JP3531335B2 - Liquid flow path switching device with bubble removal mechanism - Google Patents

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an apparatus for switching and supplying two or more liquids while removing bubbles mixed in the liquids. More specifically, the present invention relates to an apparatus for generating a step gradient in the field of liquid chromatography or for sequentially supplying two or more eluents having different actions.

[0002]

2. Description of the Related Art Especially in the field of liquid chromatography, an operation of switching two or more kinds of solutions and supplying them to a column is frequently performed. For example, in the case of separation / purification of biological components by ion exchange chromatography, a column packed with a gel carrying an ion exchanger is used,
First, the sample is provided to adsorb the target component to the gel, and then,
A first solution having a first ionic strength is provided, followed by a second solution having a second ionic strength.

In this case, the target component may be eluted from the column with the first solution and the column may be washed with the second solution or the column may be re-equilibrated for the next operation. In some cases, the impurities are eluted and the target component is eluted with the second solution. Further, for example, in the analysis of glycated hemoglobin, a hemolyzed blood sample is first provided in a column filled with a cation exchange resin, the column is washed with a solution having a relatively low salt concentration, and then a higher concentration solution is applied to the column. This is analyzed by eluting the glycated hemoglobin of interest.

In any case, the first solution and the second solution may have different components, or the components may be the same but their concentrations may differ (so-called step gradient). In some cases.

On the other hand, when the solution is supplied to the column,
If air bubbles such as air are mixed in the solution, the supply rate (flow rate) of the eluent to the column becomes unstable, which causes errors in the measurement results, and causes inconvenience in the baseline of the detector. is there.

[0006]

In the switching device, a lag occurs at the time of switching the liquid to be supplied to the column, and these mixed liquids are supplied until the switching from the first liquid to the second liquid. The conventional switching device has a problem that this lag is large. As a result, there have been problems that some of the target components to be separated and purified are lost, and that elution operation using a sharp step gradient is difficult. Further, for example, in the analysis of glycated hemoglobin, there is a possibility that an error may occur in the measurement result due to a difference in the elution time of the target glycated hemoglobin due to the lag generated when the eluent is switched.

On the other hand, regarding an apparatus for removing bubbles from a solution to be supplied to a column, for example, Japanese Utility Model Publication No. 57-57761.
Although the one described in Japanese Patent Laid-Open Publication has been proposed, there is a problem that the entire device is large and the configuration is complicated.

[0008]

DISCLOSURE OF THE INVENTION The inventors of the present invention are directed to a liquid flow path switching device which is a small-sized and simple-structured device and which is equipped with a bubble removal mechanism with a small lag when switching solutions to be provided. As a result of intensive studies, the present invention has been completed.

That is, the present invention is a fluid flow path switching device having two or more liquid inflow ports, one liquid outflow port, one gas outflow port, and a chamber having a void continuous to these ports. The void continuous with each port communicates with one communication part in the chamber, wherein the gas outlet and the void continuous with the gas outlet are formed above the communication part in the chamber, and the liquid outlet. Further, the liquid flow path switching device having the bubble removing mechanism is characterized in that the void continuous with the liquid outlet is formed below the gas outlet and the void continuous with the gas outlet.

Further, according to the present invention, two or more liquid inlets, one liquid outlet and one gas outlet, a chamber having a void continuous to these ports, and a liquid inlet of each of the chambers are provided with conduits. Two or more liquid containers connected together, a pump means connected to the liquid outlet of the chamber via a conduit, and a conduit connected to the gas outlet of the chamber,
In the fluid flow path switching device, each of the openings of the chamber is communicated with a cavity communicating with one communication part in the chamber, and two or more liquid containers and a conduit connecting the liquid container and the chamber are connected by gravity. The liquid held in the container is installed above the communication part so that the liquid can naturally flow into the communication part inside the chamber, and the gas discharge port and the void continuous with the gas discharge port are located above the communication part inside the chamber. A liquid flow provided with a bubble removing mechanism, characterized in that the liquid outlet and the void continuous with the liquid outlet are formed below the gas outlet and the void continuous with the gas outlet. It is a road switching device. The present invention will be described in detail below.

The main body of the apparatus of the present invention, that is, the chamber may be made of, for example, metal, resin, or the like, which does not cause a chemical reaction with a liquid whose supply is switched using the apparatus of the present invention. Among them, for example, Delrin, PT
FE and the like are preferable because they are easy to process and are inert to liquids such as eluents used in ordinary liquid chromatography.

The chamber is provided with two or more liquid inflow ports, one liquid outflow port and one gas outflow port, and these ports are connected to the conduit described later. The conduit may be connected to each port as long as the liquid does not leak. For example, a screw may be cut on the chamber side and an appropriate adapter compatible with the screw may be added to the conduit side. In particular, in the switching device of the present invention, the configuration can be appropriately determined in consideration of the pressure generated at the connection portion.

Inside the chamber, voids are provided which are continuous with the above-mentioned ports. More specifically, this void is not limited as long as liquid or gas can flow therethrough, and may be, for example, about a hole drilled. A void continuous from each port to the inside of the chamber extends to a point (communication portion) inside the chamber. This communication is therefore in communication with all the mouths of the chamber.

The liquid inlets of the chambers are each connected to a liquid container via a conduit. It is possible to hold any liquid in each liquid container. For example, in the case of glycated hemoglobin analysis, if three liquid solutions are used and buffer solutions with different salt concentrations are held, respectively. good.

All of these two or more liquid containers and the conduits connecting each liquid container to the chamber are such that the liquid naturally retained in the containers by gravity can flow into the communication in the chamber. It is installed above.

In the apparatus of the present invention, a valve is provided in a conduit connecting the liquid inlet of the chamber and the liquid container so that the liquid held in the liquid container cannot flow into the chamber by closing the conduit. Is preferably arranged. If only one of the valves related to the plurality of liquid containers is closed and the other is closed, it is suitable when only the solution is supplied to the column or the like. In particular, if an electromagnetic valve or the like is used to open and close the valve and link it to a control unit (microcomputer or the like) of the analyzer, it is suitable for a fully automatic analyzer.

The liquid outlet of the chamber is connected to the pump means via a conduit. The pump is usually connected to an analytical column or the like, for example, via a sample injector. Although there is no particular limitation in the present invention, examples of the pump include a syringe pump, a plunger pump, and a peristaltic pump.

The gas outlet of the chamber is connected to the conduit, but the gas outlet and the voids continuous with the gas outlet are all located above the communicating portion in the chamber, and
The liquid outlet and the voids continuous with the liquid outlet are all formed below these. With this configuration and the configuration related to the conduit connected to the gas outlet, the device of the present invention prevents the liquid flowing into the communication part in the chamber from flowing out of the chamber via the gas outlet. . Further, in the present invention, a gap that communicates from the gas outlet to the communication portion of the chamber, and particularly a portion that faces the communication portion (so-called an opening portion of the gap in the communication portion) from the liquid inlet and the liquid outlet. It is preferable to make the gap sufficiently larger than that of the void communicating with the communicating portion. With such a configuration, the gas in the liquid can be easily guided to the gas discharge port.
For example, if the void that communicates from the gas outlet to the communicating portion of the chamber is cylindrical, its inner diameter is at least twice the inner diameter of the void that communicates from the liquid inlet and the liquid outlet to the communicating portion, preferably 2.5. It can be exemplified that the number is about double.

The conduit connected to the gas outlet can be exemplified as an expandable / contractible conduit having a closed tip. For example, the silicone tube itself with the tip closed may be used, or at the tip of the conduit that does not have elasticity,
A silicone tube may be connected. This causes air bubbles in the solution to accumulate in the conduit. Further, since the tip portion is closed, it is easy to guide the liquid in the liquid container to the communicating portion in the chamber by connecting a syringe or the like to the suction portion and sucking the liquid. With this configuration, gas such as bubbles in the solution is trapped in the stretchable portion,
On the other hand, the liquid that has flowed in does not flow out of the chamber via the gas outlet.

The tip of the conduit connected to the gas outlet may be open to the atmosphere above all the liquid holding containers, unlike the above-mentioned embodiment. In this case, in order to prevent dust and the like from entering the chamber from the outside, it is preferable to bend the conduit. With this configuration as well, it is possible to prevent the inflowing liquid from flowing out of the chamber via the gas outlet.

In the apparatus of the present invention, the sum of the volumes of the void and the communicating portion communicating from the one liquid inlet to the communicating portion in the chamber is defined as the liquid amount per minute flowing out from the liquid outlet by the pump means. It is preferable to set it to less than 1%, particularly preferably less than 0.3%. Thereby, the lag at the time of switching the solution can be minimized. For example, when the flow rate by the pump means is 1.5 ml / min, that is, the flow rate per minute is 1.5 ml, the sum of the volume of the void communicating with the communicating part from the liquid inlet and the communicating part is preferably 15 μl. More preferably, it can be exemplified to be less than 4.5 μl.

[0022]

According to the apparatus of the present invention, it is possible to minimize the lag at the time of switching of each solution while removing bubbles in the solution. As a result, it is possible to improve the accuracy of the analysis result in the analysis by liquid chromatography and the like which requires switching of the solution.

According to the present invention, it is possible to improve reproducibility when the same device is used, such as baseline transduction, and to reduce the fluctuation caused by a single device. Therefore, the device of the present invention is provided. This has the effect of making it possible to reduce fluctuations between devices that operate.

[0024]

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the present invention will be described in more detail with reference to the drawings, but the present invention is not limited to the invention described in these drawings.

FIG. 1 is a cross-sectional view of the apparatus of the present invention, in which 1 is a chamber body, 2 is a liquid inlet, 3 is a conduit connected to the liquid inlet, 4 is a valve, 5 is a liquid container. Show. As is clear from this figure, the liquid container 5 and the conduit 3 connecting the liquid container and the chamber are connected to each other so that the liquid held in the container can naturally flow into the communication part 6 in the chamber by gravity. It is installed above. In this figure,
The void 7 continuous from the communication portion 6 to the liquid inlet 2 is horizontal, but it may have an inclination. Communication part 6
From, the void 8 is continuous with the gas outlet 9. A conduit 10 is connected to the gas outlet 9
A silicone tube 11 is connected to the tip of the and the end is closed with a plug 12. As is clear from this figure, the gas outlet 9 and the void 8 continuous with the gas outlet are formed above the communication portion 6 in the chamber.

On the other hand, from the communicating portion 6 in the chamber 2, a void 14 is continuous with the liquid outlet 13, and a conduit 15 is connected. The conduit 15 is connected to pump means 16. As is clear from this figure, the liquid outlet 13 and the void 14 continuous with the liquid outlet are formed below the gas outlet 9 and the void 8 continuous with the gas outlet.

In the apparatus of the present invention shown in FIG. 1, the cavity communicating from the liquid inlet of the chamber to the communicating portion and the cavity communicating from the liquid outlet to the communicating portion are cylindrical with a length of 5 mm and an inner diameter of 0.8 mm. The void communicating with the communication part from the gas outlet is cylindrical with a length of 5 mm and an inner diameter of 2 mm.
The flow rate is set to 1.5 ml / min.

FIG. 2 is a side view of the switching device of the present invention shown in FIG. The symbols in the figure are the same as the symbols in FIG. The liquid container and the like in FIG. 1 are omitted.

[Brief description of drawings]

FIG. 1 shows a cross section of a switching device of the present invention.

FIG. 2 is a side view of the switching device of the present invention.

[Explanation of symbols]

1 chamber 2 Liquid inlet 3 Conduit connected to the liquid inlet 4 valves 5 liquid containers 6 communication section 7 Void that communicates from the liquid inlet to the communication part 8 Void that communicates from the gas outlet to the communication part 9 gas outlet 10 Conduit connected to gas outlet 11 Stretchable tubing connected to conduit 12 Plugs that block elastic tubes 13 Liquid outlet 14 Void that communicates from the liquid outlet to the communication part 15 Conduit connected to liquid outlet 16 Pumping means

Claims (5)

(57) [Claims] 1. Two or more liquid inlets, one liquid outlet, and
One gas outlet and a cheek with a continuous void at these ports.
A chamber through a conduit to each of the liquid inlets of the chamber.
Two or more liquid containers connected together, liquid flow in the chamber
Pump means connected to the outlet via a conduit, and
Fluid flow consisting of a conduit connected to the gas outlet of the chamber
A directional switching device that connects to each
The void that communicates with one communication part in the chamber
The conduits connecting the body and liquid containers to the chamber are
Therefore, the liquid held in the container naturally
Installed above the communication part so that it can flow into the communication part.
The gas outlet and the void that continues to the gas outlet are
It is configured above the communication part in the chamber and the liquid flow
The void that is continuous with the outlet and the liquid outlet is the gas outlet and
And below the void that is continuous with the gas outlet.
The liquid flow path switching device having a bubble removing mechanism , wherein the conduit connected to the gas outlet is an expandable conduit whose tip is closed. 2. A conduit connected to the gas outlet comprises a silicone
The liquid flow path switching device having the bubble removing mechanism according to claim 1 , wherein the liquid flow path switching device is a tube of another member connected to a liquid tube or a silicone tube . 3. Two or more liquid inlets, one liquid outlet, and
One gas outlet and a cheek with a continuous void at these ports.
A chamber through a conduit to each of the liquid inlets of the chamber.
Two or more liquid containers connected together, liquid flow in the chamber
Pump means connected to the outlet via a conduit, and
Fluid flow consisting of a conduit connected to the gas outlet of the chamber
A directional switching device that connects to each
The void that communicates with one communication part in the chamber
The conduits connecting the body and liquid containers to the chamber are
Therefore, the liquid held in the container naturally
Installed above the communication part so that it can flow into the communication part.
The gas outlet and the void that continues to the gas outlet are
It is configured above the communication part in the chamber and the liquid flow
The void that is continuous with the outlet and the liquid outlet is the gas outlet and
And below the void that is continuous with the gas outlet.
According to another aspect of the present invention, there is provided a liquid flow path switching device having a bubble removing mechanism , wherein a tip of a conduit connected to the gas outlet is open to the atmosphere above all liquid holding containers. 4. Two or more liquid inlets, one liquid outlet, and
One gas outlet and a cheek with a continuous void at these ports.
A fluid flow path switching device having a chamber, comprising:
A continuous void in each mouth is one communicating part in the chamber
To the gas outlet where it continues to the gas outlet
The void is formed above the communication part in the chamber, and
The liquid outlet and the void that is continuous with the liquid outlet are
The structure is located below the gas outlet and the void that is continuous with the gas outlet.
Liquid flow path switching device with bubble removal mechanism
In addition, the sum of the volumes of the voids communicating with the communicating portion from the one liquid inlet and the communicating portion in the chamber is less than 1% of the liquid amount per minute flowing out from the liquid outlet by the pump means. A liquid flow path switching device having a bubble removing mechanism. 5. The sum of the volumes of the void and the communicating portion communicating from one liquid inlet to the communicating portion in the chamber is 0.3% of the liquid amount per minute flowing out from the liquid outlet by the pump means.
The liquid flow path switching device having the bubble removing mechanism according to claim 4 , wherein