JPH0677004B2 - Gradient device - Google Patents

Description

TECHNICAL FIELD The present invention relates to a gradient device for controlling a liquid composition by selectively mixing a plurality of developing liquids from the various developing liquids with the passage of time.

[Conventional technology]

In liquid chromatography, a developing solution is allowed to flow through a column with a pump, and a sample is introduced into the column from the sampler with the developing solution. When the developing solution is continuously flown in this manner, each component is separated in the column at different elution times. That is, in the column, since the ease of sticking to each component in the sample differs depending on the degree of adsorption force of the ion-exchange resin or other filler particles, the time to be retained in the column, in other words, the passing speed differs. Therefore, each component emerges from the column with the elution time corresponding to this passage rate as a peak. In this case, the component that is difficult to be adsorbed in the column passes straight through the column, so that it elutes with a sharp peak in a short time after the start of analysis. On the other hand, the components adsorbed in the column elute with a time lag corresponding to the degree of the adsorption power thereof, and as a broad peak due to the influence of diffusion. Therefore, the analysis time becomes long, and the detection sensitivity of the components that elute at a late time is significantly reduced. In order to detect components that elute at such a slow time as sharp peaks, the liquid composition is controlled using multiple developing solutions to control the degree of adsorption force of each component in the column in a time series. The gradient method is used.

By the way, the low pressure mixing type gradient device is roughly classified into a time division method and an inhalation time division method.

FIG. 6 is a diagram for explaining the time division method, and FIG. 7 is a diagram for explaining the inhalation time division method.

In the time division method, as shown in FIG. 6, the required liquid composition (the ratio of liquid A and liquid B that changes with time) is quantized at a sampling period T (usually 5 sec or more). Then, the time T is divided so that the value becomes the required A and B composition ratio, and the valve is switched to control the supply of the A liquid and the B liquid. In this way, the amount of liquid A and the amount of liquid B are controlled by the time so that the required liquid composition is obtained. In the example shown in FIG. 6, the sampling cycle T is decomposed into 30 units to control the supply of the A liquid and the B liquid.

On the other hand, the suction time division method is a method of controlling an intermittent flow, unlike the method of the time-resolving method which is based on the assumption of a constant continuous flow. That is, the suction start time is detected by the pump suction signal, and the time during suction is divided so that the required liquid composition is obtained, and the suction amounts of A and B are controlled. For example, FIG. 7 (a)
As shown in Fig. 7, if the pump has a uniform suction, the suction time is divided as it is, and if it is a pump with variable suction as shown in Fig. 7 (b), it is divided by the time corrected by the suction amount (area). To do.

[Problems to be solved by the invention]

However, in the time division method, the suction of the pump is usually intermittent, so even if the liquid composition requirement of A: B = 3: 5 is divided into 1: 3, as shown in FIG. As shown in FIGS. 8 (a) and 8 (b), if the timing of the pump is deviated, the ratio may change. In order to overcome such a problem, an air damper or the like is attached to the suction side so as to make the suction flow constant and continuous. However, a completely constant flow cannot be obtained, and the suction resistance difference between liquid A and liquid B is not obtained. The change in the inflow rate will also occur. Further, if the gradient division ability is set to 1%, for example, the division of the sampling period T must be 1/100, and if the sampling period T is 5 sec, valve switching of 0.05 sec is required, but in reality, There is a problem in that the accuracy of the transient response of the switching valve is poor, so that the accuracy of the gradient is reduced.

In the suction time division method, since the suction start time is normally detected in synchronization with the pump cam, the ratio of the liquid composition does not change as in the former case, but it does not change, but the actual liquid suction is shown in FIG. As shown, the desired liquid composition is not obtained because it changes depending on the discharge pressure. In addition, since there is a cam manufacturing error in the suction speed, in the case of the pump of the type shown in FIG. 7 (a), there is a deviation between the ideal value and the actual value as indicated by the diagonal lines in FIG. Accumulated. Generally, the pump cycle is
Since it is 0.5 sec to 2 sec, if the dividing power is 0.5%, it will be 0.0
It is difficult to improve the accuracy in practice because it requires operation of 025 to 0.01 sec.

The present invention has been made to solve the above-mentioned problems, and an object of the present invention is to provide a gradient device that can obtain high accuracy by using a conventional control system.

[Means for solving problems]

Therefore, the gradient device of the present invention detects the timing signal of the discharge-suction operation of the pump in the gradient device in which the developing liquid is selected by switching the valve according to the required liquid composition and the liquid is sent to the column by the pump. It is characterized in that a means is provided, and the suction liquid is switched by the valve in synchronization with the operation cycle of the discharge-suction operation of the pump.

[Action]

In the gradient device of the present invention, the discharge-suction operation cycle of the pump is used as a unit, and the suction liquid is switched by the valve in synchronization with the operation cycle. Therefore, the liquid composition is controlled by the number of times of liquid suction according to the liquid composition required. As a result, the liquid suction amount can be accurately grasped.

Therefore, the difference between the ideal value and the realized value can be reduced, and the control accuracy is improved.

〔Example〕

 Hereinafter, embodiments will be described with reference to the drawings.

FIG. 1 is a diagram for explaining one embodiment of a gradient device according to the present invention, FIG. 2 is a diagram for explaining detection timing of a pump signal, and FIG. 3 is a diagram showing an example of a linear gradient. , FIG. 4 is a diagram for explaining the flow of the operation of the system in the linear gradient.

In FIG. 1, 1 and 2 are liquid storage containers, 3 is a valve, 4
Is a controller, 5 is a mixer, 6 is a sensor, 7 is a pump, and 8 is a column. The pump 7 is for intermittent inhalation, and the sensor 6 is for detecting the timing of the discharge-inhalation operation of the pump 7. For example, as shown in FIG. A micro switch, a photo sensor, or the like is used to detect immediately before the process. The controller 4 recognizes the signal immediately after the pre-suction process or immediately before the current suction process of the pump 7 by taking in the signal from the sensor 6, and controls the valve 3 while calculating the liquid composition and comparing it with the required liquid composition. A → B within the switchable section
Liquid, liquid B → liquid A is switched.

Next, the control flow for the example of the linear gradient shown in FIG. 3 will be described with reference to FIG. First, assuming that the required liquid composition is changed as shown in FIG. 3 (a), the controller 4 causes the controller 4 to set the initial values of the system as shown in FIG. Pre-set and input whether to start with solution A or solution B. Then, when the system is activated, the controller 4 counts the time, calculates the corresponding required liquid composition, and compares the present required liquid composition with the initial value (~).

If the solution A concentration is lower than the required solution composition, the valve 3 is controlled to inhale the solution A. When the liquid A is inhaled, the concentration of the liquid A increases, and the composition at that time changes. Therefore, the changed liquid composition A ′ is calculated (,).

On the other hand, if the concentration of the liquid A is higher than the required composition, the valve 3 is controlled to inhale the liquid B, and the similarly changed liquid composition A ′ is calculated (,).

After inhaling the liquid A or the liquid B, the pump starts the discharge operation,
This inhalation signal is detected by the sensor 6 and taken into the controller 4 from the sensor 6. The controller 4 calculates the required liquid composition at that time, and compares (-) with the previously (or) calculated liquid composition A '. Hereinafter, the solvent having the required liquid composition is sent to the column by repeating the same process (to) until the gradient is completed (YES at).

FIG. 5 is a diagram showing an operation example of the valve with respect to an arbitrary gradient, and the suction time of the liquid A or the liquid B is changed according to the change of the required liquid composition in units of the cycle of the discharge-suction operation of the pump.

The present invention is not limited to the above embodiment, and various modifications can be made. For example, in the above-mentioned embodiment, the control of the required liquid composition by the two liquids has been described, but it goes without saying that the same can be applied to the case of a gradient of a plurality of liquids, and even if it is not a linear gradient.

〔The invention's effect〕

As is clear from the above description, according to the present invention, the solenoid valve is controlled in synchronism with the discharge-suction operation of the pump to switch the suction liquid, so that the intermittent suction pump is used as in the conventional case. The liquid composition can be controlled with higher accuracy than before. Further, since the pump suction liquid is 100% distributed to all liquid A or liquid B, it is not necessary to particularly increase the response speed of the solenoid valve. Further, by controlling the pump suction and recovery, it becomes irrelevant to the variation of the suction point, the uniformity of the operation timing of the pump, etc. as in the conventional case, and the error caused by these is not accumulated.

[Brief description of drawings]

FIG. 1 is a diagram for explaining one embodiment of a gradient device according to the present invention, FIG. 2 is a diagram for explaining detection timing of a pump signal, and FIG. 3 is a diagram showing an example of a linear gradient. , FIG. 4 is a diagram for explaining the flow of the operation of the system in the linear gradient, FIG. 5 is a diagram showing an example of the operation of the solenoid valve for an arbitrary gradient, and FIG. 6 is a diagram for explaining the time division method. FIG. 7, FIG. 7 is a diagram for explaining the suction time division method, FIG. 8 is a diagram for explaining the relationship between the liquid composition demand and the actual liquid composition, and FIG. 9 is the actual liquid suction and discharge. FIG. 10 is a diagram for explaining the relationship with the pressure, and FIG. 10 is a diagram for explaining the deviation between the ideal value and the actual value during pump suction. 1 and 2 ... Liquid storage container, 3 ... Valve, 4 ... Controller, 5 ... Mixer, 6 ... Sensor, 7 ... Pump, 8 ... Column.

Claims (1)

[Claims] 1. A gradient device for switching a valve according to a required liquid composition to select a developing liquid and sending the developing liquid to a column by a pump, is provided with a means for detecting a timing signal of discharge-suction operation of the pump, A gradient device characterized in that a discharge-suction operation cycle is used as a unit and a suction valve is switched in synchronization with the operation cycle.