JPH0331748A - Biochemical analysis apparatus - Google Patents

Abstract

PURPOSE:To obtain the biochemical analysis apparatus which detects a spotting defect independently from other factors by providing a spotting abnormality detecting means which detects the presence or absence of the abnormality in spotting by monitoring a concn. signal. CONSTITUTION:The constitution having a concn. measuring means (included in a photometric section 60) for obtaining the time series concn. signal by measuring the optical concn. of an inspecting body before and after the timing at which the spotting is executed and the spotting abnormality detecting means (function of a computer 22) for monitoring the concn. signal and detecting the presence or absence of the spotting abnormality in accordance with the change in the optical concn. of the inspecting body at the timing of spotting is adopted for the biochemical analysis apparatus 10 for determining the material concn. of the prescribed biochemical material in the liquid to be inspected in which the prescribed biochemical material is incorporated by measuring the optical concn. of the inspecting body which is spotted with the liquid to be inspected and contains a reagent to generate a change in the optical concn. by the chemical reaction with the prescribed biochemical material. There is no need for the additional installation of hardware in this constitution and the abnormality of the spotting is detected separately from the other factors to affect the results of measurement and, therefore, the rapid dealing with the abnormality is possible.

Description

DETAILED DESCRIPTION OF THE INVENTION (Industrial Field of Application) The present invention is directed to the use of blood, for example, blood containing predetermined biochemical substances.
By measuring the optical density of a specimen containing a reagent that causes a change in optical density due to a chemical reaction with the predetermined biochemical substance, on which a test liquid such as urine is spotted, the predetermined concentration in the test liquid can be detected. This invention relates to a biochemical analyzer that determines the concentration of biochemical substances.

(Prior Art) Qualitative or quantitative analysis of specific chemical components in a test liquid is a commonly performed operation in various industrial fields. In particular, quantitative analysis of chemical components or formed components in biological body fluids such as blood and urine is extremely important in the field of clinical biochemistry.

In recent years, dry-type chemical analysis slides and long tests have been developed that allow quantitative analysis of specific chemical components or solid components contained in a liquid to be tested by simply applying small droplets of the liquid to be tested. A film was developed (Special Publication Act 1973-21).
No. 877, JP-A-55-164356, U.S. Patent No. 3
, No. 528,480, Tokukaihei! -20453.

JP-A No. 1-20454, JP-A No. 1-20455, etc.)
, has been put into practical use. By using these chemical analysis slides and long test films, it is possible to analyze sample liquids more easily and quickly than with conventional wet analysis methods. This is preferable for medical institutions, research institutes, etc. that require

In order to quantitatively analyze the chemical components, etc. in a test liquid using a test object such as a chemical analysis slide or a long test film, after placing a measured amount of the test liquid on the test object,
This is kept at a constant temperature (incubation) for a predetermined period of time in an incubator (constant temperature machine) for a color reaction (pigment formation reaction).
Then, the test sample is irradiated with measurement irradiation light containing a wavelength pre-selected based on the combination of the predetermined biochemical substance in the test liquid and the reagent contained in the test sample, and its reflected optical density is measured. , the optical density is configured to determine the substance concentration of a predetermined biochemical substance in the test liquid using a calibration curve representing the correspondence between the optical density determined in advance and the substance concentration of the predetermined biochemical substance. A biochemical analyzer is used.

(Problems to be Solved by the Invention) In the biochemical analyzer configured as described above, the concentration of a predetermined biochemical substance finally determined may exhibit an abnormal value. In this case, whether the concentration of the above-mentioned biochemical substance in the test liquid is actually abnormal, or whether the concentration of the above-mentioned biochemical substance in the test liquid is normal, but due to poor spotting, for example, the concentration of the above-mentioned biochemical substance is abnormal. In some cases, it was unclear whether an abnormal value was obtained because the number was abnormally low. In addition, even if it turns out that the abnormal value is the result of poor spotting, it will only be known after the final measurement results have been obtained, which means that re-measurement will be delayed, and for example, the patient may have to wait for the test. This was especially a big hassle when you wanted to get results quickly.

In view of the above circumstances, it is an object of the present invention to provide a biochemical analyzer that can detect spotting defects independently of other factors without having to wait for the final measurement results. be.

(Means for Solving the Problems) The biochemical analyzer of the present invention is characterized in that a test liquid containing a predetermined biochemical substance is deposited, and the optical density changes due to a chemical reaction with the predetermined biochemical substance. In a biochemical analyzer that determines the substance concentration of the predetermined biochemical substance in the test liquid by measuring the optical density of a test sample containing a reagent that produces a concentration measuring means for obtaining a time-series concentration signal by determining the optical density of the object to be inspected; The apparatus is characterized by comprising a spotting abnormality detection means for detecting the presence or absence of a spotting abnormality.

Here, the test object may be a chemical analysis slide provided separately for each measurement, or may be in the form of a long tape. For long tapes, 1f of each session.
Each part used in the J1 constant is considered as one test object.

Further, the density measuring means may be one that continuously measures the optical density of the object to be inspected, or may be one that measures the optical density of the object to be inspected intermittently at a predetermined period.

(Function) A detailed study of the temporal change in the optical density of the test object shows that at the moment of spotting, the test object becomes wet with the test liquid, the test object bends a little, etc., and the optical density changes more rapidly than at other times. It has been found that a density change (not an actual density change, but a change in the amount of light incident on the light receiver for density measurement) occurs.

The present invention has been made based on this fact, and since it is equipped with the above-mentioned concentration measuring means and the above-mentioned spotting abnormality detecting means, when a spotting abnormality occurs, other measurement results are not affected. The spotting abnormality can be detected separately from the cause, and the spotting abnormality can be detected at the moment of spotting or before obtaining the final measurement result.

(Example) Examples of the present invention will be described below.

FIG. 2 is a perspective view showing an embodiment of the biochemical analyzer of the present invention.

The illustrated biochemical analyzer 10 is equipped with a transparent lid 11, and when the lid 11 is opened, a test liquid, a long test film 12 in the form of a long tape, which is the test object of the present invention, etc. are released. It is configured to be received within and removed from the device IO. This device IO is equipped with a test liquid storage means 13 that stores test liquids such as serum and urine in a circular arrangement, and the test liquid stored here is stored in a manner described below. It is taken out and spotted by the spotting means 14. The long test film 12 contains multiple types of reagents corresponding to all specified items, such as containing a reagent that exhibits a color reaction with only the specific chemical component or formed component that is desired to be determined. A long test film 12 is prepared. The unused portion of this long test film 12 is wound in the film supply cassette 15, and
The regularly used portion is wound in a film winding cassette 16. Also, the glue inside these cassettes 15 and 16
The central portions of the rolls 15a and 18a are provided with a space for pulling out the long test film 12 from the film supply cassette 15 and for rewinding it into the film supply cassette 15 after storing the long test film 12 in the apparatus IO as described later. Holes tsb and tab are provided to engage with the rotating shaft of the motor. The long test film 12 is placed in a cassette 15.1
6 is housed in the case ff1O. The film supply cassette 15 and the film winding cassette 1B are
Separated as shown in this figure. A plurality of long test films 12 are provided in the test film storage means I7 so that measurements of a plurality of items can be performed simultaneously using this device IO.
It is constructed so that the unused parts of the can be stored in parallel.

The spotting means 14 has a spotting nozzle 14a at its tip,
The rail 1 is moved by the moving means 19 placed on the rail 18.
8 is moved in the extending direction, the test liquid is taken out from the test liquid storage means 13, and is spotted on the long test film 12 pulled out from the test film storage means 17 as will be described later. Further, the moving means 19 includes the spotting means 1
When the moving means 19 moves the spotting means 14 in the horizontal direction in which the rail I8 extends, the spotting means 14 is in a raised position and the spotting means 14 is moved in the vertical direction. It is lowered when taking out the test liquid, applying it, and cleaning as described later.

After the spotting nozzle 14a is spotted on the test film 12, it is cleaned by a nozzle cleaning section 20 disposed between the test film storage means 17 and the test liquid storage means 13 in close proximity to both. Reused for dotting.

The spotted test film I2 is incubated in an incubator, and the optical density is measured in a photometry section, as will be described later.

Control of the entire operation of the device, processing of M1 constant data, etc.
This is performed by a circuit section 21 and a computer 22 connected to this circuit section 21. The operation/display section 23 provided on the front side of the circuit section 21 includes a power switch and a device f for the device IO.
An ammeter and the like are provided to monitor the current consumption at f1o. The computer 22 includes a keyboard 24 for giving instructions to the device lO, auxiliary information for instructions and n1
It houses a CRT display 25 for displaying measurement results, etc., a printer 2B for printing out measurement results, and a floppy disk for storing commands for giving various instructions to the device 10, data for Δ1 measurement results, etc. A floppy disk device 27 is provided.

Figure 3 shows the biochemical analyzer lO whose perspective view is shown in Figure 2.
FIG.

The test film accommodating means 17 is configured such that the spotting positions 28 of all the test films pulled out from therein are arranged in a straight line, and furthermore, the nozzle cleaning section 20 and the test liquid accommodating means are located on this straight line. The inspection liquid extraction positions fif13b in the test liquid take-out positions fif13b are arranged.

The test liquid storage means 13 is configured to store a plurality of test liquids in a substantially circularly arranged storage section 13a. In addition, this test liquid storage means 13 is configured such that a storage section 13a arranged in a circular shape is rotated, and the next measurement of the test liquid stored in this storage section 13a is performed. The liquid to be tested is automatically rotated by a rotating means (not shown) so that the liquid to be tested is located at the take-out position 13b. In order to prevent deterioration of the test liquid contained in the storage part 13a due to evaporation, a lid (not shown) is placed over the storage part 13a other than the extraction position 1W13b.

The spotting means 14 is moved in the direction in which the rail extends by a moving means 19 mounted on the rail I8, and is moved to the take-out position 13b.
The liquid to be tested is taken out and spotted at the spotting position 28 on the long test film.

FIG. 3 is a cross-sectional view showing a main part of the cross section taken along the line xx' in FIG. 2. FIG.

The long test film 12 is stored in a film supply cassette 15.
and loaded into the device IO, and as they are used in the device IO, they are sequentially wound into the film winding cassette 1B. The film supply cassette 15 is housed in a cold storage 50 whose interior is temperature-controlled at, for example, 15° C., and the film winding cassette 1B is housed in a winding chamber 51. The cold storage 50 accommodates the film supply cassette 15 in a cassette accommodating section 50c surrounded by a wall section 50a made of a heat insulating material. Cooling device 58 for cooling to temperature
is attached, and the inside of the cassette accommodating portion 50c is maintained at a substantially uniform temperature. By keeping the cassette accommodating part 50c at a low temperature as described above, the cassette accommodating part 50c
The temperature of the film supply cassette 15 in c is also maintained at the above-mentioned low temperature. Further, a desiccant (not shown) is stored in the film supply cassette 15, and the inside of the cassette 15 is kept in a dry state. The long test film 12 pulled out from the film outlet +5d of the cassette 15 passes through the film outlet 50b of the wall portion 50a, and is finally wound up into the film winding cassette 16.

A rotating shaft of a winding motor 53 provided in the winding chamber 51 is engaged with the hole tab provided in the center of the roll tea in the film winding cassette 16.
3, the long test film 12 is intermittently pulled out from the film supply cassette 15 via the film draw-out port 50b of the cold storage 50, and wound onto the film winding cassette 16.

Film supply cassette 15 and film winding cassette 16
An incubator 55 is disposed in the exposed portion of the long test film 12 between the two, and this incubator 55 holds the film therein and sequentially passes the film through the incubator 5.
A photometry section 60 is installed in the inside of the test film 5 for measuring optical density based on a color reaction between the long test film 12 and the liquid to be tested. This photometric section 60 is considered to include the optical density measuring means according to the present invention.

As described above, the long test film I2 is intermittently pulled out from the cold storage 50 by the rotation of the motor 53, and is intermittently fed to the left in the figure. When the film 12 is being fed, the top lid 55a of the incubator 55 is raised in the direction of arrow A. When the long test film 12 moves, the upper lid 55a descends in the direction of arrow B and the long test film 12
Press. Next, the shutter 54 that was blocking the nozzle insertion hole 55b of the upper lid 55a moves to the right in the figure, and then the nozzle 14a descends as shown in the figure and closes the nozzle insertion hole 55.
The liquid to be tested is spotted onto the long test film 12 through b. After that, the nozzle 14a rises, and the shutter 54 moves to the left to close the nozzle insertion hole 55b.
The inside of the incubator 55 is kept at a predetermined temperature (for example, 37° C.) by preventing air from entering and exiting the incubator 55 and the outside. The target Δ-j fixed part 12a on which the test liquid is spotted is
The temperature is maintained within this incubator 55 for a predetermined period of time (for example, 4 minutes). By the 1lFI light section 60,
The optical density of the part to be measured 12a on which the long test film 12 has been spotted is measured before and after the spotting, after the end of incubation, or during the spotting.

In this density measurement, as will be described later, light containing a preselected wavelength emitted from the light irradiation means 61 is applied to the film I2.
The photodetector 82.63 detects the incident light on the film 12 and the reflected light from the film 12, respectively.

The density signal measured and determined by the n1 light unit 60 is input to spotting abnormality detection means (not shown). In this embodiment, the function (combination of hardware and software) of the computer 22 (see FIG. 2) for monitoring the concentration signal and detecting the presence or absence of a spotting abnormality is considered to be a spotting abnormality detection means. be done.

The spotting abnormality detection means of the computer 22 detects a spotting abnormality in the following manner.

FIG. 1A is a diagram showing temporal changes in optical density of the long test film 12 before and after spotting. At the spotting time to, the concentration of the long test film 12 itself (
The fog density changes rapidly from Do. In this embodiment, since the spotting is performed automatically, the spotting time to
is known by the device itself, and it is determined whether or not the spotting was performed normally depending on whether the optical density exceeds a predetermined threshold Thl within a predetermined time interval T1 starting from the spotting time Lo. is detected. In this embodiment, the amount of spotting does not exceed a predetermined amount due to limitations such as the internal volume of the spotting means, so there is no possibility that more than the predetermined amount will be spotted.

If it is detected that the spotting is abnormal, the operator is notified by a buzzer or the like (not shown).

Furthermore, if it is detected that the spotting is normal, the optical density is also measured after incubation, and the substance concentration in the test liquid is finally determined.

When the spotting, incubation, and measurement of one liquid to be tested are completed in this way, the next liquid to be tested can be spotted. The long test film 12 remains in the incubator even after the measurement is completed, and is transferred again just before spotting for the next analysis.

Here, in the above embodiment, regardless of whether or not a function for monitoring the presence or absence of spotting abnormalities is built-in, it is necessary to measure the optical density of the test object, so the photometry section 60 is originally necessary. The computer 20 also serves as a spotting abnormality detection means.
Therefore, in order to detect the presence or absence of spotting abnormalities as described above, fewer configurations are required to be added, and it is possible to monitor the presence or absence of spotting abnormalities without increasing costs. can do.

FIG. 1B is a diagram showing the temporal change in the differential value ΔD of the optical density of the specimen before and after spotting in another embodiment of the present invention.

Since the optical density changes rapidly at the spotting time to, it is determined whether the spotting was performed normally or not depending on whether the differential value ΔD of the optical density exceeds a predetermined threshold Th2, as shown in this figure. may be detected.

In addition, in a biochemical analyzer where there is a possibility that a predetermined amount or more is deposited, the threshold value Th3 (Th3>Th
2) is established, and when the threshold value Th2 is exceeded and the threshold value Th3 is not exceeded, it is determined that the spotting has been performed normally.If the threshold value Th3 is exceeded, the amount of spotting is too large. You may judge that.

In addition, in the case of a device that performs manual spotting and for which it is not possible to accurately know the spotting time to, monitoring may be started from a timing before spotting, such as the time to when the specimen is placed at the spotting position. , the timing when dotting is definitely completed (
For example, the threshold value Th2 is exceeded (or the threshold value Th2 is exceeded and the threshold value Th3 is exceeded) during the time interval T2 (for example, the timing when the specimen is moved from the spotting position for incubation). It may be detected whether or not spotting has been performed normally based on whether or not there exists a condition in which the spotting is not performed.

(Effects of the Invention) As explained in detail above, the biochemical analyzer of the present invention measures the optical density of the specimen before and after the timing of spotting, and obtains a time-series concentration signal. It is equipped with a measurement means and a spotting abnormality detection means that monitors this concentration signal and detects the presence or absence of a spotting abnormality based on the optical density change of the specimen at the timing when spotting is performed. If an abnormality occurs, this spotting abnormality can be known without having to wait for the final measurement result, and quicker countermeasures can be taken. Moreover, this spotting abnormality can be known separately from other factors that affect the final measurement results.

In addition, measurement equipment (hardware) is originally required regardless of whether spotting abnormalities are detected, and the above-mentioned means for detecting spotting abnormalities can be made possible by adding software, for example, and the cost is minimal. Abnormalities in spotting can be detected without close-up.

[Brief explanation of drawings]

Figure 1A is a diagram showing the temporal change in the optical density of a long test film before and after spotting. Figure 1B is a diagram showing the temporal change in the differential value of the optical density of the test piece before and after spotting. 2 is a perspective view showing a biochemical analyzer according to an embodiment of the present invention, FIG. 3 is a plan view of main parts of the biochemical analyzer shown in FIG. 2, and FIG. FIG. 4 is a cross-sectional view showing a main part of a cross section taken along line xx' in FIG. 3; DESCRIPTION OF SYMBOLS 10...Biochemical analyzer 12...Long test film 12a...N' running part 12b...Measurement surface 13...Test liquid storage means 14...Spotting means 14a. ... Spotting nozzle 50 ... Cold storage 51 ... Winding chamber 55 ... Incubator 60 ... Photometry section 6
1...Light irradiation means 62, 63...Photodetector diagram rOrt")

Claims (1)

[Scope of Claims] The optical density of a test object containing a reagent that causes a change in optical density due to a chemical reaction with the predetermined biochemical substance, on which a test solution containing a predetermined biochemical substance is spotted. In a biochemical analyzer that determines the substance concentration of the predetermined biochemical substance in the liquid to be tested by measuring, the optical density of the specimen is measured before and after the timing of the spotting, and the optical density of the specimen is measured over time. a concentration measuring means for obtaining a serial density signal; and a spotting abnormality that monitors the concentration signal and detects whether or not there is an abnormality in the spotting based on a change in optical density of the test object at the timing when the spotting is performed. A biochemical analyzer characterized by comprising: a detection means.