JPH0348768A - Method for using test film for biochemical analysis apparatus - Google Patents

Abstract

PURPOSE:To prevent the execution of analysis with a deteriorated film by continuously detecting the temp. and/or humidity of the ambient atmosphere of a cassette and determining the integrated value from the value at the time of the previous analysis of this temp. and/or humidity. CONSTITUTION:A suction spotting means 5 has a nozzle 7 for suction spotting at the front end thereof and is moved along rails 8 by a moving means 9 mounted on the rails 8. This means sucks the liquid to be inspected from a device 100 for housing the liquid to be inspected and spots the liquid onto a long-sized test film 3 drawn out of the inside of a test film housing means 6. The film 3 is then incubated by an incubator and the optical density of the film 3 is measured by a photometric means. The temp. and/or humidity or the atmosphere where the cassette is placed is continuously detected and the integrated value from the previous analysis of this temp. and/or humidity is determined. The measurement is executed after the film 3 is fed idle longer as the integrated value is larger. The analysis by using the deteriorated film is, therefore, prevented.

Description

Detailed Description of the Invention (Field of Industrial Application) The present invention relates to a method of using a test film in an apparatus for performing biochemical analysis using a long tape-shaped test film containing a reagent. This invention relates to a biochemical analyzer that can prevent a deteriorated portion of a test film from being subjected to analysis.

(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.-21677, JP-A-55-1843
No. 58, etc.) has been put into practical use. 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 the test film is pulled out one after another to perform biochemical analysis. Devices have also been proposed to do so (eg, U.S. Pat. No. 3.52B, 480).

To perform quantitative analysis of chemical components, etc. in a test liquid using such a test film, the test liquid is deposited on the test film, and then placed in an incubator for a predetermined period of time. A color reaction (pigment formation reaction) is carried out by holding at a constant temperature (incubation temperature), and then a measurement that includes a wavelength selected in advance by a combination of the components in the test liquid and the reagent contained in the reagent layer of the test film. The chemical analysis slide is irradiated with a specific irradiation light and its reflected optical density is measured.

(Problems to be Solved by the Invention) By the way, if the above-mentioned test film containing a reagent is left in the air, it will gradually deteriorate, making it impossible to perform correct analysis. This deterioration of the test film becomes more pronounced as the temperature or humidity of the surrounding atmosphere increases.

Therefore, in many cases, this test film is wound and held in a cassette, and is used by pulling it out of the cassette little by little from the leading end. However, even if this is done, it is impossible to completely prevent outside air from entering the cassette through the film outlet. Therefore, it has been considered to send low-temperature dry air into the area near the film outlet in the cassette, but this dry air feeding may be interrupted to replace the desiccant, etc., so it is not possible to completely prevent test film deterioration. The current situation is that it cannot be prevented.

The present invention has been made in view of the above circumstances, and it is an object of the present invention to provide a method for using a test film that can prevent a deteriorated test film from being subjected to analysis and obtaining erroneous analysis results. This is the purpose.

(Means for Solving the Problems) The method of using the test film in the biochemical analyzer according to the present invention is as described above, by winding and holding a long tape-shaped test film in a cassette, and rolling this test film toward the distal end. In a biochemical analyzer, a specific component in the test liquid is analyzed by pulling out a small amount of the test liquid from the cassette, spotting the test liquid on top of the cassette, and then measuring the optical density of the spotted area. The temperature and/or humidity of the surrounding atmosphere is continuously detected, and before an analysis is performed, the integral value of the temperature and/or humidity after the previous analysis is determined, and the test film is This method is characterized by long-distance feeding 12 and spotting the liquid to be inspected on the test film on the rear side (that is, on the side of the same portion inside the cassette) of the portion that has been fed emptyly.

(Function) According to the research conducted by the present inventors, when a test film is stored in a cassette as described above, its deterioration is more noticeable in the area near the film outlet, and It has been found that the higher the temperature or humidity of the film, the further this deterioration extends from the film outlet. Therefore, if you perform the above-mentioned blank feed and analyze using the test film on the rear side,
It is possible to prevent a deteriorated portion of the test film from being subjected to analysis, and at the same time, it is also possible to prevent the test film from being fed for an unnecessarily long time.

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

FIG. 1 shows an example of a biochemical analyzer that implements the method of the present invention. This biochemical analyzer 1 is transparent! !
2 is provided, and by opening the second lid 2, a liquid to be tested, a long tape-shaped test film 3, etc., which will be described below, are stored in and taken out from the device 1. This device 1 includes a sample disk section 102 that accommodates sample cups containing sample liquids such as serum and urine arranged on the circumference, and a sample disk section 102 disposed inside the sample disk section 102. Centrifugal separation cup 1 containing the entire surface etc.
A test liquid storage device 100 is provided, which has a centrifugal separator 104 that holds 03 and performs centrifugal separation. It is spotted on the shaku test film 3. The long test film 3 contains a reagent that exhibits a color reaction with only the specific chemical component or formed component to be measured in the test liquid, and is made of multiple types depending on the measurement item. A long test film 3 is prepared. The unused portion of the long test film 3 is wound inside the film supply cassette s, and the portion used for the above measurement is wound up into the film winding cassette 19. Also, the number of rolls in these cassettes 18.19 is 188%19.
Holes 18bS19b are provided in the center of each hole 18b and S19b, respectively, to engage with the rotating shaft of a motor for pulling out the long test film 3 from the film supply cassette 18 and winding it there after the long test film 3 is housed in the device. is provided. The long test film 3 is accommodated in the apparatus 1 in a cassette 18, 19. The film supply cassette 18 and the film take-up cassette 19 are separated as shown in FIG. Further, so that measurements of a plurality of items can be performed simultaneously using this device 1, the test film storage means 6 is configured to be able to store unused portions of a plurality of long test films 3 in parallel.

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 sucks the test liquid from the test liquid storage device lOO. 5. Place the spot on the long test film 3 pulled out from the test film 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 liquid to be inspected, and cleaning to be described later.

A nozzle cleaning section IO is arranged between the test film storage means 6 and the test liquid storage device 100 in close proximity to both. After the suction spotting nozzle 7 spots the liquid to be inspected on the test film 3, it is cleaned in the cleaning section IO and is reused for the next spotting.

The test film 3 on which the test liquid has been spotted is incubated in an incubator as described later,
Thereafter, the optical density of the film 3 is measured by 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 computer for giving various instructions to the device 1. It is composed of a floppy disk drive device 17 that drives a floppy disk for storing commands, measurement data, etc.

Next, the outline of the test liquid storage device 100 will be explained with reference to FIG. 2 showing the planar shape of the peripheral portion of the test liquid storage device 100. The test film storage 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 storage device are located on this straight line. Three test liquid suction positions P indicated by diagonal lines in 100 are arranged.

The test liquid storage device 100 has a sample disk section 102 that holds sample cups 1O1 containing the test liquid side by side on two concentric circumferences.

This sample disk portion 102 is rotated by a drive system (not shown) by a predetermined angle in the direction indicated by the arrow, and the sample cup 101 is successively positioned at the suction position P. In addition, in the test liquid storage device 100, the sample disk section 10
The centrifugal separation unit 104 disposed inside the 2 is capable of holding, for example, four centrifugal separation cups LO3 on a circumference concentric with the two circumferences, and by rotating at high speed, Body fluid (for example, whole blood) in centrifugation cup 103
Centrifuge. Further, after the centrifugation is completed, the centrifugation section 104 is rotated by a predetermined angle in the same manner as the sample disk section 102 to sequentially position the centrifuge cup 103 at the test liquid suction position P. That is, when whole blood is centrifuged, plasma or serum floats to the top and blood clots sink to the bottom, but according to the present storage device 100, the plasma or serum, which is the liquid to be tested, is separated from the blood clots and placed in a separate container. It can be taken out by the suction spotting means 5 without being transferred.

The suction spotting means 5 is moved along the rail 8 by a moving means 9 mounted on the rail 8, sucks the test liquid from the suction position P, and deposits it on the spotting position 22 on the long test film. do.

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 long test film 3 is stored in a film supply cassette 18 and a film winding cassette 19.
The device is loaded into the device while the device is still housed in the device. The film supply cassette 18 is housed in a cold storage 50 whose interior is temperature-controlled at, for example, 4°C. On the other hand, the film winding cassette 19
is accommodated in the winding chamber 51. If the unused portion of the long test film 3 is stored in the film supply cassette 18 in this manner, the unused long test film 3 can be stored in the cold storage 50 without being touched. The cold storage 50 is surrounded by a cold storage wall 50a using a heat insulating material.

A cooling/dehumidifying device 58 for keeping the inside of the cold storage 50 at a predetermined low temperature and low humidity is attached to one side of the cold storage wall 50a, and a fan 60 circulates the air inside the cold storage 50.

When the film supply cassette I8 and the film winding cassette 19 are stored in the cold storage 50 and the winding chamber 51, respectively, as described above, the reel 19 of the film winding cassette 19
A rotating shaft of a winding motor 53A provided in the winding chamber 51 engages with the hole 19b of a. And this motor 53
By the rotation of A, the long test film 3 is pulled out from the film supply cassette 18 via the outlet 50b of the cold storage 50 and wound into the film winding cassette 19. On the other hand, the rotation shaft of the motor 53B for rewinding the film 3 is engaged with the hole 18b provided in the center of the reel 188 of the film supply cassette 18.

Film supply cassette 18 and film winding cassette ■9
An incubator 55 is arranged in the exposed part of the long test film 3 in between, and is arranged to hold the film 3 therein and allow the film 3 to pass through the incubator 55. An M1 light section 57 is arranged for measuring optical density due to a color reaction with a liquid.

The long test film 3 is intermittently fed to the left in the figure by the rotation of the motor 53A. When the film 3 is fed, the upper lid 55a of the incubator 55 rises in the direction of arrow B. When the long test film 3 stops, the top lid 5
5a descends in the direction of arrow C to suppress and fix the film 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, passes through the nozzle insertion hole 55a, and the test liquid is spotted onto the long test film 3. After that, the shutter 54 moves to the left to close the nozzle insertion hole 55b, preventing air from entering and exiting between the inside of the incubator 55 and the outside, and keeping 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 UJ light section 57 measures the optical density of the spotted portion of the long test film 3. This concentration measurement is performed by emitting light from the light irradiation means 57a.
This is carried out 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 measurement of one liquid to be tested are completed in this way, the next liquid to be tested can be spotted. Immediately before spotting for the next analysis, the long test film 3 is transported so that the part of the film to be used for the next analysis comes to the spotting position 22.

Next, a method of using the test film 3, which is a feature of the present invention, will be explained. As shown in FIG. 3, a temperature sensor 40 and a temperature sensor 41 are disposed near the portion where the cassettes 18 and 19 are arranged to detect the temperature and humidity of this portion, respectively. These sensors 40
．． The output of 41 is input to the computer 12. FIG. 4 shows the flow of the test film 3 management process by the computer 12, and this process will be explained below.

First, in step P1, the test film management program starts, and in step P2, the elapsed time t since the last temperature/humidity monitor, the elapsed time tN since the previous cassette exchange + the elapsed time tM since the previous calibration, and the elapsed time tM since the previous measurement. All timers that measure the elapsed time tL are reset to zero. Note that these times t, tN+ tM+
tL will be described later. Also, the integral values M and N, which will be described in detail later, are each reset to 0.

Next, in step P3, it is determined whether the time t exceeds one hour, for example. Since t≦1 time at the beginning of the program, it is then determined in step P7 whether or not there is a request for item measurement. If this request has not been issued, the flow of processing returns to step P3.

If this measurement request has been issued, the magnitude of the integral value and a predetermined threshold value f11 is determined in step P8. Since L-0 here, L<j! 1, and then in step P14, the measurement as described above, that is, the spotting of the liquid to be inspected and the optical density measurement are performed. Note that during this measurement, as explained earlier with reference to Figure 3,
The test film 3 is sent by one pitch of a predetermined length from the cassette 18 to the cassette 19 side, and the unused portion thereof is provided for analysis. This pitch feeding is, of course, always performed for each measurement, and is different from the idle feeding described later. When this measurement is completed, in step P1.5,
The timer that measures the elapsed time tL mentioned above is reset. The process flow then returns to step P3.

On the other hand, if it is determined in step P3 that it is 1 hour, then in step P4 the integral value M,
N is determined, and a timer for measuring the elapsed time t is reset. The integral value is determined from the temperature T detected by the temperature sensor 40, the humidity H detected by the humidity sensor 41, and the time tL. In this embodiment, since the temperature T and humidity H are monitored hourly in step P4, the integral value is defined based on the hourly absolute moisture content Q determined from these temperature T and humidity H. . The saturated moisture content (g/m3) at temperature T is f (T
), then Q-f(T) ・H/ 100 and f (T) -7,48-0,088T+0.027
It is T2. Here, the environmental temperature of biochemical analyzer 1 is 15
~32°C, and assuming that the environmental humidity is controlled within the range of 30 to 80%, the absolute water molecule fiQ is at a temperature of 15°C.
When the temperature and humidity are 30%, the minimum value is 3°8g/7FL3, and on the other hand, when the temperature is 32°C and the humidity is 80%, the maximum value is 2B, 29/m3. The integral value is the value obtained by calculating the absolute water content every hour as described above and integrating it.The above integration continues until the time tL is reset to O, and from the time tL to When it is reset, the integrated value up to that point is canceled, and from then on, the absolute moisture content Q is newly integrated.

Similarly to the above, the integral values M and N are values obtained by successively integrating the absolute water molecules fiQ obtained every hour, and this integration is continued until the times tH and tH are reset to 0, respectively.

In step P4, the integral value as described above is calculated.

Once M and N have been determined, the magnitude of the integral value N and a predetermined threshold value n is determined in step P5.

This determination process is for determining whether or not to perform a cassette exchange, which will be described later.Since the initial value is Nun, the process flow advances to step P6.

In this step P6, the magnitude of the integral value M and a predetermined threshold value m is determined. This determination process is to determine whether or not to perform calibration, which will be described later. Initially, since M<m, the process flow advances to step P7.

When it is determined in step P7 that a request for item measurement has been issued, it is determined in step P8 whether L<11, as described above. If L<Jl, the measurement is directly performed in step P14 as described above. On the other hand, if L≧11, step P
In step 9, it is determined whether or not it is correctly 12, and L≧(2
If so, it is further determined in step Pil whether the number is 13 or not. Note that Jz, 1s is also a predetermined threshold value, and Jll < J! It is assumed that Z <13 <man. Specifically, for example, values as shown in the table below are adopted (unit: g/TrL3).

The test film 3 is used that contains a unique reagent for each measurement item, and the degree of susceptibility to deterioration varies depending on the reagent, so the above-mentioned threshold value should be adjusted accordingly (in other words, depending on the measurement item). It is preferable to change the

When it is determined that L<Jz in step P9 above,
In other words, when 11≦12, the test film 3 is fed from the cassette 18 to the cassette 19 side by the aforementioned one pitch in step PLO. This empty feed also
This is done by driving the winding motor 53A shown in FIG.

After this idle feeding is performed, the measurement as described above is then performed in step S1.4. In this measurement as well, the test film 3 is fed one pitch, so the analysis is performed on the rear side of the portion where the above-mentioned empty feeding was performed, that is, on the cassette 18.
This is done by using the inner part of the body that has not deteriorated.

Further, when the step pH is determined to be 13, that is, when 12≦13, the test film 3 is transferred from the cassette 18 to the cassette 19 in step P12.
It is sent two pitches to the side. Furthermore, when it is determined that J23≦L at step pH, step P13
At this point, the test film 3 is fed three pitches.

The larger the integral value of the test film 3, the more likely it is to deteriorate from the film outlet 50b (see FIG. 3) to the inner part of the cassette 18. Therefore, as mentioned above, if the length of the blank feed is increased as the integral value becomes larger, the deteriorated portion of the test film 3 will not be subjected to measurement. This eliminates the need to waste test film parts that are not available.

Next, replacement of the cassette 18.1.9 and carburation to deal with deterioration of the test film 3 will be explained. If it is determined in step P5 that the integral value N has become equal to or greater than the threshold value 9, step P16
A request to replace the cassette is issued. As a result, for example, in the CRT display 15 shown in FIG.
A message will appear prompting you to replace the cassette. After the operator replaces the cassette j, L 19 with a new one, for example, if the operator provides an input indicating the end of cassette replacement, or if the cassette replacement is detected by known means, step P17
At step P, it is determined that the cassette exchange is complete, and then step P
At 1B, the cassette exchange request is released.

Then, in step P19, time tH, which is a reference for performing this cassette exchange, is reset to O. Furthermore, the time tL that serves as a reference for the above-mentioned blank feeding of the test film 3, and the time tM that serves as a reference for performing the calibration described below, are meaningless due to the cassette exchange. Therefore, 0
It will be reset to

As mentioned above, when the integral value N becomes extremely large, the cassette 18.19 is replaced with a new one.As a result, the test film 3 deteriorates to the extent that it cannot be treated even with the above-mentioned 3-pitch feed. In other words, the majority of the test film 3 wound in the cassette 18
If the test film 3 appears to have deteriorated, Nino submits the test film 3 for analysis.

can be prevented.

In this embodiment, the cassette 18.
In order to be able to perform the measurement even if 19 is not replaced, in step P17, force cera! - If it is determined that the exchange has not been completed, the flow of processing moves to step P6.

Further, when it is determined in step P6 that the integral value M has become equal to or greater than the threshold value m, a request for calibration is issued in step P20.

This calibration is performed using the photodetector 5 shown in FIG.
7b calibration work. That is, when the deterioration of the test film 3 progresses to a certain extent, the density of the film 3 before the coloring reaction increases, albeit slightly, so the output of the photodetector 57b is calibrated in response to this. After performing this calibration, if the operator gives an input indicating the end of the calibration, for example, it is determined in step P2 that the calibration has ended, and then in step P22 the calibration request is canceled or entered. Then, in step P23, time tM, which serves as a reference for performing this calibration, is reset to zero.

In this case as well, the nj constant can be executed even if the calibration is not performed according to the above requirements.
When it is determined in step P21 that the calibration has not been completed, the flow of processing moves to step P7.

In the embodiments described above, the length of the blank feed of the test film 3 is controlled based on the integral value of absolute humidity. The length of the above-mentioned blank feed may be controlled based on the value. It should be noted that the deterioration characteristics of each test film 3 are that it is more likely to deteriorate due to humidity than temperature, or conversely, it is particularly susceptible to temperature rather than humidity.
They are often different from each other, such as C: easily deteriorated. Therefore, when using the integral values of both temperature and humidity as described above, weighting that differs for each test film 3 is added by giving a coefficient to the integral value of temperature and the integral value of humidity. The length of the test film empty feeding may be controlled based on the added value.

(Effects of the Invention) As explained in detail above, in the method of using the test film in the biochemical analyzer of the present invention, the temperature and/or humidity of the atmosphere in which the cassette containing the test film is placed is continuously detected. However, the integrated value of this temperature and/or humidity from the previous analysis was calculated, and the larger the integrated value, the longer the test film was fed before the analysis. Therefore, it is possible to sufficiently improve the accuracy and reliability of biochemical analysis.

Furthermore, in this method, by controlling the length of the test film idly feeding as described above, it is possible to prevent the test film from being idly fed for an unnecessarily long time. Therefore, according to this method, it is possible to prevent the test film from being wasted and the running cost of the biochemical analyzer increasing.

[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. 4 is a flowchart showing the flow of test film management processing in the biochemical analyzer. DESCRIPTION OF SYMBOLS 1... Biochemical analyzer 3... Long test film 5... Suction spotting means 7... Suction spotting nozzle 9... Moving means 12... Computer 18... Film supply cassette 19... Film winding cassette 57a... Light irradiation means 57b... Photodetector diagram X'J

Claims (1)

[Scope of Claims] A long tape-shaped test film containing a reagent is wound and held in a cassette, the test film is pulled out of the cassette little by little from the tip side, and a liquid to be tested is spotted on it. After that, in a biochemical analyzer that analyzes a specific component in the test liquid by measuring the optical density of the spotted portion, continuously detecting the temperature and/or humidity of the atmosphere surrounding the cassette, Before conducting the analysis, the integrated value of the temperature and/or humidity after the previous analysis is determined, and the larger the integrated value, the longer the test film is fed. A method for using a test film in a biochemical analyzer, characterized in that the liquid to be tested is spotted on the test film on the rear side.