JPH01169361A - Biochemical analysis - Google Patents

Abstract

PURPOSE:To achieve an accurate analysis, by varying the amount of a test film withdrawn from a cold reserving storage for subsequent spotting according to conditions after the end of measurement in a biochemical analysis method using a long-sized test film. CONSTITUTION:A liquid to be inspected is spotted on a long-sized test film 3 with a spotting nozzle 7 being transferred to a film winding cassette 19 from a film supply cassette 18 to perform an incubation with an incubator 55 and the degree of coloration is measured with a photometry section 57. When a standby time to the subsequent analysis is prolonged, to counter deterioration caused in the test film 3 left outside a cold reserving storage 50, a feed of the test film 3 for the subsequent analysis is increased according to conditions such as elapsed time after one analysis so that a portion deteriorated of the film is not used. This always enables accurate analysis with a test film not deteriorated.

Description

Detailed Description of the Invention (Industrial Application Field) The present invention involves spotting a test liquid onto a long test film having one or more reagent layers, maintaining the temperature at a constant temperature (incubation) for a predetermined period of time, and It relates to a biochemical analysis method that measures the degree of coloration (degree of pigment formation) due to the reaction between a reagent and a test liquid during or after the process, and in particular, it is a biochemical analysis method that allows accurate measurements at all times. It is about the method.

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

In recent years, dry type chemical analysis slides have been developed that can quantitatively analyze specific chemical components or formed components contained in a test liquid by simply applying small droplets of the test liquid ( Special Publication No. 53-21677, Japanese Patent Publication No. 55
-164356, etc.) has been put into practical use. Using these chemical analysis slides, it is possible to analyze sample liquids more easily and quickly than conventional wet analysis methods, so they are especially useful for medical institutions that need to analyze a large number of test liquids. This is preferable in research institutes, etc.

In order to 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 for a predetermined period of time. It is kept at constant temperature (incubation) to cause a color reaction (pigment formation reaction), and then a measurement irradiation light containing a wavelength selected in advance by the combination of the components in the test liquid and the reagent contained in the reagent layer of the chemical analysis slide is applied. The chemical analysis slide is irradiated with light and its reflected optical density is measured, thereby performing a quantitative analysis of the chemical components, etc.

In this case, in the above-mentioned analysis at the medical institution, research institute, etc., it is necessary to analyze a large number of test liquids, and it is desirable to be able to perform this analysis automatically and continuously. For this reason, various proposals have been made regarding chemical analyzers that can automatically and continuously analyze test liquids using the above-mentioned chemical analysis slides (for example, Japanese Patent Laid-Open No. 56-77748 issue). In addition, as a means of automatically and continuously analyzing the test 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 by one. spotting, incubation,
Apparatus for making measurements have also been proposed (eg, US Pat. No. 3,526,480). 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, and also has a simple mechanism that allows it to measure a large number of test liquids in succession. It can be done.

(Problems to be Solved by the Invention) By the way, a long test film is wound around a supply reel and loaded into an apparatus, but this film is affected by temperature or humidity, and its chemical properties may vary. Therefore, in order to prevent deterioration even after a long time has passed after being loaded into the equipment, a cold storage kept at low temperature and low humidity is installed inside the equipment, and long test tubes are stored in this cold storage. A biochemical analyzer loaded with film has been proposed by the applicant of the present invention. In this biochemical analyzer, when conducting an analysis, a long test film is pulled out from a cold storage to a predetermined spotting position by a test film conveying means, a test liquid is spotted, and then incubation and measurement are performed. . Therefore, when a plurality of test liquids are continuously analyzed using this film, the film is sequentially pulled out by the length necessary for one analysis immediately before each test liquid is spotted.

However, when multiple test liquids are analyzed while feeding a long test film as described above, the film exit from the cold storage box is a certain distance from the spotting position, so the film cannot be used for the next analysis. A portion of the film will come out of the cooler, and this portion of the film will no longer be kept in a low temperature, low humidity environment like the film stored inside the cooler. Therefore, if the analysis is interrupted and the time elapses until the next test liquid is spotted, the part of the film outside the cold storage and the surrounding parts will deteriorate, making it difficult to perform accurate nj determination. The problem is that it becomes impossible to do so.

The present invention has been made in view of the above-mentioned problems, and is intended to ensure accurate measurement at all times even when the time interval between analyzes becomes long when performing analysis using a biochemical analyzer using the long test film described above. The purpose of this invention is to provide a biochemical analysis method that can be performed.

(Means for Solving the Problems) The biochemical analysis method of the present invention adjusts the amount of the long test film pulled out from the cold storage and placed at the spotting position according to the conditions after the previous measurement. This feature is characterized in that it can be changed by

Note that the conditions after measurement are various conditions related to film deterioration, and include temperature, humidity, film type, etc. in addition to the elapsed time after measurement, and these conditions may be changed as necessary. The above conditions may be set by combining appropriate conditions from among them.

(Effect) According to this method, if a long time has passed since the previous measurement, etc.
If deterioration of the part of the film to be used for the next analysis was expected, we increased the feed rate of the long test film so that the deteriorated part would not be used for the next analysis, so we could always use a film with the specified characteristics. It is possible to perform accurate C1 determination using

(Example) Hereinafter, an example of the present invention will be described with reference to the drawings.

FIG. 1 is a perspective view of an apparatus for implementing the biochemical analysis method of the present invention.

The illustrated biochemical analyzer 1 is equipped with a transparent lid 2, and when the lid 2 is opened, the test liquid described below, a long test film 3 in the form of a long tape, etc. are inserted into the device 1. It is adapted to contain and retrieve. This device 1 includes
For example, a test liquid storage means 4 is provided for storing test liquids such as serum and urine in a circular arrangement, and the test liquid stored here is taken out by a spotting means 5 as described later. It will be spotted. The long test film 3 is made of multiple types of long films corresponding to measurement items, such as containing a reagent that exhibits a color reaction with only the specific chemical component or tangible component to be measured in the test liquid. Test film 3 is prepared. The unused portion of the long test film 3 is wound in a film supply cassette 18, and the portion used for the above measurement is wound in a film winding cassette 19. In addition, in the center of the roll 2° in the film winding cassette 19, a motor for rotating a long test film 3 is placed in the apparatus 1 and then pulled out from the film supply cassette 18, as will be described later. A hole 21 is provided for engaging the shaft. The long test film 3 is stored in the apparatus 1 while being wound around a cassette 18, 19. The film supply cassette 18 and the film take-up cassette 19 are separated as shown in this figure.

The test film storage means 6 is configured to store unused portions of a plurality of long test films 3 side by side so that measurements of a plurality of items can be performed simultaneously using this device 1.

The spotting means 5 has a spotting nozzle 7 at its tip, is moved in the direction in which the rail 8 extends by a moving means 9 placed on the rail 8, takes out the test liquid from the test liquid storage means 4, It is spotted onto the long test film 3 pulled out from the test film storage means 6 as will be described later.

Furthermore, the moving means 9 is configured to move the spotting means 5 in the vertical direction as well, and when the moving means 9 moves the spotting means 5 in the horizontal direction in which the rail 8 extends,
This spotting means is in an elevated position, and is lowered when taking out the test liquid, spotting it, and cleaning as described later.

After spotting on the test film, the spotting nozzle 7 is placed between the test film storage means 6 and the test liquid storage means 4.
It is cleaned by a nozzle cleaning section 10 arranged close to both of them, and is reused for the next spotting.

The spotted test film is incubated in an incubator as described below, and measured by a photometric means.

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 includes a keyboard 14 for giving instructions to the device 1, a CRT display 15 for displaying auxiliary information for instructions, measurement results, etc., a printer 1B for printing out measurement results, and a keyboard 14 for giving various instructions to the device 1. A floppy disk device 17 that accommodates a floppy disk for storing commands, measurement result data, etc.
is provided.

FIG. 2 is a plan view of the main parts of the biochemical analyzer 1 whose perspective view is shown in FIG.

The test film accommodating means 6 is configured such that the spotting positions 22 of all the test films pulled out from therein are arranged in a straight line, and furthermore, the nozzle cleaning section 10 and the test liquid accommodating means are located on this straight line. The test liquid extraction positions 4b in the test liquid take-out positions 4b are arranged in an array.

The test liquid accommodating means 4 is configured to accommodate a plurality of test liquids in a substantially circularly arranged storage section 4a. In addition, this test liquid storage means 4 has a configuration in which a storage portion 4a arranged in a roughly circular shape is rotated.
Among the test liquids stored in the test liquid, the test liquid to be used for the next measurement is automatically rotated by a rotating means (not shown) so that the test liquid to be used for the next measurement is located at the take-out position 4b. In order to prevent deterioration due to evaporation of the test liquid stored in the storage part 4a, the extraction position 4 is
A lid (not shown) is placed over the accommodating portions 4a other than b.

The spotting means 5 is moved in the direction in which the rail extends by a moving means 9 mounted on the rail 8, takes out the liquid to be tested from the take-out position 4b, and spots it on the spotting position 22 on the long test film.

FIG. 3 shows a main part of a cross section taken along line xx' in FIG. 2.

The long test film 3 is placed in a film supply cassette 1.
8 and the film winding cassette 19,
loaded into the device. The film supply cassette 18 is housed in a cold storage 50 whose interior is temperature-controlled at, for example, 4° C., and the film winding cassette 19 is housed in a winding chamber 51. If the unused portion of the long test film 3 is stored in the film supply cassette 18 in this way, the unused long test film 3 can be stored in the cold storage 5o without being touched. The cold storage 50 has a cold storage wall 50a using a heat insulating material.
On one side of this cold storage wall 50a, there is a cold storage 5o.
A cooling/dehumidifying device 58 is attached to keep the inside at a predetermined low temperature and low humidity, and a fan 60 circulates the air inside the cold storage 5o.

When the film winding cassette 19 is housed in the winding chamber 51 as described above, the film inside the film winding cassette 19 is
This winding chamber 51
The rotating shaft of a winding motor 53, which is a conveyance means for the long test film 3 provided in 50b and is taken up into the film winding cassette 19.

If the used part of the long test film 3 is stored in the film winding cassette 19 in this way, the used film that has been spotted with the test liquid and soiled can be removed from the apparatus 1 without touching it. can be disposed of, etc. Regarding this disposal, instead of winding the used film in the film winding cassette 19, the film winding cassette 19 is eliminated and the film can be freely attached to and removed from the device 1 that stores the film in the winding chamber 51. A cutter for cutting the used film is placed near the entrance of the winding chamber 51, and the used film is cut and stored in the box. It may be possible to take out the entire box from the device 1 without touching the film and dispose of the used film. In this case, the transport of the test film is as follows:
This may be carried out by providing conveyance rollers that grip and convey the test film.

Film supply cassette 18 and film winding cassette 19
An incubator 55 is arranged in the exposed part of the long test film 3 in between, and the long test film 3 and the liquid to be tested are placed inside the incubator 55, which can hold the film inside and allow it to pass through it one after another. A 1T11 light section 57 is arranged for measuring optical density due to a color reaction with the 1T11 light section 57.

The long test film 3 is intermittently pulled out from the cold storage 50 by the rotation of the motor 53, and is intermittently fed to the left in the figure, and when the film 3 is fed, the top lid 55a of the incubator 55 moves in the direction of arrow A. rise in the direction. When the long test film 3 is moved, the upper lid 55a descends in the direction of arrow B and pushes the long test film 3. Then top lid 5
The shutter 54 that was blocking the nozzle insertion hole 55b of 5a moves to the right in the figure, and then the nozzle 7 descends as shown in the figure, and the liquid to be tested is deposited onto the long test film 3 through the nozzle insertion hole 55b. It is spotted. Furthermore, the shutter 54 moves leftward to close the nozzle insertion hole 55b, preventing air from entering or leaving the incubator 55, and maintaining the inside of the incubator at a predetermined temperature (for example, 37° C.). The part of the film on which the liquid to be tested has been spotted and developed (the part shown with diagonal lines in FIG. 3) is kept at a constant temperature in the incubator 55 for a predetermined period of time (for example, 4 minutes). After or during the incubation, the i'IPJ optical unit 57 measures the optical density of the portion of the long test film 3 where the spotting has been performed. This concentration measurement is performed by emitting light from the light irradiation means 57a.
This is performed by irradiating the film 3 with light containing a preselected wavelength and detecting the reflected light from the film 3 with the photodetector 57b.

When the spotting, incubation, and 11-time period for one liquid to be tested are completed in this way, the next liquid to be tested can be spotted. The long test film 3 remains in the incubator even after the above-mentioned measurement is completed, so that the part of the film to be used for the next analysis is placed at the spotting position immediately before the spotting for the next analysis. will be transferred to.

By the way, the incubator 55 and the spotting position (nozzle 7) of the long test film 3 when the above-mentioned analysis is completed.
, and the positional relationship with the cold storage 50 as shown in FIG. 4(a). The part 3a of the long test film 3 is the part where the liquid to be tested is spotted and spread and the measurement has been completed, and the part 3b is the part where the liquid to be tested will be spotted and spread as the film 3 is transferred. It is. In this case, the length of the film 3 required for -times of analysis is eliminated. Figure 4 (a
), there is a certain distance between the film drawer position of the cold storage 50 and the spotting position, and part of the film portion 3b to be used for the next analysis comes out of the cold storage 50. In particular, in the above device, since there is a gap 59 between the cold storage box 50 and the incubator 55, it becomes particularly difficult to maintain the portion of the film located within this gap at a desired temperature and humidity state.

If there are a large number of liquids to be tested and these liquids to be tested are to be analyzed continuously, the waiting time for each portion 3b outside the cold storage 50 will be approximately 4 minutes (that is, the time required for incubation). Although there is no practical problem, if the waiting time until the next analysis is long, the film will deteriorate from the portion exposed in the gap 59, making it impossible to perform accurate measurements. If the waiting time becomes even longer, the deterioration will extend to the film portion on the cold storage wall 50a (see FIG. 3). Therefore, in this biochemical analysis method, depending on conditions such as the elapsed time after the end of one analysis, the amount of film feed before spotting for the next analysis is increased to use the deteriorated film part. It is designed not to. The film feed amount can be increased by an arbitrary amount based on various setting conditions. For example, if the length of the film 3 required for one analysis is not sufficient as described above, and the waiting time exceeds a certain set time, the next point will be determined as shown in Figure 4(b). The feed amount of the film before arrival is set to 22 by adding the length allowance to the normal length.

If the feed rate is 2Q, the part where the test liquid will be spotted and spread for the next analysis will be the part shown by 3b'.
The deteriorated film portion is sent to the downstream side of the spotting position and is no longer used, thereby preventing the accuracy of the next analysis from being impaired. Note that the above-mentioned setting time for increasing the feed amount can be determined variously. For example, if analysis is carried out somewhat frequently during the day, the film feed amount may be set to 29 J each time the apparatus is used on -day.

In addition, there are several types of test films for each measurement item in the liquid to be tested, and the degree of deterioration due to the effects of temperature and humidity varies depending on the type, as shown in Table 1 below, for example.

Table 1 Therefore, for example, types of UA, ALB, G with a small degree of deterioration
For films to be measured for GT, GPT, and ALP, the feed rate at the beginning of use is 29J1 for TCH with a large degree of deterioration.
O, TG, BUN, CRE.

In the case of film for which TBIL is to be measured, the feed amount is 39J.
The feed amount may be changed depending on the film. Further, the feed increase amount does not necessarily have to be an integral multiple of the predetermined feed amount, but may be an amount that can at least send the deteriorated portion to the downstream side of the spotting position. In either case, if an operating section is provided and the motor 53 is controlled by an external operation, the feed amount can be increased as necessary.

Additionally, if the frequency of equipment use is irregular and the equipment may be unused for many days, the feed increase may be increased in stages depending on the type of film and the elapsed time (days) since the last analysis. You may change it to Feed amount depending on elapsed time and film type (1
Amount of predetermined feed for analysis ff1L plus increase amount)
- As an example, it is as shown in Table 2 below. In Table 2, the types of test films are represented by their measurement items, and the numerical values in the table are feed amounts when the above-mentioned predetermined feed ff1L, which is unique to each film, is set to 1.

Table 2 If it is desirable to adjust the feed rate of the long test film more precisely, temperature and humidity may be incorporated into the feed rate setting conditions in addition to the elapsed time. The feed ff1L in this case is expressed as follows as an example.

However, in the above formula, T1 is the environmental temperature measured every hour until n hours elapsed after the end of the previous measurement (as an example, the temperature of the gap 59 mentioned above, unit "C"), and Hl is the temperature measured in the same way. K is a constant determined according to the type of test film, INT[] is an integer rounded up to the nearest whole number, 24 is 24 hours, 25 is standard temperature ('C ), 50 is the standard humidity (%).In addition, in the above, CRE, TBLITFI regular film is 2, TCHO, TG, BUN measurement film 4
, G.G.T.

GPT and GOT measurement films are 101UA and ALBn.
It is a regular film and a small film.

In this way, when determining the film feed amount based on temperature and humidity as well as elapsed time, a timer, temperature sensor,
Preferably, a humidity sensor is installed within the device to automatically control the motor based on the output from these means prior to dosing. It goes without saying that the relationship between the elapsed time, temperature, humidity, and feed amount can be determined as appropriate other than the above-mentioned relational expression.

(Effect of the invention) As explained above, according to the biochemical analysis method of the present invention,
If the waiting time for a long test film before spotting the test liquid is long, increase the amount of film feed and move at least the part of the film that was outside the cold storage to the downstream side of the spotting position. Since this part is not used for analysis, it is possible to always perform accurate analysis using a test film that is free from deterioration.

[Brief explanation of the drawing]

Figure 1 is a perspective view of an apparatus for implementing the biochemical analysis method of the present invention, Figure 2 is a plan view of the main parts of the apparatus, and Figure 3 is a cross-sectional view taken along line xx' in Figure 2. A schematic diagram showing the main parts, and FIGS. 4(a) and 4(b) are plan views of a long test film. 3... Long test film 7... Nozzle 50...
・Cold storage 55...Incubator 57
...ill light part 59...gap Fig. 1 Fig. 4

Claims (1)

[Claims] 1) A long test film containing a reagent that reacts with the test liquid to cause a change in optical density is stored in a cold storage, and the long test film is placed at a predetermined spot position from the cold storage. The liquid to be tested is spotted on the long test film at the spotting position, and the spotted portion of the long test film is held at a predetermined temperature for a predetermined time in an incubator. A biochemical analysis method in which the part is irradiated with light and the optical density due to the reaction is measured, and the long test film is pulled out from the cold storage before the next spotting, depending on the conditions after the measurement is completed. A biochemical analysis method characterized in that the amount of withdrawal is varied. 2) The biochemical analysis method according to claim 1, wherein the amount of withdrawal of the long test film is determined by the elapsed time since the previous measurement and the type of film. 3) The first aspect of the present invention is characterized in that the amount of withdrawal of the long test film is determined by the elapsed time since the previous measurement, humidity, temperature, and the type of film.
Biochemical analysis method described in section.