JP2007271482A - Specimen analyzer - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a specimen analyzer capable of measuring bacteria with the sensitivity corresponding to each clinical target. <P>SOLUTION: The specimen analyzer for analyzing the bacteria contained in a specimen includes a sample preparing part for preparing a measuring sample by mixing the specimen with a dyeing reagent for dyeing bacteria, a measuring part for irradiating the measuring sample prepared by the sample preparing part with light to detect the fluorescence from the dyed bacteria to measure the bacteria contained in the measuring sample, a measuring sensitivity input means for inputting the measuring sensitivity bacteria and a control part for controlling the amount of the measuring sample measured by the measuring part corresponding to the input measuring sensitivity. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

  The present invention relates to a sample analyzer, and more particularly to a sample analyzer that stains and analyzes bacteria in a sample.

  Conventionally, in order to find a disease or estimate an infection, a test for bacteria has been performed using specimens such as blood and urine collected from patients. Analysis of components such as bacteria contained in urine is performed by visual inspection mainly using a microscope in a general laboratory. In this visual inspection, urine is centrifuged and concentrated, and the sediment is optionally stained and then placed on a microscope slide for classification and counting under a microscope. In addition to the above-mentioned bacteria, erythrocytes, leukocytes, epithelial cells, and cylinders are commonly used as tests for urine components.

  In the examination using this microscope, first, the presence or absence of the urine formation and the state of the urine specimen are grasped with a low magnification field of view (LPF) of 100 times, and the classification of each component with a high magnification field of view (HPF) of 400 times. Is done. Among the measurement items, even when a cylinder appears, the number is very small. However, since its detection is highly useful clinically, detection is performed with a low-power field (LPF). Other formed components are classified by high-power field (HPF), and red blood cells and white blood cells are counted by high-power field (HPF).

Thus, the urinary component test is said to be a qualitative test (bacteria ++), a quantitative test (5 red blood cells / HPF), and a morphological test (recognized deformed red blood cells).
An automatic microscope apparatus has been proposed as an apparatus for automating urine formed component inspection. The flow type automatic microscope apparatus UA-2000 (Sysmex Corp.) flows a flat flow cell without concentrating a urine sample, images particles flowing in the flow cell, and stores the captured image. The stored captured images are sorted according to the size of the particles, and are used so that the user sees the images and classifies them into each formed component.

  In recent years, an apparatus for automatically classifying the formed components has been proposed even in such an automatic microscope method, but the formed components in urine have various forms, and there are many formed components that have been damaged. Is difficult to classify with high accuracy. In particular, it is difficult to classify red blood cells (particularly broken red blood cells), bacteria, and crystals, which are small components, with high accuracy, and the user often performs reclassification after visual confirmation.

  A urine sediment measuring device using a flow cytometer has been proposed as an automatic classification device that is further automated. In this device, urine components are stained with a staining reagent, light is applied to the sample that has flowed through the flow cell to detect scattered light signals and fluorescent signals, and these scattered light signals and fluorescent signals are combined to produce red blood cells. , White blood cells, epithelial cells, cylinders, bacteria classification.

  As described above, the urine formed components have various forms and many damaged components are formed, and it is difficult to classify them with high accuracy only by combining the scattered light signal and the fluorescence signal. Therefore, this apparatus uses a staining reagent configured to stain each formed component by membrane staining without damaging the formed component in urine (Patent Document 1). By combining the pulse width and the intensity of the fluorescence signal and the pulse width, the urine formed components are classified (Patent Document 2). This makes it possible to automatically classify the urine formed components, which contributes greatly to the automation of urinalysis. Further, the urinary sediment measuring device using this flow cytometer is configured to provide classification and morphological information of urinary sediment with various devices. For example, by analyzing the scattered light signal of red blood cells, information on the origin of urinary red blood cells (from glomeruli or non-glomeruli) is provided (Patent Document 3).

However, there are some specimens that are difficult to measure with high accuracy even if they are analyzed using scattered light signals and fluorescent signals. This is because the bacteria contained in the urine are very small and the sizes are very diverse. The above-mentioned urinary material measuring device is configured to measure large sized material (columns, epithelial cells), medium sized material (white blood cells, erythrocytes), and small sized material (bacteria) in a single measurement. Has been. However, it is difficult to accurately detect a wide range of 1 μm to several tens of μm over the whole, and it is difficult to detect small bacteria, that is, noncoagulant cocci. Bacterial testing in the urinary particle examination with this apparatus is a test to check the amount of bacteria as can be confirmed by microscopic examination has appeared in the urine, typically 10 ⁴ / ml ( When the concentration of urine components is 10 ⁴ cells / ml, the test has a sensitivity of about (sensitivity of measurement) capable of classifying and measuring bacteria in urine. Cocci are often proliferated and agglomerated, so this sensitivity satisfies the requirements for normal urine sediment testing, but there are also specimens in which only small cocci appear. In such a case, accurate measurement results could not be obtained. In addition, when a large bacterium, that is, a coccus having a large clump or a large gonococcus, appears, it may enter the region of red blood cells or white blood cells, which may cause erroneous measurement.

  On the other hand, urinary bacterial tests are also required to be performed with higher sensitivity depending on clinical purposes. In that case, a culture test in which a sample is cultured to inspect bacteria is performed in a bacterial laboratory separately from the urine sediment test. However, since the culture test takes days to cultivate, it is desired to perform a highly sensitive bacterial test without culturing.

  Bacteria analysis using a flow cytometer, that is, a method of measuring bacteria with a scattered light signal and a fluorescence signal by staining the bacteria with a staining reagent has been proposed. In Patent Document 4, by using a staining reagent containing a cationic surfactant so as to dissolve foreign substances other than bacteria, a sample such as urine containing foreign substances of the same size as bacteria can be obtained. A method for measuring with high accuracy is described.

JP-A-8-170960 JP-A-5-322285 JP 11-295207 A JP 2001-258590 A

  As described above, the conventional urine sediment measuring device cannot obtain sufficient measurement accuracy for a specimen containing a large amount of small bacteria or large bacteria. In addition, the measurement sensitivity required for clinical tests for bacterial tests in specimens varies, and there is a need for an automatic analyzer capable of measuring with the measurement sensitivity corresponding to each clinical purpose.

  The present invention has been made in view of such circumstances, and an object thereof is to provide a sample analyzer that can perform bacterial measurement with sensitivity according to each clinical purpose.

The sample analyzer of the present invention is a sample analyzer for analyzing bacteria contained in a sample,
A sample preparation unit for adjusting a measurement sample by mixing a specimen and a staining reagent for staining bacteria;
A measurement unit that irradiates light to the measurement sample prepared by the sample preparation unit, receives fluorescence from the stained bacteria, and measures bacteria contained in the measurement sample;
Measurement sensitivity input means for inputting the sensitivity of bacterial measurement;
A control unit for controlling the amount of the measurement sample measured by the measurement unit according to the input measurement sensitivity;
It is characterized by having.

  In the sample analyzer of the present invention, it is possible to select measurement sensitivity when measuring bacteria, and perform bacterial measurement according to the selected measurement sensitivity, so that it is possible to cope with bacterial measurement with various measurement sensitivity. it can. In addition, the measurement sensitivity can be adjusted by the measurement unit by controlling the amount of the measurement sample. For example, by increasing the amount of the measurement sample as compared with the standard measurement, the measurement can be performed with a higher measurement sensitivity than in the normal measurement sensitivity.

The measurement sensitivity input means is configured to accept a selection between a standard mode for performing measurement at a standard sensitivity and a scrutiny mode for performing measurement with higher sensitivity than the standard mode, and the control The unit may be configured to operate the measurement unit in the standard mode when the standard mode is selected, and operate the measurement unit in the scrutinization mode when the scrutiny mode is selected. In this case, the user selects the standard mode when performing bacterial measurement at a standard sensitivity (for example, 10 ⁵ cells / ml), for example, in a urine test, and performs high sensitivity (for example, 10 ³ cells / ml) bacterial measurement. Sometimes it is only necessary to select a scrutiny mode, and a user can automatically perform a desired measurement only by selecting an operation mode according to the purpose.

  The control unit preferably controls the measurement operation of the measurement unit such that the measurement operation time in the scrutiny mode is longer than the measurement operation time in the standard mode. By extending the operation time in the scrutiny mode as compared to the standard mode, the resolution in the measurement unit can be increased, and high-sensitivity measurement can be handled.

  The control unit may be configured to cause the measurement unit to perform a measurement operation using a larger amount of measurement sample in the scrutiny mode than when measuring in the standard mode. By increasing the amount of measurement sample used in the scrutinization mode than in the standard mode, it is possible to secure more opportunities for bacteria detection, and even for low-concentration bacteria, bacteria can be detected according to the concentration. Therefore, it can cope with highly sensitive measurement.

The specimen is urine,
It can be configured to be able to measure urinary formed components containing at least leukocytes. According to this configuration, it is possible to measure the urinary formation substantially excluding bacteria, and it is possible to cope with a general urinalysis, and the versatility of the apparatus can be enhanced. In addition, although it changes with diseases, examples of the component contained in urine include erythrocytes, leukocytes, epithelial cells, cylinders, bacteria, fungi, crystals and mucus threads, and contaminants such as cell fragments. it can. In the present specification, for clarity, erythrocytes, white blood cells, epithelial cells, and cylinders, which are relatively large particles, are referred to as “urinary tangible components”. It shall not be included in “Neutral formation”. However, when it is simply referred to as “formed component” in urine, bacteria are included in this “formed component”.

The sample preparation unit mixes the staining reagent with a urine sample to prepare a first sample for bacterial measurement, and mixes the urine sample with a reagent for measuring a urine component. A second sample preparation unit that prepares a second sample for measurement of urine components containing at least leukocytes,
The measurement unit is configured to be able to measure bacteria contained in the first sample and to measure urine formed components including at least leukocytes contained in the second sample. can do. According to this configuration, since the measurement of bacteria and the measurement of urinary formation can be performed using a single measurement unit, the cost of the product can be reduced and the apparatus can be downsized.

  According to the sample analyzer of the present invention, in addition to measurement with standard sensitivity, highly sensitive bacterial measurement can be performed in real time.

Hereinafter, embodiments of a sample analyzer of the present invention will be described in detail with reference to the accompanying drawings.
FIG. 1 is an explanatory perspective view of a sample analyzer according to an embodiment of the present invention. In FIG. 1, a housing that accommodates the components of the sample analyzer is partially omitted for easy understanding.

[Device configuration]
In FIG. 1, a urine analyzer U as a sample analyzer includes a sample preparation unit 2 for preparing a sample, a rack table 4 for transferring a sample rack (test tube stand) 3, and a urine formed component from the sample. And an optical detection unit 5 for detecting information on bacteria and a circuit unit 14. A support base 16 is attached to the side surface of the housing via an arm 15, and a personal computer 13 is installed thereon. The personal computer 13 is LAN-connected to the circuit unit 14 of the urine analyzer U.

  In the present embodiment, a measurement unit that measures a patient's clinical specimen is mainly configured by the optical detection unit 5 and the circuit unit 14, and a measurement result by the measurement unit is output by the display 13 a of the personal computer 13. An output unit (display unit) is configured. The personal computer 13 is connected to, for example, an in-hospital host computer, and can be configured to acquire patient information related to the patient such as name, date of birth (age), medical department being examined from the host computer. Has been.

More specifically, the personal computer 13 has the following configuration.
As shown in FIG. 2, the personal computer 13 includes a CPU 104a, a ROM 104b, a RAM 104c, a hard disk 104d, a reading device 104e, an input / output interface 104f, a communication interface 104g, and an image output interface 104h. The CPU 104a, the ROM 104b, the RAM 104c, the hard disk 104d, the reading device 104e, the input / output interface 104f, and the image output interface 104h are connected by a bus 104i so that data communication is possible.

The CPU 104a can execute computer programs stored in the ROM 104b and computer programs loaded in the RAM 104c. The personal computer 13 functions as a system when the CPU 104a executes an application program 140a as described later.
The ROM 104b is configured by a mask ROM, PROM, EPROM, EEPROM, or the like, and stores a computer program executed by the CPU 104a, data used for the same, and the like.

The RAM 4c is configured by SRAM, DRAM, or the like. The RAM 4c is used for reading out computer programs recorded in the ROM 4b and the hard disk 4d. Moreover, when these computer programs are executed, it is used as a work area of the CPU 4a.
The hard disk 104d is installed with various computer programs to be executed by the CPU 104a, such as an operating system and application programs, and data used for executing the computer programs. An application program 140a described later is also installed in the hard disk 104d.

  The reading device 104e is configured by a flexible disk drive, a CD-ROM drive, a DVD-ROM drive, or the like, and can read a computer program or data recorded on the portable recording medium 140. Further, the portable recording medium 140 stores an application program 140a for causing the personal computer 13 to function as the system of the present invention, and the personal computer 13 reads the application program 140a according to the present invention from the portable recording medium 140. The application program 140a can be installed in the hard disk 104d.

The application program 140a is not only provided by the portable recording medium 140, but also from an external device that is communicably connected to the personal computer 13 by an electric communication line (whether wired or wireless). It is also possible to provide through. For example, the application program 140a is stored in a hard disk of a server computer on the Internet. The personal computer 13 can access the server computer, download the computer program, and install it on the hard disk 104d. is there.
The hard disk 104d is installed with an operating system that provides a graphical user interface environment such as Windows (registered trademark) manufactured and sold by Microsoft Corporation. In the following description, it is assumed that the application program 140a according to the present embodiment operates on the operating system.

The input / output interface 104f includes, for example, a serial interface such as USB, IEEE 1394, and RS-232C, a parallel interface such as SCSI, IDE, and IEEE 1284, and an analog interface including a D / A converter and an A / D converter. ing. An input device (input means) 13b such as a keyboard or a mouse is connected to the input / output interface 104f, and the user can input data to the personal computer 13 by using the input device 13b. .
The image output interface 104h is connected to a display 13a constituted by an LCD, a CRT, or the like, and outputs a video signal corresponding to image data given from the CPU 104a to the display 13a. The display 13a displays an image (screen) according to the input video signal.

  FIG. 3 is a diagram showing a schematic functional configuration of the sample preparation unit 2 and the optical detection unit 5. In the figure, urine (specimen) that has entered the test tube T is aspirated by a syringe pump (not shown) using the aspirating tube 17, and dispensed to the sample preparation unit 2 by the sample distribution unit 1. The sample preparation unit 2 in the present embodiment includes a sample preparation unit (first sample preparation unit) 2u and a sample preparation unit (second sample preparation unit) 2b. The sample preparation unit 2u includes red blood cells, white blood cells, It contains a sediment-type aliquot (first aliquot) for analyzing relatively large urine formed components such as epithelial cells, cylinders, etc., while the sample preparation unit 2b has relatively small formed components such as bacteria. A bacterial aliquot (second aliquot) is stored for analysis.

  The urine of each sample preparation unit 2u, 2b is diluted with the diluents 19u, 19b, respectively, and then mixed with the staining solutions (staining reagents) 18u, 18b, and the dye contained in the staining solutions (staining reagents) 18u, 18b. Each is dyed to form a suspension for the formation. The sample preparation unit 2u prepares a first sample for measuring a urine sediment containing at least leukocytes, while the sample preparation unit 2b prepares a second sample for measuring bacteria. .

  As for the two types of suspensions (samples) prepared as described above, the suspension (first sample) of the sample preparation unit 2 u is first guided to the optical detection unit 5, and the sheath liquid is obtained in the sheath flow cell 51. A thin flow wrapped in the film is formed and irradiated with laser light. Thereafter, similarly, the suspension (second sample) of the sample preparation unit 2b is guided to the optical detection unit 5, forms a thin flow in the sheath flow cell 51, and is irradiated with laser light. Such an operation is automatically performed by operating a driving unit, a solenoid valve, and the like (not shown) under the control of a microcomputer 11 (control device) described later.

  FIG. 4 is a diagram illustrating a configuration of the optical detection unit 5. In the figure, a condenser lens 52 condenses laser light emitted from a semiconductor laser 53, which is a light source, on a sheath flow cell 51, and a condensing lens 54 converts forward scattered light in urine in a scattered light receiving unit. The light is condensed on a certain photodiode 55. The other condensing lens 56 condenses the formed side scattered light and side fluorescent light on the dichroic mirror 57. The dichroic mirror 57 reflects the side scattered light to the photomultiplier 58 that is the scattered light receiving unit, and transmits the side fluorescence toward the photomultiplier 59 that is the fluorescent light receiving unit. These optical signals reflect the characteristics of the components in urine. The photodiode 55, the photomultiplier 58, and the photomultiplier 59 convert the optical signal into an electrical signal, and the forward scattered light signal (FSC), the side scattered light signal (SSC), and the side fluorescent signal (SFL), respectively. ) Is output. These outputs are amplified by a preamplifier (not shown) and then subjected to the next stage processing.

  FIG. 5 is a block diagram showing the overall configuration of the urine analyzer U. As shown in FIG. In the figure, the urine analyzer U performs amplification, filter processing, etc. on the sample distribution unit 1, sample preparation unit 2, optical detection unit 5 and the output of the optical detection unit 5 amplified by a preamplifier. An analog signal processing circuit 6, an A / D converter 7 that converts the output of the analog signal processing circuit 6 into a digital signal, a digital signal processing circuit 8 that performs predetermined waveform processing on the digital signal, and a digital signal processing circuit 8 A microcomputer 9 connected to the analog signal processing circuit 6 and the digital signal processing circuit 8, and a LAN adapter 12 connected to the microcomputer 11. The external personal computer 13 is LAN-connected to the urine analyzer U via the LAN adapter 12, and the personal computer 13 analyzes data acquired by the urine analyzer U. The analog signal processing circuit 6, the A / D converter 7, the digital signal processing circuit 8, and the memory 9 constitute a signal processing circuit 10 for the electric signal output from the optical detection unit 5.

  FIG. 6 is a perspective explanatory view of a quantitative mechanism and a sample preparation unit of the urine analyzer according to the present embodiment, and FIG. 7 is an explanatory view thereof. In the present embodiment, a sampling valve 30 that is commonly used as a quantitative mechanism for distributing a predetermined amount of urine specimen to the sample preparation section (first sample preparation section) 2u and the sample preparation section (second sample preparation section) 2b. Is adopted. The sampling valve 30 includes two disk-shaped fixed elements and a movable element sandwiched between the two fixed elements. The movable element is rotated by a motor 31.

  The sampling valve 30 includes two alumina ceramic disks 30a and 30b that are overlapped with each other. A flow path for circulating a sample is formed inside the disks 30a and 30b, and the flow path is divided when one of the disks 30b rotates about its central axis as a center of rotation. It is configured integrally with the sample preparation section 2b through a fluid cassette 33 having a flow path 32. That is, the sampling valve 30, the fluid cassette 33, and the sample preparation unit 2b are disposed in close contact with each other so as to be thermally integrated, and the temperature of the sampling valve 30 is equal to the temperature of the sample preparation unit 2b. It is comprised so that it may become substantially equal. On the other hand, the sample preparation unit 2u is provided with a predetermined clearance S on a mounting plate 34 fixed to the casing and fixed with bolts 35. For this reason, the sample preparation unit 2u includes the sampling valve 30 and the sample preparation. The part 2b is in a state of being substantially thermally isolated.

  The sample preparation unit 2u and the sample preparation unit 2b are heated by heaters 36u and 36b constituting a temperature control unit, respectively, and prepare a first sample for measuring a urinary component containing at least white blood cells. The temperature of the sample preparation unit 2u is adjusted to the first temperature, and the temperature of the sample preparation unit 2b for preparing the second sample for measuring bacteria is adjusted to a second temperature higher than the first temperature. is doing. Specifically, the sample preparation unit 2u is adjusted to be about 35 ± 2 ° C., and the sample preparation unit 2b is adjusted to be about 42 ± 2 ° C., which is higher than this. The higher the temperature of the sample, the faster the predetermined site (membrane or nucleus) such as red blood cells and bacteria contained in the sample can be stained, and the measurement time can be shortened. It is susceptible to damage, and accurate measurements cannot be made if the temperature is too high. Therefore, the temperature of the second sample for measuring bacteria having higher heat resistance than other urine formed components is made higher than the temperature of the first sample for measuring urine formed components. In other words, by adjusting the sample preparation unit 2u and the sample preparation unit 2b to temperatures suitable for measurement, both the urine components including red blood cells and bacteria can be measured with high accuracy. be able to. In addition, the temperature of the sample preparation part 2u and the sample preparation part 2b can be measured, for example with a thermistor. Then, the sample preparation unit 2u and the sample preparation unit 2b can be adjusted to a temperature within the predetermined range by controlling the heaters 36u and 36b on and off based on the measurement result.

  In addition, by configuring the sampling valve 30 and the sample preparation unit 2b to be thermally integrated, the sample whose temperature has been adjusted by the sampling valve 30 is prevented from being cooled when supplied to the sample preparation unit 2b. Therefore, loss of temperature control can be reduced. In this case, with respect to the sample supplied to the sample preparation unit 2u that is kept at a lower temperature than the sample preparation unit 2b, when the sample is supplied from the sampling valve 30, the clearance of the sample passes through the clearance S. Can be reduced naturally.

[Measurement mode selection]
In the present invention, when measuring bacteria using the second sample adjusted by the sample preparation unit 2b, the measurement sensitivity of the contact bacteria can be selected. That is, the urine analyzer includes measurement sensitivity input means for inputting the sensitivity of bacterial measurement, and a control unit for controlling the amount of the measurement sample measured by the measurement unit according to the input measurement sensitivity. Therefore, the measurement sensitivity for measuring bacteria can be selected, and the bacteria measurement according to the selected measurement sensitivity is performed, so that it is possible to cope with the bacteria measurement with various measurement sensitivities. Moreover, this bacterial measurement can be automatically performed by the control unit, and therefore, a highly sensitive bacterial measurement can be performed in real time in addition to the standard sensitivity measurement.

  The measurement sensitivity input means can be, for example, a keyboard or a mouse that is an input device of the personal computer 13. In this case, a setting screen is displayed on the display 13 a that is an output unit (display unit) of the personal computer 13. The selection can be performed by clicking a predetermined button on the setting screen. Further, as the control unit, for example, the microcomputer 11 described above can be used.

Further, the measurement sensitivity input means is configured to accept selection of either a standard mode for performing measurement at standard sensitivity or a scrutiny mode for performing measurement with higher sensitivity than the standard mode, and the control When the standard mode is selected, the measurement unit can be configured to operate in the standard mode, and when the scrutiny mode is selected, the measurement unit can be configured to operate in the scrutiny mode. In this case, the user selects the standard mode when performing bacterial measurement at a standard sensitivity (for example, 10 ⁵ cells / ml), for example, in a urine test, and performs high sensitivity (for example, 10 ³ cells / ml) bacterial measurement. Sometimes it is only necessary to select a scrutiny mode, and a user can automatically perform a desired measurement only by selecting an operation mode according to the purpose.

In the case of conventional bacterial measurement (standard mode), the amount of the measurement sample is usually about 1 μL. By setting this amount to, for example, 6 μL, measurement in the scrutiny mode can be performed. By increasing the amount of measurement sample used in the scrutinization mode than in the standard mode, it is possible to secure more opportunities for bacteria detection, and even for low-concentration bacteria, bacteria can be detected according to the concentration. Therefore, it can cope with highly sensitive measurement. Specifically, in the case of bacteria having a low density of 10 ³ cells / ml, since the amount of the sample to be measured is 1 μL, the amount of the sample is such that one is present in 1 μL. However, if the amount of the measurement sample is 6 μL, for example, a measurement result corresponding to the actual concentration can be obtained with a high probability from the probability distribution.

  Moreover, it is preferable that the control unit controls the measurement operation of the measurement unit so that the measurement operation in the scrutiny mode has a longer operation time than the measurement operation in the standard mode. By extending the operation time in the scrutiny mode as compared to the standard mode, the resolution in the measurement unit can be increased, and high-sensitivity measurement can be handled.

[Analysis procedure]
Next, a procedure for analyzing urine using the urine analyzer of the present embodiment will be described according to the flowcharts shown in FIGS.
First, the sample number managed by the host computer, the patient's name, age, gender, clinical department information associated with the sample number, and sample information such as measurement items are acquired in advance from the host computer. (Step S1). Next, a measurement execution instruction is given by the input device 13b including the keyboard and mouse of the personal computer 13 described above (step S2). At this time, prior to the measurement execution instruction, the measurement mode is selected by the input device 13b. The microcomputer 11 serving as a control unit operates the measurement unit in the standard mode when the standard mode is selected, and operates the measurement unit in the scrutinization mode when the scrutiny mode is selected. Let Specifically, when the standard mode is selected, the amount of the measurement sample is, for example, 1 μL, and when the inspection mode is selected, the amount of the measurement sample is, for example, 6 μL.

  In response to the measurement execution instruction, the sample rack 3 on which the test tube T containing the sample is set is transferred to a predetermined suction position by the rack table 4 (step S3). At this suction position, the test tube T is rotated, and the barcode of the ID label attached to the outer peripheral surface of the test tube T is read (step S4). Thereby, the sample number of the sample can be known, and the measurement item of the sample can be specified by comparing the sample number with the sample information acquired in step S1.

  Next, the suction tube 17 is lowered and the tip of the suction tube 17 is inserted into the sample in the test tube T. In this state, the sample is agitated by repeatedly aspirating and discharging the sample. (Step S5). After stirring, a predetermined amount (800 μL) of the sample is aspirated, and the sampling valve 30 prepares a sample for measuring the urine sediment (SED) containing at least white blood cells, and is included in the urine. 150 μL and 62.5 μL are respectively dispensed to the sample preparation unit 2 b that prepares a sample for measuring the bacteria (BAC) to be measured (step S 7 and step S 11).

  A predetermined amount of staining solution (staining reagent) and diluent are quantified and dispensed to the sample preparation unit 2u together with the sample (steps S8 and S9). On the other hand, a predetermined amount of staining solution (staining reagent) and diluent are also quantified and dispensed together with the sample in the sample preparation unit 2b (steps S12 and S13). The sample preparation unit 2u and the sample preparation unit 2b are heated to a predetermined temperature by the heaters 36u and 36b, respectively, and in this state, the sample is stirred by a propeller-shaped stirring tool (not shown) ( Step S10 and Step S14). Note that the diluent dispensed to the sample preparation unit 2u in step S9 contains a surfactant, which damages the bacterial membrane and makes it possible to efficiently stain bacterial nuclei. .

  Next, a sheath liquid is sent to the sheath flow cell 51 of the optical detection unit 5 (step S15), and then a sample for measuring a urine sediment (SED) is first guided to the optical detection unit 5, and the sheath flow cell 51 A thin flow (sheath flow) wrapped in the sheath liquid is formed (step S16). The sheath flow thus formed is irradiated with a laser beam from the semiconductor laser 53 (step S17). The reason why the urine components are measured first is that the bacteria measurement sample contains a surfactant, so if the urine components are measured after measuring the bacteria, the sample will carry over. This is because a surfactant may be mixed into a sample for measuring urine particles, damaging the urine particles containing red blood cells and affecting the measurement of the urine particles.

  The forward scattered light, fluorescence and side scattered light in the urine formed by the laser beam irradiation are received by the photodiode 55, the photomultiplier 59, and the photomultiplier 58, respectively, and converted into an electrical signal. The scattered light signal (FSC), the fluorescence signal (FL), and the side scattered light signal (SSC) are output (steps S18 to S20). These outputs are amplified by the preamplifier (steps S21 to S23).

  On the other hand, when the measurement with the sample for measuring urinary sediment (SED) is completed, the bacteria in the urine are subsequently measured using the sample prepared in step S14. In this case, the forward scattered light signal (FSC) and the fluorescence signal (FL) are output and amplified by the optical detection unit 5 used in the measurement of the urinary component, as in Steps S15 to S23.

  The amplified forward scattered light signal (FSC), fluorescent signal (FL), and side scattered light signal (SSC) are converted into digital signals in the signal processing circuit 10 (see FIG. 6) and predetermined waveform processing is performed. (Steps S24 to S27) and sent to the personal computer 13 via the LAN adapter 12. Note that “FLH” in step S25 is obtained by amplifying the fluorescence signal (FL) with a high gain, and step S26 “FLL” is obtained by amplifying the fluorescence signal (FL) with a low gain.

  Then, raw data of urine sediment (SED) is created in the personal computer 13 (step S28), and a scattergram is created based on this data (step S29). Next, clustering of the scattergram created by the algorithm analysis is performed (step S30), and particles are counted for each cluster (step S31).

  Similarly, for bacteria, the amplified forward scattered light signal (FSC) and fluorescence signal (FL) are converted into digital signals and subjected to predetermined waveform processing in the signal processing circuit 10 ( Steps S32 to 34). Note that “FSCH” in step S32 is obtained by amplifying the forward scattered light signal (FSC) with a high gain, and step S33 “FSCL” is obtained by amplifying the forward scattered light signal (FSC) with a low gain. .

Then, it is sent to the personal computer 13 via the LAN adapter 12. Then, raw data of bacteria (BAC) is created in the personal computer 13 (step S35), and a scattergram is created based on this data (step S36). Next, clustering of the scattergram created by the algorithm analysis is performed (step S37), and particles are counted for each cluster (step S38).
The measurement result obtained as described above is displayed on a display which is a display means of the personal computer 13 (step S39).

  In the above embodiment, since both the bacteria and the urinary component are measured using the same optical detection unit, the cost of the product can be reduced and the apparatus can be downsized. In addition, at present, there are many cases where measurement results for both bacteria and urinary formation are required, so when the standard mode is selected, the control unit operates in the standard mode. In addition, the measuring unit can be configured to perform the measuring operation of the urine formed component containing at least white blood cells. According to this configuration, when the standard mode is selected, it is possible to perform general measurement in the standard mode by performing both the bacterial measurement in the standard mode and the measurement of the urinary formation substantially excluding the bacteria. Therefore, the versatility of the apparatus can be improved.

In this embodiment, bacteria are measured only in either the standard mode or the scrutinization mode. However, if it is difficult to determine the symptom or the like based on the measurement results in the standard mode, re- Measurements can also be made automatically. FIG. 10 shows a flow chart in such a case. Bacteria are measured in the standard mode (1 μL) by the above-described steps (step S101), and then the obtained measurement result is near a predetermined cut-off value. A determination of whether or not is made (step S102). For example, in the case of urinary tract infection, the cut-off value that is a criterion for determining whether or not there is a strong suspicion of the urinary tract infection is 1.0 × 10 ⁴ (pieces / mL). When the result is 5 × 10 ³ (pieces / mL), remeasurement can be performed. If it is near the cut-off value, the standard mode is changed to the scrutinization mode, and the bacteria are measured again (retest) (step S103).
In addition, the urine analyzer according to the embodiment can measure both bacteria and urine components, but can also be a device that can measure only bacteria.

BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a perspective explanatory view of a urine analyzer that is an embodiment of a clinical test apparatus of the present invention. It is a block diagram which shows the hardware constitutions of the personal computer shown by FIG. It is a figure which shows schematic function structure of the sample preparation part and optical detection part of a urine analyzer. It is a figure which shows the structure of an optical detection part. It is a block diagram which shows the whole structure of the urine analyzer shown by FIG. It is perspective explanatory drawing of the fixed_quantity | assay mechanism of a urine analyzer, and a sample preparation part. It is explanatory drawing of the fixed_quantity | assay mechanism and sample preparation part of a urine analyzer. It is a flowchart (first half) which shows the analysis procedure of urine using the urine analyzer of this invention. It is a flowchart (latter half part) which shows the analysis procedure of urine using the urine analyzer of this invention. It is a flowchart in the case of performing scrutinization mode after standard mode.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Sample distribution part 2 Sample preparation part 3 Sample rack 4 Rack table 5 Optical detection part 13 Personal computer 15 Arm 16 Support stand 17 Suction pipe 18 Staining liquid 19 Dilution liquid 30 Sampling valve 31 Motor 32 Flow path 33 Fluid cassette 34 Mounting plate 36 Heater U Urine analyzer T Test tube S Clearance

Claims (6)

A sample analyzer for analyzing bacteria contained in a sample,
A sample preparation unit for adjusting a measurement sample by mixing a specimen and a staining reagent for staining bacteria;
A measurement unit that irradiates light to the measurement sample prepared by the sample preparation unit, receives fluorescence from the stained bacteria, and measures bacteria contained in the measurement sample;
Measurement sensitivity input means for inputting the sensitivity of bacterial measurement;
A control unit for controlling the amount of the measurement sample measured by the measurement unit according to the input measurement sensitivity;
A specimen analyzer characterized by comprising: The measurement sensitivity input means is configured to accept a selection between a standard mode for performing measurement at a standard sensitivity and a scrutiny mode for performing measurement with higher sensitivity than the standard mode, and the control The unit is configured to operate the measurement unit in a standard mode when the standard mode is selected, and to operate the measurement unit in a scrutinization mode when the scrutiny mode is selected. 2. The sample analyzer according to 1.   The sample analyzer according to claim 2, wherein the control unit controls the measurement operation of the measurement unit such that the measurement operation time in the scrutinization mode is longer than the measurement operation time in the standard mode.   4. The sample analysis according to claim 2, wherein the control unit is configured to cause the measurement unit to perform a measurement operation using a larger amount of measurement sample in the scrutiny mode than when measuring in the standard mode. apparatus. The specimen is urine,
The sample analyzer according to any one of claims 2 to 4, wherein the sample analyzer is configured to be capable of measuring a component in urine containing at least leukocytes. The sample preparation unit mixes the staining reagent with a urine sample to prepare a first sample for bacterial measurement, and mixes the urine sample with a reagent for measuring a urine component. A second sample preparation unit that prepares a second sample for measurement of urine components containing at least leukocytes,
The measurement unit is configured to be able to measure bacteria contained in the first sample and to measure urine formed components including at least leukocytes contained in the second sample. The sample analyzer according to claim 5.

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