JPH01304357A - Method and device for adhering liquid to be inspected in dot - Google Patents

Abstract

PURPOSE:To always adhere a liquid to be inspected in dots even when the thickness and supporting position of a test film fluctuate by detecting the position of the test film by means of a sensor providing at the front end of a nozzle for adhering liquid in dots. CONSTITUTION:An arm 5 is provided with a nozzle 7 for adhering liquid in dots at its front end and moved in the direction in which a rail 8 is extended by means of a moving means 9 put on the rail 8. The arm 5 takes out a liquid to be inspected from a inspecting liquid containing means 4 and adheres the liquid in dots on a long test film 3 pulled out from a test film housing section 6. Moreover, the arm 5 is lifted up to a retreated position when the arm 5 is moved in the lateral direction in which the rail 8 is extended by means of the moving means 9 and lowered to the liquid adhering position at the time of taking out the liquid to be inspected, adhering the liquid in dots, and cleaning. Moreover, the nozzle 7 is cleaned for the next use by means of a nozzle cleaning device 10 provided closely to the film housing section 6 and containing means 4 between them. Since the liquid adhering position of the nozzle 7 at the time of liquid adhesion is controlled to a position which is at a prescribed distance from the film 3, excellent liquid adhesion can be performed always.

Description

DETAILED DESCRIPTION OF THE INVENTION (Field of the Invention) The present invention relates to a method for precisely spotting a test liquid in a biochemical analysis method and a spotting device for carrying out such a 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 a clinical practice.
-Very important in the field of chemistry.

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 ( 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 test liquids more easily and quickly than with conventional wet analysis methods.
Its use is particularly preferred in medical institutions, laboratories, etc. where it is necessary to analyze a large number of test liquids.

In order to analyze the chemical components, etc. in a test liquid using such a chemical content 1J1 slide, the test liquid is placed on the chemical analysis slide in a measured amount, and then placed in a predetermined temperature in an incubator. For measurements containing wavelengths preselected by a combination of the components in the test liquid and the reagents contained in the reagent layer of the chemical analysis slide, which are incubated at a constant temperature for a certain period of time to cause a color reaction (pigment formation reaction). This chemical analysis slide is irradiated with irradiation light and its reflected optical density is measured, thereby performing quantitative analysis of the chemical components and the like.

In addition, in analyzes conducted at two consecutive medical institutions and research institutes,
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 monthly using the above-mentioned chemical analysis slides (for example, JP-A No. 5G- No. 77746). Furthermore, 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 in 1 above, and this test film is pulled out one by one. An apparatus has also been proposed that sequentially performs spotting, incubation, and Al11 determination (for example, US Pat. No. 3,52G, 480). In this way, a device using a long tape-shaped test film can reduce running costs compared to a device using chemical analysis slides, and also has a simple mechanism that allows A111 determination of a large number of test liquids. It is possible to do this continuously.

In the above-mentioned biochemical analysis apparatus, the test liquid is supplied to the test film (hereinafter, the chemical analysis slide and the long test film are collectively referred to as test film) by the test liquid spotting device. This spotting device discharges the liquid to be inspected from a spotting nozzle containing the liquid to be inspected, forms a liquid sphere at the tip of the nozzle, and lowers this spotting nozzle against the test film to form a liquid sphere. Test Fee 4 = The test film is supplied to the retest film by surface tension upon contact with the lume. In this way, the spotting method in which a liquid ball is formed at the tip of the nozzle instead of ejecting liquid from the spotting nozzle is a biochemical analysis method in which the amount of liquid to be tested is extremely small (about 4 microns, for example). suitable for

(Problem to be Solved by the Invention) In the above-mentioned spotting device, in order to always spot the test liquid well on the test film, it is necessary to adjust the distance from the tip of the spotting nozzle to the test film during spotting. The distance must always be constant. However, there are several types of reagents that test films contain, depending on the components of the test liquid to be measured. It is possible to store multiple test films containing different types of reagents, and the so-called multi-channel type spotting device can store these test films in sequence, or it can store different types of reagents even though there is one channel. In a spotting device in which spotting is performed by changing the test film containing the reagent as appropriate, if the spotting position of the spotting nozzle is kept constant, good spotting may not be possible depending on the type of reagent.

In addition, in a multi-channel type spotting device, the support position of the test film may vary for each channel due to variations in the N-method accuracy of the support means that support each test film. The distance between the spotting nozzle and the test film also changes.

The present invention has been made in view of the above problems.A')
Even if the position of the spotting surface of the test film changes depending on the type of reagent on the test film or the supporting position of the test film, a spotting method and method that can always spot a test liquid well are provided. We propose a spotting device that implements the spotting method1.
j1. The purpose is to

(Means for solving the problem of 1°C) The method for spotting the liquid to be inspected according to the present invention is to attach a test film detection sensor to the tip of the spotting nozzle, and to detect the test film before spotting the liquid to be inspected. The spotting nozzle is lowered until the sensor in item 1 contacts the test film, and this amount of descent is memorized. At the time of spotting, the spotting nozzle is moved a predetermined distance from the test film according to the memorized amount of device descent. The method is characterized in that the amount of descent is adjusted so as to descend to a spotting position that is a certain distance away.

Furthermore, the test liquid spotting device of the present invention for carrying out the above-described spotting method includes a supporting means capable of supporting the above-mentioned test film;
In a spotting device comprising a spotting nozzle, and an elevating means for moving the spotting nozzle up and down so that it can take a spotting position close to the test film and a retreat position on three sides from the spotting position, the spotting nozzle is A test film inspection + H sensor is installed at the tip, and a spotting nozzle is used to remove the drop.
The apparatus is lowered from the retracted position until it contacts the sensor or the test film, and a storage means for storing the amount of descent, and the dotting nozzle is lowered from the retracted position of the apparatus to the above-mentioned dotting position according to the memorized amount of descent. The present invention is characterized in that it includes a control means for adjusting the amount of descent to 1711.

(Function) According to the spotting method and the spotting device of the present invention, the position of the test film is detected by the test film sensor provided at the tip of the spotting nozzle prior to spotting the test liquid. The spotting position of the nozzle during spotting is controlled to be a predetermined distance from the test film according to the detected position, so even if the thickness of the test film or the supported position changes, Good spotting can be achieved.

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

FIG. 1 is a perspective view of a biochemical analyzer incorporating the spotting device of the present invention.

The illustrated biochemical analyzer] is equipped with a transparent lid 2, and by opening the lid 2, the test liquid described below, a long test film 3 in the form of a long tape, etc. are inserted into the apparatus]. It is designed to be stored and taken out again. This device 1 is equipped with a test liquid storage means 4 for storing test liquids such as serum and urine in a circular arrangement, and the test liquids stored here are stored as described below. It is taken out and spotted by a spotting arm 5 having a spotting nozzle 7. 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 8, and the portion used for the measurement is wound in a film winding cassette J9. In addition, after storing the long test film 3 in the center 81 of the roll 2o in the film winding cassette 19 (as will be described later), the motor rotates to pull out the film 3 from the film supply cassette 18. A hole 21 is provided for engaging the shaft. Long test film 3 is in cassette l-111,1
, 9 is housed in the device 1 while being wound. The film supply cassette 18 and the film take-up cassette 19 are separated as shown in this figure.

The test film accommodating section 6 is configured to accommodate unused portions of a plurality of long test films 3 in parallel so that a plurality of measurements can be performed simultaneously using this device.

The spotting arm 5 has a spot nostle 7 at its tip, and is moved by a moving means 9 mounted on the rail 8 in the direction in which the rail 8 extends, and takes out the liquid to be tested from the liquid to be tested storage means 4. The test film is spotted onto the long test film 3 pulled out from the test film collection section 6 as described below. Further, the moving means 9 has a built-in elevating means, which will be described later, for moving the spotting arm 5 in the vertical direction. When the elevating means moves the spotting arm 5 in the horizontal direction in which the rail 8 extends, This spotting arm is in the raised retreat position, and is lowered to the spotting position when taking out the liquid to be inspected, spotting, and cleaning to be described later.

After spotting on the test film, the spotting nozzle 7 is cleaned by a nozzle cleaning unit 10 disposed between the test film storage unit 6 and the test liquid storage means 4 in close proximity to both. Reused for clothing.

The spotted test film is kept at a constant temperature in an incubator as described below, and the upper concentration is measured.

Control of the operation of the entire device, 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 of the device and an ammeter for monitoring the current consumption in the device. The computer 12 includes a keyhole 14 for sending instructions to the device 1, a CRT display 15 for displaying auxiliary information for instructions and measurement results (zero), a printer 16 for printing out measurement results, and a printer 16 for printing the results. A floppy disk device 17 is provided for storing a floppy disk for storing commands for giving various instructions, data on results 7111, and the like.

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 section 6 is configured such that the spotting positions 22 of all the test films pulled out from the film supply cassette 18 are lined up in a straight line. 10 and the test liquid take-out position 4b in the test liquid storage means 4 are arranged.

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, and this storage portion 4a
Among the test liquids stored in the test liquid, the test liquid to be used for the next all determination is automatically rotated by a rotating means (not shown) so that it is located at the take-out position 4b. In order to prevent the liquid to be tested stored in the storage section 4a from deteriorating in quality due to evaporation, a lid (not shown) is placed over the storage section 4a other than the removal position 4b.

The spotting arm 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 takeout position 4b, and places it on the long test film at the spotting position 22.
Dot on.

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,
It is loaded inside the TES I film storage compartment.

That is, 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.

Therefore, in this apparatus, the supporting means for supporting the long test film 3, which is the test film, at a predetermined spotting position is the film supply cassette 18 in the cold storage 50.
and holding means for the film winding cassette 19 in the winding chamber 51. If the unused portion of the long test film 3 is stored in the film supply cassette 18 as described above, the unused long test film 3
They can be stored in the cold storage 50 without touching them. The cold storage 50 is surrounded by a cold storage wall 50a using a heat insulating material, and a cooling/dehumidifying device 58 is installed on one side of the cold storage wall 50a to keep the inside of the cold storage 50 at a predetermined low temperature and low humidity. The air inside the cold storage 50 is circulated.

”The film winding cassette 19 or the winding chamber 51
When the film is stored in the film winding cassette 19, the winding chamber 5 is inserted into the hole 21 provided in the center of the roll 20 in the film winding cassette 19.
] The rotating shaft of the winding motor 53, which is a conveying means for the film 3, is engaged, and the motor 53
As the film rotates, the long test film 3 is pulled out from the film supply cassette 18 via the drawer opening 50b of the cold storage 50 and wound into the film winding cassette J9.

If the used part of the long test film 3 is stored in the film winding cassette 9 in this way, the used film that has been spotted with the test liquid can be removed from the device 1 without touching it. You can take it out and dispose of it. Regarding this disposal, it is necessary to either wind the used film in the film winding cassette 19 or to remove the film winding cassette 19 and to attach and remove the film to the device 1 that stores the film in the winding chamber 51. A cutter for cutting the used film is arranged near the entrance of the winding chamber 51, and the used film is cut and stored in the box. The used film may be removed from the device without touching it, and the used film may be disposed of. In this case, the test film may be transported by providing transport rollers that grip and transport the test film.

Film supply cassette 18 and film winding cassette 19
An incubator 55 is disposed in the exposed part of the long test film 3 in between, and an incubator 55 is arranged to hold the film inside and allow the film to pass through it one after another. Concentration Δ1 to determine the optical density due to the color reaction between the test liquid and the test liquid.
A running section 57 is arranged.

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. rise in the direction. When the long test film 3 is moved, - ] 5 - The upper lid 55a is lowered in the direction of arrow B and pushes the long test film 3. Next, the shutter 54 that was blocking the nozzle insertion hole 55b of the lid 55a moves to the right in the figure, and then the dotting nozzle 7 descends from the retreated position on three sides of the incubator 55 as shown in the figure. The nozzle is moved to the position A where the test liquid is applied onto the long test film 3 through the nozzle insertion hole 55b. Before the spotting nozzle 7 descends to the spotting position, it discharges the aspirated test liquid and forms a liquid sphere 4 at the tip.
a, and at the above-mentioned spotting position, the liquid sphere 4a is brought into contact with the test film 3 as shown in the figure to perform spotting.

After the spotting is completed, the nozzle 7 rises again to the upper retreat position,
The shutter 54 moves to the left and the nozzle insertion hole 551)
The inside of the incubator is kept at a predetermined temperature (for example, 3
Keep at 7℃). The part of the film on which the test liquid has been applied and developed (the part shown with diagonal lines in FIG. 3) is kept in the incubator 55 for a predetermined period of time (for example, 4 minutes).
Maintained at constant temperature. After or during the incubation, the optical density of the portion of the long test film 3 where the spotting has been performed is measured by the density measuring section 57. This density measurement is performed by irradiating the film 3 with light containing a preselected wavelength emitted from the light irradiation means 57a and detecting the reflected light from the film 3 with the photodetector 57b.

In this manner, when the spotting and incubation for one liquid to be tested are completed, it becomes possible to apply the next liquid to be tested. The long test film 3 remains in the incubator even after the above-mentioned measurement is completed, and just before the spotting for the next analysis is performed, the portion of the film to be used for the next analysis is sent to the spotting position.

By the way, as mentioned above, the test film storage section 6 of this device holds a plurality of long test films 3 containing different reagents, and the thickness of the long test films varies depending on the type of reagent. different. In addition, it is difficult to maintain the accuracy of the device strictly in the direction in which the films are lined up, and depending on the position (channel) where the long test film is loaded, the film support position may vary slightly in the vertical direction. There is. Therefore, if the two continuous spotting nozzles 7 are always lowered by a certain amount from a predetermined retreat position to perform spotting, good spotting may not be possible. Therefore, in this device, a film detection sensor 30 is provided at the tip of the nozzle 7, and this sensor allows
Prior to the above-described spotting, the surface position of the long test film 3 is detected, and the amount of descent of the nozzle during spotting is adjusted in accordance with the detection result. Then the fourth
Control of the spotting position of this device will be explained with reference to the figures.

The device spotting nozzle 7 has a film detection sensor 30 at its tip as shown in FIG. The test liquid is sucked and discharged (that is, the liquid spheres 4a are formed) by increasing and decreasing the amount by rotational driving. On the other hand, a lifting means 40 for moving the spotting nozzle 7 downward is built into the moving means 9. The elevating means 40 includes a rack 41 fixed to the end of the spotting arm 5, a pinion 42 that meshes with this rack, and a motor 43 that rotates the pinion.
3 to the retreat position above the nozzle 7 or the incubator 55, the above-mentioned spotting position, and the sensor 30.
The spotting arm 5 is moved two degrees so that the spotting arm 5 can be brought into contact with the long test film 3.

When detecting the position between spots on the test film 3 prior to spotting the test liquid, the spotting nozzle 7 is gradually lowered from a fixed retreat position shown by the solid line, as shown in FIG. It will be done. When the spotting nozzle 7 is lowered one step to the position shown by the dotted chain line in the figure, it comes into contact with the placement sensor 30 or the test film 3, and the sensor 30 emits a detection signal. This detection signal is sent to the control circuit 44 of the motor 43 of the lifting means 40, and the control circuit 44 stops driving the motor 43.

At the same time, the control circuit 44 controls the downward movement of the spotting nozzle 7 according to the amount of rotation of the motor 43. is detected, and this detected value is stored in the storage means 70. The control circuit 44 and the storage means 70 may be built in the circuit section 11 and the computer 2 (see FIG. 1), respectively. Further, the position detection of the test film 3 is performed for all the test films 3 stored in the test film storage section 6, for example, before starting to use the device, and the position detection of each test film is The vertical position of the gap corresponds to the position of the channel in which each test film is mounted (=1 is subtracted), and all are stored in the storage means 70.

On the other hand, when spotting is performed, as shown in Figure 6,
At the certain retreat position, the liquid to be inspected is discharged from the nozzle 7, and a liquid ball is formed at the tip of the nozzle. At the same time, information for selecting a channel for spotting or a signal ':5' from a detection means designed to detect which channel the spotting arm 5 is located above is manually stored in the storage means 70. , the arrangement distance Wfj-L corresponding to the test film to be spotted or dropped, which is stored in advance from the storage means 70. A signal indicating this is sent to the control circuit 44. The control circuit 44 has a device distance of 9 Jo.
According to this, the amount of descent 9Jx of the nozzle 7 at the time of spotting is determined so that the distance from the tip of the nozzle 7 to the test film 3 at the spotting position is always constant, and this amount of descent 9J1
The motor 43 is driven accordingly. Therefore, regardless of the position of the surface of the test film, the spotting nozzle 7 always brings the liquid sphere 4a into contact with the surface of the test film 3 at a constant distance #9J from the surface, and The test liquid can be spotted on the test film 3. If the desired distance 9J2 changes depending on the type of liquid to be inspected, etc., control may be performed to change the distance measurement 2 in accordance with the liquid to be inspected sucked by the spotting nozzle.

In addition, the position detection of each test film in the test film storage section 6 is performed at the time of installation of the device as described above, and when the test film is replaced with a different type of test film, the The position detection may be performed again only for the test film to correct the detected data, or the position detection may be performed without fail before each test film is spotted.

Note that the spotting device of the present invention is not limited to one that can support a plurality of long test films as described above, but can support only one long test film, and as necessary. Spotting may be performed by replacing the test film containing an arbitrary reagent. In that case, it goes without saying that the position of the film may be detected every time the test film is replaced. In addition to the long test film, the present invention can of course also be applied to a biochemical analyzer using the above-mentioned chemical analysis slide.

(Effects of the Invention) As explained in detail above, according to the nail tube method and device for testing a liquid to be tested of the present invention, the sensor provided at the tip of the spotting nozzle conducts a test prior to spotting the liquid to be tested. The position of the film is detected and the amount of descent of the nozzle during spotting is adjusted according to this detected value, so regardless of the thickness of the test film or the unevenness of the support position of the test film, it is always possible to The liquid can be applied well.

[Brief explanation of the drawing]

Fig. 1 is a perspective view of a chemical analysis device incorporating a test liquid spotting device of the present invention, Fig. 2 is a plan view of the main parts of the chemical analysis device described in “1”, and Fig. 3 is a -X' line sectional view, Figure 4 is a sectional view of the vicinity of the spotting nozzle, Figure 5 is a schematic diagram showing the movement of the spotting nozzle when detecting the position of a long test film, and Figure 6 is the liquid to be tested. FIG. 2 is a schematic diagram showing the movement of a spotting nozzle during spotting.

Claims (1)

[Scope of Claims] 1) Discharging the test liquid from a spotting nozzle containing the test liquid to form a liquid ball at the tip of the nozzle, and reacting the test liquid with the test liquid. A test film containing a reagent that causes an optical density change is lowered to a spotting position close to the test film, the liquid sphere is brought into contact with the test film, and the test liquid is spotted onto the test object. A test film detection sensor is attached to the tip of the spotting nozzle, and prior to spotting the test liquid, the sensor contacts the test film with the spotting nozzle. and this lowering amount is memorized, and at the time of spotting, the spotting nozzle is lowered to the spotting position a predetermined distance away from the test film according to the memorized lowering amount. A method for spotting a liquid to be inspected, characterized by adjusting the amount of descent of a spotting nozzle. 2) Supporting means for supporting a test film containing a reagent that reacts with the test liquid to cause a change in optical density, capable of accommodating the test liquid, and discharging the test liquid to form a liquid sphere at the tip. a spotting nozzle that can be formed, and a lifting means for moving the spotting nozzle up and down so that it can take a spotting position close to the test film and a retreating position above the spotting position. In the apparatus, a test film detection sensor is provided at the tip of the spotting nozzle, the spotting nozzle is lowered from the retreated position by the elevating means until the sensor contacts the test film, and the amount of the drop is memorized. a memory means to
A spotting device for a liquid to be inspected, comprising a control means for adjusting the amount of descent of the spotting nozzle from the retreat position to the spotting position in accordance with the stored amount of descent.