Methods for Improving the Signal-to-Noise Ratio of Mass Spectrometry Signals

Abstract

The present invention relates to mass spectrometry, specifically provides a method for improving the signal-to-noise ratio of mass spectrometry signals, including steps: step 1, obtaining the mass spectrometry signal of the detection time length t1 of the sample, reading the time domain signal, obtaining the first group of peaks of the M before the ordering of peak strength from weak to strong; step 2, obtaining the detection time length t2; step 3, obtaining the mass spectrometry signal of the detection time length t2 of the sample, performing Fourier transform, and obtaining the second group of peaks; step 4, obtaining the consistency Q of the first group of peaks and the second group of peaks; if Q is not less than the second threshold value, enter step 5; if Q is less than the second threshold value, let A1=A1 / Q, enter step 2; step 5, no ions enter the detector, obtain the background signal of the detection time length t2, and normalize; step 6, the mass spectrometry signal of the sample of the detection time length t1 deducts the normalized background signal, and obtains a mass spectrogram. The present invention has the advantages of high signal-to-noise ratio and is applied in mass spectrometry.

Description

Technical Field

[0001] The present invention relates to mass spectrometry technology, and in particular to a method for improving the signal-to-noise ratio of mass spectrometry signals. Background Art

[0002] As a type of high-precision mass spectrometer, the signal of high-resolution mass spectrometer is easily interfered by various factors, such as electromagnetic interference in the laboratory environment, ground loop pollution and chemical noise, etc., resulting in the following technical problems:

[0003] 1. The mass spectrometry data has large noise and low signal-to-noise ratio, which causes the real signals of medium and low responses to be completely submerged in the noise and difficult to identify.

[0004] 2. The mass spectrometry data is interfered with and produces characteristic noise, the amount of characteristic noise is large, and the proportion of real signals is low.

[0005] In order to solve the above technical problems, the following technical solutions are usually adopted:

[0006] 1. Set a certain noise threshold, calculate the mean value of the noise and the standard deviation of the noise σ, cut the lower part of the mass spectrum at a certain intensity threshold, and then subtract the threshold from the remaining data points of the mass spectrum.

[0007] The shortcoming of this solution is that by performing data processing on the spectrum and setting a threshold to subtract the baseline, the real signal of low abundance will be subtracted together, resulting in signal loss.

[0008] 2. Referring to patent CN101088096A, the frequency data range is limited, and it is believed that the proportion of real signals is higher in shorter detection time. Therefore, the first 25% of the data in the time domain is transformed to the frequency domain, and then the threshold is set to subtract noise to improve the signal-to-noise ratio of the real signal.

[0009] The shortcoming of this solution is that the data results of mass spectrometry vary greatly under different resolutions and responses, and the fixed method of extracting the first 25% and setting the threshold cannot adapt to various conditions.

[0010] 3. Referring to patent WO2005031791A2, the signal peak range is determined by fitting the peak, the mass spectrum peak is fitted according to Gaussian distribution, and the results within the range of 2.5 times the standard deviation are identified as signal peaks.

[0011] The disadvantages of this solution are: the Gaussian fitting method is computationally complex, requires multiple iterations, has a large amount of calculations, and has a slow processing speed. Summary of the invention

[0012] In order to solve the deficiencies in the above-mentioned prior art solutions, the present invention provides a method for improving the signal-to-noise ratio of a mass spectrometry signal.

[0013] The objective of the present invention is achieved through the following technical solutions:

[0014] A method for improving the signal-to-noise ratio of a mass spectrometry signal comprises the following steps:

[0015] Step 1, obtain the mass spectrum signal of the sample with a detection time t1, perform Fourier transform on the mass spectrum signal, obtain the basic noise intensity N1, the maximum peak intensity N2, and obtain the first group of peaks with a signal-to-noise ratio greater than the first threshold A1 and a peak intensity ranked from weak to strong;

[0016] Read the time domain signal and obtain the maximum value S1 and the minimum value S2;

[0017] Step 2: Get the detection time ;

[0018] Step 3, obtaining the mass spectrum signal of the sample with a detection time t2, and performing Fourier transform to obtain a second group of peaks with a signal-to-noise ratio greater than the first threshold A1 and a peak intensity ranked from weak to strong;

[0019] Step 4, obtaining the consistency Q of the first group of peaks and the second group of peaks;

[0020] If Q is not less than the second threshold, go to step 5;

[0021] If Q is less than the second threshold, set A1=A1 / Q and go to step 2;

[0022] Step 5: No ions enter the detector, and the background signal of the detection time t2 is obtained and normalized;

[0023] Step 6: The mass spectrum signal of the sample with a detection time of t1 is deducted from the normalized background signal, and then Fourier transform is performed to obtain a mass spectrum.

[0024] Compared with the prior art, the present invention has the following beneficial effects:

[0025] 1. Compared with the noise threshold subtraction method, it can retain more low-abundance targets and increase the sensitivity of individual low-abundance isotope signals by about 1.4 times;

[0026] 2. The pre-selected time domain signal segments are determined by linking parameter settings with mass spectrometry data, which can well adapt to mass spectrometry data with different resolutions and responses, and can quickly switch between different demand ranges;

[0027] 3. The processing speed is improved. The processing speed in the time domain is faster, and the noise data is greatly reduced, and the subsequent FFT calculation time is significantly reduced. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] The disclosure of the present invention will become easier to understand with reference to the accompanying drawings. It is easy for those skilled in the art to understand that these drawings are only used to illustrate the technical solution of the present invention and are not intended to limit the scope of protection of the present invention. In the drawings:

[0029] Figure 1 Schematic diagram of a process for improving the signal-to-noise ratio of a mass spectrometry signal according to the present invention. DETAILED DESCRIPTION

[0030] Figure 1 The following description describes optional specific embodiments of the present invention to teach those skilled in the art how to implement and reproduce the present invention. In order to teach the technical solution of the present invention, some conventional aspects have been simplified or omitted. Those skilled in the art will understand that variations or replacements derived from these specific embodiments will be within the scope of the present invention. Those skilled in the art will understand that the following features can be combined in various ways to form multiple variations of the present invention. Thus, the present invention is not limited to the following optional specific embodiments, but is only limited by the claims and their equivalents.

[0031] Example 1.

[0032] A method of improving the signal-to-noise ratio of a mass spectrometer signal in this embodiment is as follows: Figure 1 As shown, including:

[0033] Step 1: Obtain the mass spectrum signal of the sample with a detection time t1, perform Fourier transform on the mass spectrum signal, obtain the basic noise intensity N1, the maximum peak intensity N2, and obtain the first group of peaks with a signal-to-noise ratio greater than the first threshold A1 and a peak intensity ranked from weak to strong.

[0034] Read the time domain signal and obtain the maximum value S1 and the minimum value S2.

[0035] Step 2: Get the detection time .

[0036] Step 3: Obtain the mass spectrum signal of the sample with a detection time t2, and perform Fourier transform to obtain a second group of peaks with a signal-to-noise ratio greater than the first threshold A1 and a peak intensity ranked from weak to strong.

[0037] Step 4: Obtain the consistency Q of the first group of peaks and the second group of peaks. The consistency is evaluated by the intra-group correlation coefficient. The sample data is the mass-to-charge ratio m / z of M peaks.

[0038] Q=(MS b -MS w ) / ( MS b +MS w ), MS b is the mean square of m / z between groups, MS w is the mean square of m / z within the group.

[0039] If Q is not less than the second threshold, such as 0.95, go to step 5.

[0040] If Q is less than the second threshold, such as 0.91, set A1=A1 / Q=3 / 0.91 and go to step 2.

[0041] The larger the second threshold is, the better the consistency is. The specific value is determined according to the requirements: the higher the requirements are, the larger the second threshold is.

[0042] Step 5: No ions enter the detector, and the background signal of the detection time t2 is obtained and normalized.

[0043] Step 6: The mass spectrum signal of the sample with a detection time of t1 is deducted from the normalized background signal, and then Fourier transform is performed to obtain a mass spectrum.

[0044] In order to obtain an accurate M value, M is further obtained as follows:

[0045] M=[k·N3 / N1], k increases as N3 / N1 increases, and N3 is the total ion current intensity obtained after the mass spectrometer signal undergoes Fourier transformation. If the obtained M is less than 10, it indicates that the obtained mass spectrometer signal does not meet the requirements, and the mass spectrometer signal needs to be obtained again until M is not less than 10.

[0046] The value of k is:

[0047] If N3 / N1<1E4, k=0.0003; if 1E4≤N3 / N1≤1E5, k=0.0004; if 1E5 <N3 / N1<1E6,k=0.0007。

[0048] To maintain consistency, further, in step 1, step 3 and step 5, the scanning parameters are the same, and the parameters include sampling time, frequency, sampling bit number and signal gain.

[0049] In order to accurately obtain the background signal, further, in step 5, the ion lens is closed and no ions enter the detector.

[0050] In order to ensure the technical effect, further, in step 6, after obtaining multiple mass spectra or reaching the set time, return to step 1.

[0051] Example 2.

[0052] An application example of the method for improving the signal-to-noise ratio of a mass spectrometry signal according to Example 1 of the present invention.

[0053] In this application example, Figure 1 As shown, the method for improving the signal-to-noise ratio of a mass spectrometer signal comprises the steps of:

[0054] Step 1: Obtain the mass spectrometry signal of the sample (a mixture containing caffeine, MRFA and Ultramark 1621) with a detection time of t1 = 100 ms, perform Fourier transform on the mass spectrometry signal, obtain the basic noise intensity N1 = 6E4, the maximum peak intensity N2 = 2E8 and the total ion current intensity N3 = 6E9. Calculate the peak selection number M.

[0055] 1E4≤N3 / N1=1E5≤1E5, k=0.0004; M=[k·N3 / N1]=40.

[0056] A first group of peaks with a signal-to-noise ratio greater than a first threshold value A1=3 and a top 40 peaks ranked from weak to strong are obtained.

[0057] Read the time domain signal and obtain the maximum value S1=500 and the minimum value S2=100.

[0058] Step 2: Get the detection time .

[0059] Step 3: Obtain the mass spectrum signal of the sample with a detection time t2, and perform Fourier transform to obtain a second group of peaks with a signal-to-noise ratio greater than the first threshold A1 and a top 40 peaks ranked from weak to strong.

[0060] Step 4: Obtain the consistency Q of the first group of peaks and the second group of peaks. The consistency is evaluated by the intra-group correlation coefficient. The sample data is the mass-to-charge ratio m / z of 40 peaks.

[0061] Q=(MS b -MS w ) / ( MS b +MS w ), MS b is the mean square of m / z between groups, MS w is the mean square of m / z within the group.

[0062] Q=0.96, which is greater than the second threshold 0.95, so go to step 5.

[0063] Step 5: close the ion lens to prevent ions from entering the detector, obtain the background signal of the detection time t2, and normalize it; the specific normalization method is the prior art in this field.

[0064] Step 6: Deduct the normalized background signal from the mass spectrometry signal of the sample with a detection time of t1 (the mass spectrometry signal obtained in step 1), and then perform Fourier transformation to obtain a mass spectrum. After obtaining multiple mass spectra or reaching the set time, return to step 1.

[0065] In step 1, step 3 and step 5, the scanning parameters are the same, and the parameters include sampling time, frequency, sampling bit number and signal gain.

[0066] Example 3.

[0067] An application example of the method for improving the signal-to-noise ratio of a mass spectrometry signal according to Example 1 of the present invention.

[0068] In this application example, Figure 1 As shown, the method for improving the signal-to-noise ratio of a mass spectrometer signal comprises the steps of:

[0069] Step 1: Obtain the mass spectrometry signal of the sample (including 18 perfluorinated compounds) with a detection time of t1=60ms, perform Fourier transform on the mass spectrometry signal, obtain the basic noise intensity N1=6E4, the maximum peak intensity N2=1E8 and the total ion current intensity N3=3E9. Calculate the peak selection number M.

[0070] E4≤N3 / N1=5E4≤1E5, k=0.0004; M=[k·N3 / N1]=20.

[0071] A first group of peaks with a signal-to-noise ratio greater than a first threshold value A1=3 and a top 20 peak strength ranking from weak to strong is obtained.

[0072] Read the time domain signal and obtain the maximum value S1=300 and the minimum value S2=100.

[0073] Step 2: Get the detection time .

[0074] Step 3: Obtain the mass spectrum signal of the sample with a detection time t2, and perform Fourier transform to obtain a second group of peaks with a signal-to-noise ratio greater than the first threshold A1 and a top 20 peaks ranked from weak to strong.

[0075] Step 4: Obtain the consistency Q of the first group of peaks and the second group of peaks. The consistency is evaluated by the intra-group correlation coefficient. The sample data is the mass-to-charge ratio m / z of 20 peaks.

[0076] Q=(MS b -MS w ) / ( MS b +MS w ), MS b is the mean square of m / z between groups, MS w is the mean square of m / z within the group.

[0077] Q=0.92, which is less than the second threshold 0.95. Let A1=A1 / Q=3 / 0.92=3.15 and go to step 2.

[0078] After n iterations, Q n =0.953>0.95, the first threshold A n =5, t2=68ms, go to step 5.

[0079] Step 5: close the ion lens to prevent ions from entering the detector, obtain the background signal of the detection time t2, and normalize it; the specific normalization method is the prior art in this field.

[0080] Step 6: Detect the mass spectrometry signal of the sample with a time length of t1 (the mass spectrometry signal of step 1 is not used, and the mass spectrometry signal of the sample with a time length of t1 is used again) and deduct the normalized background signal, and then perform Fourier transformation to obtain a mass spectrum. After obtaining multiple mass spectra or reaching the set time, return to step 1.

[0081] In step 1, step 3 and step 5, the scanning parameters are the same, and the parameters include sampling time, frequency, sampling bit number and signal gain.

Claims

1. A method for improving the signal-to-noise ratio of a mass spectrometry signal, comprising the following steps: Step 1, obtaining a mass spectrum signal of the sample with a detection time t1, performing Fourier transform on the mass spectrum signal, and obtaining a basic noise intensity N1 and a maximum peak intensity N2; Read the time domain signal, obtain the maximum value S1 and the minimum value S2, and obtain the first group of peaks with a signal-to-noise ratio greater than a first threshold A1 and a peak strength sorted from weak to strong; Step 2: Get the detection time ; Step 3, obtaining the mass spectrum signal of the sample with a detection time t2, and performing Fourier transform to obtain a second group of peaks with a signal-to-noise ratio greater than the first threshold A1 and a peak intensity ranked from weak to strong; Step 4: Obtain the consistency Q=(MS b -MS w ) / (MS b +MS w ), MS b is the mean square of m / z between groups, MS w is the mean square of m / z within the group; If Q is not less than the second threshold, go to step 5; If Q is less than the second threshold, set A1=A1 / Q and go to step 2; Step 5: No ions enter the detector, and the background signal of the detection time t2 is obtained and normalized; Step 6: The mass spectrum signal of the sample with a detection time of t1 is deducted from the normalized background signal, and then Fourier transform is performed to obtain a mass spectrum.

2. The method for improving the signal-to-noise ratio of a mass spectrometry signal according to claim 1, characterized in that: M is obtained as follows: M=[k·N3 / N1], k increases as N3 / N1 increases, and N3 is the total ion current intensity obtained after Fourier transform of the mass spectrometer signal.

3. The method for improving the signal-to-noise ratio of a mass spectrometry signal according to claim 2, characterized in that: The value of k is: If N3 / N1<1E4, k=0.0003; if 1E4≤N3 / N1≤1E5, k=0.0004; if 1E5 <N3 / N1<1E6,k=0.0007。 4. The method for improving the signal-to-noise ratio of a mass spectrometry signal according to claim 2 or 3, characterized in that: If the obtained M is less than 10, the mass spectrometry signal is obtained again until M is not less than 10.

5. The method for improving the signal-to-noise ratio of mass spectrometry signals according to claim 1, characterized in that: In step 1, step 3 and step 5, the scanning parameters are the same, and the parameters include sampling time, frequency, sampling bit number and signal gain.

6. The method for improving the signal-to-noise ratio of mass spectrometry signals according to claim 1, characterized in that: In step 5, the ion lens is closed and no ions enter the detector.

7. The method for improving the signal-to-noise ratio of mass spectrometry signals according to claim 1, characterized in that: The first threshold value A1=3, and the second threshold value is 0.

95.

8. The method for improving the signal-to-noise ratio of a mass spectrometry signal according to claim 1, characterized in that: In step 6, after a plurality of mass spectra are obtained or the set time is reached, the process returns to step 1.

9. The method for improving the signal-to-noise ratio of a mass spectrometry signal according to claim 1, characterized in that: In step 6, the mass spectrum signal of the detection time length t1 is the mass spectrum signal obtained in step 1, or the mass spectrum signal measured again.

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