JPH0337569A - Method of spot-deposition of liquid - Google Patents

Abstract

PURPOSE:To perform spot-deposition accurately by setting the distance between the tip of a nozzle and an object to be subjected to spot-deposition to a size sandwiching a liquid globule and setting the liquid discharging amount per a unit time from the nozzle so as to make the same almost equal to the development amount per a unit time of a liquid. CONSTITUTION:The development amount per a unit time to each test film 3 is stored in a computer at every solution F to be examined. When the solution F is dripped on the film 3 as a spot, the development amount is read and a value multiplied by a predetermined coefficient is inputted to a controller 84 as a set discharging amount. The controller 84 controls the driving speed of a spot deposition cylinder 74 so as to obtain the set discharging amount. By this method, the liquid globule of the solution F is generated between a spot deposition nozzle 7 and the film 3 to become such a state that the amount of the solution F entering the liquid globule from the nozzle 7 is slightly more than that of the liquid F issuing to the film 3 from the liquid globule. By this method, the liquid globule of the liquid F is divided or grown above the tip of the nozzle is prevented and the liquid can be subjected to spot-deposition accurately.

Description

[Detailed Description of the Invention] (Industrial Application Field) The present invention relates to a method for spotting a liquid, particularly for spotting a test liquid or a reagent solution onto a chemical analysis slide in a biochemical analyzer. The present invention relates to a liquid dotting method suitable for.

(Advanced technology) Qualitative or quantitative analysis of specific chemical components in test liquids is widely practiced in various fields. In particular, quantitative analysis of chemical components or formed components in biological acids 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 (sample) by simply applying small droplets of the liquid to be tested (sample). Special Publication No. 53-21677, Japanese Patent Publication No. 55-
No. 184356, etc.) has been put into practical use.

To perform quantitative analysis of chemical components in a test liquid using such a chemical analysis slide, the test wave is placed on the chemical analysis slide at a measuring point, and then placed in an incubator (
Maintain constant temperature (incubation) for a specified period of time in a constant temperature machine
A color reaction (dye-forming reaction) is caused, and then 1 l l l illumination light containing a wavelength pre-selected by a combination of the components in the wave to be inspected and the reagents contained in the reagent layer of the chemical analysis slide is applied to this chemical. The analytical slide is illuminated and its reflected optical density is measured.

In addition, in order to automatically and continuously analyze the test wave,
A device has also been proposed in which a long tape-shaped test film containing a reagent is housed instead of the slider mentioned above, and the test film is sequentially pulled out to spot, incubate, and measure the test liquid. (For example, U.S. Pat. No. 3,528.480).

In a biochemical analysis apparatus that uses the above-mentioned chemical analysis slide, test film, or the like as an object to be examined, a spotting nozzle is generally used to spot the wave to be examined on the object to be examined. This spotting nozzle enters the wave to be inspected housed in a container and holds it there by air suction, and then moves to the object to be inspected and holds the wave to be inspected by suction. A small amount of liquid is dropped. This type of spotting nostle is widely used not only for spotting the test wave, but also in biochemical analyzers that spot both the test wave and the reagent wave on the test subject. There is.

(Problem to be Solved by the Invention) Incidentally, in order to improve the accuracy of biochemical analysis, it is essential to accurately measure and deposit a predetermined amount of the test liquid or reagent wave onto the test subject. be. However, when using the above-mentioned spotting nozzle, it has been recognized that there is a problem that the spotting amount tends to be less than the intended value.

SUMMARY OF THE INVENTION Therefore, an object of the present invention is to provide a liquid spotting method that can solve the above-mentioned problems.

(Means for Solving the Problems) As described above, the liquid spotting method according to the present invention includes discharging a liquid such as a wave to be inspected from a downwardly directed spotting nozzle to a predetermined amount of liquid on a target object. In the method of spotting the liquid to be spotted, the distance from the tip of the spotting nozzle to the object to be spotted is set to a size such that the droplet of the liquid is sandwiched between them, and the time from the spotting nozzle is Qi. The amount of wave body ejected per hit is set to be approximately equal to the amount of liquid developed per unit time on the target object.

(Function) According to the research conducted by the present inventors, it was found that the above-mentioned problem in which the amount of spotting becomes smaller than the expected value occurs due to the following two causes.

1) The amount of liquid discharged per unit time from the spotting nozzle (hereinafter referred to as
(This "per unit time" is omitted) is quite small, as shown in FIG. is formed, and as soon as this liquid drop comes into contact with the object 3 to be spotted, the liquid F or the object 3 to be spotted
The amount of liquid discharged cannot keep up with the speed of this development. In other words, the spotting branch F is separated by the force of the spotting object 3 attracting the liquid drop, and a very small amount of the spotting liquid F may fall from the spotting nozzle 7 as shown in FIG. 5 (2). Suni,
It remains attached there. Therefore, the actual amount of spotting will be less than the expected value by the amount deposited on the spotting nozzle 7.

ii) On the contrary, if the amount of liquid discharged is considerably larger than the amount of development per unit time, as shown in FIG. It reaches the part above the tip of the nozzle 7. Even in this case, the spotting liquid F will eventually spread onto the object to be spotted 3, but as shown in FIG. A portion of the liquid F remains attached thereto, and in this case as well, the actual amount of spotting decreases by the amount that adheres.

On the other hand, if the distance from the tip of the spotting nozzle to the object to be spotted and the amount of liquid discharged from the spotting nozzle are set as in the method of the present invention, the spotting will occur as shown in Fig. 4 (1). After wave distortion of the dotting liquid F occurs between the dotting nozzle 7 and the dotting object 3, the amount of dotting liquid F that enters the dot and the dotting liquid that exits from there to the contact dotting object 3 When the amount of F is almost in equilibrium and the discharge of acid from the spotting nozzle 7 is completed, this kaedama will be deployed on the contacting body 3, causing wave distortion, separation, or spotting. It will not grow above the tip of the nozzle 7.

By the way, due to the surface tension of the spotting W2F, if the above-mentioned Kaidama is held down by its upper part or the tip of the spotting nozzle 7,
It grows in the direction of lateral force to a certain size without collapsing. Therefore, even if the liquid discharge amount slightly exceeds the above-described development amount, the wave distortion will not immediately reach above the tip of the spotting nozzle 7. Considering this, in order to more reliably prevent the wave distortion from being divided as described above, it is preferable to set the liquid discharge amount to be slightly larger than the above-mentioned expansion amount.

(Embodiments) Hereinafter, the present invention will be described in detail based on embodiments shown in the drawings.

FIG. 1 shows a device for spotting a test wave on a test film according to the method of the present invention, and FIGS. 2 and 3 show a biochemical analyzer 1 equipped with this spotting device. First, the biochemical analyzer 1 will be explained with reference to FIG. 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 test film 3, etc. are placed inside this device 1, and It is designed to be taken out. This device 1 includes a sample cup 101 containing a test liquid such as serum or urine.
A sample disk section 10 that accommodates the samples arranged in a circumferential manner
2, and a centrifugal separation section 104 disposed inside the sample disk section 102, which holds a centrifugal separation cup 103 containing whole blood or the like and performs centrifugation. The test liquid stored here is taken out by a suction spotting means 5, which will be described later.
It is spotted on the long 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 that is to be measured in the test liquid, and a plurality of reagents that exhibit a color reaction with only the component to be measured in the test liquid. Various types of long test films 3 are 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 up in a film winding cassette 19. Also, the rolls 18a in these cassettes 18 and 19,
, 19a are each provided with a hole that engages with a 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 has been accommodated in the device 1. L8b and 19b are provided. Long test film 3 is in cassette 18
．． It is housed in the device 1 in a state where it is housed in the container 19 .

Film supply cassette 18 and film winding cassette 19
and are separated as shown in FIG. Also,
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 so that measurements of a plurality of items can be performed simultaneously using the apparatus 1.

The suction stippling means 5 has a spotting nozzle 7 at its tip for suctioning and spotting the liquid to be inspected, and is moved along the rail 8 by a moving means 9 placed on the rail 8, and is moved to the liquid to be inspected storage device. The liquid to be tested is suctioned from the test film storage means 6 and deposited on the long test film 3 pulled out from the test film storage means 6 as will be described later. 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 cleaning unit (0) is arranged between the test film storage means 6 and the test liquid storage device 100 in close proximity to both.The spotting nozzle 7 spots the test liquid on the test film 3. After that, it undergoes cleaning treatment in this cleaning section 10 and is reused for the next spotting.

The test film 3 on which the test liquid has been spotted is incubated in an incubator (not shown), and then the optical density of the film 3 is measured by a conventionally known 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 and an ammeter for monitoring the current consumption in the device 1. The computer 12 includes a keyboard L4 for giving instructions to the device 1, a CRT display 15 for displaying auxiliary information for instructions, measurement results, etc., a printer ↓6 for printing out the measurement results, and a computer for giving various instructions to the device 1. It is composed of a floppy disk drive device 17, etc., which 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. 3 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 lined up in a straight line, and furthermore, on this straight line, there is a cleaning section 10 and a branch storage device 100. Three suction positions P to be inspected, indicated by diagonal lines inside, are arranged.

The test liquid storage device 100 has a sample disk section 102 that holds sample cups 101 containing the test liquid side by side on two concentric circumferences.

This sample disk section 102 is rotated by a drive system (not shown) in the direction of arrow A by a predetermined angle, and the sample cup 101 is successively positioned at the suction position P. In addition, in the test liquid storage device]00, the sample disk part (0
The centrifugal separation section 104 disposed inside the 2 is capable of holding, for example, four centrifugal separation cups 103 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 centrifugal separation section 104 is rotated by a predetermined angle in the same manner as the sample disk section 102 to sequentially position the centrifugal separation cup 103 at the test limb suction position P. That is, when whole blood is centrifuged, plasma or serum floats to the top and blood clots sink to the bottom. However, according to the present storage device 100, the blood plasma or serum, which is a mixture of sample 2, is separated from the blood clots and separated. It can be taken out by the suction spotting means 5 without having to be transferred to a container.

Next, referring to FIG. 1, the suction spotting of the test liquid by the spotting nozzle 7 will be described in detail. As shown in FIG. 1, the inside of the spotting nozzle 7 includes a pipe 70° and a three-way solenoid valve 72. It is connected to a syringe 74 for spotting via a tube 73 . Further, a branch pipe 75 is connected to the pipe 73, and this branch pipe 75 is connected to a washing syringe 76. A pipe 77 is connected to the three-way solenoid valve 72.
The tip extends into a cleaning tank 79 in which cleaning liquid 78 is stored. A solenoid valve 81 is interposed in the middle of the pipe 77. In addition, each of the above pipes 70.73.75.77
A flexible material is used as necessary. The spotting syringe 74 is driven by a pulse motor 83 via a power transmission mechanism 82 . The rotation amount and rotation speed of this pulse motor 83 are controlled by a controller 84.

When spotting the test liquid, the suction spotting means 5 is moved along the rail 8 by a moving means 9 placed on the rail 8,
The spotting nozzle 7 is stopped when it is located above the suction position iP. Next, the suction spotting means 5 is lowered by the moving means 9, and the tip of the spotting nozzle 7 enters the test liquid in the sample cup 101, for example. Then, the pulse motor 83 is rotated by a predetermined amount to drive the spotting syringe 74, and a predetermined amount of the test liquid is sucked into the spotting nozzle 7 and the tube 70 and held therein. At this time, the three-way solenoid valve 72
0 and the pipe 73, while the pipes 70, 73 and the pipe 77 are cut off from communicating with each other.

Next, the suction spotting means 5 is raised to a position where the spotting nozzle 7 is separated upward from the sample cup 101, for example, and then moved along the rail 8, so that the spotting nozzle 7 is placed on a predetermined long test film 3. It is stopped when positioned above the spotting position 22.

Next, when the suction spotting means 5 has been lowered by a predetermined amount, the spotting syringe 74 is driven by the pulse motor 83 in the opposite direction to the above case, whereby a small amount is deposited from the spotting nozzle 7 onto the long test film 3. waves to be inspected are spotted.

At this time, the amount of test liquid spotted is controlled to a unique value depending on the analysis item. This amount of dotting is controlled by a computer (2
This is done by sending a rotation amount control signal to the controller 84 in accordance with the measurement item, and changing the rotation amount of the pulse modulator 83, that is, the drive leg of the spotting syringe 74, accordingly.

Next, the characteristic parts of the present invention will be explained in detail. When spotting the liquid to be tested, the distance L from the tip of the spotting nozzle 7 to the test film 3 (see Fig. 4) is as follows:
The size is such that the wave distortion of the subject F is sandwiched between them. Such a distance can be determined for each test composition based on experiments or experience. Further, the predetermined distance thus obtained is actually set by controlling the amount of descent of the suction spotting means 5.

The combined discharge amount to be tested from the spotting nozzle 7 is controlled according to each test film 3. That is, the computer 12 stores the amount of development per unit time on each test film 3 for each liquid mixture F to be tested, and the computer 12 stores the amount of development per unit time on each test film 3 for each test film 3. , read out the amount of development on the film 3 of the liquid to be inspected, multiply the amount of development by k (k is a constant slightly larger than 1), obtain the set discharge amount, and indicate this set discharge amount. A signal is input to the controller 84. The controller 84 controls the rotational speed of the pulse motor 83, that is, the driving speed of the spotting syringe 74, so that this set discharge amount is obtained.

By doing this, as shown in FIG. 4 (2), a wave distortion of inspected >ff1F is generated between the spotting nozzle 7 and the test film 3, and the wave distortion enters the above-mentioned formation from the spotting nozzle 7. The amount of 't&F to be inspected is slightly larger than the amount of GF to be inspected that exits to the test film 3 from this wave distortion. If this is done, the wave distortion of the branch F to be inspected will not be split or grow above the tip of the spotting nozzle 7, as described in detail above.

Next, cleaning of the spotting nozzle 7 will be explained. After the above-mentioned spotting is completed, the suction spotting means 5 is returned to the suction position P side 6, and the spotting nozzle 7 is stopped when it is located above the cleaning section 10. Next, the tip of the spotting nozzle 7 is lowered into the cleaning section 10, and the outer peripheral surface of the nozzle tip is cleaned with the cleaning liquid stored in the cleaning section 10. On the other hand, the three-way solenoid valve 72 cuts off the communication between the pipe 70 and the pipe 73 and allows the pipe 73 to communicate with the pipe 77. Further, the solenoid valve 81 is in an open state.

Under this condition, the cleaning syringe 76 is driven, and the cleaning liquid 7
8 is aspirated into tube 73. Next, after the three-way solenoid valve 72 is returned to its original state, the cleaning syringe 76 is driven in the opposite direction to that described above. Thereby, the cleaning liquid 78 flows into the tube 70.
The liquid is sent to the inside of the dotting nozzle 7 via the spotting nozzle 7. This cleaning liquid 7
8 cleans the inside of the spotting nozzle 7 and flows out from the nozzle tip. When this nozzle cleaning is completed, the next test subject is suctioned.

Note that when the test liquid is to be spotted on many long test films 3, it may be necessary to suction and hold the test liquid in an amount greater than the capacity of the spotting syringe 74. In that case, after suctioning the dotting syringe 74 for one stroke, switch the three-way solenoid valve 72 to cut off the communication between the tube 70 and the tube 73 and connect the tube 73 to the tube 77. By returning the spotting syringe 74 to its original state, then returning the three-way solenoid valve 72 to its original state, and then suctioning the spotting syringe 74 again, the liquid to be tested that is equal to or greater than the capacity of the spotting syringe 74 is spotted. It can be held within the nozzle 7 and tube 70.

When the test liquid suctioned and held in this manner is applied, once the spotting syringe 74 moves one stroke, the three-way solenoid valve 72 is switched in the same way as above, and the spotting syringe 74 is returned to its original state. By returning it and performing the spotting operation again, the entire amount can be spotted.

As described above, when the three-way solenoid valve 72 is switched during suction and spotting of the test liquid, the pipe 70
A situation occurs in which the pipe 77 is in communication with the pipe 77. In this case, depending on the height relationship between the spotting nozzle 7 and the cleaning liquid tank 79, the liquid to be inspected held in the pipe 70 may flow toward the cleaning liquid tank 79 side. Therefore, if the solenoid valve 81 is closed before switching the three-way solenoid valve 72 as described above, and the solenoid valve 81 is opened after the switching operation of the three-way solenoid valve 72 is completed, the above problem will occur. can be prevented.

The above has described an embodiment in which the present invention is applied when a liquid to be inspected (sample) is spotted on a long test film 3, but the present invention is applicable to cases where other liquids are spotted on other objects to be spotted. It is also applicable to

(Effects of the Invention) As explained in detail above, in the liquid spotting method of the present invention, a droplet of spotted lfl is made to exist between the tip of the spotting nozzle and the object to be spotted, and the liquid from the spotting nozzle is While the liquid is being discharged, the amount of liquid flowing from the spotting nozzle to this droplet portion and the amount of liquid developing from this droplet portion toward the object to be spotted are almost balanced. This prevents the droplets from breaking up or growing above the tip of the dotting nozzle. Therefore, according to the present method, it is possible to reliably prevent a small amount of the liquid discharged from the spotting nozzle from remaining attached to the nozzle, and thus it is possible to measure and spot the skin with extremely high accuracy. It becomes like this.

[Brief explanation of drawings]

FIG. 1 is a schematic configuration diagram showing an example of a spotting device for carrying out the method of the present invention, FIG. 2 is a perspective view of a biochemical analyzer equipped with the above-mentioned spotting device, and FIG. 3 is a schematic diagram of the above-mentioned biochemical analyzer. FIG. 4 is an explanatory diagram illustrating the effects of the method of the present invention, and FIGS. 5 and 6 are explanatory diagrams illustrating the effects of the conventional spotting method. ]...Biochemical analyzer 3・Long test film 5
...Suction spotting means 7... Spotting nozzle 9...
Means of transportation 70.73.75. '17...Pipe 72...Three-way solenoid valve 74...Spotting syringe 83...Pulse motor 84...Controller F...Test liquid 0 4th (1) 1st (1) Figure (2) Figure (2) Section (1) Figure (2)

Claims (1)

[Claims] A liquid spotting method in which a predetermined amount of liquid is ejected from a downwardly directed spotting nozzle onto a target object, wherein the distance from the tip of the spotting nozzle to the target object is , the size is set so that the liquid droplets are sandwiched between them, and the amount of liquid discharged from the spotting nozzle per unit time is set to be approximately equal to the amount of liquid spread per unit time on the target object. A liquid dotting method characterized by: