail antibody reagent, according to any one of claims 10 to 12. The detection device described. The processing unit selects a first candidate for the cocktail antibody reagent and a second candidate different from the first candidate based on the measurement order,
The detection device according to any one of claims 10 to 13, wherein said display unit displays said first candidate and said second candidate selected by said processing unit. 15. The detection device according to claim 14, wherein said display unit displays said first candidate and said second candidate so as to be distinguishable from each other. Further comprising an input unit that accepts designation of the cocktail antibody reagent to be used in one of the first candidate and the second candidate displayed by the display unit,
The detection device according to claim 14 or 15, wherein the processing unit changes a display mode of the cocktail antibody reagent corresponding to the designation in each of the first candidate and the second candidate. A detection device for detecting multiple types of antigens contained in a specimen using flow cytometry,
an acquisition unit that acquires a measurement order that targets the plurality of types of antigens to be measured;
Read out the information of the cocktail antibody reagent used to detect the plurality of antigens to be measured, and based on the measurement order acquired by the acquisition unit and the read information of the cocktail antibody reagent, the cocktail a processing unit that selects an antibody reagent;
a display unit for displaying information on the cocktail antibody reagent selected by the processing unit;
and a detection unit that detects multiple types of antigens contained in a specimen using the cocktail antibody reagent. A detection device for detecting multiple types of antigens contained in a specimen using flow cytometry,
an acquisition unit that acquires a measurement order that targets the plurality of types of antigens to be measured;
Based on the measurement order acquired by the acquisition unit, a first candidate and a second candidate different from the first candidate are selected as cocktail antibody reagents to be used for detecting the plurality of types of antigens to be measured. a processing unit;
a display unit that displays information about the first candidate and the second candidate cocktail antibody reagents selected by the processing unit;
an input unit that receives designation of the cocktail antibody reagent to be used in one of the first candidate and the second candidate displayed by the display unit;
and a detection unit that detects multiple types of antigens contained in a specimen using the cocktail antibody reagent.

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