JPH0320708B2 - - Google Patents

Description

[Detailed Description of the Invention] (a) Field of Industrial Application The present invention relates to a sample dispensing method and apparatus for performing flow-based automatic analysis, and particularly to a flow-injection method for clinical chemistry or biochemistry. This invention relates to a sample dispensing method and device for automatic analysis.

(b) Prior art In conventional flow type automatic analyzers,
After sucking the sample through the cut valve, the rotor of the cut valve is rotated to transfer the sample in the rotor portion of the sample line to the rotor portion of the analysis flow line, and the sample is subjected to analysis. However, in this method using a cut valve, only the sample in-rotor portion is subjected to analysis, and the stator portion of the sample line is not subjected to analysis. Since the volume of this stator part is larger than that of the rotor part, the amount of sample in the stator part is wasted, but its presence is essential to avoid dilution of the sample in the rotor part. teeth,
Even now, with improved analytical methods, the amount still ranges from tens to hundreds of microliters, and this has been a problem. Also, when using a cut valve,
Since the amount of sample to be analyzed is determined by the size of the rotor portion of the sample line of the cut valve, for example, in multi-item analysis with different analysis conditions, it is easy to have too much or too little, which is a problem.

In addition, the cut valve has a mirror finish to ensure that the surfaces in contact with each other are airtight.
Since they are expensive and involve handling liquids mixed with reagents and the like, they tend to suffer from corrosion, precipitation of crystals, and other troubles such as liquid leakage.

In addition, in order to avoid such problems with the cut valve method, the dispensing nozzle is provided so as to communicate with the carrier liquid flow path through a three-way path, and the dispensing nozzle that has sucked and held the sample is connected to the carrier liquid reservoir. There is a method of introducing the sample into the carrier liquid flow path from a three-way path by sucking it into the carrier liquid flow path, but after introducing the sample into the carrier liquid flow path, the tip of the dispensing nozzle is pressed against an elastic member, etc. to seal it off. In order to flow the carrier liquid into the carrier liquid flow path and guide the sample to the analysis system, the operating procedures such as valve operation are complicated, and foreign substances such as sealing members are likely to be mixed in.
Moreover, it took a lot of time and was problematic.

(c) Purpose The present invention solves these problems in the sample dispensing devices of conventional automatic chemical analyzers by forming the carrier liquid flow path so that it can be separated and connected, and by placing the dispensing nozzle in the carrier liquid flow path. The solution is to make it easy to introduce, only the sample to be used for analysis can be collected, and the amount of the sample can be adjusted freely, which prevents contamination by foreign substances, and the operation procedure is simple and the dispensing time is shortened. It is an object of the present invention to provide a sample dispensing method and a sample dispensing device which can shorten the time, are relatively inexpensive, and have few troubles.

(d) Configuration The present invention connects the suction side end of the dispensing nozzle that holds the aspirated sample inside to the liquid supply path side of the carrier liquid flow path to form a carrier liquid flow path, and the dispensing A carrier liquid is introduced under pressure from a suction side end of the nozzle into the dispensing nozzle from a carrier liquid supply path, and the sample suctioned and held within the dispensing nozzle is transported to the analysis system. The present invention relates to a sample dispensing method, and the present invention also provides a dispensing nozzle comprising a pipe line communicating with a reaction section of an automatic analyzer, a connecting part connected to the pipe line at one end, and a nozzle part at the other end, a sealing lid member into which the dispensing nozzle is inserted with the nozzle portion protruding and having a sealing member; a carrier liquid having an opening that can be in airtight contact with the sealing lid member and communicating with the opening; A sample dispensing device characterized by comprising a carrier liquid supply tank having an introduction path.

In the sample dispensing method of the present invention, the carrier liquid flow path refers to a flow path through which the carrier liquid flows from the carrier liquid source to the reaction section of the analyzer, and the present invention provides for a carrier liquid flow path that can be freely connected to one end of this flow path. A dispensing nozzle member is provided to easily introduce the sample sucked and held within the dispensing nozzle into the reaction section.

In the present invention, in order to introduce the carrier liquid into the nozzle from the tip of the dispensing nozzle, it is preferable to feed the carrier liquid under pressure. It is also possible to pressurize the carrier liquid into the nozzle by suctioning the nozzle side, but in this case, after sucking and holding the sample in the nozzle, close the valve, etc. to temporarily stop the suction, and then supply the carrier liquid. After connecting with the side flow path, suction will be restarted.

In the sample dispensing device of the present invention, the dispensing nozzle is formed such that one end can be freely connected to a pipe member forming a carrier liquid flow path, and is inserted and fixed into the sealing lid member with the nozzle tip protruding. The sealing lid member is at least liquid-tight with the top of the carrier liquid supply tank.
Preferably, the contact is gas-tight and the use of a sealing lid member facilitates the delivery of carrier liquid from the nozzle tip. The sealing lid member may be provided with an arm member to facilitate handling and automation of the dispensing nozzle.

A carrier liquid supply tank, ie, a nozzle box, is provided to introduce carrier liquid into the dispensing nozzle, and is connected to a carrier liquid supply source. The nozzle box is constantly filled with carrier liquid during analysis so as to be able to engage the dispensing nozzle member and deliver carrier liquid at any time. In particular, this is done because when the carrier liquid is forced into the nozzle tip, the presence of an air layer causes air to get mixed into the nozzle, making the flow rate of the carrier liquid inconsistent and unfavorable for measurements. be. Therefore, the wall surrounding the nozzle box top opening is formed into a weir member. Therefore, the nozzle box may be provided with a dish member around the nozzle box to receive the overflowing carrier liquid. The nozzle box is preferably supported by an elastic member, such as a compression coil spring, on a support member or the like in order to ensure contact with the lid member of the dispensing nozzle section.

(e) Embodiment FIG. 1 shows a schematic cross-sectional view of an embodiment of the sample dispensing method and apparatus of the present invention, centering on a dispensing nozzle and a nozzle box. Second
The figure shows a schematic flow diagram of an example of the sample dispensing method and device of the present invention when used in an automatic glucose analyzer.
FIG. 3 shows another example. Hereinafter, embodiments of the present invention will be described in detail with reference to these drawings.
It is not limited in any way.

In the dispensing nozzle section 1, the seal block 3 for inserting the nozzle 2 into the seal block 3 is supported by an arm 4, and the dispensing nozzle section can be moved vertically or horizontally by this arm 4. be. One end 5 of the nozzle 2 is connected via a connector 6 to a tube 7 that communicates with an analysis-side flow line. The seal block 3 is formed in airtight contact with the nozzle box portion 9 by an O-ring 8 so that it can be sealed.

The nozzle box part 9 is formed into a double cylindrical container, and is formed of an inner cylindrical wall part 10, an outer cylindrical wall part 12, a bottom wall part 14, and a spring 17.
is held in The inner cylindrical wall 10 forms a carrier liquid overflow storage tank 11 and acts as a weir, and the outer cylindrical wall 12 forms a flow path 13 for the carrier liquid overflowing the inner cylindrical wall 11.
form. The outer cylindrical wall 12 is formed at a sufficient height to prevent overflow liquid from flowing outside. A carrier liquid introduction hole 15 that opens into the carrier liquid overflow storage tank 11 and a discharge port 16 that opens into the overflow channel 13 are provided in the bottom part 14 of the nozzle box part 9. It is connected to a conduit 18 that communicates with a carrier liquid tank 20 via a liquid sending pump 19, and a discharge conduit 2 is connected to the discharge port 16.
1 is connected.

In this example, the liquid pump 19 is constantly driven during analysis, and the carrier liquid is transferred from the carrier liquid container 20 into the carrier liquid overflow storage tank 11 through the channel 1.
8 and the carrier liquid inlet 15. The carrier liquid overflows the inner cylindrical wall 10 into the overflow channel 13 and is discharged from the outlet 16 via the discharge conduit 21. The dispensing nozzle section 1, which has sucked and held the sample there, operates the arm 4 to introduce the nozzle 2 into the carrier liquid overflow storage tank 11, and the seal block 3 of the dispensing nozzle section 1 is closed.
The carrier liquid is fitted into the opening of the liquid storage tank 11 of the nozzle box part 9 through which the carrier liquid constantly overflows, and the opening is airtightly sealed. The sample held at 7 is sent to the analytical flow line along with the carrier liquid stream.

In the embodiment of the automatic chemical analyzer shown in FIG. 2, the same reference numerals are used for parts having the same functions as in FIG.

Sample turntable 23 having a rotating shaft 24
A sample container 22 is supported by the sample container 22, and the sample container 22 is sequentially sent to a sample collection position by rotation of a sample turntable 23. turntable 2
At the sample sampling position 3, a dispensing nozzle section 1 and a nozzle box section 9 of a sample dispensing device are arranged. The dispensing nozzle section 1 is provided so as to be movable in the horizontal and vertical directions by a horizontal movement device and a vertical movement device (both not shown). A three-way pipe 2 is connected to a pipe 7 connected to the nozzle part 2. One of the two flow paths other than the flow path 7 connected to the three-way pipe 27 is connected to a pipe 26 that connects to the pipette pump 25, and the other is connected to the reaction section 29 of the analysis side flow line via a pinch valve 28. The flow path is connected. The reaction section 29 is filled with the enzyme glucose oxidase, and an oxidation reaction of glucose by the enzyme is performed. A reaction product containing gluconic acid and hydrogen peroxide flows out from the reaction section, and this outflow path 36 is connected to a detection section 37 . At a stage before the detection section 37, the reaction product outflow path 36 is connected to flow paths 34 and 35 that communicate with reagent containers 30 and 31 via pumps 32 and 33. The detection unit 37 has a discharge flow path 3.
8 is connected.

Next, the operation when using this automatic chemical analyzer will be explained.

A sample is placed in a sample container 22 and sent to a sample collection position by intermittent rotation of a turntable 23. Therefore, the dispensing nozzle member 1 is
The nozzle 2 is lowered by the drive of the vertical movement device, the tip of which is immersed in the liquid sample in the sample container 22, and the liquid sample is aspirated by the drive of the pipette pump 25. After sucking the sample, the vertical movement device is driven to pull up the dispensing nozzle section 1 in which the sample is sucked and held, and then the horizontal movement device is driven to move it onto the nozzle box section 9, followed by vertical movement. By driving the device, the nozzle member 1
is fluid-tightly engaged with the nozzle box portion 9, the pinch valve 28 is opened, and the liquid feed pump 19 is driven to feed the carrier liquid from the carrier liquid container 20 into the dispensing nozzle portion 1. The sample is delivered to reaction section 29 along with a carrier liquid stream. There, the sample undergoes a predetermined reaction and flows out from the outflow path 36. Luminescence detection reagents such as luminol and red blood salt are applied to the reaction products that flow out from the reagent containers 30 and 31, respectively, and from the liquid sending pumps 32 and 33 to the detection unit 37.
and detect it.

FIG. 3 shows an example of a multi-item analysis device, and in this figure as well, the same reference numerals are given to the same parts in terms of function as in FIGS. 1 and 2.

The pipe 7 connected to the dispensing nozzle part 1 has a branch pipe 26 connected to the pipette pump, and the reaction part 29 is provided with reaction columns 291, 292, and 293 for each item. These reaction columns are connected to manifold 39 via pinch valves 281, 282 and 283, respectively. Reaction columns 291, 292
The outflow passages 293 and 293 are connected to the manifold 40. In the outflow path 36 from the reaction section, for example, liquid sending pumps 32 and 33 are connected to the luminescent reagent containers 30 and 31.
Flow paths 34 and 35, which communicate with each other, are connected to each other. A discharge channel 38 is connected to the detection section 37 .

The sample suctioned and held in the dispensing nozzle part 1 and the tube 7 is operated in the same manner as in FIG. A carrier liquid is introduced and sent to the reaction section 29 together with the carrier liquid. Reaction section 29
, the pinch valves except 281 are closed to send the sample to the reaction column 291, and when a predetermined reaction has been performed, the reaction product is mixed with a reagent from the channels 34 and 35, and the mixture is stopped. The detection section 36
The pinch valve 281 is closed. Then, similarly, the pinch valve 282 is opened, the sample is sent to the reaction column 292, the reaction product is mixed with the reagents in the channels 34 and 35, and sent to the detection section 37 for detection, and the pinch valve 282 is closed. Next, the pinch valve 283 is opened to send the sample to the reaction column 293, and the reaction product is mixed with the reagents in the channels 34 and 35 and sent to the detection section 37 for detection. In this way, multi-item analysis can be performed. The amount of sample collected into the dispensing nozzle section 1 is appropriately increased or decreased depending on the number of analysis items and their types.

(f) Effects In the present invention, the carrier liquid flow path is divided into two and a dispensing nozzle is provided at one end of the channel. This can be done simply by connecting the injection nozzle to the supply path side of the carrier liquid flow path to form a carrier liquid flow path to the analysis flow line, which simplifies the device structure and makes it inexpensive.

Further, in the present invention, all of the sample collected by the dispensing nozzle is sent to the analysis flow line, so only the required amount of sample is collected to the dispensing nozzle, and there is no wasteful consumption of the sample. In addition, the amount of sample dispensed is
The required amount of sample to be dispensed can be easily changed as the suction time to the dispensing nozzle can be adjusted depending on the amount of time required to aspirate the sample. It is easy to do.

In the present invention, after the sample is suctioned into the dispensing nozzle, the dispensing nozzle is connected to the supply path side of the carrier liquid flow path to form a carrier liquid flow path to the analysis flow line, and then the target sample can be analyzed. Therefore, complicated operations are not required for sample dispensing. Therefore, according to the present invention, the sample dispensing operation is troublesome, the time required for sample dispensing can be shortened, and the throughput can be improved.

In the present invention, the nozzle tip of the dispensing nozzle member is located on the supply path side of the sample container and the carrier liquid flow path;
For example, since the nozzle is simply put in and out of the nozzle box, no undue burden is placed on the nozzle tip of the dispensing nozzle member. Furthermore, since the nozzle tip does not come into contact with surrounding members, there is no risk of foreign matter getting mixed in due to damage.

As described above, the present invention is superior to conventional flow-based automatic analysis in terms of device structure, ease of operation, throughput, economic efficiency, etc. The impact is significant.

[Brief explanation of the drawing]

FIG. 1 is a schematic cross-sectional view centered on a dispensing nozzle and a nozzle box of an embodiment of the sample dispensing method and apparatus of the present invention, and FIG. 2 is a schematic sectional view of an embodiment of the sample dispensing method and apparatus of the present invention Regarding one example of
An example of use in an automatic glucose analyzer is shown in a schematic flow diagram, and FIG.
Here is another example. Regarding the symbols, 1 is the dispensing nozzle part, 2 is the nozzle, 3 is the seal block, 4 is the arm, 6 is the connector, 7 is the tube communicating with the analysis side flow line, 8 is the rolling, 9 is the nozzle box, and 10 is the nozzle box. 1 is an inner cylindrical wall, 12 is an outer cylindrical wall, 13 is an overflow passage, 1
4 is a bottom wall part, 15 is a carrier liquid introduction hole, 16 is a discharge port, 17 is a spring, 18 is a conduit, 19,
32 and 33 are liquid sending pumps, 20 is a carrier liquid container, 21 is a discharge conduit, 22 is a sample container, 23
is a turntable, 24 is a rotating shaft, 25 is a pipette pump, 26 is a tube, 27 is a three-way tube, 28, 28
1, 282 and 283 are pinch valves, 29 is a reaction section, 291, 292 and 293 are reaction columns, 3
0 and 31 are reagent containers, 34 and 35 are flow channels, 3
6 is an outflow path, 37 is a detection unit, 38 is a discharge flow path, 3
9 and 40 are manifolds.

Claims (1)

[Scope of Claims] 1. The suction side end of the dispensing nozzle that holds the aspirated sample inside is connected to the liquid supply path side of the carrier liquid flow path to form a carrier liquid flow path, and the dispensing nozzle A sample dispenser characterized in that a carrier liquid is introduced under pressure from a suction side end into the dispensing nozzle from a carrier liquid supply path, and the sample suctioned and held within the dispensing nozzle is transported to an analysis system. Note method. 2. A pipe line that communicates with the reaction section of an automatic analyzer, a dispensing nozzle that has a connection part connected to the pipe line at one end and a nozzle part at the other end, and the pipette nozzle is inserted with the nozzle part protruding. The carrier liquid supply tank includes a sealing lid member that is attached to the container and includes a sealing member, and a carrier liquid supply tank that has an opening that can be in air-tight contact with the sealing lid member and a carrier liquid introduction passage that communicates with the opening. A sample dispensing device characterized by: