JPH08114600A - Living body sample analyzing system - Google Patents

Abstract

PURPOSE: To provide an analyzing system for automatically executing the measurement of a secondary inspection on the basis of a primary inspection result with respect to a living body sample. CONSTITUTION: In a primary inspection, a morbid state index item is measured by a biochemical analyzing device 111, and the measurement result is compared with a preliminarily registered check index. When it corresponds to the check index, a sample is advanced to the secondary inspecting treatment for a specified item. In the secondary inspection, the sample is measured by an immunological analyzing device 112 or nucleic acid analyzing device 113, and the measurement result is outputted.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a biological sample analysis system, and more particularly to an analysis system suitable for measuring a plurality of analysis items in a biological sample.

[0002]

2. Description of the Related Art The procedure by which a doctor obtains analytical data of a biological sample in order to know the state of the pathological condition of a patient is generally as follows. First, the patient's blood is taken for a screening test. To measure this biological sample with an automatic analyzer, for example, a biochemical automatic analyzer as shown in US Pat.No. 5,037,612 and an immunoassay device as shown in US Pat.No. 5,051,238 can be used. . The doctor then makes a preliminary diagnosis, considering the analytical data obtained as a result of the screening test. Then, if there is a possibility of illness in the preliminary diagnosis, the blood of the patient is collected again. This biological sample is used for specific test items for definitive diagnosis in order to accurately grasp the pathological condition. The doctor determines the final disease name based on the result of this specific test item. In order to execute a specific inspection item, in addition to the above-mentioned known technique, for example
The gene analysis as shown in JP-A 2-92300 can be applied.

[0003]

According to the above-described procedure, the patient must go to the hospital for the second blood sampling on a day after the first blood sampling day. In addition, the physician must make a preliminary diagnosis based on the primary test results and a definitive diagnosis based on the secondary test results on different days. Thus, conventional methods are painful for the patient and inefficient for the physician.

An object of the present invention is to provide an analysis system in which the measurement of the secondary test for the same sample is automatically executed based on the measurement result of the biological sample in the primary test.

Another object of the present invention is to provide an analysis system in which the measurement in the primary test and the secondary test can be carried out with a biological sample once taken from a patient. Still another object of the present invention is to provide an analysis system capable of performing measurement of a sample by biochemical analysis, immunological analysis or nucleic acid analysis as needed, and thus obtaining analytical data useful for diagnosing a disease. Especially.

[0006]

Means for Solving the Problems The present invention provides a means for registering a preliminary analysis item which is an index of a pathological condition measured in a primary test and an analysis item selected to be measured in a secondary test, and for the primary test. Means for measuring the preliminary analysis items, means for measuring the secondary inspection analysis items for the secondary inspection, and means for registering the check level for the secondary inspection analysis items on the sample for which the preliminary analysis items have been measured And a means for deciding that a specific analysis item should be subjected to a secondary inspection based on the comparison between the measurement data of the preliminary analysis item and the check level, and the sample subject to the determination by this determination means is subjected to the secondary inspection analysis. It is provided with means for controlling so as to analyze by means of item measuring means and means for outputting the measurement result of the secondary inspection analysis item.

The measurement result output means includes a display means for displaying a preliminary analysis item for the primary inspection, an analysis item for the secondary inspection, and an appropriate value for the check level in association with each other, and inputting the appropriate value. The means has a function of selecting an analyzer for executing the measurement operation of the secondary inspection analysis item from a plurality of analyzers in the system. A biochemical analyzer, an immunological analyzer, a nucleic acid analyzer, a chromatographic analyzer, etc. can be used as the measuring means for the secondary inspection analysis item, and among these, the one suitable for the diagnosis of a specific disease is the primary inspection. Is automatically selected based on the result of.

Further, the present invention provides a biochemical analysis means for measuring GOT and GPT for a primary test of an analysis item of a biological sample, an immunoassay means for measuring an immune component for a secondary test, a GOT and Means for registering a plurality of types of check indexes that can detect the possibility of illness with respect to GPT, and GOT and G of a sample by means of biochemical analysis
Secondary inspection measurement analysis that is a means for determining which of a plurality of types of check indexes the measurement result of at least one of PTs corresponds to, and that corresponds to the corresponding check index A means for determining an item, and a control means for controlling the operation of the biochemical analysis means or the immunoassay means for measuring the analysis item determined to be subjected to the secondary test are provided. The control means can control the operation of the immunoassay means for the secondary test when the GOT and GPT measurement results of the sample both correspond to their respective check indexes.

[0009]

In the present invention, the object of analysis or inspection is
A biological sample such as blood or serum collected from a patient.
With respect to these samples, processing such as mixing of reagents, transfer of reaction solution, and detection of reaction products is automatically performed.

Samples derived from patients are sorted into those with a possibility of disease and those with no possibility of disease according to the measurement results in the primary test for measuring the preliminary analysis items. The measurement result obtained in the primary test is compared with a preset check level or check index, and if there is a high possibility of illness as a result, the corresponding sample is used as an analysis target in the secondary test.

In the secondary examination, a specific analysis item for definitive diagnosis that more surely determines the disease name is measured. In this secondary test, immunoassay, nucleic acid analysis, or chromatography, which is different from the biochemical analysis applied in the primary test, is often applied as necessary for sample measurement.

The underlying check level or check index for determining the measurement result of the primary test is registered in the memory within the system via the input device by the operator of the analysis system prior to the sample processing operation. Is entered. It is possible to input the check index each time the test data of the sample is needed, but rather, the numerical value once input is used as the subsequent check index.

When inputting the check index,
The operator instructs the system to display the secondary inspection condition setting menu on a screen such as a CRT.
The check index is the size, numerical value, or concentration of the preliminary analysis item that teaches the possibility of illness, and the size of the measurement result of the preliminary analysis item in the primary examination that exceeds a specific numerical range or a specific limit value. It is input from the input device so that it can be instructed. The size of the check index differs depending on the type of the preliminary analysis item, and the type of analysis item adopted in the secondary inspection is selected according to the difference of the check index. The measurement result of a specific analysis item in the secondary inspection is output to an output device such as a printer. Preferably, the measurement result of the secondary inspection and the measurement result of the primary inspection are output so as to be associated with each other and displayed. The doctor can diagnose the disease name in consideration of the measurement result of the specific analysis item.

[0014]

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS An embodiment according to the present invention will be described with reference to FIGS. The analysis system of FIG. 1 includes a composite analysis unit 105 capable of continuously performing the measurement of the primary inspection and the measurement of the secondary inspection. The compound analyzer 105 includes a biochemical analyzer 111 for optically measuring a reaction liquid obtained by chemically reacting a component contained in a blood or serum sample with a reagent,
An immunoanalyzer 112 for optically measuring an antigen or an antibody in a sample by utilizing an immune reaction, and a nucleic acid analyzer 113 for detecting the presence of a specific oligonucleotide in the sample by using a labeled nucleotide as a reagent, A chromatographic analyzer 114 is included for chromatographically separating and detecting glycated hemoglobin in the sample. Note that the specific sample processing in the devices 111, 112, and 113 is the same as in the case of FIG. 4 or 5 described below.

The composite analyzer 105 includes a sample supply station 115, a sample storage station 116,
A common sampler including sampling pipettors 106a-106d is provided. The sample cup containing the sample to be analyzed is transported from station 115 toward station 116 through transport path 117. The control device 102 can control the operation of each unit in the system, perform arithmetic processing of measurement data obtained by each analyzer, and output the processing result to the display device 104. From the input device 101, various data necessary for the analysis processing of the sample is sent to the control device 10.
2 can be entered, and the entered information is stored in the memory 10
Registered in 3. Various menus registered in the memory 103 are displayed on the CRT 107 according to an operator's instruction from the input device 101. By operating the keyboard of the input device 101 while the menu screen is displayed on the CRT 107 of the display device 104, the registration and change of the measurement conditions are executed. Display device 10
The measurement result is printed on the printer 108 in FIG.

When measuring a preliminary analysis item in the primary inspection, the supply station 1 in the common sampler
The sample cup from 15 is transferred to the position of the pipetter 106a so as to stop, and a part of the sample to be analyzed is introduced into the biochemical analyzer 111 at this position.

When the measurement result of the preliminary analysis item of interest by the analyzer 111 corresponds to the check index for the item, the cup of the sample giving such a result was selected for the secondary examination. Depending on the analysis item, the pipettors 106a, 106b, 106c, 10
It is transported so as to stop at any position of 6d. A part of the sample in the sample cup is introduced by the corresponding pipettor into any of the analyzers designated according to the analysis item for the secondary inspection.

When the measurement result of the preliminary item for the primary inspection by the analyzer 111 does not correspond to the check index for the item, the sample cup of the sample which gives the result is stopped at any pipette position. Instead, it is transferred to the storage station 116 and the sample cup is collected.

Before the composite analysis unit 105 executes the analysis operation, the operator sets the sample cup in the supply station 115 and operates the input device 101 to operate the condition from the memory 103 to the CRT 107 for the secondary inspection. Call the menu screen for setting. FIG. 2 is an example of such a menu screen.

"No." in the screen of FIG. 2 indicates types classified according to the pathological condition. "1ST" in the screen is
It is a preliminary analysis item that can be analyzed in the primary inspection. “CHECK INDEX” on the screen indicates the condition or the degree of abnormality for judging that the analysis by the secondary inspection is necessary due to the measurement result by the primary inspection, and is defined by the range or limit value by numbers. It This check index is a standard for specifying an analysis item in the secondary inspection, and is input by the operator from the input device 101. Further, the once registered value of this check index can be changed by the operator thereafter. The input check index data is
It is registered in the memory 103 in association with the analysis item “1ST”. “2ND” in the screen in FIG. 2 is a specific analysis item for the secondary inspection that is selected according to the difference in the check index. These specific analysis items are defined for each type. “DEVICE” in the screen is “2
An analyzer for analyzing and processing the analysis item selected by ND ″. An apparatus A is a biochemical analyzer 111, an apparatus B is an immunoanalyzer 112, an apparatus C is a nucleic acid analyzer 113, Device D is a chromatographic analysis device 11
It is 4. The analysis function displayed in the "DEVICE" column depends on the type of analyzer used in this analysis system, and can be freely changed by the operator.

When all the conditions have already been set in the menu and there is no need for subsequent changes, the operator calls the sample number to be analyzed in the upper right column of the screen, All you have to do is select the type of number your doctor wants to test. By repeating the operation of sequentially calling the sample number on the screen and selecting the type number, each sample is associated with the analysis item of the primary inspection and the analysis item of the secondary inspection, and the conditions for all samples are stored in the memory. It is registered in 103.

As the types of hepatitis, chronic hepatitis caused by alcoholic liver damage, chronic hepatitis caused by virus, and acute hepatitis caused by virus are known. In order to find out what kind of illnesses are possible among these, GOT and GP are the analysis items in the primary examination.
In many cases, T is the measurement target.

In the case of chronic hepatitis caused by alcohol, which corresponds to type 1 in FIG. 2, the GOT activity value is 200 to
It shows a high value of 300 IU (international units). In such a sample, GPT shows an activity value higher than the normal value, but the degree of increase is not so large. Therefore, the value of GOT is larger than the value of GPT. In the secondary inspection of such samples, γ-GTP, ALP, LA
P is the measurement target. In chronic hepatitis caused by alcohol, γ-GTP shows a high value of 50 to 400 IU, and ALP and LAP rise above the upper limit of the normal value.

In the case of chronic hepatitis caused by a virus corresponding to type 2 in FIG. 2, the GOT activity value is 20 to 2
It shows a high value of 00 IU and the activity value of GPT is
It shows a high value of 100 to 500 IU. For such a sample, the HBsAg antigen is used as the measurement target in the secondary test. In case of chronic hepatitis B virus, HBsAg is positive.

In acute hepatitis caused by a virus corresponding to type 3 in FIG. 2, both GOT and GPT show extremely high values of 200 to 3000 IU. In such a sample, HBsAg
The antigen is measured. In case of acute hepatitis, HBsA
g is positive.

If no clear data are available in the secondary test to identify the illness, eg if the measurement result is false positive, it is possible to have the analysis system perform a tertiary test. For example, HB in type 3
When the sAg measurement result is falsely positive, the corresponding sample is measured by the nucleic acid analyzer 113, and the viral DNA
The presence or absence of is confirmed.

When familial hyperlipidemia, which corresponds to type 4 in FIG. 2, is suspected, the biochemical analyzer 111 is used for the primary examination and the nucleic acid analyzer 113 for the secondary examination. Is used. In this case, in the primary examination, TG shows a high value exceeding the upper limit of the normal value range of 35 to 148 mg / dl, and CHO shows a high value exceeding the upper limit of the normal value range of 130 to 230 mg / dl. Samples are advanced to secondary inspection. In the secondary test, the LDL receptor gene is measured and it is confirmed whether or not this gene is abnormal.

When nephrosis, which corresponds to type 5 in FIG. 2, is suspected, the biochemical analyzer 111 is used for the primary examination and the biochemical analyzer 111 and the immunological analyzer for the secondary examination. 112 is used. A sample showing a high concentration of CHO exceeding 230 mg / dl in the primary test is advanced to the secondary test. In this secondary inspection, LDL-CHO and HDL-CHO are measured. In the case of nephrase, LDL-CHO increases,
And HDL-CHO shows normal or lowered.

When diabetes or hyperthyroidism, which corresponds to type 6 in FIG. 2, is suspected, the biochemical analyzer 111 is used to measure GLU in the primary test, and thyroxine (T4) in the secondary test. The immunological analyzer 112 for measuring) and the chromatographic analyzer 114 for measuring glycohemoglobin are used. In the case of diabetes, the measured value of the A1c component of glycated hemoglobin is high. T in case of hyperthyroidism
The measured value of 4 becomes higher.

Next, the analysis operation when hepatitis is suspected in the patient will be described.

The operator of the analysis system calls up the menu screen for condition setting as shown in FIG. 2 on the CRT 107, inputs the number of the sample to be measured, and checks index for each of type 1, type 2 and type 3. Enter. Next, the operator selects γ-GTP, ALP, LAP, HBsAg, which are the analysis items in the secondary inspection.
Input an analyzer for measuring The operator operates the input device 101 to register the conditions of types 1 to 3 for the sample in the memory 103. Such a procedure can be repeated for other samples.

After the above preparations are completed, the operator gives the start instruction in step 301 of FIG. 3 to cause the composite analysis section 105 to start the analysis operation. In step 302, the sample is pipettor 1.
It is supplied to the biochemical analyzer 111 by 06a, and GO
T and GPT are measured.

Step 303 is a step of deciding an analysis item for the secondary inspection, and step 304 is a step of selecting an analyzer. GOT and G
When the measured value of PT corresponds to the type 1 check index, γ is determined by the analyzer 111 in the secondary inspection.
-The control device 102 determines that GTP, ALP and LAP should be analyzed, and the corresponding sample is supplied to the analysis device 111. When the measured values of GOT and GPT correspond to the type 2 or type 3 check index, the HBsAg immunoassay device 1 is used in the secondary test.
The control device 102 determines that the sample should be analyzed at 12, and the corresponding sample is supplied to the analysis device 112. When the measured values of GOT and GPT do not correspond to any of the check indexes of types 1 to 3,
The sample cup is collected in the storage station 116.

In step 305, the analytical items selected for the secondary inspection in the designated analytical device based on the respective type are measured. Step 306
In, the control device 102 operates the printer 108 so as to output the measurement result obtained in the primary inspection and the measurement result obtained in the secondary inspection in association with each analysis item. If there are more samples to be analyzed, the same operation is repeated, but if there is no sample to be analyzed thereafter, the analysis system proceeds to step 307 and ends the operation.

FIG. 4 is a schematic configuration of another embodiment according to the present invention. The analysis system of FIG. 4 shares the biochemical analysis function and the nucleic acid analysis function in many parts.
Input device 101 and control device 10 in FIG.
2, memory 103, CRT display unit 107, printer 10
8 and the like have the same functions as in the embodiment of FIG.
Sample table 1, reaction table 2, reagent table 3
5 and the pipetting mechanism 39 are operated in the primary and secondary inspection.

In FIG. 4, a sample turntable 1 comprises a plurality of sample containers 3 containing samples such as serum.
3 is a table for storing and rotating 3. The reaction turntable 2 is a table in which a plurality of reaction vessels 34 also serving as measurement cells are arranged in a circle and rotated. The plurality of reaction vessels 34 are kept at a constant temperature by a reaction thermostatic bath (not shown) arranged below the reaction table 2.

Sample table 1 and reaction table 2
Are rotatably driven by pulse motors 91 and 92 controlled by the control device 102 so that predetermined sample containers 33 and reaction containers 34 are stopped at predetermined positions. The magnet 13 is arranged outside the reaction table 2 and in a predetermined region near the rotation circumference of the reaction container 34. The magnetic lines of force of the magnet 13 act on the inside of the reaction container 34 passing through the predetermined region.

At positions on both sides of the reaction container 34,
A light source lamp 11 is provided at a predetermined position inside the outer edge of the reaction table 2, and a spectroscope 10 is provided at a predetermined position outside the outer edge.
The light source lamp 11 and the spectroscope 10 face each other. Further, the spectroscope 10 is a multi-wavelength simultaneous photometric type having a plurality of detectors, and functions as a photometer at the time of primary inspection.
When the reaction table 2 is rotating, the row of the reaction vessels 34 is configured to cross the light flux 12 from the light source lamp 11 to the spectroscope 10. When the reaction turntable 2 is stopped, the light flux 12 is transmitted through the center of the reaction container 34, which is located at a predetermined position counted in the clockwise direction from the sample discharge position.

The reagent turntable 35 is a table for storing and rotating various reagent liquid containers necessary for the analysis operation, and is rotated by a pulse motor 94 controlled by the control device 102, and a predetermined timing is set at a necessary timing. Stop the reagent container in the inhalation position. Various reagent liquid containers are stored on a circle near the outer edge of the reagent table 35.

The various reagent solution containers are containers 80a and 80b containing reagents necessary for measuring biochemical analysis as the first analysis component and necessary for measuring nucleic acid analysis as the second analysis component. Containers 90a and 90b containing magnetic particle labeling probe solutions corresponding to various analysis items
And containers 36a, 3 containing the fluorescent particle-labeled probe liquid
6b, a restriction enzyme solution storage container 38, and other necessary buffer solution containers (not shown) and the like.

As the labeled particles, it is most preferable to use magnetic fine particles or fluorescent fine particles. The fluorescent fine particles are latex particles or inorganic particles having a fluorescent substance layer formed on the surface thereof. A mixture of the particle-forming composition and the fluorescent substance can be used in the form of particles. In this case, the particle size of the fluorescent fine particles is preferably 0.1 to 1.0 μm.

The automatic pipette mechanism is composed of the pipette mechanism body 3
9, a syringe pump 40 connected to the syringe pump 9 via a pipe 41, and a cleaning liquid tank 37 connected to the syringe pump 40 for storing a cleaning liquid that also functions as an extruding liquid. The pipette mechanism body 39 includes a pipetting nozzle 43 for sucking and discharging a reagent and a sample, and a movable arm 42 to which the nozzle 43 is attached. The movable arm 42 is the controller 1
It is driven by a horizontal rotation drive unit 45 and a vertical drive unit 44 controlled by 02. Along with the operation of the movable arm 42, the nozzle 43 is provided with a predetermined sample container position on the sample table 1, a reaction container position on the reaction table 2, a reagent container position on the reagent table 35, a flow cell 47 through which a liquid to be measured flows, and The nozzle can be rotated so as to be moved to the position of the nozzle cleaning tank 46, and its rotation locus has arcs a and b.
Is. Then, it can descend and rise at the respective positions.

The sheath flow cell 47 is a flow cytometer in which the liquid to be measured flows in the inner space and the fine particles therein are measured. An injection chamber inlet 48 is provided above the flow cell 47, and the nozzle 43 is connected to the injection chamber inlet 48.
The liquid to be measured enters the inside of the flow cell 47 and is discharged into the flow cell 47. The sheath liquid flowing along the inner wall of the flow cell 47 is fed from the sheath liquid tank 6 at a constant flow rate by the liquid feed pump 9, and is discharged from the flow cell 47 to a waste liquid reservoir 95 provided below the flow cell 47. The liquid to be measured after the reaction flows in the center of the sheath liquid flow.

The measuring section is as follows.

The laser light source 49 has an oscillation wavelength of 488 nm.
Of the argon laser beam, and the beam width of the laser beam is expanded by the beam expander 50.
1, the flow cell 47 is irradiated so as to focus on the flow of the liquid to be measured. The laser light beam irradiates the flow cell 47, and the fluorescence emitted by the laser light beam is collected by, for example, an objective lens 52 for a microscope.
Is used. Further, in front of the photomultiplier 53 as a photoelectric detector, a spatial filter 54 and a wavelength selection filter 55 are provided to remove scattered light and Raman light.

After the output of the photomultiplier 53 is amplified by the preamplifier 18, it is amplified by the linear amplifier 19 and noise is removed by the lower limit wave height discriminator 20a and the upper limit wave height discriminator 20b. After that, the counter 56 integrates the pulses between the two threshold values. A high voltage is applied to the photomultiplier 53 via the transformer 96 and the high-voltage power supply 97.

The sample number, counting result, calibration curve, histogram of fluorescence measurement, etc. are output to the CRT display 107, printer 108, and memory 103. The counter 56, the display 107, the printer 108, and the memory 103 are connected to and controlled by the controller 102.

Next, the operation of the analysis system according to the embodiment shown in FIG. 4 will be described.

First, the sample table 1 rotates, the sample container 33 is transferred to the sample suction position, and a certain amount of the sample is sucked from the sample container 33 at the suction position by the nozzle 43. The reaction table 2 rotates, and a certain amount of the sample in the nozzle 43 is discharged into the reaction container 34 transferred to the sample discharge position.

Next, the specific reaction container 34 into which the sample has been dispensed is transferred to the dispensing position of the first reagent by rotating the reaction table 2 for the measurement of the biochemical component of the primary test. By the nozzle 43, the reagent container 80a on the reagent table 35
A certain amount of the first reagent for measuring the first component therein is inhaled and dispensed into the reaction container 34 at the reagent dispensing position of the reaction table 2. Therefore, in the reaction container 34, a chemical reaction between the sample and the first reagent proceeds.

When the dispensing operation is completed, the reaction table 2
Rotate counterclockwise by 360 ° + one pitch of the reaction container, that is, rotate for one cycle and stop. While the reaction table 2 is rotating, the reaction container 34 on the reaction table 2 passes the light flux 12. Each reaction container 34 has a luminous flux 12
When passing through, the optical absorption measurement is performed by the spectroscope 10. The measurement is repeated by the spectroscope 10 for a certain period of time until the liquid is drained by the drainage device 59, for example, with 20 seconds as one cycle.

Now, when the second reagent for the measurement of the primary test is required, if the time during which the reaction table 2 is rotated and stopped is, for example, 20 seconds, 20 seconds is set as one cycle and the above is performed. The operation of is repeated. That is, the position of a particular reaction vessel 34 will change as the cycle progresses.
The position when the reaction table 2 is stopped is the reaction container 1
Proceeding counterclockwise by the pitch, it becomes the second reagent dispensing position.

At the second reagent dispensing position of the specific reaction container 34, the second reagent is dispensed from the reagent container 80b on the reagent table 35 by the nozzle 43. In this way, the sample, the first reagent, and the second reagent are dispensed into the specific reaction container 34, and the chemical reaction proceeds.

When the dispensing operation in the primary inspection is completed, the reaction table 2 is rotated counterclockwise by 360 ° + one pitch of the reaction container, that is, rotated by one cycle and stopped. While the reaction table 2 is rotating, the light flux 12 passes through the reaction container 34 on the reaction table 2.

When the light flux 12 passes through the respective reaction vessels 34, the spectroscope 10 measures the light absorption. For the signal value of the spectroscope 10, the required measurement wavelength signal is selected by the multiplexer 60, and the concentration of the analysis component of the primary inspection is obtained. The concentration signal is taken into the controller 102 by the A / D converter 61 and compared with the check index to determine whether or not the component analysis of the secondary inspection is necessary. The result is stored in the read / write storage device 103.

Next, the case of analyzing a nucleic acid in the secondary test will be described by taking HBV, that is, hepatitis B virus as an example.

The analysis item is specified by the type of particle probe added after the start of the operation. The particle-labeled probe liquid container 90a is provided with a magnetic latex particle reagent having a single-stranded HBV-DNA probe type 1 immobilized thereon.

On the other hand, fluorescent particle labeled probe liquid container 36
In a, a fluorescent-labeled latex particle reagent in which single-stranded HBV-DNA probe type 2 is bound to fluorescent latex particles containing a coumarin derivative as a fluorescent substance is prepared.

Each single-stranded HBV-DNA probe, that is, single-stranded HBV-DNA probe type 1 and single-stranded HBV-DNA probe type 2 has a nucleotide sequence complementary to the nucleic acid component to be measured. However, they do not have complementary nucleotide sequences. The restriction enzyme solution is, for example, HaeIII, which is a restriction enzyme for cleaving the double-stranded DNA formed by hybridizing the single-stranded HBV-DNA probe type 2 bound to the fluorescent labeled latex particles and the nucleic acid component to be measured. To prepare.

When the analysis operation is started, the sample collected from the sample container 33 by the nozzle 43 is injected into the reaction container 34. Next, the magnetic latex particle reagent is fractionated from the magnetic latex particle reagent liquid container 90a by the nozzle 43 and discharged into the specific reaction container 34 in which the sample is injected. As a result, HBV-D in the sample
NA undergoes a binding reaction with magnetic latex particles having single-stranded HBV-DNA probe type 1 immobilized thereon. The reaction in the specific reaction container 34 is maintained on the reaction table at a predetermined temperature, for example, 37 ° C., for a predetermined time, for example, 15 minutes.

Next, the fluorescent labeled latex particle reagent is sucked from the container 36a on the reagent table 35 by the nozzle 43 in a fixed amount and discharged into the corresponding reaction container 34. The reaction container 34 maintains the reaction on the reaction table 2 under a predetermined temperature, for example, 37 ° C., for a predetermined time, for example, 15 minutes. As a result, the single-stranded HBV-DNA probe type 2 reacts with the reaction product of the magnetic latex particles.

When the specific reaction container 34 is transferred to a predetermined area where the magnet 13 is arranged around the reaction container 34, the reaction product hybridized with the magnetic latex particles and the unreacted magnetic latex particles. Is adsorbed on the inner wall of the reaction vessel 34 by the action of the magnet 13, but the unreacted fluorescent labeled latex particles are released into the liquid. The unreacted fluorescent labeled latex particles are washed with a washing liquid discharged from the nozzle 43, and the washing liquid is discharged to the outside of the reaction container 34. In this way, the cleaning liquid is discharged into the reaction container 34, and the operation of discharging the cleaning liquid is repeated. As a result, the surplus fluorescent labeled latex particles in the reaction container 34 are discharged to the outside of the reaction container 34.

Then, by rotating the reagent table 35,
The restriction enzyme solution container 38 is positioned at the suction position on the reagent table 35. Restriction enzyme HaeI in the restriction enzyme solution container 38
A liquid containing II25 is sucked in a fixed amount by the nozzle 43 and discharged into the corresponding reaction container 34 on the reaction table 2.
In the reaction container 34, a double-stranded DN formed by hybridizing the single-stranded HBV-DNA probe type 2 bound to the fluorescently labeled latex particles and the nucleic acid component to be measured.
A is cut at a predetermined cutting point. As a result, the fluorescently labeled latex particles are released into the liquid in the reaction container 34.
For such a liberation reaction, a predetermined time, for example, 15
Minutes are needed. The liquid to be measured containing these educts is
It is sucked by the nozzle 43 and discharged into the sheath flow cell 47. The free particles in the flow cell 47 are counted to determine the nucleic acid concentration of the second component.

Table 1 shows an example of measurement results by the analysis system shown in FIG.

[0065]

[Table 1]

As the primary test, the measurement results of biochemical analysis items GOT and GPT were 30 or more and 42, respectively.
When the above is the case, nucleic acid analysis was performed as a secondary test to determine whether hepatitis virus was infected.

An analysis system according to another embodiment of the present invention will be described with reference to FIG.

FIG. 5 is a schematic explanatory view including a partial block diagram showing an analysis system according to an embodiment of the present invention. In FIG. 5, those having the same reference numerals as those in FIG. 4 have the same functional parts, and thus detailed description thereof will be omitted. In addition, sample table 1, reaction table 2, reaction table 3,
Reagent table 35, automatic pipette mechanism, flow cell 4
Since the measuring unit including the laser light source 49 and the laser light source 49 is almost the same as the analyzing system shown in FIG. 4, detailed description thereof will be omitted.

The various reagents of the reagent table 35, the reaction table 3, and the automatic pipette mechanism will be described only with respect to differences from FIG.

Various reagent solution containers on the reagent table 35 are containers 80a (80b and below are not shown) accommodating necessary reagents and nucleic acid analysis items as secondary tests when immunoassay items are measured as a primary test. When measuring, the containers 90a and 90b containing the particle-labeled probe liquids corresponding to the various necessary analysis items, the containers 36a and 36b containing the fluorescent particle-labeled probe liquids, the restriction enzyme liquid-containing container 38, and others It is a necessary buffer container (not shown) and the like. The particle diameter of the particle-labeled probe is different from that of the fluorescent particle-labeled probe.

The structure of the reaction table 3 is as follows:
However, the structure of the plurality of reaction vessels 34b arranged on the circle is as follows.

The reaction vessel 34b comprises a small chamber having a filter at the top and a small hole in the wall, and the filter has such a pore size that allows one of the particle labels to pass through and the other to block the other. It has become. Further, the suction device 101 is connected to the small hole so that the reagent solution in the small chamber is discharged to the outside of the previous-stage reaction container 34b through the small hole.

The reaction table 3 is the sample table 1,
Similar to the reaction table 2, the pulse motor 94 controlled by the controller C is configured to be rotatable so that a predetermined reaction container 34b is at a predetermined position.

The automatic pipette mechanism is the same as that of the example shown in FIG. 4, except that the sample table 1, the reagent table 35 and the reaction table 2 are dispensed with samples, reagents and the like, and the sample table 1, the reagent table 35, A sample, a reagent, a reaction solution, or the like is dispensed between the reaction table 2 and the reaction table 3, and its operation loci are a and b.

The operation of the analysis system according to the embodiment shown in FIG. 5 will be described.

The immunoassay items for the primary test are measured by the reaction table 2, the reaction container 34a, the light source 11, the spectroscope 10 and the like in the same manner as in the example of FIG. 4, so detailed description thereof will be omitted and the secondary test will be omitted. The nucleic acid analysis for use will be described.

In the sample transfer, the nozzle 43 sucks a fixed amount of the sample in the sample container 33 at the sample suction position. A fixed amount of the sample is discharged into the reaction container 34a that has been transferred to the sample discharge position. Reagent table 35
Is rotated by a predetermined angle by the pulse motor 94 and positioned so that the designated reagent container is stopped at the suction position by the nozzle 43 at a necessary timing. The particle-labeled probe of the first reagent is injected by the nozzle 43 into the reaction container 34a at the first reagent dispensing position. The fluorescent particle-labeled probe of the second reagent is injected into the reaction container 34a at the second reagent dispensing position by the nozzle 43.

The hybridization reaction liquid of the sample, the particle-labeled probe, and the fluorescent particle-labeled probe reacted in the reaction chamber of the reaction container 34a is moved by the nozzle 43 at the reaction liquid dispensing position of the reaction table 2 by the nozzle 43.
It is injected into the filter part of b.

At the filter washing position of the reaction table 3, the suction device 101 is operated to load the unreacted fluorescent particle probe smaller than the pore diameter of the filter into the reaction container 34.
It is discharged to the outside of the small chamber through a small hole provided in the wall of the small chamber of b. The washing liquid is injected into the filter portion in the reaction container 34b by the nozzle 43 and the suction device 101 is operated repeatedly, and the filter portion is completely washed.

At the restriction enzyme solution dispensing position of the reaction table 3, the restriction enzyme solution is dispensed from the restriction enzyme solution storage container 38 by the nozzle 43 to the filter portion of the reaction container 34b which has been cleaned. After the elapse of a predetermined time, the suction device 1 is placed at the measurement liquid take-out position on the reaction table 3.
01 operates and the measurement liquid is taken out and introduced into the flow cell by the nozzle 43. The fluorescent particles of the measurement liquid introduced into the flow cell 47 are measured by the measuring unit.

Regarding the case where HIV is measured as the secondary test, the reagent is specifically specified and the analytical operation assumption in the reaction container 34b will be described.

A latex particle reagent having a single-stranded HIV-DNA probe type 1 immobilized thereon, for example, a diameter of 0.9 μm is prepared in the particle labeled probe liquid container 90a.

On the other hand, fluorescent particle-labeled probe liquid container 36
In a, fluorescent latex particles containing a coumarin derivative as a fluorescent substance, for example, a fluorescent labeled latex particle reagent in which a single-stranded HIV-DNA probe type 2 is bound to a diameter of 0.1 μm is prepared.

Each of the single-stranded HIV-DNA probes, that is, the single-stranded HIV-DNA probe type 1 and the single-stranded HIV-DNA probe type 2, is a nucleotide complementary to the nucleic acid component to be measured. Those having a sequence but not having nucleotide sequences complementary to each other were used.

As the restriction enzyme solution, a restriction enzyme for cleaving the double-stranded DNA formed by hybridizing the single-stranded HIV-DNA probe type 2 bound to the fluorescent labeled latex particles and the nucleic acid component to be measured, For example HaeIII
To prepare.

At the reaction solution dispensing position on the reaction table 3,
A pump is arranged as the suction device 101 below the reaction container 34b. As the filter, a main blend filter having a pore size of 0.6 μm and a diameter of 10 mm was used.

When the analysis operation is started, the latex particle reagent is separated from the latex particle reagent liquid container 90a by the nozzle 43 and discharged into the corresponding small chamber in the reaction container 34b, so that the reaction container HIV analysis can be performed. Identify that there is.

The reaction vessel 34b thus prepared
Then, the sample collected by the nozzle 43 from the sample container 33 is added to the small chamber. HI in the sample
V-DNA is a single-stranded HIV-DNA probe type 1
React with the immobilized latex particles. This reaction 1
Allow 5 minutes to form a hybridization reaction.

Next, the fluorescent labeled latex particle reagent is sucked from the reagent container 36a through the nozzle 43 in a constant volume and discharged into the reaction chamber of the corresponding reaction container 34b.

The reaction vessel 34b has a predetermined temperature, for example, 37.
The reaction is maintained on the reaction table 3 at a temperature of 0 ° C. for a certain time, for example, 15 minutes. As a result, the single-stranded HIV-DNA probe type 2 further reacts with the hybridization reaction product.

At the filter cleaning position on the reaction table 3, the cleaning liquid is injected into the filter portion in the reaction container 34b by the nozzle 43, and the suction pump is operated repeatedly to repeat the cleaning.

Then, by rotating the reagent table 35, the restriction enzyme liquid container 38 is positioned at the suction position. A certain amount of the liquid containing the restriction enzyme HaeIII25 in the container 38 is inhaled by the nozzle 43 and is discharged to the filter portion of the corresponding previous-stage reaction container 34b on the reaction table 3. In the filter section, single-stranded HI bound to the fluorescently labeled latex particles
The double-stranded DNA formed by hybridizing the V-DNA probe type 2 and the nucleic acid component of the measurement target is cleaved at a predetermined cleavage site. As a result, the fluorescently labeled latex particles float in the liquid in the reaction container 34b.

The solution to be measured containing the educt was prepared according to Reaction Table 3
At the above-mentioned measurement liquid take-out position, the suction pump operates to take out the measurement liquid, which is sucked by the nozzle 43 and discharged to the flow cell 47. The free particles are counted to obtain the nucleic acid concentration which is a component of the secondary test.

[0094]

According to the present invention, whether a secondary analysis should be carried out by executing a primary analysis with a specific analysis device by using a preliminary analysis item, which is an index indicating the possibility of illness according to the inspection result, as a target of the primary inspection. A check level or check index is set in advance for multiple types as a criterion for categorizing whether or not to make it possible to selectively measure an analysis item that can identify a disease more when performing a secondary test than when performing a primary test. For this reason, since it is possible to selectively select the analysis device and the analysis item for the secondary examination in which a plurality of kinds of analysis devices are provided in the analysis system, it is possible to promptly provide the appropriate information for the diagnosis of the pathological condition. In addition, since the primary and secondary tests can be continuously and automatically analyzed and measured for the primary sample, and the measurement results can be reported at the same time,
The burden on patients and doctors can be greatly reduced.

[Brief description of drawings]

FIG. 1 is a block diagram showing an overall schematic configuration of an analysis system according to an embodiment of the present invention.

FIG. 2 is a view showing an example of a condition setting menu screen for a secondary inspection displayed on the display device in the embodiment of FIG.

FIG. 3 is a flowchart showing main processing in the embodiment of FIG.

FIG. 4 is a diagram showing a schematic configuration of an analysis system according to another embodiment of the present invention.

FIG. 5 is a diagram showing a schematic configuration of another embodiment of the present invention.

[Explanation of symbols]

1 ... sample table, 2, 3 ... reaction table, 33 ...
Sample container, 35 ... Reagent table, 47 ... Flow cell, 102 ... Control device, 103 ... Memory, 10
4 ... Display device, 105 ... Complex analysis part, 107 ... CRT,
111 ... Biochemical analyzer, 112 ... Immunoanalyzer, 11
3 ... Nucleic acid analyzer, 114 ... Chromatographic analyzer, 117 ... Conveyance path.

Claims (9)

[Claims] 1. A means for registering a preliminary analysis item to be measured in the primary inspection and an analysis item to be measured in the secondary inspection, a means for measuring the preliminary analysis item for the primary inspection, and a secondary device. Means for measuring the secondary inspection analysis item for inspection, means for registering the check level for the secondary inspection analysis item for the sample for which the preliminary analysis item was measured, measurement data of the preliminary analysis item and the above check level A means for deciding that a specific analysis item should be subjected to a secondary inspection based on a comparison with the above, and a sample subject to the determination by this determination means should be analyzed by the measurement means for the secondary inspection analysis item. A biological sample analysis system comprising: a control means; and a means for outputting the measurement result of the secondary inspection analysis item. 2. The analysis system according to claim 1, wherein the measurement result output means associates a preliminary analysis item for a primary inspection, an analysis item for a secondary inspection, and an appropriate value for a check level. A biological sample analysis system comprising display means for displaying on a screen. 3. The biological sample analysis system according to claim 2, further comprising input means for inputting the appropriate value. 4. The analysis system according to claim 3, wherein the input means has a function of selecting an analyzer for executing the measurement operation of the secondary inspection analysis item from a plurality of analyzers in the system. A biological sample analysis system characterized by having. 5. The analysis system according to claim 1, wherein the measurement means for the preliminary analysis item is a biochemical analysis device, and the measurement means for the secondary test analysis item is an immune analysis device or a nucleic acid analysis device, and , A biological sample analysis system comprising sample supply means shared by these analyzers. 6. The biological sample analysis system according to claim 5, further comprising a chromatographic analysis device as the secondary inspection analysis item measuring means. 7. The analysis system according to claim 1, wherein the measurement result output means is configured to output the measurement result of the preliminary analysis item together with the measurement result of the secondary inspection analysis item. Biological sample analysis system. 8. A G for primary inspection of an analysis item of a biological sample.
Biochemical analysis means for measuring OT and GPT, immunoassay means for measuring immune components for secondary examination, and GOT
And a means for registering a plurality of types of check indexes that can detect the possibility of illness with respect to GPT, and a measurement result of at least one of GOT and GPT of a sample by the biochemical analysis means, among the plurality of types of check indexes. A means for determining which is applicable, and a means for determining the secondary inspection measurement analysis item corresponding to the applicable check index, and it is determined that the secondary inspection should be performed. And a control means for controlling the operation of the biochemical analysis means or the immunological analysis means for measuring the analyzed items. 9. The analysis system according to claim 8, wherein the control means performs the immunoassay for the secondary test when the GOT and GPT measurement results of the sample both correspond to their respective check indexes. A biological sample analysis system characterized by controlling the operation of the means.