JPS62157551A - Boichemical analysis method - Google Patents

Abstract

PURPOSE:To eliminate an opening for dripping a liquid to an incuvation means, by carrying a measuring element to a liquid dripping position off the incuvation means to accomplish the dripping of a liquid sample. CONSTITUTION:As a measuring element 2 is put into an element insertion port 11 of a device body 1, the element 2 is inserted and held in a element holding section 331 of an incuvation means 3 to be detected with a sensor. A disc 33 is sent by one pitch and subsequently, the element 2 is inserted and held in the holding section 331. Upon the end of the insertion of the element 2, a preheating is done. Then, the element 2 is sent under an external dripping hole of the disc 33 by a means 5, and the liquid sample is dripped into a through hole of the element 2. Then, the element 2 is put back to the holding section 331, and returned after all the elements 2 are dripped with the samples and then, an incuvation is performed. Then, a photometry is done with a measuring section 6 and the elements are discharged at discharge port 14. This eliminates the need for the opening for dripping liquids to the means 3 thereby preventing the evaporation of the liquids in the elements 2.

Description

Detailed Description of the Invention [Industrial Application Field] The present invention involves dropping a biochemical liquid sample such as blood, serum, or urine onto a measuring element impregnated with a reaction reagent, and causing the blood, etc. to react with the reagent. This invention relates to a biochemical analysis method for analyzing liquid samples.

(Prior art) This type of biochemical analysis involves promoting a reaction with a liquid sample of a reaction reagent under specific temperature conditions, and measuring the progress and results of the reaction based on changes in color concentration caused by the reaction. This is to analyze the presence or absence and content of specific components in the sample.

Incidentally, conventionally, such an analytical device uses a disk having a fitting groove formed in its peripheral portion into which a measuring element is fitted, and is configured so that the disk can be rotated intermittently.
A biochemical liquid sample is dropped onto a measuring element fitted to the disk to promote a reaction under a constant temperature atmosphere, and after a predetermined period of time, the sample is transported to a photometry section to detect the color density of the measuring element. was.

In this analysis, the steps are as follows: 1) Setting the measurement elements onto the disk one by one → Preincubation (preheating) for each one - Dropping of the biochemical liquid sample, which is taken out of the device for each measurement element. Incubation by setting on the disk again (acceleration of reaction progress during incubation) - photometry → discharge from the disk, or ■ Bulk setting of measurement elements on the disk → pre-incubation - incubation through holes formed in the device One method involved dropping a liquid sample onto each measuring element at once, incubation, photometry, and discharging.

However, the process (2) requires repeating the steps from setting the measurement element to dropping the liquid sample, making the work complicated.Moreover, if sufficient pre-incubation is performed, the time required for analysis becomes longer. There is a problem of poor analytical processing efficiency.

On the other hand, the process (2) does not have the same problems as the process (2), but it involves drilling a hole in the measuring element fitting part of the disk and aligning the hole with the drip hole formed in the main body of the device.
Since the liquid material is dripped onto the measuring element from there, the measuring element is constantly exposed through the hole in the disk, making the measuring element insufficiently airtight during incubation, and causing reagents and samples to evaporate. There is a problem with putting it away.

[Purpose of the invention]

An object of the present invention is to provide a biochemical analysis method that can improve analysis efficiency and prevent evaporation.

[Structure of the invention]

For this purpose, the present invention includes a first step of setting a plurality of measurement elements in an incubation means, a second step of pre-incubating the set plurality of measurement elements, and a step of incubating each of the pre-incubated measurement elements. A third step of individually moving the liquid sample from the means to the liquid sample dropping position, dropping the liquid sample, and setting it at the original position, a fourth step of incubating each measuring element on which the liquid has been dropped, and a fourth step of incubating each measuring element after the liquid has been dropped. It consists of a fifth step in which each photometer is measured individually.

〔Example〕

Examples of the present invention will be described below. Fig. 1 is a diagram showing the external appearance of an analyzer for carrying out the method of one embodiment, Fig. 2 is an exploded perspective view of a measuring element, Fig. 3 is a diagram showing a disk as a conveying means, and Fig. 4 is IV-I in Figure 3.
FIG. 5 is a diagram showing a cross section along the V line, and FIG. 5 is a diagram showing a lid that makes the measurement element airtight.

In the figure, 1 is the main body of the analyzer, and 2 is a measuring element.

As shown in FIG. 2, this measuring element 2 has a through hole 2 for photometry.
A film 23 impregnated with a certain reagent is sandwiched between a mount base 21 having a diameter 1a and a mount cover 22 having a through hole 22a for dropping a liquid sample, and reagent data is printed on the surface of the mount cover 22. (Analysis items) A code 24 for determining other items is displayed in, for example, 5 bits.

The measuring element 2 is inserted into the device body 1 through the element insertion opening 11 provided on the front surface thereof, and is moved by a pair of upper and lower rollers 41 for carrying the element installed inside the main body 1, as shown in FIG. It is held and carried into the incubation means 3. This roller 41 also has a heat-retaining function that isolates the incubation means 3 from the insertion port 11.

The incubation means 3 has the function of holding the measuring element 2 at a set temperature and conveying it in the circumferential direction, and is rotatably supported by a shaft 32 on a constant temperature plate 31 that is heated and held at a constant temperature. A disk 33 is provided, and a heat-retaining cover 34 is provided above the disk 33 so as to surround it with a gap therebetween.

This disk 33 has element holding portions 331 consisting of fitting grooves (formed in the radial direction and open at the outer peripheral portion) at equal angular intervals on the peripheral edge thereof.
An airtight lid 332 is engaged with an opening 331a on the top surface of the housing.

The lid 332 has a truncated conical shape as shown in FIG. 5, and has a plurality of elastic pieces 332a bent upward at the flange on the opening side. And this elastic piece 332
a is the recess 3 on the inner periphery of the opening 331a of the element holding part 331.
31a (see FIG. 6(a)), it is attached to the element holding portion 331.

Therefore, when the measuring element 2 is pushed into the element holding part 331, a part of the periphery of the element 2 slides under the slope of the side surface of the lid 322, as shown in FIG. 6(a). In this state, the lid 332 is pushed upward and the elastic piece 332a is compressed.

Therefore, the measuring element 2 set in the element holding part 331 is in the state shown in FIGS. 6(b) and 6(c), and the lid 33
Due to the elastic force of the second elastic piece 332a, the bottom surface is strongly pressed against the constant temperature plate 31, and the through hole 22a is inserted into the lid 33.
2 is completely closed.

As a result, the film 23 of the measuring element 2 is kept airtight from the outside, and the reagent impregnated into the film 23 is prevented from evaporating.

On the other hand, when the surface layer element 2 is set in one element holding part 331 of the disc 33, the next adjacent element holding part 33
1 rotates to a position corresponding to the insertion opening 11, and the next measuring element 2 can be inserted.

In this embodiment, the drive means for the disk 33 is radially arranged so as to partition the element holding portion 331 at the peripheral edge of the disk 33. R33'3 is formed. And motor 3
5 is received through the gears 341 and 334 and transmitted to the rotary disk 335, and a pin 336 provided at an eccentric position of the rotary disk 335 is engaged with the groove 333 to rotate the disk 3.
3 is rotated intermittently. 337 is a click mechanism for stabilizing the stopping position of the disk 33.

The measuring element 2 inserted into the element holding part 331 is placed on the thermostatic plate 3
1, the disk 33 is rotated intermittently in the clockwise direction so as to come close to the lower part of the liquid dripping hole 12.

The liquid dripping hole 12 is arranged on the outside of the disk 33, and an element reciprocating means 5 is configured to position the measuring element 2 with respect to the dripping hole 12.

This element reciprocating means 5 has locking pins 51a at the rear end and front part.
, 51b (see FIG. 6(d)),
A lever 52 connected to the moving plate 51, the lever 51
The lever 52 is rotatable around a shaft 54, so that when the solenoid 53 is activated and its piston is attracted, the moving plate 5
1 moves in the direction of arrow a, and the measuring element 2 located on the moving plate 51 is brought directly below the droplet hole 12 (FIGS. 6(d) and (e)), and the solenoid 53 is activated. When it stops, it returns in the direction opposite to the direction of arrow a and returns the measuring element 2 to the original element holding part 331. Note that the moving plate 51 is the constant temperature plate 3.
The measuring element 2 is disposed so as to be movable within a groove 31a formed on the upper surface of the measuring element 2, and the groove 31a has a width that does not hinder the movement of the measuring element 2.

6 is a photometry section, and a light source 61 consisting of a halogen lamp, etc.
, a switchable filter 62 , a light receiving element 63 that detects the light emitted from the light source 61 and reflected by the film 23 of the measuring element 2 , and a lens 64 that focuses the reflected light on the light receiving element 63 . The information obtained by the light receiving element 63 is sent to a concentration measuring device (not shown), where the optical concentration is detected and biochemical analysis of the liquid is performed.

Reference numeral 7 denotes a discharge section, which is composed of a discharge plate 71, a lever 72 connected to the discharge plate 71, and a solenoid 73 that drives the lever 72. The lever 72 is rotatable about a shaft 74, and thus By driving the solenoid 73, the discharge plate 71 moves in the direction of the arrow, and the measuring element 2 is discharged to the outside from the discharge port 14. Note that a curtain 42 for heat retention is provided at the back of the discharge port 14.

Now, when measuring, power switch 15 of main body 1
Turn on. As a result, if any measurement elements remain in the disk 33, they are ejected, and then the disk 33 is set at its original reference position.

Next, press the mode setting button 16 to select the measurement mode.
This is done by Here, either or both of the modes of the end point method and the rate point method can be selected. The end point method is a mode in which a liquid sample is dropped and colorimetric measurement is performed after a certain period of time has elapsed.When this mode is selected, the filter 62 of the photometry section 6 is switched to a predetermined spectral filter, and the rate point method This mode measures concentration changes over time, and the selected filter 62 is switched to another spectral filter.

Next, the numeric keys 17 are operated to input the sample number. Inputting this sample number is necessary for distinguishing between multiple people who have collected the sample.

After the above preparatory work, the measuring element 2 whose film 23 is pre-impregnated with a reagent is inserted through the element insertion opening 11. As a result, the first measuring element is placed in the element holding portion 3 of the disk 33.
When inserted and held in 31, it becomes a sensor (not shown).
Since the disk 33 is moved one pitch clockwise, the measuring elements are inserted one after another.

The disk 33 rotates clockwise each time an element is inserted, and is preheated when all measurement elements have been inserted.

After this preheating, a specific measuring element approaches the vicinity of the dropping hole 12 and is positioned directly below the dropping hole 12 by the element reciprocating means 5. Here, the sample number located directly below the dripping hole 12 is displayed on the display 18, so after checking this display, collect the necessary liquid sample to be measured with the pipette P, and then 12 into the through hole 22a of the measuring element 2 (Fig. 6(d), +
See 111). ).

After this, when the dropping end button 13 is pressed, the moving plate 51 of the element reciprocating means 5 returns to its original position, and the measuring element 2 is returned to the element holding part 331 of the disk 33.

In this way, when the dropping end button 13 is pressed again after dropping the liquid sample to all the measurement elements in each element holding part 331 is completed, the timer is activated and incubation is performed, and the reaction between the reaction reagent and the liquid sample is started. is promoted.

When the timer time has elapsed, each of the measuring elements 2 is sequentially conveyed to the measuring section 6, where photometry is performed, and the results are displayed on the display 18 and printed on the printing section 19. It will be printed out on a recording sheet along with the sample number.

When photometry has been completed for all the measuring elements set in this manner, the measuring elements are transported to a position where the element ejecting means 7 is provided, where they are sequentially ejected to the outside through the ejecting port 14.

When one analysis operation is completed in this way, the disk 33 is moved and set at the reference position for the second analysis operation. The above process is shown in a flow chart in FIG.

The above steps are as follows: Insertion of measuring element (all at once) - Pre-incubation (all at once) - Dropping of liquid sample by once removing measuring element (all at once) -> Incubation (all at once) - Photometry (
Biochemical analysis is performed in the process of batch) - discharge (collectively), and as mentioned above, in this embodiment, the measurement element 2 is held in the element holding part 331 of the disk 33, and the measurement element 2 is held in the film 23 of the element. The structure is such that the permeating liquid (reaction reagent and liquid sample) is difficult to evaporate.

As mentioned above, this is because M2B5 is the through hole 2 of the measuring element 2.
2a to close it, and as a result, compared to traditional lidless incubation,
As shown in FIG. 8, the color density changes greatly in a short period of time, making it possible to shorten the analysis processing time.

FIG. 9 is a timing chart of analysis using the endpoint method. The horizontal axis is time, and the vertical axis is the number of the measuring element. This example shows the liquid sample dropping timing (indicated by "-").

) for a maximum of 30 seconds (in other words, it is possible to drop a drop at a certain time within that 30 seconds), and the time from the drop to photometry 1. This is for the case where the time is 6 minutes and 30 seconds and the photometry timing (indicated by "-") is 30 seconds at maximum. Therefore, since it takes 6 minutes and 30 seconds from dropping the liquid sample to the first measuring element until photometry, it becomes possible to drop the liquid sample to 13 more measuring elements during this time.

Then, the time t2 until the photometry of all 14 measurement elements is completed becomes the drop-disabled time. This time is 30 seconds x 14 pieces, which is 7 minutes. Moreover, once photometry is completed, it is possible to continue dropping onto another measuring element. In the end, the plurality of measurement elements set in the analyzer can be set to 14 in one group, and dropping and photometry can be performed for each group.

FIG. 10 is a timing chart of analysis using the late point method. This example also shows the timing of dropping the liquid sample (
-” indicates. ) for a maximum of 30 seconds, the time t from the drop to the first photometry is 1 minute 30 seconds, the time from the first photometry to the second photometry is also tl, and the timing of photometry (indicated by "-") is also the maximum. This is about the case where the time is 30 seconds. Therefore, after dropping the liquid sample onto the first measuring element, it takes 1
Since the time is 30 minutes, it is possible to drop three more liquid samples onto the measurement samples during this time. Then, the drop-disabled time t2 is the first and second photometry time that are successively performed, and is 4 minutes. Moreover, when the second photometry is completed, it is possible to continue dropping onto a new measurement element. In the end, it is possible to set a plurality of measurement elements set in the analyzer to four in one group, and perform the dropping and first and second photometry for each group.

FIG. 11 is a timing chart of a mixed mode in which the end point method, which requires a relatively long time, and the late point method, which requires a short amount of time, are mixed and implemented. Here, the timing of dropping the liquid sample is set to a maximum of 15 seconds, and the timing of photometry is also set to a maximum of 15 seconds.The time from droplet dropping to photometry using the end point method is 6 minutes 45 seconds, and the time from dropping the droplet to photometry using the late point method. It is set as 1 minute 45 seconds.

Therefore, when a droplet is first applied using the end point method, it takes 6 minutes and 45 seconds to measure the light of the first element, and during this time the droplet is added and the first and second photometry using the late point method are performed. Taking this into consideration, it becomes possible to drop drops of 11 new elements, and the 6 elements after placement can be used for the late point method. Therefore, the first and second photometry of the six elements using the late point method can be completed before photometry using the end point method is started. From the above, in this mixed mode, among the multiple measurement elements set, 6 for the end point method,
A total of 12 items, 6 for the late point method, are treated as one group, and processing can be performed for each group. If you perform processing using the late point method, which takes a short time, while processing continues using the end point method, which requires a long time,
Becomes very efficient.

Note that the lid 332 described in the above embodiments is
As shown in FIG. 2(a), the elastic piece 332b may be shaped to protrude in the opposite direction, or as shown in FIG. 2(b), a cylindrical elastic rubber 33 may be provided inside the lid 332. , this elastic rubber 332c can also be replaced with a compression spring of similar diameter.

Furthermore, (as shown in C1, another bent ring-shaped leaf spring 332h may be mounted on the flange of the lid 332, and as shown in (d), the opening may be closed by a cover 332d. It may be placed on top of the measuring element 2 due to its own weight, and the bottom portion may be curved outward in a convex shape as shown in (e) to more completely seal the through hole 22a of the measuring element 2. Furthermore, as shown in (f), a recess 332f may be formed at the bottom to increase the space in the closed portion of the measuring element 2, so that sufficient oxygen for reaction can be supplied. This is also possible by forming a ring-shaped collar 332g on the bottom as shown in tg>.

Furthermore, the means for transferring the measuring element 2 is not limited to one using the disk 33, but may also be a transfer means using a pusher as shown in FIG. 13, or a transfer means using a Lenless belt as shown in FIG. It is also possible to use

In FIG. 13, 80 is a rectangular outer frame, and 81 is the outer frame 8.
This shoe 81 has a fitting groove 109 for the measuring element 2, and a lid 119 fits on the top surface. A photometric window (not shown) is formed on the bottom surface. 83
- 86 are buttons that press the shoes 81 against the four corners of the outer frame 80 in the advancing direction. This bushsha 83-86
When the shoe 81 is in the state shown, that is, the shoe 81 is in the state shown in the figure.
If there is a space 82 immediately in front of 3, the button 84 is activated to push out the shoe 81 immediately in front of it, then the button 85 is activated, and the buttons 86 and 83 are activated to change the order of operations. Thereby, the shoe 81 circulates within the outer frame 80 as shown by the arrow. Therefore, during the circulation, the insertion part 107 of the measuring element 2,
Reciprocating means installation section 150 for dropping liquid sample, photometry section 15
3 and the discharge section 134, the same operation as shown in the above embodiment becomes possible.

On the other hand, in FIG. 14, 90 is an elongated outer frame, 91 is an endless belt extending between shafts 92 and 93, and 94 is supported at one point on the lendless belt 91 and has a measuring element fitting groove 109. It's a shoe. In this example, the shoes 94. can be moved in the direction of the arrow, and as in the example shown in FIG.
Reciprocating means installation section 150 for dropping liquid sample, photometry section 15
3 and the discharge section 134, it becomes possible to operate in the same manner as in the above embodiment.

〔Effect of the invention〕

As described above, according to the present invention, the measuring elements are set in the incubation means all at once, and the droplet dropping and photometry are performed all at once, which improves the processing efficiency. Since the measurement is carried out by reciprocating to the position, there is no need to provide an opening for dripping the liquid in the incubation means, which prevents the liquid from evaporating inside the measuring element and keeps the amount of water constant. This enables highly accurate measurements. Furthermore, if a step is provided in the incubation means to close the opening of the measuring element, liquid evaporation can be more effectively prevented.

[Brief explanation of drawings]

FIG. 1 is a diagram showing the appearance of an analysis device according to an embodiment of the present invention;
Fig. 2 is an exploded perspective view of the measuring element used in this example, Fig. 3 is a plan view showing the disk as a transport means in the analyzer and its vicinity, and Fig. 4 is taken along the line IV-IV in Fig. 3. Figure 5 is a diagram showing the lid that makes the measuring element airtight, Figure 6 (al to (e) is an explanatory diagram of the process of setting the measuring element and dropping the liquid, and Figure 7 is the overall view. Flowchart of the process, Fig. 8 is a color development characteristic diagram with and without a lid, Fig. 9 is a timing chart of the end point method, Fig. 10
The figure is a timing chart of the late point method, FIG. 11 is a timing chart of a mixed mode of end point method and late point method, FIG. 12 (a) to (gl is an explanatory diagram of another embodiment of the lid, and FIG. 13 is and Fig. 14 are diagrams showing another embodiment of the means for transporting the measuring element. 1...Biochemical analyzer, 2... Measuring element, 3...
Incubation means, 332... Lid, 5... Element reciprocating means, 6... Photometry section, 7... Element ejection means. Figure 3 Ω Pulse Figure 4 Figure 5 332a 332

Claims (2)

[Claims] (1) In a biochemical analysis method in which a liquid to be analyzed is dropped from an opening into a measuring element impregnated with a reagent to measure the characteristics of the liquid, a first method in which a plurality of measuring elements are set in an incubation means. a second step of pre-incubating the plurality of set measuring elements, and individually moving each of the pre-incubated measuring elements from the incubation means to a liquid sample dropping position to drop the liquid sample. A biochemistry method characterized by having a third step of setting the measuring element in its original position, a fourth step of incubating each measuring element onto which a liquid has been dropped, and a fifth step of photometrically measuring each of the incubated measuring elements. Analysis method. (2) The biochemical analysis method according to claim 1, wherein the incubation means includes means for closing an opening of the measurement element.