JPH10133747A - Temperature controller for lc/ms - Google Patents

Abstract

(57) Abstract: Provided is a LC / MS temperature controller including means for appropriately changing a control parameter for temperature control in response to occurrence of an external factor such as a change in a liquid flow rate. SOLUTION: The data of the temperature (temperature from time t1 to time t2) determined by the temperature determination unit to be outside the allowable range is stored in a data storage unit. After the temperature stabilizes again, the parameter calculation unit examines the temperature fluctuation pattern, and based on the fluctuation width w and the difference d between the lower limit Tb and the minimum value Tmin, a control parameter for temperature control (PID control). In the case of, the optimum value of Kp, Ti, Td) is calculated.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a temperature control device used for a liquid chromatograph mass spectrometer or the like.

[0002]

2. Description of the Related Art Liquid chromatograph mass spectrometer (LC)
/ MS), the liquid sample separated for each component in the liquid chromatograph unit (LC) is introduced into an interface for ionizing the liquid sample, where it is vaporized and ionized, and is subjected to quadrupole and ion detection. Mass spectrometer (M
S).

Conventionally, various methods for ionizing a liquid sample have been proposed. In one such method, atmospheric pressure chemical ionization (APCI), a liquid sample is desolvated as it passes through a heated nozzle and then sprayed into a vaporization chamber.
Then, in the vaporization chamber, the sample is ionized (chemically ionized) by buffer ions generated by corona discharge. Here, when heating the liquid sample, if the sample is overheated, the vaporization of the sample will proceed excessively and the components weak to heat will be decomposed, while if the sample is insufficiently heated,
Components having a high boiling point remain in the interface without being vaporized, and in either case, a correct analysis result (for example, a quantitative result) cannot be obtained. Therefore, in order to perform accurate and reproducible analysis in an LC / MS analysis having an interface for ionizing a sample by a method including a step of heating a liquid sample, temperature control (for example, liquid sample It is necessary to perform the spraying with high accuracy.

As a general method for performing highly accurate feedback control, there is a method called PID control. This method is a method of determining an operation amount M by a proportional operation (P operation), an integral operation (I operation), and a differential operation (D operation) based on a deviation e obtained by subtracting a control amount from a target value. . For example, as an example of PID control,
Consider a case in which the temperature of the control target is stabilized at the target value by monitoring the temperature (control amount) at the sampling cycle Ts and appropriately changing the current value (operating amount) to the heater according to the monitored temperature. Try. According to the PID control, assuming that the deviation obtained by subtracting the monitor temperature from the target value at the k-th sampling time is ek, the current value Mk is expressed by the following equation: Mk = Kp × ｛ek + (Ts / Ti) × Σek + (Td / Ts) ×
(ek-ek-1)｝. Here, Kp is a proportional gain, Ti is an integration time, and Td is a parameter called a differentiation time. These parameters are hereinafter referred to as “control parameters”.

[0005]

In an LC, the flow rate of a solvent used as a mobile phase is generally set to a different value by analysis, and as one shifts from one analysis to another analysis. In some cases, the flow rate of the solvent may be greatly changed. For example, FIG. 3 is a diagram showing a temperature fluctuation pattern when PID control is performed by a conventional method so that the temperature of the nozzle of the LC / MS interface is stabilized at the target temperature T0. During temperature control, FIG.
As shown in FIG. 3, when the flow rate of the solvent increases at time t5, a sharp temperature drop occurs from time t5, as shown in FIG. Thereafter, due to the PID control, the temperature has recovered to T0 at time t6, but after time t6, the amplitude of the temperature fluctuation has increased compared to before time t5.
This is because the total amount of heat required to vaporize all the solvent flowing in per unit time also increased with an increase in the flow rate of the solvent.

[0006] The above-mentioned phenomenon can be caused by factors other than the change in the flow rate of the solvent. For example, in low-pressure gradient elution, the composition of the solvent changes over time, but if the composition of the solvent changes, the amount of heat required to vaporize the same amount of solvent also changes, and accordingly, the temperature increases. Also changes.

As described above, in the temperature control at the time of vaporizing the liquid, even if the temperature control becomes unstable due to an external factor (change in the flow rate, composition, etc. of the liquid), the control parameters of the PID control are appropriately adjusted. By resetting the temperature, the temperature can be stabilized at the target value again. However, in the conventional temperature control device, after performing tuning at the time of installation of the device and performing initial setting of control parameters,
Since temperature control was performed using the initially set parameters throughout all the analysis, it was not possible to appropriately respond to the occurrence of external factors, and the temperature control became unstable, and as a result, for example, LC / In the analysis using MS, there is a problem that the accuracy and reproducibility of the analysis decrease.

The present invention has been made to solve such a problem, and an object of the present invention is to provide a control for temperature control in response to an external factor such as a change in the flow rate of a liquid. An object of the present invention is to provide a temperature control device for LC / MS having a means for appropriately changing parameters.

[0009]

According to the present invention, there is provided a temperature control apparatus for a liquid chromatograph mass spectrometer, comprising: a) a temperature for monitoring a temperature of a means for vaporizing a liquid; Monitoring means; andb) an operation amount for obtaining an operation amount for controlling the temperature of the means for vaporizing the liquid by a predetermined formula based on a difference between the temperature monitored by the temperature monitoring means and the target temperature. Calculation means, c) according to the operation amount calculated by the operation amount calculation means,
A temperature control unit including a vaporization temperature adjusting means for adjusting the temperature of the means for vaporizing the liquid, d) determining whether the temperature monitored by the temperature monitoring means is within a predetermined allowable range, Parameter calculation means for obtaining an optimum value of a control parameter included in the predetermined calculation formula based on a fluctuation pattern of the temperature data determined not to be within the allowable range.

[0010]

DESCRIPTION OF THE PREFERRED EMBODIMENTS In the above description, the temperature of the means for vaporizing a liquid means, for example, the temperature of the nozzle of the LC / MS interface or the temperature in the vaporization chamber. The temperature monitoring means includes, for example, a temperature sensor,
It can be composed of an A / D converter for converting the intensity of the output signal of the temperature sensor into digital data, a computer program for calculating a temperature value based on the digital data, and the like. The operation amount calculation means can be constituted by a computer program.

The manipulated variable is a physical quantity that can control the temperature of the means for vaporizing the liquid by appropriately changing the value. For example, the manipulated variable is obtained by turning on / off the power supply to the heater. To control the temperature,
When the ON / OFF duty ratio is an operation amount and the temperature is controlled by changing the magnitude of the current flowing through the heater, the magnitude of the current is the operation amount. Further, for example, in the case of an apparatus having a configuration in which the temperature of a heater is kept constant and the temperature is controlled by a cooling fan, a current value, a resistance value, and the like for controlling the operation (rotation speed, etc.) of the fan are controlled by operating amounts. It can be. Note that, for example, in the case of PID control, the above-described formula corresponds to the predetermined calculation formula for obtaining the operation amount.

[0012] The vaporization temperature adjusting means outputs, for example, digital data indicating the operation amount output from the operation amount calculating means,
A D / A converter that converts the signal into an analog signal and outputs the signal; and
It can be constituted by an electric circuit or the like that operates according to the intensity of the output signal of the D / A converter. Further, the parameter calculation means can be constituted by a computer program.

The operation of the LC / MS temperature controller according to the present invention is as follows. First, while the temperature monitored by the temperature monitoring unit is stabilized at the target temperature by the operation of the temperature control unit, an external factor (such as a liquid amount) that affects the amount of heat required to vaporize the liquid. (Changes in flow rate, composition, etc.), and the temperature goes out of a predetermined allowable range. The temperature eventually returns to within the allowable range due to the operation of the temperature control unit.
Based on the temperature fluctuation pattern from when the temperature first goes out of the allowable range to when the temperature returns to the allowable range again, the parameter calculation means calculates the predetermined calculation formula used to calculate the manipulated variable. To find the optimal value of the control parameter included in. The new control parameters thus obtained are sent to the manipulated variable calculation means. After that, the manipulated variable calculating means calculates the manipulated variable using the new control parameter.

[0014]

According to the temperature control device for LC / MS according to the present invention, the amount of heat required for vaporization changes due to the occurrence of external factors such as changes in the flow rate and composition of the liquid to be vaporized. However, according to the change, the control parameters of the calculation formula for calculating the manipulated variable are recalculated to obtain the optimum value, and thereafter, the temperature control is performed using the optimum control parameter. Temperature control can be stably performed even after the occurrence of a physical factor.

[0015]

FIG. 1 is a schematic configuration diagram of an embodiment of a temperature control device for LC / MS (hereinafter, referred to as "temperature control device") according to the present invention. The temperature control device of the present embodiment includes a temperature sensor 12, an A / D converter 14, a temperature monitor 16, a manipulated variable calculator 18, a D / A converter 20, and a heater drive circuit 22.
Is provided, and thereby,
The temperature of the heater 30 is feedback-controlled. That is, the signal output from the temperature sensor 12 according to the temperature of the heater 30 is converted into a digital signal by the A / D converter 14, further converted into temperature data by the temperature monitor 16, and transmitted to the manipulated variable calculator 18. Will be transferred. Operation amount calculation unit 1
8 is based on a difference between the temperature indicated by the transferred data and a predetermined target temperature, and is based on a predetermined calculation formula (for example, P
An operation amount (for example, a duty ratio for controlling ON / OFF of a current flowing through the heater) is calculated using the ID control equation). The digital signal indicating the operation amount is supplied to the D / A converter 2
After being converted to an analog signal by 0, it is input to the heater drive circuit 22. The heater drive circuit 22 controls a current value supplied to the heater 30 according to the intensity of the input analog signal. Note that the temperature monitor 16 and the manipulated variable calculator 18 are configured by a computer program.

In addition to the temperature control section, the temperature control apparatus of this embodiment includes a temperature determination section 24, a data storage section 26, and a parameter calculation section 28. Temperature determination unit 24
Receives the temperature data output from the temperature monitor 16 and determines whether the difference between the temperature indicated by the data and the target temperature is within a predetermined allowable range.

If it is determined that the temperature indicated by the temperature data is not within the allowable range, the temperature data is stored in the data storage unit 2.
6 is stored. In the data storage unit 26, each temperature data is stored in a state where the time when the temperature is measured can be identified.
Since the data is stored, if this data is read out again, a pattern indicating the fluctuation of the temperature while the temperature is outside the predetermined range can be formed.

The parameter calculation unit 28 includes the data storage unit 2
6 is read, and a variation pattern of the temperature in a time interval in which it is determined that the temperature is not within the predetermined range is checked. Based on the variation pattern, the control parameter ( For PID control,
Kp, Ti, Td) are calculated.

The above-described temperature determination unit 24 and parameter calculation unit 28 are operated by a computer program.
The data storage unit 26 can be configured using a storage device such as a hard disk.

Next, the operation of the temperature control device of this embodiment will be described.
This will be described with reference to FIGS. FIG. 2 is a diagram showing a temperature fluctuation pattern when the temperature is controlled by the temperature control device according to the present invention.

Referring to FIG. 2, the temperature monitored by the temperature monitor 16 is within an allowable range (upper limit Ta, lower limit Tb) before the time t1 due to the operation of the temperature controller 10.
Thus, the temperature is almost stabilized at the target temperature T0. However, at time t1, a change in an external factor, for example, an increase in the flow rate of the liquid occurs, so that the temperature starts to drop sharply, and falls below the lower limit Tb after time t2. After that, the temperature continues to decrease for a while. During this time, the temperature control unit 10 is constantly operating to return the temperature to the target temperature T0. As a result, the temperature decreases to the minimum value Tmin at time t3. After reaching, it starts to rise again, and returns to the lower limit Tb again at time t4.

When the temperature changes as described above, the temperature measured during the time interval from time t2 to time t4 is determined by the temperature determination unit 24 to be outside the predetermined range. Therefore, all data indicating the temperature measured during the time interval is stored in the data storage unit 26.

When the temperature reaches the lower limit Tb of the allowable range at time t4, the temperature determining unit 24 sends a signal indicating that the temperature has returned to the allowable range to the parameter calculating unit 28. Upon receiving this signal, the parameter calculation unit 28 sets the data storage unit 2
The data indicating the temperature measured during the time interval from time t2 to t4, which is stored in No. 6, is read out to configure the temperature fluctuation pattern in that time interval and calculate the optimum value of the control parameter. Find the value of a given item.

Items necessary for calculating the optimum value of the control parameter include, for example, t as shown in FIG.
The width w of the time interval from 2 to t4, the difference d between the lower limit Tb of the allowable range and the minimum value Tmin of the temperature, the integral value S of the difference between the lower limit Tb and the monitor temperature T in the above time interval, or the time t2 Temperature change amount ΔT during the very short time Δt immediately after
And so on. Based on the data of such various items, the parameter calculation unit 28 calculates the optimum value of the control parameter included in the calculation formula for calculating the operation amount by a predetermined method.

The new control parameter value thus obtained is sent from the parameter calculator 28 to the manipulated variable calculator 18. Thereafter, the manipulated variable calculator 18 calculates the manipulated variable using the new and optimized control parameters. Therefore, in the temperature control after the temperature returns to the allowable range, the fluctuation of the temperature does not increase as in the case of FIG. 3, and the temperature stabilizes to the target temperature T0 with high accuracy as before time t1. I will be.

As a method of obtaining control parameters based on each item obtained from the temperature fluctuation pattern, for example, for each control parameter Kp, Ti, Td, Kp = f (w, d, S, ΔT ,...) Ti = g (w, d, S, ΔT,...) Td = h (w, d, S, ΔT,...) However, the present invention is not limited to this, and any method for obtaining a control parameter based on the above-described temperature fluctuation pattern can be used for implementing the present invention.

[Brief description of the drawings]

FIG. 1 is a schematic configuration diagram of an embodiment of a temperature control device according to the present invention.

FIG. 2 is a diagram showing a temperature fluctuation pattern when the temperature is controlled by the temperature control device according to the present invention.

FIG. 3 is a diagram showing a temperature fluctuation pattern under conventional PID control.

FIG. 4 is a diagram showing a temporal change of a flow rate of a liquid.

[Explanation of symbols]

 DESCRIPTION OF SYMBOLS 10 ... Temperature control part 12 ... Temperature sensor 16 ... Temperature monitor part 18 ... Manipulation amount calculation part 24 ... Temperature judgment part 26 ... Data storage part 28 ... Parameter calculation part

Claims (1)

[Claims] 1. A temperature monitoring means for monitoring the temperature of a means for vaporizing a liquid, and b) a predetermined calculation formula based on a difference between the temperature monitored by the temperature monitoring means and a target temperature. A manipulated variable calculating means for calculating a manipulated variable for controlling the temperature of the means for vaporizing the liquid, and c) according to the manipulated variable calculated by the manipulated variable calculating means.
A temperature control unit including a vaporization temperature adjusting means for adjusting the temperature of the means for vaporizing the liquid, d) determining whether the temperature monitored by the temperature monitoring means is within a predetermined allowable range, LC / MS for calculating the optimum value of the control parameter included in the predetermined calculation formula based on the fluctuation pattern of the temperature data determined not to be within the allowable range. Temperature control device.