JPH0378646A - Method of biochemical analysis - Google Patents

Abstract

PURPOSE:To enable easy analysis of a cause of abnormality of an apparatus by a method wherein a measured value of a factor affecting a computed value of the density of a substance is recorded in a medium for each sample liquid. CONSTITUTION:A sample liquid is applied by a pipet 22 onto an inspecting body such as a chemical analysis slide, the optical density of the inspecting body is measured 40 while the inspecting body is kept at a constant temperature, and the density of a substance of a specific component in the sample liquid is computed. On the occasion, a measured value of a factor affecting the computed value of the density of the substance is recorded in a recording medium for each sample liquid. As to the measured value to be recorded in the medium, it is one of a measured value of a reference density plate with the passage of time, a measured value of the optical density and the temperature of a constant temperature device.

Description

Detailed Description of the Invention (Industrial Field of Application) The present invention relates to a biochemical analysis method for chemically analyzing a specific component in a sample solution, and in particular, it relates to a biochemical analysis method that chemically analyzes a specific component in a sample solution. Using chemical analysis slides and test films,
The present invention relates to a biochemical analysis method that measures the optical density of substances that have undergone a color reaction.

(Prior Art) Qualitative or quantitative analysis of specific chemical components in sample liquids is widely practiced in various 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, a dry type chemical analysis slide has been developed that can measure the concentration of a specific chemical component or organic component contained in a sample solution by simply applying a small droplet of the sample solution. -21677.

(Japanese Patent Application Laid-Open No. 55-164358, etc.) has been put into practical use. These chemical analysis slides allow you to analyze sample liquids more easily and quickly than traditional wet analysis methods.
This chemical analysis slide is being used particularly favorably in medical institutions, laboratories, etc. where it is necessary to analyze a large number of sample liquids.

In order to determine the substance concentration of a specific component in a sample solution using such a chemical analysis slide, the sample solution is placed on the chemical analysis slide, and then placed in an incubator.
The sample solution is kept at a constant temperature (incubation) for a predetermined period of time to cause a color reaction (dye production reaction), and then contains a preselected wavelength based on the combination of the components in the sample solution and the reagents contained in the reagent layer of the chemical analysis slide. The chemical analysis slide is irradiated with measurement irradiation light and its reflected optical density is measured.

In addition, in order to automatically and continuously analyze the sample liquid, a long tape-shaped test film containing a reagent is stored in place of the slide described above, and the test film is pulled out one after another and the sample liquid is spotted. , incubation, and measurement devices have also been proposed (for example, US Pat. No. 3,528,480).

Generally, in the biochemical analysis method using specimens such as slides and test films mentioned above, for calibration purposes, light is also irradiated to a reference white board and a reference blackboard, and the amount of light reflected from them is measured, and these reflected light ′ The reflected optical density of the test object is determined based on the 6Jj constant data and the reflected light measurement data from the test object. In other words, the reflected optical density OD of the test object
However, W: Photometric data of the reference white board: of the reference blackboard S: of the test object ODw: OD value of the reference white board measured by the density standard device ODb: a
It is determined as the OD value of the standard blackboard using a degree standard machine.

(Problem to be Solved by the Invention) By the way, when determining the optical density of the specimen as described above, various noises may enter the density measuring device, and if affected by this noise, the optical density value may be inaccurate. Become something. Furthermore, the measured optical density value may become inaccurate due to a malfunction of the measurement head itself that irradiates light onto the object to be inspected and measures the amount of light reflected therefrom. If the optical density value is incorrectly measured as described above, the substance concentration value will also be inaccurate.

Previously, only the measurement results were displayed or printed. For this reason, there is a problem in that the progress until the measurement result changes is not known, and even if the measurement value becomes abnormal, it is unclear what caused it.

The present invention was made in view of the above-mentioned circumstances, and an object of the present invention is to provide a biochemical analysis method that makes it possible to easily investigate the cause when an analysis value shows an abnormality. It is something to do.

(Means and effects for solving the problem) The biochemical analysis method according to the present invention involves spotting a sample liquid onto a specimen such as a chemical analysis slide, and measuring the optical density of the specimen while maintaining the specimen at a constant temperature. In a biochemical analysis method that calculates the substance concentration of a specific component in a sample solution, the measured value of a factor that influences the calculated value of the substance concentration is
It is characterized by recording each sample liquid on a recording medium. The measured values to be recorded on the recording medium include the measured values of the reference density plate over time, and the optical density n1.
It is at least one of constant value and incubator temperature.

The measurement values may be recorded, for example, by printing on recording paper, but it is more preferable to record them using a magnetic recording medium such as a magnetic disk or an optical recording medium such as an optical disk. In other words, by doing so, you can read out the recorded information and print or display it only when the analysis value shows an abnormality, thereby avoiding wasting recording paper by recording normal measurement results. It can be avoided.

(Example) Hereinafter, an example of the present invention will be described based on the drawings.

FIG. 2 is a perspective view showing an example of a biochemical analyzer for carrying out the method of the present invention. An incubator, slide transport means, slide insertion means, etc. are arranged inside the main body 1O, and these are covered with a cover 11. Externally, this biochemical analyzer includes a display section 13 for displaying 7111j constant data, etc., an output port 12 for sending out 12A from which the displayed data is printed out, and operations for operating this display, etc. A key 14 is provided. Furthermore, the slide special section 15 on the right side has a slide guide 15 that holds unused chemical analysis slides.
A is formed, and a plurality of unused chemical analysis slides are normally held in a stacked manner on this slide guide 15a.

Note that a cartridge storing and holding a plurality of stacked chemical analysis slides may be attached to this slide guide 15a. On the back side of this slide special equipment section 15,
A spotting means 20 is provided for spotting a predetermined sample liquid onto the reagent layer of the chemical analysis slide. The spotting means 20 includes a spotting arm 21 that protrudes forward and rotates up and down around its rear end, a spotting pipette 22 that extends downward from the front end of the spotting arm 21, and a spotting arm 21 that rotates vertically and It consists of an operation button 23 for aspirating and spotting the sample liquid onto the spotting pipette 22. When spotting is performed using this spotting means 20, by operating the operation button 23, the dim sum arm 21 is rotated upward and the spotting pipette 22 is rotated upward.
Lift the pipette 22 and drop it into the sample liquid in the container.
The tip of the spotting arm 21 is moved downward to aspirate a predetermined amount of sample liquid into the spotting pipette 22, and then the spotting arm 21 is rotated downward again to remove the sample from the spotting pipette 22 onto the chemical analysis slide located below. A predetermined amount of sample solution is spotted onto the reagent layer.

Fig. 3 shows the main parts of the biochemical analyzer shown in Fig. 2 with the cover removed, and Fig. 4 shows the I-I of Fig. 3.
It is a sectional view of a part along one line.

The internal structure of this biochemical analyzer will be explained below with reference to both figures.

Inside the biochemical analyzer, there is an incubator 30 for maintaining a constant temperature of the chemical analysis slide 1 onto which a sample solution is applied by the above-mentioned spotting means 20, and an incubator 30 for maintaining a constant temperature of the chemical analysis slide 1, which is kept at a constant temperature. Furthermore, the chemical analysis slide 1 is transferred from the slide special equipment section 15 to each storage chamber 3 of the incubator 30.
It has a slide conveyance system that conveys the material to the inside of the container. This slide conveyance system will be described in detail later with reference to FIG. In addition to the above means, a battery 1B, a printed wiring board 17 for the control circuit, and a light source 111 for the measuring means 40 are provided.
a, a magnetic disk drive mechanism 1111b, and the like are arranged, but detailed explanation thereof will be omitted. In the following description, the direction indicated by arrow F will be referred to as the front, the direction indicated by arrow R will be referred to as rear, and the right and left sides in FIG. 3 will be referred to as right and left, respectively.

The incubator 30 extends in the left-right direction,
Inside it, there are multiple storage rooms 33.33. ...33 are formed side by side in the left and right direction. These storage rooms 33.
33. . . 33 each have an inlet opening and an outlet opening, the inlet openings are formed side by side in the rear of the storage chamber 33 and the outlet openings are formed in line in the left and right in front of the storage chamber 33. The chemical analysis slide 1 is inserted into the storage chamber 33 from the entrance opening and is discharged from the exit opening. Disposal box 8
Will be discarded within 0.

Further, the storage chamber 33 has a lower member 32 on which the chemical analysis slide 1 is placed, and an upper member 31 that presses down the chemical analysis slide 1 placed on the lower member 32 from above. The chemical analysis slide 1 is kept at a constant temperature.

The lower member 32 has a long groove 32b1 and a measuring head 41 extending in the left-right direction and receiving an Ap1 constant head 41 for measuring the reflected optical density of the chemical analysis slide 1 stored in the storage chamber 33 below. It has an aperture 32c for determining the reflection optical density of 1llJ.

The measuring head 41 is guided by guide rods 43a and 43b and moved left and right within the long groove 32b by a wire 44 connected to a holding base 42 that holds the measurement head 41 being pulled by a drive motor 45, and then stored. The reflected optical density of each chemical analysis slide 1 stored in the chamber 33 is measured. The measurement head 41 is, for example, disclosed in Japanese Patent Application Laid-Open No. 63-10856.
As shown in Publication No. 8, the slide 1 is irradiated with light containing a wavelength pre-selected based on the combination of the component to be analyzed and the reagent on the slide 1, and the amount of reflected light is detected by a photodetector. .

This 111J constant is for one slide 1, for example, 1
This is carried out every 0 to 15 seconds for a predetermined period of time (for example, about 5 to 6 minutes). The measurement head 41 also moves below the white board 2a and the blackboard 2b, which are two density reference boards.
These reference whiteboard 2a and reference blackboard 2b are used for calibration.
Also measure the amount of light reflected from the The measurement of the amount of reflected light from the reference white board 2a and the reference blackboard 2b is performed every time the amount of reflected light is measured once for the slide 1. Furthermore, this measuring head 41 also moves below the supply table 9,
While the chemical analysis slide 1 in the slide special section I5 is being transferred by the supply lever 52, which will be described later, the reflective optical density (fog) of the chemical analysis slide 1 is measured.

Slide 1 and reference white board 2a measured as above
and reflected light amount measurement data SSW and B from the reference blackboard 2b are input to the calculation unit 65, and these measurement data SSW and B are input to the calculation unit 65.
, WSB, the reflective optical density OD of the slide 1 is calculated. This operation is performed according to the above-mentioned formula. Then, from the multiple reflected optical density OD values obtained in this way, for example, the optical density value at the time when a predetermined analysis time has elapsed after spotting is obtained, and from this optical density value, the substance concentration of the specific component to be analyzed is determined. is required.

In addition, a barcode reader 25 is provided below the slide transfer path from the slide special equipment section 15 to the supply stand 19, and when the chemical analysis slide 1 passes there, the barcode reader 25 is provided with a barcode reader 25, and when the chemical analysis slide 1 passes there, A barcode indicating the type of reagent, lot number, etc. is read.

The calculation unit 65 sends a signal indicating the substance concentration calculated as described above to the output control unit 66, and the output control unit 66 displays the substance concentration value on the display unit 13 or displays it using a printer (not shown). and recorded on the sheet 12A. In addition, the light intensity measurement data SSW and B for slide 1, reference whiteboard 2a, and reference blackboard 2b are as follows:
After taking correspondence with each other for each batch, all data are recorded on a magnetic disk (for example, a floppy disk) using the magnetic disk drive mechanism 18b. This data recording is performed according to a predetermined format so that it can be read by a personal computer or the like.

FIG. 5 is a front view of the incubator 30 showing the arrangement of heaters for maintaining a constant temperature inside the incubator 30. The arrangement of the heaters in the incubator 30 will be described below with reference to FIGS. 3, 4, and 5.

Heaters 32d, 32e; 32r, 32g are arranged vertically near both left and right ends of a portion of the lower member 32 of the incubator 30 that extends downward across the groove 32b (see FIG. 4). A temperature sensor 32h is arranged further to the left of the heater 32d, and the currents of the left heaters 32d and 32e are controlled so that the temperature sensor 32h always indicates a constant temperature. A temperature sensor 321 is arranged further to the right of the heater 32r, and the heaters 32f' and 32 on the right side are arranged so that the temperature sensor 321 always indicates a constant temperature.
g current is controlled.

Three heaters 3 are installed in the upper member 3I of the incubator 30.
1a, 31b, and 31c are arranged horizontally. Further, a temperature sensor 31d is arranged to the left of the heater 3La.

These heaters 31a, 31b, and 31c are for heating the incubator 30 almost uniformly from above.
The current flowing through these heaters 31a, 31b, and 31c is controlled so that the temperature sensor 31d always indicates a constant temperature.

Next, the slide conveyance system will be explained with reference to FIG. A block 51 is held on two guide rods 50 extending in the front-rear direction so as to be movable along them.
A slide supply lever 52 is attached to this block 51. The block 51 is moved back and forth by a supply lever drive motor 53.

A supply stand 19 is disposed behind the slide special unit I5, and a shuttle (left-right movable stand) 54 that moves in the left-right direction is located further behind it. This shuttle 54 is fixed to the upper part of the holding table 55,
The holding table 55 is movable along two guide rods 56. A part of a wire 57 (see FIG. 4) stretched in an endless manner is locked in this holding joint 55, and as this wire 57 is moved by a shuttle drive motor 58, the holding stand 55, that is, the shuttle 54 moves in the left and right direction. A slide insertion bar 59 is held above the shuttle 54 so as to be movable back and forth. The slide insertion bar 59 also has an insertion claw 60 at a position facing the entrance opening of each storage chamber 33 of the incubator 30. This slide insertion bar 5
9 is moved in the above direction by the insertion bar drive motor 61.

The operation of the slide conveyance system having the above configuration will be explained below. First, the block 51 is placed in the position shown in FIG. When the lever drive motor 53 is activated from this state and the block 51 is moved to the rear side, the lowest one of the chemical analysis slides 1 stored in, for example, a cartridge and stacked on the slide special equipment section 15 is moved. It is pushed by the slide supply lever 52 and transferred onto the supply table 19. The supply stage 19 is provided with an opening 19a, through which the fog density of the chemical analysis slide 1 is measured by the measuring head 41.

Thereafter, a predetermined amount of sample liquid is spotted onto the chemical analysis slide 1 using the spotting pipette 22 . Next, by moving the slide supply lever 52 further backward, the chemical analysis slide 1 is transferred onto the shuttle 54. When the chemical analysis slide 1 has been advanced to this position, the lever drive motor 53 is reversed and the block 51 is returned to the position shown in FIG. Furthermore, when the block 51 returns to its original position in this way, the slide supply lever 52 can swing freely in the direction in which the tip thereof faces rearward so that the slide supply lever 52 does not move the slide 1 on the slide special section 15. has been done.

Chemical analysis slide 1 is placed on shuttle 54 as described above.
When it is transferred, the shuttle drive motor 58 is activated, and the shuttle 54 is moved to a position facing the predetermined storage chamber 33. Then, the insertion bar drive motor 61 operates,
The slide insertion bar 59 is moved forward a predetermined distance from the position shown in FIG. As a result, the chemical analysis slide 1 on the shuttle 54 is inserted into the insertion claw 60 of the slide insertion bar 59.
is pushed forward by the storage chamber 3 through said inlet opening.
It can be kept within 3. At this time, if there is a slide 1 whose optical density has been measured in the storage chamber 33, that slide 1 is pushed by the newly inserted slide 1 and dropped into the waste box 80.

The chemical analysis slide 1 stored in the storage chamber 33 as described above is maintained at a constant temperature as described above, and the optical density of the portion that reacts with the sample liquid and develops a color is determined by the allJ constant head 4.
1.

In this embodiment, one of the members that guides the left and right ends of the slide 1 on the shuttle 54 is designed so that the chemical analysis slide 1 stored in each storage chamber 33 at the end in a series of biochemical analyzes can be discarded. , configured to also act as a sliding waste lever. That is, this slide disposal lever 62 is provided with an abutting protrusion 63 on the inside, is movable in the front and rear directions on the shuttle 54, and is biased rearward by a biasing means (not shown). When discarding the last chemical analysis slide 1, the shuttle 54 is stopped at a position where the slide discard lever 62 faces the central portion of the storage chamber 33. In this state, when the slide insertion bar 59 moves forward as described above, the insertion claw 60
comes into contact with the abutment protrusion 63 and slides the discard lever 62
Press. As a result, the lever 62 moves forward against the urging force, and moves the slide 1 in the storage chamber 33 to the waste box 8.
Drop it into 0.

The data recorded on the magnetic disk in the magnetic disk drive mechanism 18b described above is read out by applying the disk to a personal computer or the like as necessary. The read data can then be output using a printer connected to the personal computer or the like.

FIG. 1 shows an example of recorded data printed on the recording sheet 90 in this manner. In the figure, ■ is a serial number indicating the measurement time, and the columns ■, ■, and ■ are the measurement data of the amount of reflected light from the slide 1, the reference white board 2a, and the reference blackboard 2b, respectively. These data are obtained by converting the output voltage of a photodetector that detects reflected light into digital values. In addition to these data, in this example, the measurement time (■ column), the continuous time from the point of spotting (■ column), the time interval from the previous measurement (■ column), and the calculated optical density value (■ column) and the temperature of the incubator 30 (■ column) are also recorded.

As mentioned above, if the measurement data related to optical density measurement is recorded as is, when the analysis value takes an abnormal value as mentioned earlier, it is possible to investigate the cause of the abnormality by examining these recorded data. It becomes possible. For example, in a certain measurement, the amount of reflected light/1llll constant data S1W and B
If all of the measured values are abnormal values, that is, values significantly different from the measurement data of the successive times, it is considered that the measuring head 41 is malfunctioning. On the other hand, if, for example, the reflected light amount measurement data W, B for the reference white board 2a and the reference blackboard 2b are normal, but the data S for slide 1 shows an abnormal value, the abnormality is due to some kind of noise. It can be determined that, etc.

Although the embodiments applied to a biochemical analyzer using chemical analysis slides have been described above, the present invention can also be applied to a biochemical analyzer using a test film as described above.

(Effects of the Invention) As explained in detail above, in the biochemical analysis method of the present invention, 7fIJ of factors that influence the calculated value of substance concentration.
Since the fixed values are recorded in their raw form, there is no need to perform new measurements to analyze the cause of the abnormality.
By examining these measurements as appropriate,
The cause of equipment abnormality can be easily analyzed.

[Brief explanation of drawings]

FIG. 1 is a schematic diagram showing an example of recording light amount measurement data according to the present invention. FIG. 2 is a perspective view showing an example of a biochemical analyzer for carrying out the method of the present invention; FIG. 3 is a plan view showing the main parts of the biochemical analyzer shown in FIG. 2 with the cover removed; Figure 4 is a cross-sectional view showing the cross-sectional shape of the portion along line I-1 in Figure 3, Figure 5 is a front view of the incubator showing the arrangement of heaters, and Figure 6 is the above-mentioned biochemical analysis. FIG. 2 is a perspective view showing a slide conveyance system of the apparatus. 1...Chemical analysis slide 10...Main body 12A,
90...Record sheet 15...Slide special equipment section 15
a...Slide guide 18b...Magnetic disk drive mechanism 20...Spotting means 25...Barcode reader 30...
Incubator 31...upper member 31a, 31b
, 31c, 32d, 32e, 32f, 32g - Heaters 31d, 32h, 321... Temperature sensor 32... Lower member 33... Storage chamber 40... Measuring means 41... Measuring head 42... holding stand
52... Slide supply lever 53... Supply lever drive motor 54... Shuttle 58... Shuttle drive motor

Claims (2)

[Claims] (1) Spot the sample liquid on a test body containing a reagent that chemically reacts with a specific component in the sample liquid, measure the optical density while keeping the test body at a constant temperature, A biochemical analysis method for calculating concentration, characterized in that measured values of factors that influence the calculated value of the substance concentration are recorded on a recording medium for each sample liquid. (2) The biochemical analysis method according to claim 1, wherein the measured value is at least one of a measured value of a reference concentration plate over time, a measured value of optical density, and a temperature of an incubator. .