JP2009231035A - Mass spectrometer - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To simplify construction of current-to-voltage converter switching in characteristics according to scan speed, and to improve stability of a circuit at the time of the switching. <P>SOLUTION: A current-to-voltage converter 11 is arranged to insert a circuit formed by series-connecting a first resistor R1 with a parallel circuit of a second resistor R2 and a switch SW1, between a non-inverting input terminal and an output terminal of an operational amplifier A1. A control section 10 controls the switch SW1 to be closed when scan speed is high to reduce a feedback resistance and reduce a gain but to widen a frequency band. Only one switch for the current-to-voltage converter 11 is required, so that cost reduction is achieved; and a feedback loop is not opened at the switching time, so that operation of the current-to-voltage converter 11 becomes stable. <P>COPYRIGHT: (C)2010,JPO&INPIT

Description

  The present invention relates to a mass spectrometer, and more particularly to a mass spectrometer that performs mass scanning over a predetermined mass range.

  A mass spectrometer using a quadrupole mass filter scans the mass-to-charge ratio m / z of ions to be detected by changing the high-frequency voltage and DC voltage applied to the quadrupole mass filter while maintaining a predetermined relationship. And the resulting data can be used to create a mass spectrum.

  In LC / MS using such a mass spectrometer (MS) as a detector of a liquid chromatograph (LC), a method such as increasing the flow rate of the mobile phase in the LC is adopted in order to improve the analysis throughput. In this case, the change of the sample components in the eluate eluted from the LC column becomes faster. Therefore, in order to ensure the accuracy of detection of sample components, it is necessary to increase the speed of mass scanning (hereinafter referred to as scanning speed). However, when the scanning speed is increased, the frequency band of the signal output from the detector increases, and problems such as a decrease in intensity and a broadening of the peak occur due to insufficient frequency band in the analog processing circuit.

  In order to solve the above problem, in the mass spectrometer described in Patent Document 1, the gain can be switched in the current-voltage converter that converts the current signal from the detector into a voltage signal, and the scan speed is slow when the scan speed is fast. The frequency band is widened by lowering the gain. When the gain is increased, the frequency band is narrowed, but the noise characteristic is improved instead, and the signal-to-noise ratio of the signal can be improved. As a result, when the scan speed is fast, amplification with an emphasis on frequency characteristics can be performed, and when the scan speed is slow, amplification with an emphasis on noise characteristics can be performed.

  In the device described in the embodiment of Patent Document 1, the gain is switched by switching the two resistors. However, two open / close switches are necessary for this purpose, which increases costs. In addition, when the switch is switched, there is a possibility that the feedback resistor is not inserted into the operational amplifier, and there is a possibility that the circuit becomes unstable such as oscillation.

JP 2008-52996 A

  The present invention has been made in view of the above problems, and the object of the present invention is to employ a circuit that can reduce costs and guarantee a more stable operation when realizing the invention according to Patent Document 1. An object of the present invention is to provide a mass spectrometer.

A first invention made to solve the above problems is a mass separator that selectively passes ions having a specific mass among various ions, and the current that is detected by detecting the ions that have passed through the mass separator. In a mass spectrometer comprising: a detector that outputs a signal; and a control unit that controls the mass separator so as to sequentially change the mass of ions passing through the mass separator with time.
a) Converting a current signal from the detector into a voltage signal, a first resistor between an inverting input terminal and an output terminal of an operational amplifier having a non-inverting input terminal connected to a reference potential; A current-voltage converter formed by inserting a circuit in which a second resistor and a first switch are connected in parallel;
b) A gain that is arranged at a subsequent stage of the current-voltage converter and has a gain ratio that is opposite to the gain ratio determined by the feedback resistance when the first switch is closed and opened is determined according to the closing and opening of the second switch. A voltage amplifier having
The control means closes the first and second switches when the mass scanning speed is equal to or higher than a predetermined value, and opens the first and second switches at other times. Yes.

The second invention made to solve the above problems is to detect a mass separator that selectively passes ions having a specific mass among various ions, and to detect ions that have passed through the mass separator. In a mass spectrometer comprising: a detector that outputs a current signal; and a control unit that controls the mass separator so that the mass of ions passing through the mass separator is sequentially changed over time.
a) Converting a current signal from the detector into a voltage signal, a first resistor between an inverting input terminal and an output terminal of an operational amplifier having a non-inverting input terminal connected to a reference potential; A current-voltage converter formed by inserting a circuit in which a second resistor and a first switch are connected in parallel;
b) analog-to-digital conversion means for converting the output voltage of the current-voltage converter or a voltage obtained by amplifying the output voltage with a predetermined gain into a digital signal;
c) calculating a digital signal by the analog-to-digital conversion means, the multiplication or division giving a gain opposite to the gain ratio respectively determined by the feedback resistance at the closing and opening of the first switch; Arithmetic means for executing in conjunction with closing and opening of the first switch;
The control means closes the first switch when the speed of mass scanning is equal to or higher than a predetermined value, and opens the first switch at other times.

  In both mass spectrometers according to the first and second inventions, when the first switch is closed, the feedback resistance of the current-voltage converter is only the first resistor, and when the first switch is opened, the first resistor A feedback resistor is formed by connecting the second resistor in series. The gain of the current-voltage converter is proportional to this feedback resistance. Therefore, in the mass spectrometers according to the first and second inventions, the gain of the current-voltage converter can be switched only by closing / opening one switch, and the cost can be reduced.

  Unlike the case where two open / close switches are closed and opened in a complementary manner or the case where a switch which selectively connects the first signal path to one of the two signal paths is used, the current-voltage converter The feedback loop is not opened even when the gain is switched. Therefore, even when oscillation or the like is unlikely to occur and switching is required at high speed during analysis, for example, the current-voltage conversion operation can be performed stably.

  A mass spectrometer which is one embodiment of the present invention will be described with reference to the accompanying drawings. FIG. 4 is a schematic configuration diagram of the mass spectrometer according to the present embodiment. This mass spectrometer is equipped with an electrospray ion (ESI) source.

  In this mass spectrometer, between the ionization chamber 21 in which the ESI nozzle 22 is disposed and the analysis chamber 31 in which the pre-quadrupole mass filter 32, the main quadrupole mass filter 33, and the ion detector 34 are disposed. In addition, a first intermediate vacuum chamber 24 and a second intermediate vacuum chamber 28 which are separated from each other by a partition are provided. The structure of the multistage differential evacuation system in which the inside of the ionization chamber 21 is at substantially atmospheric pressure, the inside of the analysis chamber 31 is maintained in a high vacuum state, and the two intermediate vacuum chambers 24 and 28 in between are gradually increased in vacuum. Has been adopted. The ionization chamber 21 and the first intermediate vacuum chamber 24 communicate with each other via a small-diameter solvent removal pipe 23, and the top portion of the skimmer 26 is between the first intermediate vacuum chamber 24 and the second intermediate vacuum chamber 28. The second intermediate vacuum chamber 28 and the analysis chamber 31 communicate with each other through a small opening provided in the partition wall 30.

  Although the structures of the first intermediate vacuum chamber 24 and the second intermediate vacuum chamber 28 are different from each other, ion guides 25 and 29 are provided for efficiently transporting ions to the subsequent stage. A predetermined voltage is applied to the ion guides 25 and 29 and the quadrupole mass filters 32 and 33 from the voltage generator 40. Among these, the quadrupole mass filters 32 and 33 are applied with a voltage ± (U + V · cosωt) in which a predetermined high-frequency voltage and a predetermined DC voltage are superimposed according to the mass-to-charge ratio to be selected. It has become. The operation of the voltage generation unit 40 and the like is comprehensively controlled by the control unit 10 mainly composed of the CPU, and analysis conditions for the analysis are set from the input unit 41 by the user.

  The operation of this mass spectrometer will be schematically described. For example, a liquid sample continuously supplied from a column of a liquid chromatograph is electrosprayed into the ionization chamber 21 from the tip of the ESI nozzle 22, and the sample molecules are ionized in the process of evaporating the solvent in the charged droplets. Fine droplets mixed with ions are drawn into the desolvation pipe 23 due to the differential pressure between the ionization chamber 21 and the first intermediate vacuum chamber 24, and further vaporize the solvent in the process of passing through the heated desolvation pipe 23. Is promoted and ionization proceeds. With the help of an electric field formed by an ion guide 25 disposed in the first intermediate vacuum chamber 24, ions enter the first intermediate vacuum chamber 24, are converged, and pass through the passage hole 27 to form the second intermediate vacuum chamber 28. Sent to.

  In the second intermediate vacuum chamber 28, the ions are further converged and sent to the analysis chamber 31 by the action of the electric field formed by the ion guide 29. In the analysis chamber 31, only ions having a specific mass-to-charge ratio determined by the voltage applied to each rod electrode pass through the space in the long axis direction of the quadrupole mass filters 32 and 33, and the other mass charges. Ions with a ratio diverge on the way. Then, ions that have passed through the quadrupole mass filters 32 and 33 reach the ion detector 34, and the ion detector 34 outputs a current signal corresponding to the amount of ions as a detection signal. This current signal is converted into a voltage signal by the amplification unit 35, converted into a digital signal by the AD conversion unit 36, and input to the data processing unit 37.

  In the case of scan measurement, the control unit 10 controls the voltage generation unit 40 based on analysis conditions such as a scan speed and a mass range set in advance from the input unit 41, and scans the voltage applied to each unit over time. . As a result, the mass-to-charge ratio m / z of ions that can reach the ion detector 34 changes with time. The data processing unit 37 repeatedly creates a mass spectrum based on the data obtained with mass scanning as described above. FIG. 2 schematically shows a state of mass change when mass scanning over the same mass range M1 to M2 is performed at different scanning speeds.

  FIG. 1 is a schematic diagram showing the circuit configuration of the amplifier 35 and the AD converter 36. The current signal i output from the ion detector 34 is converted into a voltage signal by the current-voltage converter 11, amplified by the voltage amplifier 12, and unnecessary high frequency components are removed by the analog filter 13. The analog / digital converter (ADC) 14 samples the sample with a predetermined sampling period and then converts the sample into digital data.

  The current-voltage converter 11 includes an operational amplifier A1, a first resistor R1, a second resistor R2, and a switch SW1. The non-inverting input terminal of the operational amplifier A1 is connected to a reference potential V0 (for example, GND), and a current signal is input to the inverting input terminal. The second resistor R2 and the switch SW1 are connected in parallel, and a series connection circuit of the second resistor R2 and the first resistor R1 is connected between the inverting input terminal and the output terminal of the operational amplifier A1. The switch SW1 is turned on / off by a control signal from the control unit 10. Here, R1 = 1 MΩ and R2 = 9 MΩ. When the switch SW1 is turned on, the feedback resistance is R1 = 1 MΩ, and when the switch SW1 is turned off, the feedback resistance is R1 + R2 = 10 MΩ. Since the voltage appearing at the output terminal of the operational amplifier A1 is proportional to the feedback resistance, the gain when the switch SW1 is in the off state is 10 times the gain when the switch SW1 is in the on state.

  The voltage amplifier 12 includes an operational amplifier A2, a third resistor R3, a fourth resistor R4, and a switch SW2. The output voltage of the current-voltage converter 11 is input to the non-inverting input terminal of the operational amplifier A2, a fourth resistor R4 is inserted between the inverting input terminal and the output terminal, and the inverting input terminal is a third resistor. It is connected to the reference potential via the device R3 and the switch SW2. Similarly to the switch SW1, the switch SW2 is driven on and off by a control signal from the control unit 10. The voltage amplifier 12 has a voltage gain of (R3 + R4) / R3 when the switch SW2 is turned on, and the voltage gain becomes 1 when the switch SW2 is turned off.

  Here, the resistance values of the first to fourth resistors R1 to R4 are set to have a relationship of R1: R2 = R3: R4 = 1: n (where n ≧ 1). In this example, n = 9, as described above, R1 = 1 MΩ and R2 = 9 MΩ, and R3 and R4 are, for example, R3 = 1 kΩ and R4 = 9 kΩ. When the switches SW1 and SW2 are in the OFF state, the gain of the current-voltage converter 11 is 10 times and the gain of the voltage amplifier 12 is 1 time. When the switches SW1 and SW2 are in the ON state, the current-voltage converter 11 Is 1 times, and the gain of the voltage amplifier 12 is 10 times. Therefore, regardless of whether the switches SW1 and SW2 are both in the on state or the off state, the combined gain of the current-voltage converter 11 and the voltage amplifier 12 does not change, and the voltage signal output for the same current signal Are the same.

  The frequency band of the current-voltage converter 11 is determined by the feedback resistance and the stray capacitance C, and the frequency band becomes narrower as the feedback resistance is increased, that is, as the gain is increased. Since the frequency of the signal increases when the scanning speed is high, the control unit 10 closes the switch SW1 so as to widen the frequency band of the current-voltage converter 11 (lower the gain). As a result, high-frequency components can easily pass through. On the other hand, since the noise from the current-voltage converter 11 and the voltage amplifier 12 is dominated by the noise of the current-voltage converter 11 in the first stage, the noise is relatively lowered by increasing the gain of the current-voltage converter 11. This will lower the overall noise level. Therefore, when the scan speed is low and it is not necessary to widen the frequency band of the current-voltage converter 11, the control unit 10 opens the switch SW1 so as to increase the gain of the current-voltage converter 11. This reduces the noise level and improves the signal-to-noise ratio of the signal.

  The control unit 10 closes the switches SW1 and SW2 as described above according to the scan speed which is one of the analysis conditions set from the input unit 41, that is, according to whether or not the scan speed is equal to or higher than a predetermined value.・ Control the opening. Thereby, appropriate detection data corresponding to the scan speed can be acquired.

  In particular, in the configuration of the present invention, the frequency-oriented configuration and the noise-oriented configuration correspond to the closing and opening of one switch SW1, respectively, and there is no intermediate state associated with switching. In other words, since the state where the feedback resistor is always inserted is maintained in the negative feedback loop of the operational amplifier A1, the circuit can be kept stable even when the switching is performed, and a problem such as oscillation is avoided. be able to. Although the switch itself has a stray capacitance, only one switch SW1 is included in the feedback loop here, which is advantageous for reducing the stray capacitance and widening the frequency band. Moreover, since only one switch is required, it is advantageous in terms of cost.

  FIG. 5 and FIG. 6 show actually detected waveforms in the mass spectrometer of this example. FIG. 5 is a detection waveform when polyethylene glycol (PEG) is analyzed as a sample. (A) is a frequency characteristic-oriented configuration (low gain of current-voltage converter), and (B) is a noise-oriented configuration (current). -The gain of the voltage converter is large). In addition, the apparatus used for this measurement is guaranteed to have a reproducibility of ± 1% or less when the same sample is analyzed under the same conditions. Comparing FIG. 5A and FIG. 5B, the detected waveform is sharp and the intensity is high in the configuration emphasizing frequency characteristics. This is because a signal having a higher frequency component can be detected. FIG. 6 shows a detection waveform in a state where a sample is not introduced, that is, a waveform of a noise component. FIG. 6A shows a configuration emphasizing frequency characteristics, and FIG. Comparing FIGS. 6A and 6B, the detected waveform fluctuation amplitude is small and smooth in the configuration emphasizing the noise characteristics.

  From the above measurement results, the frequency component-oriented configuration that is selected when the scan speed set by the user is fast can detect the target component with high sensitivity and high mass accuracy, and is selected when the scan speed is slow. It can be seen that the noise characteristic-reduced configuration can reduce the noise and detect the target component with a high S / N ratio.

  FIG. 3 is a configuration diagram of an amplification unit 35 and an AD conversion unit 36 of a mass spectrometer according to another embodiment of the present invention. The same components as those in FIG. 1 are denoted by the same reference numerals, and description thereof is omitted. In the configuration of this embodiment, a digital multiplier 17 is provided after the ADC 14 in place of the voltage amplifier 12 with variable voltage gain. The digital multiplier 17 receives the switch control signal of the switch SW1 output from the control unit 10, and multiplies by 10 when the switch SW1 is in the closed state and simply multiplies by 1 when the switch SW1 is in the open state. Therefore, the function of the voltage amplifier 12 is digitally realized, and the same operation and effect as the above embodiment can be achieved.

Schematic which shows the circuit structure of the amplification part and AD conversion part in the mass spectrometer by one Example of this invention. The figure which shows typically the mode of the mass change at the time of performing mass scanning over the same mass range M1-M2 with a different scanning speed. Schematic which shows the circuit structure of the amplifier part and AD conversion part in the mass spectrometer by the other Example of this invention. 1 is an overall configuration diagram of a mass spectrometer according to an embodiment of the present invention. The figure which shows the actual detection waveform in the mass spectrometer of a present Example. The figure which shows the actual detection waveform in the mass spectrometer of a present Example.

Explanation of symbols

DESCRIPTION OF SYMBOLS 11 ... Current-voltage converter 12 ... Voltage amplifier 13 ... Analog filter 14 ... Analog / digital converter (ADC)
DESCRIPTION OF SYMBOLS 17 ... Digital multiplier SW1, SW2 ... Switch A1, A2 ... Operational amplifier R1, R2, R3, R4 ... Resistor 10 ... Control part 21 ... Ionization chamber 22 ... ESI nozzle 23 ... Desolvation pipe 24 ... 1st intermediate | middle vacuum chamber 25, 29 ... ion guide 26 ... skimmer 27 ... passage hole 28 ... second intermediate vacuum chamber 30 ... partition wall 31 ... analysis chamber 32 ... pre-quadrupole mass filter 33 ... main quadrupole mass filter 34 ... ion detector 35 ... Amplifier 36 ... AD converter 37 ... Data processor 40 ... Voltage generator 41 ... Input unit

Claims (2)

A mass separator that selectively passes ions having a specific mass among various ions, a detector that detects ions that have passed through the mass separator and outputs them as current signals, and passes through the mass separator A mass spectrometer comprising: control means for controlling the mass separator so as to sequentially change the mass of ions with time.
a) Converting a current signal from the detector into a voltage signal, a first resistor between an inverting input terminal and an output terminal of an operational amplifier having a non-inverting input terminal connected to a reference potential; A current-voltage converter formed by inserting a circuit in which a second resistor and a first switch are connected in parallel;
b) A gain that is arranged at a subsequent stage of the current-voltage converter and has a gain ratio that is opposite to the gain ratio determined by the feedback resistance when the first switch is closed and opened is determined according to the closing and opening of the second switch. A voltage amplifier having
The control means closes the first and second switches when the mass scanning speed is equal to or higher than a predetermined value, and opens the first and second switches at other times. Mass spectrometer. A mass separator that selectively passes ions having a specific mass among various ions, a detector that detects ions that have passed through the mass separator and outputs them as current signals, and passes through the mass separator A mass spectrometer comprising: control means for controlling the mass separator so as to sequentially change the mass of ions with time.
a) Converting a current signal from the detector into a voltage signal, a first resistor between an inverting input terminal and an output terminal of an operational amplifier having a non-inverting input terminal connected to a reference potential; A parallel connection circuit of the second resistor and the first switch, and a current-voltage converter formed by inserting a circuit connected in series;
b) analog-to-digital conversion means for converting the output voltage of the current-voltage converter or a voltage obtained by amplifying the output voltage with a predetermined gain into a digital signal;
c) calculating a digital signal by the analog-to-digital conversion means, the multiplication or division giving a gain opposite to the gain ratio respectively determined by the feedback resistance at the closing and opening of the first switch; Arithmetic means for executing in conjunction with closing and opening of the first switch;
And the control means closes the first switch when the mass scanning speed is equal to or higher than a predetermined value, and opens the first switch at other times.

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