JPH0790163B2 - Pumped liquid supply device - Google Patents

Description

TECHNICAL FIELD The present invention relates to a pressure-feed type liquid supply device. More specifically, the present invention relates to a pressure-feeding liquid supply device which can supply various liquids in a predetermined amount by gas pressure and is particularly useful as a supply device for various reagents and solvents in a device that performs continuous chemical treatment such as an automatic DNA synthesizer. .

(B) Conventional technology Conventionally, various reagents and solvents have been used in chemical synthesis processing devices such as automatic DNA synthesizers, and these liquids are pumped by a predetermined amount to a reaction container or analysis cell. There are known systems for doing this. In such a system, normally, a pressure-feeding gas inlet and outlet are provided in the upper part,
A liquid storage tank (reservoir) having a liquid discharge port at the bottom is used.

The management of the residual liquid amount of the reagent or the solvent in these reservoirs is usually performed by the operator's visual observation or using a liquid sensor provided in the liquid feeding path.

(C) Problems to be Solved by the Invention However, the reagents used in the chemical synthesis processing apparatus such as the above-mentioned automatic DNA synthesis apparatus are generally expensive. Therefore, interruption of the synthesis reaction step due to lack of a solvent or reagents causes a situation such as re-synthesis and should be avoided. In this respect, it is necessary to carefully manage the residual liquid of the reagents and solvents, but as described above, the method of performing this management by the operator's eyes is difficult to complete and often causes failure. In addition, in the method of detecting a liquid shortage by providing a liquid sensor in the liquid feeding path, it is often meaningless because the liquid shortage is detected after the synthesis has already started.

For this reason, an optical detection type liquid level sensor is also provided in the reservoir. In this case, however, it is necessary to provide a dedicated thin liquid level tube for liquid level detection in the reservoir. It is inconvenient in handling such as desorption and cleaning, and is disadvantageous in that an expensive liquid level sensor needs to be provided for each reservoir.

Further, it is conceivable to provide a weight scale in the reservoir to manage the remaining amount, but in this case as well, it is necessary to provide an expensive weight scale individually, which is disadvantageous.

The present invention has been made under such circumstances, and particularly aims to provide a liquid supply device capable of easily and economically managing the residual liquid amount for a large number of reservoirs.

(D) Means for Solving the Problems Thus, according to the present invention, a pressurizing pipe system having pressurizing means, (b) a gas exhaust pipe system having an opening / closing valve, and (c) a closed upper part It is composed of a container, and inside thereof, a gas feed port for pressure feed connected to the pressure pipe system and a gas discharge port connected to the gas discharge pipe system, and a liquid discharge port connected to a liquid supply pipe below. A liquid storage tank provided; (d) a pressure sensor provided in the pressurizing pipe system or the gas exhaust pipe system; and (e) a void volume and a pressure change rate in the liquid storage tank, which are input in advance. The actual void volume is calculated by comparing the calibration curve with the measured pressure change rate, and the residual liquid amount is calculated by further subtracting the calculated void volume from the total volume in the liquid storage tank. There is provided a pressure-feeding type liquid supply device including a display unit and a display unit.

The most important feature of this invention is when starting the introduction of gas for pressure feeding,
Based on the fact that the pressure fluctuation characteristics in the pressure pipe system and the gas discharge pipe system due to opening of the on-off valve of the gas discharge pipe system, that is, the pressure rising curve and pressure decrease curve differ depending on the volume of the void portion in the liquid storage tank, It is configured so that the amount of residual liquid in the void space, and hence in the liquid storage tank, can be monitored based on the pressure fluctuation.

The liquid supply apparatus of the present invention may be configured by connecting a plurality of liquid storage tanks to one pressurization pipe system and one gas discharge pipe system in a branched manner, whereby the residual liquid of the plurality of liquid storage tanks is formed. The quantity can be managed efficiently. However, in this case, it is necessary to provide an opening / closing valve in each branch passage so that gas introduction at the time of pressure feeding can be selectively performed for any of the liquid storage tanks.

As the pressure sensor in this invention, for example, a semiconductor pressure sensor is preferably used, and two or more pressure sensors may be provided.

(E) Action The pressure increase in the system at the start of pressurization when the void in the liquid storage tank is small (that is, when the residual liquid amount is large) is when the void is large (that is, when the residual liquid amount is small). Faster than. Therefore, the void volume and the residual liquid amount are calculated by using the time until the pressure reaches a constant value and the rate of change of the pressure value as factors.

Further, since the pressure drop in the system during depressurization is slower as the size of the void is larger, the volume of the void and the residual liquid amount can be calculated similarly.

(F) Embodiment 1 FIG. 1 is a structural explanatory view showing a liquid supply device for a DNA synthesizer of an embodiment of the pressure-feeding liquid supply device of the present invention. In the figure, a liquid supply apparatus 1 comprises a liquid supply pipe system (A), a pressurization pipe system (B), three pipe line systems of a gas discharge pipe system (C), and respective liquid storage tanks 2 to 11. . Here, 2 to 4 of the reservoirs are nucleotide reagent solutions, 5 are activation reagent solutions, 6 and 7 are masking reagent solutions, and 8
Is an oxidant solution, 9 is a deprotection reagent solution, 10 is a synthesis solvent, and 11 is a washing solvent. The liquid supply pipe system (A) is extended from the purge gas supply means 24 to the liquid sensor 48 via the solenoid valve 23 and the three-way valves (switching valves) 13 to 22, and the branch pipes (a) are respectively provided from the switching valves. It consists of a pipeline that is connected. The pressurizing pipe system (B) is composed of a pipe line extending from the gas supply means 36 for pressure feeding through the electromagnetic valve 35 and connecting a plurality of branch pipes (b) in the middle of the pipe line. The sensor 12 is internally provided.

Here, the tip of the branch pipe (a) of the liquid supply pipeline (A) is inserted up to near the bottom of each storage tank, whereby the liquid discharge port is set below the storage tank. On the other hand, the tip of the branch pipe (b) of the pressurizing pipe system (B) is inserted in the upper part of each storage tank, whereby the pressure-feeding gas introduction port is set above the storage tank.

On the other hand, the gas discharge pipe system (B) is composed of pipe lines connected to the gas discharge port via the solenoid valve 47 and each having a branch pipe (c), and the tip of the branch pipe (c) is a reservoir tank. Is inserted in the upper part of the storage tank, so that the gas outlet is set above the storage tank.

The pressure sensor 12 is connected to the calculation unit 53 via the A / D converter 52, and the calculation unit 53 calculates the void volume and the residual liquid amount in each storage tank based on the detection output of the pressure sensor. .

Further, the branch pipes (b) and (c) are provided with electromagnetic valves 25 to 34 and 37 to 46, respectively, and start and stop of pressure feeding are performed by controlling opening and closing of these valves.

The liquid supply conduit (A) is connected to a DNA synthesis reaction container 50 via a three-way valve 49, and this container 50 is further extended to the drain via an electromagnetic valve 51.

This liquid supply device functions to supply one of the liquids stored in the liquid storage tanks 2 to 11 to the reaction container 50 by pressure feeding. This operation and the operation of the arithmetic unit will be described below.

First, for example, when supplying the cleaning solvent in the storage tank 11 to the reaction container 50, the solenoid valve 34 is opened and the solenoid valve 46 is closed. In this state, the solenoid valve 35 is opened and the pump 36 is turned on. To drive. At this time, the three-way valves 13 to 22 are set to the lateral connection positions and are not connected to the branch pipe (a). Further, the three-way valve 49 is in a connection position with the reaction container 50, and the solenoid valve 51 is in an open state.

As a result, the pressure in the upper voids in the pressure pipe system (B) and in the storage tank 11 increases. When the pressure exceeds a predetermined value, the solvent in the storage tank 11 is switched to the connecting position of the branch pipe (a) by switching the three-way valve 22 to the branch pipe (a) and the three-way valve.
It is transferred to the reaction tube 50 via 22.

At this time, the pressure fluctuation in the pressurizing pipe system (B) after the start of pressurization by the gas supply means 36, especially the pressure P detected by the pressure sensor 12, is the pressure resistance in the pressurizing pipe system (B) R And the void volume in the storage tank 11 as C, and the pressure of the feed gas as
If P _o , then the following formula: Indicates the value indicated by. Here, R is a value determined by the configuration of the apparatus, and P _o is determined by the gas supply amount and increases with the drive time of the gas supply means 36. Therefore, the initial pressure fluctuation has a characteristic that it rises in a curve with time, and the slope of this curve varies depending on the size of the void volume C. This state is shown in FIG. In the figure, (a) shows a relative pressure-time characteristic when the void volume C is small (b) and is large, and thus rises to a certain value with time, but its rising angle is different. Therefore, based on this pressure fluctuation, more specifically, the threshold value T
The rise time up to and the pressure change rate at each rise are functions of the void volume C. Here, the arithmetic unit 53 calculates the actual void volume by comparing the calibration curve of the void volume and the pressure change rate (slope) input in advance with the actually measured pressure change rate, and further calculates the total void volume in the storage tank 11. This calculated void volume is subtracted from the volume to calculate and display the residual liquid amount.

Similarly, by switching each solenoid valve or three-way valve, the remaining liquid amount can be automatically checked before the pressure feeding of each liquid.

In addition, in this embodiment, when the residual liquid amount becomes a certain value or less, a circuit that emits a buzzer is attached to the arithmetic unit, and the operator can easily stop the liquid delivery based on this. It is configured to be able to.

On the other hand, in the above embodiment, when the solenoid valve 35 is closed and the solenoid valve 46 of the gas exhaust pipe system (C) is opened after being pressurized to a constant value, for example, the pressure P (t) after a predetermined time is changed. The following formula: The pressure drop curve has a small slope when the void volume is large. Therefore, the void volume and / or the residual liquid amount can be calculated based on the pressure decrease time to the predetermined threshold value or the falling pressure change rate.

When the calculated void volume is larger than the storage tank volume in the detection at the time of pressurization, it means that the connection of the storage tank is incomplete, or that gas leakage has occurred in the pipeline system. Means Therefore, such a leak check can be performed by calculating the void volume by the calculation unit.

(G) Effect of the Invention According to the pressure-feeding type liquid supply apparatus of the present invention, it is possible to manage the residual liquid in the plurality of liquid storage tanks with at least one pressure sensor. Therefore, the residual liquid can be managed simply and economically, and its usefulness is extremely great as a liquid supply device for an automatic chemical synthesis device using a particularly expensive reagent.

[Brief description of drawings]

FIG. 1 is a configuration explanatory view showing an embodiment of a pressure-feeding type liquid supply apparatus of the present invention, and FIG. 2 is a graph for illustrating a variation of detection output by a pressure sensor. 1 ... Pressure-feeding type liquid supply device, 2-11 ... liquid storage tank, 12
〜 Pressure sensor, 13〜22,49 …… 3-way valve, 23,25〜35,37〜4
7,51 …… Solenoid valve, 24 …… Purging gas supply means, 36 ……
Gas supply means for pressure feed, 48 ... Liquid sensor, 52 ... A / D converter, 53 ... Computing unit, (A) ... Liquid supply pipe system,
(B) ... Pressure pipe system, (C) ... Gas discharge pipe system.

Claims (2)

[Claims] 1. A pressurizing pipe system provided with (a) a pressurizing means, (b) a gas exhaust pipe system having an on-off valve, and (c) a container whose upper part is closed, the inside of which is the above-mentioned pressurizing member. A gas feed port for pressure feed connected to the pressure pipe system and a gas discharge port connected to the gas discharge pipe system are also provided in the inner lower part,
A liquid storage tank having a liquid outlet connected to a liquid supply pipe; (d) a pressure sensor provided in the pressurizing pipe system or in a gas exhaust pipe system; (e) the liquid inputted in advance The actual void volume is calculated by comparing the calibration curve of the void volume and pressure change rate in the storage tank with the actually measured pressure change rate, and the void calculated from the total volume in the liquid storage tank is calculated. A pressure-feeding type liquid supply device comprising: a calculation unit that calculates the remaining liquid amount by subtracting the volume and displays the remaining liquid amount. 2. The liquid supply apparatus according to claim 1, wherein a plurality of liquid storage tanks are provided.