JPH0331750A - Chemical analysis - Google Patents

Abstract

PURPOSE:To extremely efficiently make chemical analysis while letting off a long-sized tape-like base which is wound and held by measuring and spotting a reagent and liquid to be inspected onto the base and measuring the optical concn. by the coloration reaction thereof. CONSTITUTION:The unused part of the long-sized tape-like base 3 is wound in a base supplying cassette 18 and the used part in a base take-up cassette 19, respectively. The reagent sucked from a reagent housing means 100 and the liquid to be inspected are measured and spotted by a suction spotting means 5 having a nozzle 7 for suction spotting to a part of the base 3 drawn out of the cassette 18 by motor driving. While the spotted and developed base part is kept at a constant temp. in the specified time in an incubator 55, the coloration reaction of the reagent and the liquid to be inspected is effected. The base 3 is irradiated with the light which is emitted from a photoirradiating means 57a and contains a preliminarily selected wavelength in a photometric section 57 after the end. The reflected light thereof is detected by a photodetecting device 57b and the optical concn. is measured.

Description

Detailed Description of the Invention (Industrial Field of Application) The present invention relates to a method for chemically analyzing a specific component in a test liquid, and more particularly, the present invention relates to a method for chemically analyzing a specific component in a test liquid. The present invention relates to a chemical analysis method in which a color reaction is caused and the optical density of the color reaction area is measured.

(Prior Art) Qualitative or quantitative analysis of specific chemical components in a test liquid 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, dry-type chemical analysis slides have been developed that can quantitatively analyze specific chemical components or formed components contained in a liquid to be tested by simply applying small droplets of the liquid to be tested. No.-21877, JP-A-55-1643
No. 56, etc.) has been put into practical use. These chemical analysis slides can be used to analyze sample liquids more easily and quickly than traditional wet analysis methods, so these chemical analysis slides are suitable for medical institutions that need to analyze a large number of test liquids,
It is becoming particularly suitable for use in research institutes and the like.

In order to quantitatively analyze the chemical components in a test liquid using such a chemical analysis slide, the test liquid is placed on the chemical analysis slide in a measured amount, and then placed in an incubator (
Maintain constant temperature (incubation) for a specified period of time in a constant temperature machine
A color reaction (pigment formation reaction) is then carried out, and then measurement irradiation light containing a wavelength pre-selected by the combination of the components in the test liquid and the reagents contained in the reagent layer of the chemical analysis slide is applied to this chemical analysis. The slide is irradiated and its reflected optical density is determined by a-1.

In this case, in the above-mentioned medical institutions, laboratories, etc., it is generally necessary to analyze a large number of test liquids, and therefore it is desirable to be able to perform this analysis automatically and continuously. Therefore, various proposals have been made regarding chemical analyzers that can automatically and continuously analyze test liquids using the chemical analysis slides described above (for example, Japanese Patent Laid-Open No. 77748/1983). In addition, in order to automatically and continuously analyze the test liquid, a long tape-shaped test film containing a reagent is stored in place of the slide described above, and this test film is pulled out one after another to analyze the test liquid. Apparatus for spotting, incubating, and measuring have also been proposed (e.g., U.S. Pat. No. 3.5).
26.480). In this way, a device that uses a long tape-shaped test film can reduce running costs compared to a device that uses chemical analysis slides.
Furthermore, the simple mechanism allows measurements of a large number of liquids to be tested to be carried out in succession.

(Problem to be solved by the invention) On the other hand, when using the above-mentioned long test film,
In order to prevent the film from deteriorating due to temperature and humidity, it is necessary to provide a low-temperature, low-humidity film storage section, and there is a risk that this film storage section and a relatively high-temperature incubator are adjacent to each other, causing thermal effects on each other. Rationality arises. Naturally, this will lead to an increase in the energy consumption of the analyzer.

In addition, in the above-mentioned analyzer, it is necessary to accommodate as many long test films as the number of analysis items. Therefore, increasing the number of analysis items will increase the size of the device, and avoiding the increase in the size of the device will limit the number of analysis items. There is a problem that it becomes difficult.

Furthermore, even if a long test film containing reagents is stored in a low-temperature, low-humidity storage section as described above, if it is not used for a long time, the tip of the test film near the film drawer opening of this storage section deterioration is inevitable.

Therefore, in such a case, the leading end of the film must be discarded instead of being used, leading to a problem in that the film is wasted and the running cost of the apparatus increases.

Therefore, the present invention can solve the various problems mentioned above, and in the same way as when using the above long test film,
The object of the present invention is to provide a method that allows chemical analysis of a test liquid to be carried out extremely simply.

(Means and effects for solving the problem) The chemical analysis method according to the present invention involves winding and holding a long tape-like support, and exposing a part of the support with a reagent when pulled out from the wound portion. A measured amount of the test solution is spotted, and the part of the support where this spot is applied is kept at a constant temperature to cause a color reaction between the reagent and the test solution.After that, the above-mentioned long test film or chemical analysis slide is In the same way as when using a test liquid, the part of the support where the color reaction has occurred is irradiated with light containing a predetermined wavelength, and the optical density of the part is measured to quantitatively analyze the specific component in the test liquid. This is what I did.

Since the long tape-shaped support described above does not contain a reagent in advance, it is not necessary to store it in a particularly low temperature and low humidity atmosphere. Therefore, when carrying out this method, the incubator and the low-temperature, low-humidity storage section are not adjacent to each other, unlike when using the long test film described above.

Since such a long tape-like support does not suffer from deterioration due to temperature and humidity, its entire length can be effectively utilized.

In addition, in this method, it is possible to analyze multiple different items by selecting reagents, and the long tape-shaped support can be used in common even if the analysis items are different, so the device becomes larger to enable multi-item analysis. It can also be avoided.

(Embodiments) Hereinafter, embodiments of the present invention will be described in detail with reference to the drawings.

FIG. 1 shows an example of a biochemical analyzer for carrying out the method of the present invention. This biochemical analyzer 1 is equipped with a transparent lid 2, and when the lid 2 is opened, the test liquid described below, a long tape-shaped support 3, etc. are accommodated in the device 1, and It is designed to be taken out. This device 1 includes a sample cup 1 containing a test liquid such as serum or urine.
01, and a rotating disk section 102 that accommodates reagent cups 101A arranged on the circumference, and a centrifugal separation cup 103 disposed inside this rotating disk section 102 that holds whole blood or the like. Centrifugal separation unit 1 that performs centrifugation
04 is provided, and the reagent and the test liquid stored therein are taken out by a suction spotting means 5, which will be described later, and spotted on the support 3.

The reagent cup 10IA stores reagents that exhibit a color reaction with only the specific chemical components or formed components that are to be measured in the test liquid, and can accommodate multiple types of reagents corresponding to the n1 standard items. Cup 10IA is prepared. Specifically, the following reagents are used, for example.

For measuring blood glucose level from whole blood〉 A mixture of glucose oxidase, 1,7-hydroxynaphthalene, and 4-aminoantipyrine derivative For measuring blood urea nitrogen from serum or plasma〉 A mixture of urease and bromcresol green For measuring blood creatinine from serum or plasma〉 Mixture of creatinine deiminase and bromphenol blue For measuring blood uric acid from serum or plasma〉 Mixture of uricase and diallylimidazole leuco dye Blood ammonia from plasma For measurement〉 Bromophenol blue for measuring total blood cholesterol from serum or plasma〉 A mixture of cholesterol oxidase and diallylimidazole leuco dye.As the support 3, PET (polyethylene terephthalate), TAC (triacetyl cellulose), etc. Preferably, a base is formed with a spreading layer made of a porous material that is highly effective in uniformly dispersing liquid, such as cloth or felt. In addition, between the above base and the developing layer, if necessary, a film with a reflection optical density of 1lF, which will be described later, is provided.
A reflective layer or the like may be provided to improve J-determining accuracy.

This unused portion of the support 3 is stored in the support supply cassette t.
The part used for the above measurement is wound up in the support winding cassette 19. In addition, in the central part of the rolls 18a, 19a in these cassettes 18, 19 there are provided for pulling out the support 3 from the supply cassette 18 and for winding it there after the support 3 has been accommodated in the device 1. Hole 18bS that engages with the rotating shaft of the motor
19b is provided. Support 3 is cassette I8.1
9 is housed in the device 1. The supply cassette 18 and the take-up cassette 19 are separated as shown in FIG. Further, in this embodiment, in particular, the support housing means 6 is configured to be able to accommodate unused portions of a plurality of supports 3 in parallel so that a plurality of items can be measured at the same time.

The suction spotting means 5 has a suction spotting nozzle 7 at its tip, is moved along the rail 8 by a moving means 9 placed on the rail 8, and collects the test liquid from the test liquid and reagent storage device 100. The reagents are aspirated and spotted on the support 3 pulled out from the support storage means 6 as described below. The moving means 9 is also configured to move the suction spotting means 5 in the vertical direction, and when the suction spotting means 5 is moved along the rail 8 by the moving means 9, the suction spotting means 5 is moved vertically. 5 is in an elevated position, and is lowered during suction and spotting of the test liquid and reagent, and during cleaning to be described later.

Support storage means 6 and test liquid and reagent storage device +00
A nozzle cleaning section 10 is arranged between and close to both. After the suction spotting nozzle 7 spots the test liquid or reagent on the support 3, it is cleaned in the cleaning section 10 and is reused for the next spotting.

The support 3 on which the reagent and test liquid are spotted is incubated in an incubator as described later, and then the optical density of the support 3 is measured by means 411.

Control of the overall operation of the device 1, processing of measurement data, etc. are performed by a circuit section 11 and a computer 12 connected to this circuit section 11.
This is done by The operation/display section 13 provided on the front side of the circuit section 11 is equipped with a power switch for the device 1, an ammeter for monitoring the current consumption in the device 1, and the like. The computer 12 is a device! A keyboard that gives instructions for ¥1! 4. A CRT display 15 that displays auxiliary information for instructions, measurement results, etc., a printer 16 that prints out measurement results, and stores instructions, measurement data, etc. for giving various instructions to the device 1. Floppy disk drive device 1 that drives a floppy disk for
It consists of 7 mag.

Next, the outline of this storage device 100 will be explained with reference to FIG. 2 showing the shape of the back surface of the peripheral part of the test liquid and reagent storage device +00. The support housing means 6 is configured such that the spotting positions 22 of all the supports pulled out from therein are aligned on a straight line, and furthermore, the nozzle cleaning section IO1 and the diagonal lines in the housing device 100 are arranged on this straight line. Three liquid suction positions P shown in are arranged.

This storage device 100 includes a sample cup 1.01 containing a test liquid and a reagent cup 101A containing a reagent.
It has a rotating disk part 102 that holds the discs arranged side by side on two concentric circumferences. The rotating disk portion 102 is rotated by a drive system (not shown) by a predetermined angle in the direction of arrow A, and the reagent cup 101A on the outer periphery or the sample cup +01 on the inner periphery is sequentially positioned at the suction position P. In addition, in the storage device 100, the rotating disk portion +02
The centrifugal separator 104 disposed inside the centrifugal separator 104 is capable of holding, for example, four centrifugal cups 103 on the 222 circumferentially concentric part III l;i, and can rotate at high speed. The body fluid (for example, whole blood) in the centrifugal cup 103 is separated by centrifugation. More centrifuge section! 04
After centrifugation ends, the centrifugal separation cup 103 is sequentially positioned at the suction position P by being rotated by a predetermined angle in the same way as the rotary disk unit 102. That is, whole blood is centrifuged 5
)ilif, plasma or serum floats to the top and blood clots sink to r.However, according to the present storage device 100, the plasma or serum, which is the test liquid, does not have to be separated from the blood clots and transferred to another container. It can be taken out by the suction spotting means 5).

The suction spotting means 5 is moved along the rail 8 by the moving means 9 mounted on the rail 8J-, sucks the reagent and the test liquid from the suction position P, and transfers it to the spotting position 22 on the support 31-.
Weigh and spot.

FIG. 3 shows a main part of a cross section taken along the line xx' in FIG. 2, and the analysis of the test liquid will be explained below with reference to FIG. The support body 3 is loaded into the apparatus while being accommodated in the supply cassette 18 and the winding cassette 19. The supply cassette 18 is housed in a supply chamber 50, and the -J film winding cassette 19 is housed in a winding chamber 51. In this way, the unused portion of the support 3 is supplied to the cassette 1.
8, the unused supports 3 can be stored in the supply chamber 50 without touching them.

Supply cassette 18 and take-up cassette 19 as described above.
is housed in the supply chamber 50 and the winding chamber 51, respectively, the rotation shaft of the winding motor 53A provided in the winding chamber 51 engages with the hole 19b of the reel 19a of the winding cassette 19. By the rotation of this motor 53A, the support body 3
is pulled out from the supply cassette 18 via the outlet 50b of the supply chamber 50 and wound into the winding cassette 19. On the other hand, a rotation shaft of a motor 53B for winding and storing the support 3 is engaged with a hole 18b provided in the center of the supply cassette 18, 8a.

An incubator 55 is disposed in the exposed portion of the support 3 between the supply cassette 18 and the winding cassette 19, and is capable of holding the support 3 therein and allowing it to pass therethrough one after another. A photometry section 57 is arranged to measure the optical density resulting from a color reaction between the reagent spotted on the support 3 and the test liquid.

The support body 3 is intermittently sent to the left in the figure by the rotation of the motor 53A. When the support body 3 is sent, the upper part 1f55a of the incubator 55 rises in the direction of arrow B. When the support body 3 stops, the upper lid 55a descends in the direction of arrow C to suppress and fix the support body 3.

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 7 descends, passing through the nozzle insertion hole 55a and depositing the reagent and the test liquid onto the support 3. are given sequentially.

After that, the shutter 54 moves leftward to close the nozzle insertion hole 55b, preventing air from entering and exiting between the inside and outside of the incubator 55, and maintaining the inside of the incubator at a predetermined temperature (for example, 37° C.). The part of the support (the shaded part in FIG. 3) on which the reagent and test liquid are spotted and developed is kept in the incubator 55 for a predetermined time (
- for example 4 minutes). After or during the incubation, the optical density of the spot-applied portion of the support 3 is measured by the photometer 57. This concentration measurement is performed by irradiating the support 3 with light including a preselected wavelength emitted from the light irradiation means 57a, and detecting the reflected light from the support 3 by the photodetector W57b.

In this way, when reagent spotting, test liquid spotting, incubation, and LiF2 determination are completed for one analysis item,
It becomes possible to apply the next reagent and test liquid. Support 3
is transferred so that the part to be used for the next analysis is at the spotting position 22 immediately before spotting for the next analysis is performed.

Note that the above reagents may be stored in a low temperature and low humidity place, for example, in a reagent cup 10IA, and may be appropriately selected and set in the storage device 100 when used. Further, the reagent cup 101A may be housed in a storage means that is completely different from the storage means for the test liquid, and furthermore, the reagent cup 101A may be housed in a storage means that is completely different from the storage means for the test liquid. may be used.

As explained above, in this method, various items can be analyzed depending on the selection of reagents used.

Therefore, basically, only one support 3 can be used for multi-item analysis. However, in order to increase the analysis throughput, it is preferable to arrange a plurality of supports 3 as in this embodiment. In other words, by providing a plurality of supports 3, it becomes possible to perform analyzes on a plurality of test liquids and/or a plurality of items in parallel.

Furthermore, the arrangement interval between the supply cassette 18 and the winding cassette 19 is made larger, and the support body 3 is placed between them.
so that it is stretched longer, and the supporting body 3 of this part
By providing a plurality of incubators 55 and photometering sections 57 along the length of the support 3, it is also possible to perform analyzes of a number of test liquids and/or a plurality of items in parallel on one support 3. .

(Effects of the Invention) As explained in detail above, in the chemical analysis method of the present invention, a reagent and a test liquid are metered and spotted on a long tape-shaped support held in a rolled manner, and the color reaction occurs. Since the optical density is fixed at Al1, chemical analysis can be carried out extremely efficiently while sequentially unwinding the supports.

Moreover, in the method of the present invention, there is no need to place a relatively high-temperature incubator and a low-temperature, low-humidity test film storage section adjacent to each other, which prevents them from exerting a thermal influence on each other and increasing energy consumption. It can be prevented. Further, since the support used in the method of the present invention does not contain a reagent in advance, there is no risk of deterioration, and therefore, its entire length can be effectively utilized, and the running cost of the analyzer can be kept low.

Furthermore, since the above-mentioned support can be used in common for multiple analysis items, in the apparatus for carrying out this method, the size of the apparatus may be increased to increase the number of analysis items, or
On the other hand, the number of analysis items is not limited due to the miniaturization of the device.

[Brief explanation of drawings]

FIG. 1 is a perspective view showing an example of a biochemical analyzer for carrying out the method of the present invention, FIG. 2 is a plan view of essential parts of the biochemical analyzer, and FIG. 3 is a line xx' in FIG. 2. FIG. DESCRIPTION OF SYMBOLS 1...Biochemical analyzer 3...Support 5...Suction spotting means 6...Support accommodation means 7...Suction spotting nozzle 9...Moving means 18...Support Supply cassette 19... Support winding cassette 22... Front position 55... Incubator 57... Photometry section 100... Test liquid and reagent storage device 101...
Sample cup 10IA... Reagent cup +03...
・Centrifugal separation cup 104...Centrifugal separation section P...
liquid suction position

Claims (1)

[Claims] A long tape-shaped support is wound and held, and a reagent and a test liquid are metered and spotted on a part of this support pulled out from the wound part, and this spotting is carried out. The reagent and the test liquid are caused to undergo a color reaction while the part of the support is kept at a constant temperature, and then the part of the support where the color reaction has occurred is irradiated with light containing a predetermined wavelength. A chemical analysis method comprising quantitatively analyzing a specific component in the test liquid by measuring optical density.