Mass spectrometer mass axis calibration device and method

Abstract

The application discloses a mass spectrometer mass axis calibration device and method, containing a one-time nonvolatile memory solidified mass axis calibration lookup table, which realizes mapping conversion of measured mass-to-charge ratio values and standard mass-to-charge ratio values. An analog feature encoder directly encodes analog signals output by a front-stage feature extraction device into digital addresses, inputs the mass axis calibration lookup table, and the lookup table outputs corresponding accurate mass-to-charge ratio values according to the addresses. The application solves the problems of existing mass spectrometer mass axis calibration, such as delay, easy drift and easy tampering, caused by dependence on software algorithms, realizes nanosecond-level real-time calibration of the mass axis, and significantly improves quantitative accuracy, long-term stability and data security of the mass spectrometer.

Description

Technical Field

[0001] This invention relates to the field of mass spectrometry analysis technology, and in particular to a mass axis calibration device and method for a mass spectrometer. Background Technology

[0002] Mass spectrometers analyze the composition and content of samples by measuring the mass-to-charge ratio of ions. The accuracy of the mass axis is one of the most critical performance indicators of a mass spectrometer, directly determining the reliability of qualitative and quantitative analysis results. Due to factors such as temperature changes, mechanical vibration, aging of electronic components, and vacuum fluctuations, the mass axis of a mass spectrometer can drift during operation, thus requiring periodic calibration.

[0003] Current mass spectrometers generally employ a software-driven approach for mass axis calibration: during analysis, standards are periodically injected, and software algorithms acquire the mass spectra of the standards, calculate the deviation between the measured mass number and the standard mass number, and then adjust the calibration parameters of the mass axis using software. Some high-end mass spectrometers also employ adaptive calibration algorithms based on real-time signal quality feedback, which can automatically adjust the calibration frequency and calibration parameters.

[0004] This traditional software calibration method has the following serious drawbacks: First, the calibration latency is high, making real-time calibration impossible. Software calibration requires multiple steps, including standard sample injection, data acquisition, algorithm calculation, and parameter updates, a process that typically takes several minutes or even longer. During this time, mass axis drift cannot be corrected in time, leading to errors in the analytical results. For rapidly changing samples and online monitoring applications, this latency is unacceptable.

[0005] Second, calibration parameters are easily tampered with, resulting in poor data security. Calibration parameters are stored in erasable and rewritable memory, which can be arbitrarily modified by software. Attackers can falsify analysis results by altering calibration parameters, which could have serious consequences in areas such as food safety supervision, environmental enforcement, and forensic identification.

[0006] Third, adaptive calibration algorithms suffer from uncertainties and low reliability. Adaptive calibration algorithms based on real-time signal quality feedback are susceptible to noise, interference, and abnormal samples, potentially leading to erroneous calibration results or even severe deviations from the mass axis. Furthermore, the software algorithms themselves contain vulnerabilities and flaws, which may result in calculation errors and program crashes.

[0007] Fourth, poor long-term stability. Software calibration can only be performed at discrete time points, making it impossible to continuously monitor and correct mass axis drift. Between calibrations, mass axis drift gradually accumulates, leading to a gradual decrease in the accuracy of analytical results. This problem is particularly prominent for online monitoring mass spectrometers that require long-term continuous operation. Summary of the Invention

[0008] The purpose of this invention is to overcome the above-mentioned shortcomings of the prior art and provide a mass axis calibration device and method for a mass spectrometer. It uses a disposable non-volatile memory to store the mass axis calibration lookup table and realizes real-time calibration of the mass axis through a pure hardware lookup table method without the need for any software algorithm. This fundamentally solves the problems of high latency, easy tampering, and poor reliability of the prior art.

[0009] To achieve the above objectives, the present invention adopts the following technical solution: A mass axis calibration device for a mass spectrometer includes a mass axis calibration lookup table stored in a disposable non-volatile memory. This lookup table maps and converts measured mass-to-charge ratio values ​​to standard mass-to-charge ratio values. An analog feature encoder directly encodes the analog signal output from the preceding feature extraction device into a digital address, which is then input into the mass axis calibration lookup table. The lookup table outputs the corresponding accurate mass-to-charge ratio value based on the address. The device does not contain any adaptive calibration algorithm based on real-time signal quality feedback.

[0010] Furthermore, a real-time mass axis drift compensation circuit is also provided, with temporary compensation coefficients superimposed on the calibration curve stored in a one-time non-volatile memory, which is automatically cleared after the device is powered off.

[0011] Furthermore, a quality discrimination compensation module is also included, with the compensation coefficients fixed at the factory and automatically looking up a table to complete the compensation each time the hardware performs an analysis.

[0012] Furthermore, a standard sample signal strength adjustment circuit and a standard sample stability monitoring circuit are also provided.

[0013] Furthermore, a calibration frequency adaptive circuit and a calibration failure degradation processing circuit are also provided.

[0014] Furthermore, a retention time drift tracking circuit and a standard curve anomaly detection circuit are also included.

[0015] Furthermore, it is equipped with an internal standard interference detection circuit and a space charge effect compensation circuit.

[0016] Furthermore, the mass axis calibration lookup table is stored using a piecewise linear interpolation method for compressed storage. Beneficial effects

[0017] Compared with the prior art, the present invention has the following significant advantages: 1. Extremely low calibration latency, enabling nanosecond-level real-time calibration. This invention employs a pure hardware lookup table method for mass axis calibration, completely eliminating the need for software calculations and parameter updates, reducing calibration latency to the nanosecond level. This means that mass axis calibration is performed in real-time during signal processing, without any time lag, enabling timely correction of minute drifts in the mass axis and ensuring the highest accuracy in the mass-to-charge ratio measurement of each ion signal. This has revolutionary significance for applications such as high-speed scanning mass spectrometry and rapid chromatography-mass spectrometry.

[0018] 2. Calibration parameters are absolutely safe and cannot be tampered with. The mass axis calibration lookup table and all calibration parameters of this invention are stored in a one-time non-volatile memory, which is fixed at the factory and cannot be modified, erased, or rewritten in any way during operation. This fundamentally eliminates the possibility of malicious tampering with calibration parameters, ensures the authenticity and reliability of mass spectrometry analysis data, and fully meets the stringent data security requirements of forensic identification, law enforcement supervision, and other fields.

[0019] 3. The calibration results are stable and reliable, with no uncertainty. This invention does not contain any adaptive calibration algorithms based on real-time signal quality feedback; all calibration logic is fixed and predictable. The calibration results depend only on the factory-fixed calibration lookup table and the real-time acquired signal, and are unaffected by noise, interference, or abnormal samples. There are no uncertainties or vulnerabilities inherent in software algorithms. This significantly improves the reliability and consistency of mass axis calibration.

[0020] 4. Excellent long-term stability and low maintenance costs. This invention combines a factory-installed high-precision calibration lookup table with a real-time mass axis drift compensation circuit, maintaining extremely high mass axis accuracy throughout the instrument's entire lifespan. The real-time drift compensation circuit automatically corrects short-term drift caused by factors such as temperature changes and electronic component aging, while the installed calibration lookup table ensures long-term stability. This significantly reduces instrument maintenance workload and calibration frequency, lowering user costs.

[0021] 5. High system integration and good compatibility. The device of this invention can be directly connected to the preceding ion signal feature extraction device without modifying other components of the mass spectrometer, and can be seamlessly integrated into existing mass spectrometer products. Furthermore, the device of this invention employs a pure hardware design, resulting in high integration, small size, and low power consumption, making it particularly suitable for portable and on-site rapid detection mass spectrometers. Attached Figure Description

[0022] This application does not include drawings. Detailed Implementation

[0023] The present invention will now be described in detail with reference to specific embodiments.

[0024] The mass axis calibration device for a mass spectrometer disclosed in this invention is integrated into a dedicated control chip of the mass spectrometer, located between the pre-stage ion signal feature extraction device and the post-stage data processing unit. The entire device consists of pure hardware circuitry and a one-time non-volatile memory, and does not contain any processor, microcontroller, digital signal processor, or programmable logic device. All calibration logic is implemented through combinational logic circuits and sequential logic circuits.

[0025] The one-time non-volatile memory uses a fuse-type one-time programmable memory. All calibration parameters, lookup table data, compensation coefficients, and thresholds are fixed at the factory by blowing the fuse once using a dedicated device. Once fixed, this data cannot be modified, erased, or rewritten throughout the entire lifespan of the device.

[0026] The mass axis calibration lookup table is precisely calibrated using a series of standards during factory calibration. During calibration, various standard compounds with known mass-to-charge ratios are used, and their corresponding measured mass-to-charge ratio values ​​are measured under different experimental conditions to establish a mapping relationship between the measured mass-to-charge ratio and the standard mass-to-charge ratio. To save storage space, the lookup table is compressed and stored using piecewise linear interpolation, and the interpolation coefficients are also permanently stored in disposable non-volatile memory.

[0027] The analog feature encoder directly receives the analog voltage signal output from the preceding feature extraction device. The amplitude of this voltage signal is proportional to the measured mass-to-charge ratio of the ion. The analog feature encoder converts the continuous analog voltage signal into discrete digital addresses, which are directly used as input addresses for the mass axis calibration lookup table. The lookup table outputs the corresponding standard mass-to-charge ratio value based on the input address, completing the mass axis calibration. The entire process is implemented entirely by hardware circuitry, requiring no software intervention and exhibiting extremely low latency.

[0028] During each analysis, the real-time mass axis drift compensation circuit automatically acquires the signal peak positions of standard background ions present in the mass spectrometer. The mass-to-charge ratios of these standard background ions are known and stable. The measured positions are compared with the fixed standard positions stored in a disposable non-volatile memory to automatically calculate the current mass axis offset and update the temporary compensation coefficients. These temporary compensation coefficients are superimposed on the fixed calibration curve to correct the output mass-to-charge ratio value in real time. The temporary compensation coefficients are stored in volatile memory and are automatically cleared when the device is powered off, without affecting the fixed calibration data.

[0029] The mass discrimination compensation module is used to correct for response differences between ions of different masses during mass spectrometry transmission. At the factory, response factors for different mass ions are obtained through measurements with a series of standards with varying mass-to-charge ratios, and these response factors are stored in a disposable non-volatile memory. During actual analysis, this module automatically looks up the corresponding response factor based on the output mass-to-charge ratio value, compensating for the signal intensity and improving the accuracy of quantitative analysis.

[0030] At the beginning of each calibration, the standard signal intensity adjustment circuit first uses a low concentration of standard to detect the signal intensity. Based on the response, it automatically adjusts the injection volume or detector gain to ensure the standard signal intensity is within the optimal linear range. During each online calibration, the standard stability monitoring circuit compares the relative abundance of each signal peak in the standard with the values ​​of the standard spectrum stored in a disposable non-volatile memory to determine whether the standard has deteriorated or become contaminated.

[0031] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A mass axis calibration device for a mass spectrometer, characterized in that, It includes a mass axis calibration lookup table with one-time non-volatile memory, which enables the mapping and conversion between measured mass-to-charge ratio values ​​and standard mass-to-charge ratio values; The analog feature encoder directly encodes the analog signal output from the front-end feature extraction device into a digital address, and inputs the digital address into the mass axis calibration lookup table; the lookup table outputs the corresponding accurate mass-to-charge ratio value based on the address; it does not contain any adaptive calibration algorithm based on real-time signal quality feedback.

2. The apparatus according to claim 1, characterized in that, It is also equipped with a real-time mass axis drift compensation circuit. During each analysis, the hardware automatically collects the signal peak position of the standard background ions, compares it with the standard value solidified in the disposable non-volatile memory, automatically calculates the offset value and updates the temporary compensation coefficient. The temporary compensation coefficient is superimposed on the calibration curve solidified in the disposable non-volatile memory. The temporary compensation coefficient is automatically cleared after the device is powered off.

3. The apparatus according to claim 1, characterized in that, It also features a mass discrimination compensation module. At the time of manufacture, the response factors of ions of different masses are tested using standard samples, and the corresponding compensation coefficients are stored in a disposable non-volatile memory. The hardware automatically looks up the table to complete the compensation based on the mass-to-charge ratio value each time it performs an analysis.

4. The apparatus according to claim 1, characterized in that, It is also equipped with a standard sample signal intensity adjustment circuit and a standard sample stability monitoring circuit. The standard sample signal intensity adjustment circuit first uses a low concentration of standard sample to detect the signal intensity during the initial stage of calibration, and automatically adjusts the injection volume or detector gain based on the response result. The standard sample stability monitoring circuit compares the relative abundance of each signal peak of the standard sample with the standard spectrum value solidified in a disposable non-volatile memory during each online calibration.

5. The apparatus according to claim 1, characterized in that, It is also equipped with a calibration frequency adaptive circuit and a calibration failure degradation processing circuit; the calibration frequency adaptive circuit records the offset value of each calibration and automatically adjusts the calibration interval according to the offset change trend; the calibration failure degradation processing circuit executes a degradation operation strategy according to the rules of the one-time non-volatile memory when the calibration fails.

6. The apparatus according to claim 1, characterized in that, It is also equipped with a retention time drift tracking circuit and a standard curve anomaly detection circuit; the retention time drift tracking circuit automatically records the retention time of the main signal peak when analyzing the standard and compares it with the reference value solidified in a one-time non-volatile memory; the standard curve anomaly detection circuit automatically calculates the residual and coefficient of determination of each data point after the standard curve is established.

7. The apparatus according to claim 1, characterized in that, It is also equipped with an internal standard interference detection circuit and a space charge effect compensation circuit; the internal standard interference detection circuit performs a pre-scan on the mixed internal standards before analysis and compares the response values ​​with those of a single internal standard solidified in a disposable non-volatile memory; when the ion flux of the space charge effect compensation circuit exceeds the solidification threshold of the disposable non-volatile memory, it automatically corrects the output mass-to-charge ratio and signal peak intensity.

8. The apparatus according to claim 1, characterized in that, The mass axis calibration lookup table is compressed and stored using a piecewise linear interpolation method, and the interpolation coefficients are fixed in a one-time non-volatile memory; a hardware safety monitoring circuit is also provided to detect abnormal operating conditions of the internal circuit of the equipment.

9. The apparatus according to claim 8, characterized in that, The hardware security monitoring circuit includes a hardware Trojan detection sub-circuit, which detects changes in circuit delay through monitoring units deployed inside the chip to determine whether there is a risk of abnormal operation.

10. The apparatus according to claim 8, characterized in that, The hardware security monitoring circuit includes a physical unique identifier generation sub-circuit, which uses process differences in chip manufacturing to generate a unique identifier for the security protection of data in one-time non-volatile memory.