JPH1144632A - Method for determining abnormality in data of particle-measuring device - Google Patents

Abstract

PROBLEM TO BE SOLVED: To quantatively determine abnormality of a particle weighing device by supplying a reference specimen on a particle measuring device which is reference and an object, making a degree of deviation for the normal distribution of obtained frequency distribution a degree of reference deviation and a degree of comparison deviation, and comparing them with each other. SOLUTION: When valves 1, 2 are opened, sample liquid from a suction nozzle 3 is filled between the valves 1, 2. Next, the sample liquid between the valves 1, 2 is pushed from a sample nozzle 6 in a constant flow rate with a syringe 4, discharged to a flow cell 5, and when a valve 8 is opened, sheath liquid is supplied from a sheath liquid vessel 9 to the flow cell 5, the sample liquid is wrapped by the sheath liquid, and previously contained particles are arranged in one row to be flowed. A laser beam from a light source 17 to the sample liquid flow 26 of an orifice 11 is irradiated through a condenser lens 18, and low and high angle dispersion light is received on a photodiodes 21, 22 through a collector lens 20. An analysis part 23 compares a degree of deviation for normal distribution of frequency distribution obtained from the sample liquid with a degree of reference deviation.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for judging data abnormality of a particle measuring device, and more particularly to a method for determining whether or not various measurement conditions of the particle measuring device are stably maintained. The present invention relates to a method for determining anomalies in distribution data obtained.

[0002]

2. Description of the Related Art The measurement results of a particle measuring device are affected by fluctuations in the output of a measuring section and contamination, and when a sample is reacted, the results are affected by fluctuations in the reaction section and reagents. Receive. Therefore, in order to confirm whether or not the measurement conditions are normally maintained, a precision measurement is performed by measuring a standard sample whose measurement result is known in advance.

However, in analyzing biological samples such as blood and urine, not only the counting of the number of target particles but also a comprehensive particle size analysis for examining the state of the particles and the appearance of other particles. Has been desired.

[0004] Accordingly, it has often been experienced that the accuracy control is not sufficient only by determining the number of target particles or the peak position of the target particle population. The present invention has been made in view of such circumstances, and provides a determination method for accurately determining the distribution state of particle size distribution data of a particle measuring device.

[0005]

According to the present invention, a standard sample is supplied to a reference particle measuring apparatus, and the degree of deviation of the obtained frequency distribution from a normal distribution is calculated as a reference deviation degree, and the target particle is measured. The standard sample is supplied to the measuring device, the degree of deviation of the obtained frequency distribution from the normal distribution is calculated as a comparative deviation, and the standard deviation and the comparative deviation are compared.
An object of the present invention is to provide a data abnormality determination method for a particle measurement device that determines whether or not a frequency distribution obtained from a target particle measurement device is abnormal based on the comparison result.

[0006]

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS A particle measuring device according to the present invention is a device which optically or electrically detects a parameter representing a characteristic of each particle contained in a liquid and outputs a frequency distribution, a counting result, and the like. For example, a commercially available blood cell analyzer NE series (manufactured by Toa Medical Electronics Co., Ltd.) or SF-3000 (manufactured by the company) can be applied to this.

[0007] The standard sample in the present invention is a sample in which the control items of the target particles are known in advance. Unless the sample is reacted, an artificial carrier such as latex can be used as a standard sample. When the sample is reacted to control the state of the reagent, it is preferable to use the same biological material as the measurement sample, for example, blood or urine, as the standard sample. For this purpose, a sample in which preservatives and stability are improved while maintaining its properties, for example, SF check and UF check (both manufactured by Toa Medical Electronics Co., Ltd.) can be similarly used.

The degree of deviation of the frequency distribution from the normal distribution is a statistic that indicates how much the frequency distribution deviates from the normal distribution. The degree of skewness b1 expressed by the following equations (1) and (2) is Kurtosis b2. The skewness b1 represents the degree of asymmetry of the distribution, and the kurtosis b2 is an index representing the length of the tail of the distribution.

[0009]

(Equation 1)

In the present invention, either the skewness or the kurtosis may be used as the degree of deviation of the frequency distribution from the normal distribution, but if the skewness is used, the direction of the deviation is determined by the sign of the value. Is preferred. Also,
In the present invention, the reference particle measurement device and the target particle measurement device may be the same,
In this case, the reference particle measurement device is one whose optical system and fluid system have been normally calibrated, adjusted, and cleaned, and the one that has been used for an arbitrary period of time is used as the target particle measurement device. Corresponding.

Further, the reference particle measuring device and the target particle measuring device are not necessarily the same, and may be of the same model. In this case, one normal particle measurement device can be used as a reference particle measurement device, and another particle measurement device can be used as a target particle measurement device.

In the present invention, an operation for calculating and comparing the degree of deviation of the frequency distribution from the normal distribution from the frequency distribution data obtained from a normal particle measuring device is required. For example, the measurement may be performed by a personal computer provided separately, or a function of performing the calculation may be provided in advance in the particle measuring device itself.

The present invention will be described below in detail based on an embodiment shown in the drawings. Note that the present invention is not limited to this.

FIG. 1 is an explanatory diagram showing a main configuration of a particle measuring apparatus having a data abnormality determining function according to the present invention.
1 and 2 are valves, 3 is a suction nozzle for sucking a sample liquid which has been subjected to pretreatment such as dilution and staining in the pretreatment unit 3a,
Reference numeral 4 denotes a syringe, 5 denotes a flow cell, 6 denotes a sample nozzle, 8 denotes a valve, 9 denotes a sheath liquid container, and 10 denotes a sheath liquid.
, A sample liquid output from the sample nozzle 6, a pore 11 provided in the flow cell 5,
Including orifices (hereinafter referred to as orifices).

Reference numeral 17 denotes a semiconductor laser light source (wavelength: 6).
50 nm), 18 is a condenser lens, 19 is a beam stopper, 20 is a collector lens, 21 is a photodiode for detecting low-angle scattered light of 1 to 6 degrees, and 22 is 8 to 20
A photodiode 23 for detecting high-angle scattered light is an analysis unit for receiving and analyzing the output signals of the photodiodes 21 and 22.

In such a configuration, first, the valves 1, 2
Is opened for a predetermined time, the sample liquid is filled between the valves 1 and 2 from the suction nozzle 3 by the negative pressure.

Next, the syringe 4 pushes the sample liquid between the valves 1 and 2 to the sample nozzle 6 at a constant flow rate, so that the sample liquid is discharged from the sample nozzle 6 to the flow cell 5. At the same time, the sheath liquid is supplied to the flow cell 5 by opening the valve 8.

Thus, the sample solution is wrapped in the sheath solution,
Further, the sheath flow is narrowed down by the orifice 11.

By forming the sheath flow in this manner, particles contained in the sample solution in advance can be flowed in a line through the orifice 11 one by one.

On the other hand, the sample liquid flow 2 flowing through the orifice 11
The laser light oscillated from the light source 17 is squeezed by the condenser lens 18 and emitted to 6.

The laser beam that has passed through the flow cell 5 as it is without hitting particles in the sample liquid is shielded by the beam stopper 19. The low-angle scattered light and the high-angle scattered light emitted from the particles that have received the laser light are collected by the collector lens 20 and received by the photodiodes 21 and 22, respectively.

FIG. 2 is a block diagram showing the configuration of the analysis unit 23. In FIG. 2, reference numeral 61 denotes a data input unit for setting conditions such as various numerical values and regions in advance, and includes, for example, a keyboard and a mouse.

Reference numeral 61a denotes a set condition storage unit for storing various set conditions, and reference numeral 47 denotes a photo die auto 21 and 22.
Is a data storage unit for storing parameter information obtained from the output signal of the first embodiment. Reference numeral 62 denotes a distribution map creating unit for creating a scattergram based on the parameter information stored in the data storage unit 47, that is, a scattergram of the high-angle scattered light intensity and the low-angle scattered light intensity. An extraction unit that extracts coordinates and regions from the created distribution map.

Reference numeral 64 denotes a fractionation region determining unit that determines the fractionation region of each particle in the distribution map created by the distribution diagram creation unit 62, and 65 denotes the number of particles in the fractionation region and the number of particles in each fractionation region. An operation unit that performs various calculations such as a deviation degree of the frequency distribution from the normal distribution, 66 is a warning unit that issues a warning when an abnormality is detected in the result of the fractionation or the calculation, and 67 is a warning unit that detects particles existing in the determined fractionation region. This is a determination unit for determining the type. The calculation result of the calculation unit 65 and the warning issued by the warning unit 66 are displayed on the display unit 49 in the same manner as the distribution chart created by the distribution map creation unit 62. Further, the analysis unit 23 can be constituted by a personal computer.

In the input section 61, when a desired mode is set from various modes such as "red blood cell measurement mode", "hemoglobin measurement mode", "white blood cell measurement mode", and "abnormality determination mode", a preprocessing section is set. 3a prepares a sample liquid by performing a pretreatment such as dilution and staining on a blood sample in accordance with the setting mode. The analysis unit 23 creates a two-dimensional distribution map based on the parameter information obtained from the prepared sample solution, that is, the high-angle and low-angle scattered light intensities, and displays the two-dimensional distribution map on the display unit 49 together with the fractionation results. The calculated numerical data is displayed on the display unit 49.

Here, the "abnormality determination mode" will be described in more detail using an actual measurement example. When the “abnormal measurement mode” is set in the input unit 61, the preprocessing unit 3a dilutes 33 μL of the standard sample with 0.967 mL of the leukocyte classification reagent 1 and adds 0.2 mL of the leukocyte classification reagent 2 thereto. Make a liquid.

Here, SF check (manufactured by Toa Medical Electronics Co., Ltd.) was used as a standard sample, and reagents 1 and 2 for leukocyte classification were used.
For Structural No. 2, a stoma riser FD (I) and a stoma riser FD (II) were used. The stoma riser FD (I) is used for staining only eosinophils and stabilizing the form of leukocytes.
(II) is used for hemolysis of red blood cells.

The analyzing unit 23 creates a two-dimensional distribution diagram as shown in FIG. 3 for the high-angle scattered light intensity (IH) and the low-angle scattered light intensity (IL) obtained from the sample solution reacted as described above. . Lymphocyte region L, monocyte region M, neutrophil and basophil region N, eosinophil region E and ghost region G, and the number of particles in each region other than the ghost region and the total number of leukocytes Is displayed. If the number of particles not fractionated by any of the above is equal to or more than a predetermined value, the appearance of the abnormal cell is reported according to the appearance position.

FIG. 4 shows an example of a normal particle size distribution, and FIG. 5 shows an example of a particle size distribution when the device is slightly shifted optically. The number of particles NS and the peak coordinates (Xp, Y
p), the calculation result is displayed with the distribution width in the Y-axis direction as Yw and the skewness in the Y-axis direction as b1.

When comparing the fractionation area N between FIG. 4 and FIG.
The number of particles NS does not differ from 2936 and 2923, and the peak coordinates (X
(p, Yp) also shows no difference between (195, 185) and (193, 188). Further, the distribution width Yw does not differ from 35 and 36, and it seems that there is no difference between them. However, the skewness b1 is +0.10.
There is a large difference between -0.13 and -0.13. In other words, in the normal state (FIG. 4), the distribution of the fractionation area N has an upward spread, but in FIG. 5, the distribution has a downward spread. Therefore, the distribution of normal cells may extend to areas other than the normal cell area (each area L, M, N, and E in FIG. 3). In that case, the normal cell is recognized as an abnormal cell and an incorrect result is obtained. In particular, even when the normal state is not normal distribution but spreads to one side as in this embodiment, it is possible to monitor with high accuracy by using the skewness.

[0031]

According to the present invention, it is possible to quantitatively determine the abnormality of the particle measuring device from the frequency distribution obtained by the particle measuring device, and to appropriately know the maintenance time.

[Brief description of the drawings]

FIG. 1 is an explanatory diagram of a configuration of a particle measuring device according to an embodiment.

FIG. 2 is a block diagram of a main part of the particle measuring device according to the embodiment.

FIG. 3 is an explanatory diagram illustrating a display example of an embodiment.

FIG. 4 is an explanatory diagram showing a display example of the embodiment.

FIG. 5 is an explanatory diagram showing a display example of the embodiment.

[Explanation of symbols]

 Reference Signs List 1 valve 2 valve 3 suction nozzle 4 syringe 5 flow cell 6 sample nozzle 7a first cell 7b second cell 8 valve 9 sheath liquid container 10 supply port 11 orifice 14 drain port 17 light source 18 condenser lens 19 beam stopper 20 collector lens 21 photodiode 22 Photodiode 23 Analyzer

Claims (4)

[Claims] 1. A standard sample is supplied to a reference particle measuring device, a degree of deviation of the obtained frequency distribution from a normal distribution is calculated as a reference deviation, and the standard sample is supplied to a target particle measuring device. , The degree of deviation of the obtained frequency distribution from the normal distribution is calculated as a comparative deviation, and the standard deviation and the comparative deviation are compared. Based on the comparison result, the frequency distribution obtained from the target particle measurement device is calculated. A data abnormality determination method for a particle measurement device that determines whether or not the data is abnormal. 2. The method according to claim 1, wherein the criterion and the comparative deviation are skewness. 3. The method according to claim 1, wherein the reference and the relative deviation are kurtosis. 4. The data abnormality determination method for a particle measurement device according to claim 1, wherein the reference particle measurement device and the target particle measurement device have the same model.