JPH0373828A - Biochemical analysis - Google Patents

Abstract

PURPOSE:To prolong the life of a light source by automatically stopping the light source when the state in which the light emitted by the light source is not utilized for measuring the optical density of an inspecting body continues for a prescribed period of time. CONSTITUTION:Decision is made as to whether the automatic off mode of the light source or not when processing starts. Decision is made as to whether, for example, >= 20 minutes elapses or not after the end of the measurement of the reflected light quantity from a slide 1 when the automatic off mode of the light source is decided. The light source 18a is automatically put out when the lapse of >= 20 minutes is decided. The wasteful continued lighting of the light source 18a is prevented by automatically putting out the light source 18a when the analysis operation using the slide 1 is not made in such a manner. Since a halogen lamp and tungsten lamp are used as the light source, the lighting time is suppressed shorted and the life of the lamp 18a is prolonged.

Description

Detailed Description of the Invention (Industrial Application Field) The present invention relates to a biochemical analysis method for chemically analyzing a specific component in a sample solution, and more particularly, to a biochemical analysis method that chemically analyzes a specific component in a sample solution, and more specifically, a biochemical analysis method that chemically analyzes a specific component in a sample solution. In a biochemical analysis method that uses specimens such as analytical slides and test films to measure the optical density of the specimens that have undergone a color reaction, the specimen is irradiated with measurement light in order to measure the optical density. This invention relates to a method of measuring the amount of reflected light.

(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. 55-104356, 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 constant temperature (incubation) for a predetermined period of time to allow a color reaction (pigment formation reaction), and then a preselected wavelength is generated by a 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 the measurement light contained therein, the amount of reflected light is measured, and the optical density of the specimen is determined based on the photometric value.

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 (eg, US Pat. No. 3,528,480).

In biochemical analyzers that use specimens such as slides and test films, a halogen lamp or a tungsten lamp is generally used as a light source for emitting measurement light. As is well known, this type of lamp has large fluctuations in light intensity immediately after being turned on, so in conventional biochemical analyzers, once the lamp is turned on, the main power switch of the device is turned on. As long as the lamp was on, it would remain on continuously, regardless of whether an analysis was being performed or not.

(Problems to be Solved by the Invention) However, in the above manner, the light source continues to be lit even if the sample liquid analysis work is interrupted for a considerable period of time, and the life of the light source ends quickly.

The lifespan of the halogen lamps and the like is quite short, about 1000 hours. Therefore, it can be said that continuously lighting the light source as described above is extremely disadvantageous when considering the running cost of the device.

The present invention has been made in view of the above circumstances, and has the following advantages: It is possible to suppress unnecessary lighting of the light source, and it is also possible to prevent a decrease in the accuracy of quantitative analysis due to instability of the light intensity of the light source.
-1 optical method.

(Means for Solving the Problems) The biochemical analysis method according to the present invention is characterized in that a light source that emits measurement light is automatically turned off after a predetermined period of time has elapsed after the measurement of the amount of reflected light from the specimen is completed. It is said that

Another biochemical analysis method of the present invention further includes continuously changing the amount of light emitted by the light source after the light source that has been automatically turned off as described above is turned on next time (that is, repeating the amount of light over time). or continuously), and after the amount of light reaches a predetermined stable state, measurement of the amount of reflected light is started.

(Function) If the light source is automatically turned off as described above, the light source will not continue to be turned on unnecessarily. In addition, if the amount of reflected light 711 is determined when the amount of light emitted by the light source reaches a predetermined stable state, the amount of measurement light will not become unstable, and the standby state for waiting for the amount of light to stabilize. is not set pointlessly long.

(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 measurement data, etc., a delivery port 12 for sending out a sheet 12A on which the displayed data is printed out, and operation keys 14 for operating this display, etc. is provided. Furthermore, a slide guide 15a for holding unused chemical analysis slides is formed in the slide special section 15 on the right side, 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 spotting 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.
FIG. 3 is a cross-sectional view of a portion taken along line I.

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 t5 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 power supply 1G, a printed wiring board 17 for the control circuit, a light source 18a for the measuring means 40, a magnetic disk drive mechanism 18b, etc. are arranged.
Detailed explanations of these 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 artificial openings are formed side by side at the rear of the storage chamber 33, and the outlet openings are formed at the front of the storage chamber 33, side by side from side to side. The chemical analysis slide 1 is pushed 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 3 extending in the left-right direction and receiving a measurement head 41 for measuring the reflected optical density of the chemical analysis slide 1 stored in the storage chamber 33.
2b1 and the measuring head 41 have an opening 32c for determining the reflected optical density.

The measurement head 41 is guided by guide rods 43a and 43b and moved left and right within the length 1M32b by a wire 44 connected to a holding base 42 that holds it 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 71.
Determine pI. This measuring head 41 will be explained in detail below with reference to FIG. One end of an optical fiber 89 is fixed to the apj constant head 41 . This optical fiber 8
The other end of 9 is fixed at a position facing the light source 18a. The light 92a emitted by the light source 18a is transmitted through the collimator lens 9.
6, the light is made into parallel light, passed through a condenser lens 97 via a filter plate 90, condensed by the condenser lens 97, and then irradiated onto the other end of the optical fiber 89. The filter plate 90, as shown in FIG. 8, includes - by way of example, seven interference filters 90a, 90b.

90c, 90d, 90c, 90f', and 90g are attached, and by being rotated by a pulse motor 91, one of the interference filters 90a to 90g is selectively placed in the optical path of the light 92a. do. Each of the interference filters 90a to 90g transmits light of a unique wavelength depending on the combination of the reagent and sample liquid on the chemical analysis slide 1.

The measurement light 92, which has been passed through one of the interference filters 90a to 90g and has a predetermined wavelength, is made to enter the optical fiber 89 as described above, and the δill constant head 41
Inside, the light is emitted from one end of the optical fiber 89. This measurement light 92 is condensed by a condenser lens 98, and then
Chemical analysis slide 1 is irradiated. At this time, the reflected light 92R reflected by the chemical analysis slide 1 is collected by a condensing lens 99 and received by a photodetector 94, and the amount of light is detected by the photodetector 94. The output Q of the photodetector 94 indicating the amount of light is input to a photometric circuit 95, where it undergoes processing such as amplification and digitization, and is output as reflected light amount data. The amount of reflected light is measured for one slide 1, for example, every 10 to 15 seconds for a predetermined period of time (-
For example, it is carried out for about 5 to 6 minutes).

Further, this measuring head 41 is connected to a white plate 2a which is a density reference plate.
It also moves below the blackboard 2b, and the amount of reflected light from these density reference plates 2a and 2b is also determined for calibration. Furthermore, this measurement head 41 also moves below the supply stand 19, and while the chemical analysis slide 1 of the slide special equipment section 15 is being transferred by the supply lever 52, which will be described later, the reflection optical density of the chemical analysis slide 1 ( Fog). 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.

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; 32f, 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 32c are controlled so that the temperature sensor 32h always indicates a constant temperature. A temperature sensor 32i is arranged further to the right of the heater 32f', and the currents of the right heaters 32f and 32g are controlled so that the temperature sensor 321 always indicates a constant temperature.

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

These heaters 31a, 31b, and 31c are for heating the incubator 30 almost uniformly from above.
The currents flowing through these heaters 31a, 31b, and 31c are 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 equipment section 15 described above, 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 stand 55 is movable along two guide rods 5G. A part of a wire 57 (see FIG. 4) stretched in an endless manner is locked on this holding stand 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 at a position above the shuttle 54 and is held by the longitudinal movable mill 7t. The slide insertion bar 59 also has an insertion claw 60 at a position facing the artificial opening of each storage chamber 33 of the incubator 30. This slide insertion bar 59 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 the artificial 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 kept at a constant temperature as described above, and the optical density of the portion colored by reaction with the sample acid is measured by the measurement head 41.

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 abutment protrusion 83 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 03 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.

Slide 1 outputted by the photometric circuit 95 as described above;
The reflected light amount measurement data S%W and B for the reference white board 2a and the reference blackboard 2b are input to the calculation section 65, and the reflected optical density OD of the slide 1 is calculated from these measurement data S, W, and B. This calculation is performed using the following formula: W: Photometric data of reference white board 2a B: Reference blackboard 2
ODw of I/S Nislide 1 of b: @ OD value of white board 2a by degree standard machine ODb: 1
This is done based on the OD value on the blackboard 2b by the degree standard machine. Then, a plurality of reflection optical densities O obtained as above are obtained.
From the value of D, for example, the optical density value at the time when a predetermined analysis time has elapsed after spotting is determined, and from this optical density value, the substance concentration of the specific component to be analyzed is determined.

The calculation section 65 sends a signal indicating the value of the substance concentration determined in this way to the control section 66 shown in FIG. 3.4.

The control section 66 causes the substance concentration value indicated by this signal to be displayed on the display section 13, and is also caused to be recorded on the recording sheet 12A by a printer (not shown) and discharged from the delivery port 12 (see FIG. 2).

FIG. 1 shows drive control processing of the light source 18a by the control section 65. When the process starts in step P1, it is first determined in step P2 whether or not the light source automatic OFF mode is set. This mode is set by the apparatus operator using the operation keys 14 shown in FIG. 2 described above.

If this automatic OFF mode is not set, the process flow returns to the basic process flow for determining the substance concentration Apl (step P9).

On the other hand, if it is determined in step P2 that the light source automatic OFF mode is set, then in step P3, for example, 20 minutes or more have passed since the measurement of the amount of reflected light from the slide 1 was completed.

It is determined whether the If 20 minutes or more have not elapsed, the flow of processing returns to before step P3, and the determination process of step P3 is continuously performed.

If it is determined in step P3 that 20 minutes or more have elapsed, then in step P4 the light source 18a is turned off. By automatically turning off the light source 18a in this manner, it is possible to prevent the light source 18a from continuing to be turned on uselessly even though no analysis operation using the slide 1 is being performed. light? As described above, halogen lamps and tungsten lamps are used as fi and 18a, and if their lighting time is kept short as described above, their lifespan will be reliably extended.

After that, in step P5, it is determined whether or not the lamp ON key, which is one of the operation keys (4), has been pressed. If the lamp ON key is not pressed, the flow of processing continues before step P5. Returning to step P5, the determination process of step P5 is continuously performed.

When it is determined in step P5 that the lamp ON key has been pressed, measurement of the amount of light from the light source is started in step P6. In this embodiment, when the optical density measurement of the slide 1 is completed, the measuring head 41 is returned to the position facing the reference white plate 2a (see FIG. 7), and the above-mentioned light ffi dul+ constant is Reference white board 2a
This is done by measuring the amount of light reflected from the This measurement of the amount of reflected light is repeated, for example, at intervals of 10 seconds.

Next, in step P7, the anti-#1 light fii71
The stability of the amount of light from the light source is determined from the 1+1 constant data.

In this example, the nth[1li1st reflected light ff111? Let the J constant data be Xn, and define the stability S as follows,
It is assumed that the smaller the value of S, the more stable the light source is.

Note that as the value of X, the output digital value of the -Pj optical circuit 95 can be used.

As shown in FIG. 9, for example, the stability S basically changes as the light intensity of the light source becomes more stable over time, that is, as the difference between the light intensity measurement data Xn and Xn-1 becomes smaller. It gradually decreases.

Once the stability S is determined in this way, it is then determined in step P8 whether or not the stability S has decreased to a predetermined threshold value. In the actual length example, this threshold value is 0.
．． 2 (%). If the stability S is higher than 0.2%, the process flow returns to step P6, and the processes from steps P6 to P8 are repeated.

In step P8, when it is determined that the stability S has decreased to 0.2%, that is, when it is considered that the light source light amount has entered a predetermined stable state, the process flow is to measure the substance concentration. Returning to the basic processing flow (step P9). Returning to this basic process flow, optical tA18
Using the light emitted by the measuring head 41, the measurement head 41 performs normal all-light operations, that is, the reference white plate 2aS for calibration.
Measurement of reflected light amount from reference blackboard 2b and each slide 1
The amount of reflected light al is determined.

In the above embodiment, the stability of the amount of light from the light source may be defined by a value such as S'-Xi-+/Xn. In this case, as the amount of light from the light source becomes stable, the value of so approaches 1.

Furthermore, 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 according to the present invention, the light emitted from the light source has an optical density of 71 #
If the light source is not used regularly for a specified period of time, it will automatically stop, which will prevent the light source from being turned on unnecessarily and reliably extend its lifespan. It is also possible to keep the power consumption low and reduce the running cost of the device.

Furthermore, in the method of the present invention, after the light source is automatically turned on lr1 as described above, when the light source is turned on next time, the amount of light emitted by the light source reaches a predetermined stable state. Since this light is used to measure the optical density of the specimen, it is possible to prevent the optical density measurement value from becoming inaccurate due to fluctuations in the light intensity of the l-1 constant light, thereby improving the accuracy of biochemical analysis. can be maintained high.

[Brief explanation of drawings]

FIG. 1 is a flowchart showing the process flow of light source operation control in the method of the present invention, FIG. 2 is a perspective view showing an example of a biochemical analyzer that implements the method of the present invention, and FIG. 3 is a TS2 diagram. 4 is a plan view showing the main parts of the biochemical analyzer with the cover removed, FIG. 4 is a sectional view showing the cross-sectional shape of the portion taken along line 1-1 in FIG. FIG. 6 is a perspective view showing the slide transport system of the biochemical analyzer; FIG. 7 is a schematic front view showing the measurement head and its surroundings of the biochemical analyzer. FIG. 8 is a plan view showing the filter plate of the measurement head, and FIG. 9 is a graph showing changes in the stability of the light amount of the light source. 1...Chemical analysis slide 2a...Reference white board 2b
...Reference blackboard 15...Slide special equipment section 1
5a...Slide guide 18a -0, light source 2
0... Spotting means 25... Barcode reader 30... Incubator 31... Upper member 3
1a, 31b, 31c, 32d, 32e, 32f, 32
g - 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 5
3... Supply lever drive motor 54... Shuttle 5
8... Shuttle drive motor 59... Slide insertion bar 60... Insertion claw 61
...Pushing bar drive motor 65...Calculation section 66...
- Control unit 90...filter plate 0a 1 0b 1 90c. 0d 0e 1 90r. 0g...Interference filter easy diagram Figure 5 Figure Time diagram Figure

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, In a biochemical analysis method for determining concentration, in order to measure the optical density, a test object is irradiated with measurement light, the amount of reflected light from the test object is measured, and the light source that emits the measurement light is A biochemical analysis method characterized in that the light is automatically turned off after a predetermined period of time has passed after the end of the measurement. (2) Spot the sample solution on a test body containing a reagent that chemically reacts with a specific component in the sample solution, measure the optical density while keeping the test body at a constant temperature, and determine whether the specific component in the sample solution is detected. In a biochemical analyzer for determining concentration, in order to measure the optical density, a test object is irradiated with measurement light, the amount of reflected light from the test object is measured, and the light source that emits the measurement light is set to a position corresponding to the amount of reflected light. After the measurement is completed, the light is automatically turned off after a predetermined period of time has elapsed, and then after this light source is turned on, the amount of light emitted by the light source is continuously measured, and when the amount of light reaches a predetermined stable state. A biochemical analysis method characterized in that the measurement of the amount of reflected light is started from.