JP6173683B2 - Time-of-flight mass spectrometer - Google Patents

Description

  The present invention relates to a time-of-flight mass spectrometer, and more particularly to a time-of-flight mass spectrometer that can remove signal waveform distortion that occurs when ion signals are captured at high speed.

  A mass spectrometer is an apparatus that causes ions generated from a sample to fly in a vacuum, separates ions having different masses in the course of flight, and records them as a spectrum. The mass spectrometer includes a magnetic mass spectrometer that performs mass dispersion of ions using a sector magnetic field, and a quadrupole mass spectrometer (QMS) that performs selection (filtering) of ions by mass using a quadrupole electrode. ), A time-of-flight mass spectrometer (TOFMS) that separates ions using a difference in flight time of ions according to mass, and the like are known.

  Among these mass spectrometers, the magnetic field type mass spectrometer and the QMS are suitable for ion sources that continuously generate ions, whereas the TOFMS is an ion that generates ions in a pulsed manner. Conforms to the source. Therefore, the most widely used ion source most suitable for TOFMS is a MALDI (matrix assisted laser desorption ionization) ion source that generates ions in a pulse shape. This is an orthogonal acceleration ion source devised so that a type ion source can be used as a pulse ion source.

  FIG. 1 shows the configuration of a TOFMS equipped with a typical vertical acceleration ion source. In the figure, reference numeral 1 denotes an external ion source. Ions generated by the external ion source 1 are introduced into the ion acceleration unit 4 via the ion transport unit 11. The ions accelerated in the vertical direction in the ion acceleration unit 4 fly in the drift space 3, are then reflected by the ion reflection unit 5, and further fly toward the detector 6 while causing temporal convergence.

  The ion pulse that has converged in time in the vicinity of the detector 6 reaches the detector 6 as a pulse signal having a very short time width, is converted into an electric signal by the detector 6, and is sent to the preamplifier 7. Then, the pulse signal is electrically amplified by the preamplifier 7, and then A / D converted by the subsequent digitizer, and taken into the data processing software 9 as a digital signal. FIG. 2 illustrates such a measurement flow.

Japanese Patent No. 3830344

  By the way, according to the prior art as shown in FIG. 2, since the digitized pulse signal is used as a mass spectrum without any processing, the electrical intrinsic noise contained in the signal is also converted into the mass spectrum. There was a problem of being reflected.

  In order to solve this problem, as shown in FIG. 3, only when a predetermined threshold value is exceeded among signals input to the digitizer, it is determined as valid data, A / D conversion is performed, and the digitizer is processed. When the input signal is equal to or less than a predetermined threshold value, data processing is performed in which the input value is determined to be zero for convenience and removed. Thereby, as shown in FIG. 4, the electric noise below the threshold was deleted, and the mass spectrum could be a low noise spectrum.

  However, as an actual problem, it is extremely difficult to determine the optimum size of this threshold. For example, if the threshold is too large, the true signal to be detected is also deleted and disappears. On the other hand, if the threshold value is too small, the technique as shown in FIG. 3 is hardly different from the conventional technique as shown in FIG.

  In particular, when the baseline of the spectrum fluctuates greatly with each measurement, it is assumed that data processing with a fixed threshold value does not help reduce electrical noise. The reliability of later signal strength can be greatly impaired. As a result, for example, the intensity ratio of isotope peaks may not be measured correctly.

  In view of the above-described points, an object of the present invention is to provide a TOFMS that can efficiently reduce electrical noise accompanying an ion pulse signal detected by an ion detector.

In order to achieve this object, a time-of-flight mass spectrometer according to the present invention provides:
A pulsed ion source;
A time-of-flight spectroscopic unit that performs mass separation by flying ions generated by the pulsed ion source;
An ion detector for detecting ions mass-separated by the time-of-flight spectrometer, and a digitizing means for digitizing a detection signal obtained from the ion detector and converting it into digital data;
Data processing means for obtaining mass spectrum data by performing data processing on the digital data;
In a time-of-flight mass spectrometer equipped with
The data processing means includes noise removal calculation means for removing noise included in the detection signal,
The noise removal calculation means includes:
(1) For digital data consisting of N data points D _n (n = 1, 2,..., N) ordered in time series obtained from the digitizing means , M sets (M is a natural number) of noise removal calculation data obtained by multiplying the signal intensity I _n (n = 1, 2,..., N) by a predetermined coefficient R _m (m = 1, 2,..., M), R ₁ × (I ₁ , I ₂ ,..., I _N ), R ₂ × (I ₁ , I ₂ ,..., I _N ), ..., _RM × (I ₁ , I ₂ ,..., I _N ) Correction data creation means,
(2) The M sets of noise removal calculation data are delayed-shifted in a direction in which time passes by j _m (m = 1, 2,..., M) data points for each set, and then the digital An operation execution means for performing an operation of subtracting from the data;
It is characterized by having.

In addition, the data processing means performs an integration process on the corrected data after the noise removal calculation.

Further, the data processing means is characterized in that the noise removal calculation is performed on the digital data subjected to integration processing.

According to the time-of-flight mass spectrometer of the present invention,
A pulsed ion source;
A time-of-flight spectroscopic unit that performs mass separation by flying ions generated by the pulsed ion source;
An ion detector for detecting ions separated by mass in the time-of-flight spectrometer;
Digitizing means for digitizing the detection signal obtained from the ion detector and converting it into digital data;
Data processing means for obtaining mass spectrum data by performing data processing on the digital data;
In a time-of-flight mass spectrometer equipped with
The data processing means includes noise removal calculation means for removing noise included in the detection signal,
The noise removal calculation means includes:
(1) For digital data consisting of N data points D _n (n = 1, 2,..., N) ordered in time series obtained from the digitizing means , M sets (M is a natural number) of noise removal calculation data obtained by multiplying the signal intensity I _n (n = 1, 2,..., N) by a predetermined coefficient R _m (m = 1, 2,..., M), R ₁ × (I ₁ , I ₂ ,..., I _N ), R ₂ × (I ₁ , I ₂ ,..., I _N ), ..., _RM × (I ₁ , I ₂ ,..., I _N ) Correction data creation means,
(2) The M sets of noise removal calculation data are delayed-shifted in a direction in which time passes by j _m (m = 1, 2,..., M) data points for each set, and then the digital An operation execution means for performing an operation of subtracting from the data;
Because it is characterized by having
It has become possible to provide a time-of-flight mass spectrometer that can efficiently reduce electrical noise associated with an ion pulse signal detected by an ion detector.

It is a figure which shows an example of the conventional time-of-flight mass spectrometer. It is a figure which shows the flow of the data processing of the conventional time-of-flight mass spectrometer. It is a figure which shows the flow of the data processing of the improved time-of-flight mass spectrometer. It is a figure which shows an example of the conventional data processing method. It is a figure which shows one Example of the time-of-flight mass spectrometer concerning this invention. It is a figure which shows one Example of the flow of a data processing of the time-of-flight mass spectrometer concerning this invention. It is a figure which shows the general example of an intrinsic noise waveform. It is a figure which shows the concept of the intrinsic noise removal method concerning this invention. It is a figure which shows the definition of the parameter at the time of approximating a natural noise waveform. It is a figure which shows another Example of the flow of data processing of the time-of-flight mass spectrometer concerning this invention.

  Embodiments of the present invention will be described below with reference to the drawings.

[Example 1]
FIG. 5 shows the configuration of a time-of-flight mass spectrometer according to the present invention. In the figure, reference numeral 1 denotes an external ion source. Ions generated by the external ion source 1 are introduced into the ion acceleration unit 4 via the ion transport unit 11. The ions accelerated in the vertical direction in the ion acceleration unit 4 fly in the drift space 3, are then reflected by the ion reflection unit 5, and further fly toward the detector 6 while causing temporal convergence.

  The ion pulse that has converged in time in the vicinity of the detector 6 reaches the detector 6 as a pulse signal having a very short time width, is converted into an electric signal by the detector 6, and is sent to the preamplifier 7. Then, the pulse signal is electrically amplified by the preamplifier 7, then A / D converted by the averager 10 in the subsequent stage, and taken into the data processing software 9 as a digital signal. FIG. 6 illustrates such a measurement flow.

  As shown in the flow of FIG. 6, the detected ion signal is digitized for each spectrum by the averager 10, and then subjected to data processing for subtracting the “inherent noise waveform” by an FPGA circuit (not shown) provided in the averager 10. After being applied, the processed data are accumulated one after another. A final mass spectrum is created from this accumulated data.

  The “inherent noise waveform” referred to here is generated when the ion signal is detected by the detector 6 or when the ion signal is A / D converted by the averager 10 because the ion pulse signal is a very fast pulse signal. It refers to signal distortion such as ringing. Such device noise of high-speed signals cannot be removed by the conventional threshold method. It is widely known that this type of device noise is caused mainly by the transient response of the device itself.

  FIG. 7 is an example of such “inherent noise waveform”. In the figure, reference numeral 20 denotes an ion pulse signal waveform. The ion pulse signal waveform 20 includes a main peak 21 and an electrical noise waveform 22. This electrical noise waveform 22 often appears in the form of a small sub-peak with a slight delay from the main peak 21. Such sub-peaks may appear only once or may appear repeatedly at different intensities. A method for removing such an electrical noise waveform 22 is as follows.

First, (1) signal strength I _n (n = 1) is applied to digital data including N data points Dn (n = 1, 2,..., N) that are ordered in time series. 2,..., N) multiplied by a predetermined coefficient R _m (m = 1, 2,..., M), M sets (M is a natural number) of noise removal calculation data, R ₁ × (I ₁ , I ₂ ,..., I _N ), R ₂ × (I ₁ , I ₂ ,..., I _N ), ..., R _M × (I ₁ , I ₂ ,..., I _N )
(2) The M sets of noise removal calculation data are delayed-shifted in a direction in which time passes by j _m (m = 1, 2,..., M) data points for each set, and then the digital An operation execution means for performing an operation of subtracting from the data;
The noise removal calculating means consisting of is provided.

Then, when the ion pulse signal is acquired as digital data, (1) for N data points D _n (n = 1, 2,..., N) ordered in time series (N is a natural number). , M sets (M is a natural number) of noise removal calculation data obtained by multiplying the signal intensity I _n (n = 1, 2,..., N) by a predetermined coefficient R _m (m = 1, 2,..., M). _{the, R 1 × (I 1,} I 2, ..., I N), R 2 × (I 1, I 2, ..., I N), ..., R M × (I 1, I 2, ..., I N ).

Next, the M sets of noise removal calculation data are delayed and shifted in the direction in which time passes by j _m (m = 1, 2,..., M) data points for each set. Subtraction is performed from the mass spectrum data of.

Here, M is a parameter that specifies how many times the sub-peak appears in total. D _n is an actually measured data point used for the purpose of removing the sub-peak in accordance with the spread per sub-peak. J _m is a delay parameter for designating the delay from the main peak 21 to the sub-peak with respect to the m-th sub-peak. R _m is an intensity correction parameter for fitting an actually measured waveform composed of a plurality of data points D _n obtained from the main peak 21 to the intensity of the sub peak that appears m-th.

  By applying such processing to the original data, the “inherent noise waveform” that appears in the form of a small sub-peak with a slight delay from the main peak 21 appears several times with different intensities. Even noise can be easily removed from the original data. FIG. 8 illustrates the concept of these steps.

  According to this method, for example, in a data signal (an example that could not be removed by the conventional threshold method) when a pulse ion signal with a narrow line width overlaps innumerably to form one broad ion peak. Even the “inherent noise waveform” can be removed almost completely, so the effect is extremely large.

The optimum value of the correction coefficient R _m (m = 1, 2,..., M) specifically indicates the shape of the sub-peak 22 generated when a pulse ion signal having a sufficiently narrow line width is incident on the ion detector. It can be determined experimentally by observing. As for the correction coefficient R _m (m = 1, 2,..., M), it is conceivable to take different optimum values for each target device.

Specifically, the correction coefficient R _m (m = m = _m ) is applied to the digital intensity value I _n (n = 1, 2,..., N) of the main peak 21 using a mathematical expression represented by a symbol defined by FIG. 1, 2,..., M) and the time delay j _m (m = 1, 2,..., M) from the main peak 21 are approximated to approximate the approximate shape of the “inherent noise waveform”. By subtracting the “inherent noise waveform” from the original data, the “inherent noise waveform” associated with the main peak 21 can be easily removed.

使用する補正項の数を４つ（Ｍ＝４）と設定すると、１≦ｍ≦４となり、次式を用いることができる。

If the number of correction terms to be used is set to four (M = 4), 1 ≦ m ≦ 4, and the following equation can be used.

なお、本発明は、垂直加速型飛行時間型質量分析装置に適用できるのみならず、一般のパルスレーザーイオン化イオン源やＭＡＬＤＩイオン源を備えた飛行時間型質量分析装置などにも、同じように適用することができる。

The present invention can be applied not only to a vertical acceleration time-of-flight mass spectrometer, but also to a time-of-flight mass spectrometer equipped with a general pulse laser ionization ion source or a MALDI ion source. can do.

  The time-of-flight spectroscopic unit can be applied to all time-of-flight spectroscopic units including a linear type, a reflectron type, a multiple reflection type, a multi-turn type, and a spiral type.

[Example 2]
The apparatus configuration of the present embodiment is exactly the same as that of FIG. In the present embodiment, as shown in the flow of FIG. 10, the detected ion pulse signals are digitized for each spectrum by the averager 10 and then integrated one after another. Thereafter, the integrated spectrum data is subjected to data processing for subtracting the “inherent noise waveform” by an FPGA circuit provided in the averager, and a final mass spectrum is created.

  The basic difference between the present embodiment and the first embodiment is that the order of the operation in the averager 10 is that the “inherent noise waveform” is removed before the data integration in the first embodiment. In the embodiment, the “inherent noise waveform” is removed after data integration. With either method, almost the same effect can be obtained.

  Widely applicable to time-of-flight mass spectrometers.

Claims (3)

A pulsed ion source;
A time-of-flight spectroscopic unit that performs mass separation by flying ions generated by the pulsed ion source;
An ion detector for detecting ions separated by mass in the time-of-flight spectrometer;
Digitizing means for digitizing the detection signal obtained from the ion detector and converting it into digital data;
Data processing means for obtaining mass spectrum data by performing data processing on the digital data;
In a time-of-flight mass spectrometer equipped with
The data processing means includes noise removal calculation means for removing noise included in the detection signal,
The noise removal calculation means includes:
(1) For digital data consisting of N data points D _n (n = 1, 2,..., N) ordered in time series obtained from the digitizing means, M sets (M is a natural number) of noise removal calculation data obtained by multiplying the signal intensity I _n (n = 1, 2,..., N) by a predetermined coefficient R _m (m = 1, 2,..., M), R ₁ × (I ₁ , I ₂ ,..., I _N ), R ₂ × (I ₁ , I ₂ ,..., I _N ), ..., _RM × (I ₁ , I ₂ ,..., I _N ) Correction data creation means,
(2) The M sets of noise removal calculation data are delayed-shifted in a direction in which time passes by j _m (m = 1, 2,..., M) data points for each set, and then the digital An operation execution means for performing an operation of subtracting from the data;
A time-of-flight mass spectrometer. The time-of-flight mass spectrometer according to claim 1, wherein the data processing means performs an integration process on the corrected data after the noise removal calculation. The time-of-flight mass spectrometer according to claim 1, wherein the data processing means performs the noise removal calculation on the digital data subjected to integration processing.

Images