Quantitative method for high-concentration target compound

Abstract

The invention discloses a quantitative method of a high-concentration target compound and belongs to the technical field of sample detection. The quantitative method comprises the following steps: (S.1) obtaining a corresponding relation between the concentration of a target analyte and the ion signal response intensity for fitting to obtain a quantitative model; (S.2) fitting signal response intensity data obtained by the target compound with gradient concentration according to primary reaction kinetics to obtain a quantitative model; and (S.3) through detection, substituting the sum of ion signal intensities of all products obtained by ionization of a target compound into the quantitative model to obtain a concentration parameter so as to realize quantification. The quantitative method provides a chemical kinetics modeling method for fitting a nonlinear quantitative curve in a wide analyte concentration range for various analytical instruments. The method is not only suitable for a target compound which only generates monomer product ions, but also suitable for a target compound which simultaneously generates monomer product ions and polymer product ions, so that the quantitative capability of an analytical instrument on a target analyte with unknown concentration is greatly improved.

Description

Technical Field

[0001] This invention belongs to the field of IMS detection technology, specifically relating to a quantitative method that can accurately quantify high concentrations of target compounds. Background Technology

[0002] Ion mobility spectrometry (IMS) is an analytical technique that uses an electric field to drive the movement of ions in a neutral gas, separating and detecting ions based on differences in their mobility (K). Due to its advantages such as small size, fast analysis time, high sensitivity, and good specificity, IMS is widely used in various field-based online analysis applications, including clinical diagnostics, food quality control, environmental pollutant monitoring, and national public safety. In recent years, IMS research has mainly focused on improving resolution and the limit of detection (LOD), while relatively little attention has been paid to the linear dynamic range (LDR). Literature statistics show that the dynamic range of IMS technology for detecting small molecule VOCs is approximately 10 ppbv to 1 ppmv. However, in actual industrial production environments, VOC concentrations are usually much higher, reaching tens to hundreds of ppmv.

[0003] Currently, the main methods used in IMS technology to solve the problem of quantification of high-concentration samples are as follows:

[0004] (1) Increase the reduced electric field (E / N) to reduce the influence of matrix effects on the detection sensitivity of high-concentration samples in complex samples (Anal. Chem. 2014, 86, 23), thereby broadening the linear quantitative range of the target analyte;

[0005] (2) Reduce the gas pressure to suppress the recombination process of positive and negative ions in the ionization region and solve the problem of narrow linear dynamic range of high concentration samples (Anal. Chem. 2024, 96, 9). Under the condition of 0.4 bar gas pressure, the linear dynamic range can be widened to twice that under normal pressure.

[0006] (3) The concentration of the analyte can be determined by other indicators in the experiment (such as the half-life Th ​​of peak intensity decay during membrane injection), thereby broadening the linear dynamic range (Sensors 2024, 24, 3106).

[0007] The aforementioned techniques primarily focus on broadening the linear quantitative range of target analytes, achieving quantification through linear standard curves. However, at higher injection concentrations, the target analyte signal still approaches saturation, and existing techniques cannot obtain nonlinear quantitative fitting curves over a wider concentration range. Furthermore, for compounds such as aldehydes, ketones, and alcohols that readily form hydrogen bonds, dimers, trimers, and other polymeric ions are easily formed at higher concentrations. When the analyte contains multiple product ions, accurately constructing quantitative curves based on these complex ion signals remains a problem that needs to be solved. Summary of the Invention

[0008] This invention provides a quantitative method applicable to target compounds at higher concentrations, and particularly applicable to target compounds capable of generating polymeric product ions.

[0009] The technical solution of this invention is based on the fact that it is impossible to obtain a nonlinear quantitative fitting curve when the injection concentration is too high, and it is difficult to accurately construct a quantitative curve for target substances that easily form multimeric ions.

[0010] The specific technical solution is explained below:

[0011] A quantitative method for high-concentration target compounds includes the following steps:

[0012] (S.1) The step of obtaining the correspondence between the concentration of the target analyte and the intensity of the ion signal response, which is used to fit and obtain a quantitative model;

[0013] (S.2) The steps of obtaining a quantitative model based on first-order reaction kinetics and by fitting the signal response intensity data obtained from the target compound at gradient concentrations;

[0014] (S.3) The step of obtaining the concentration parameter by detecting and substituting the sum of the signal intensities of all product ions obtained by ionization of the target compound into the quantitative model to achieve quantification.

[0015] In a preferred embodiment, in step (S.1), firstly, standard gas samples with gradient concentrations are prepared, and then the corresponding signal response intensity is obtained by detection to obtain the corresponding relationship.

[0016] In a preferred embodiment, the detection instrument is an IMS, and the quantitative model is:

[0017] ;

[0018] In the formula:

[0019] S M + The summation of the signal intensities of the product ions obtained from the ionization of the target compound is expressed in mV.

[0020] cM The injection concentration of the target compound is expressed in ppbv.

[0021] Both A and B are constants.

[0022] In a further preferred embodiment, A= ;

[0023] In the formula:

[0024] a represents the product ion signal intensity S M + With product ion number density [S M + The converted value between ];

[0025] According to the definition of current, S M + =[S M + ]qsKE, therefore a is qsKE;

[0026] Where q is the elementary charge, 1.6 * 10⁻⁶ -19 C;

[0027] s is the cross-sectional area of ​​the Faraday disk detector, in cm². 2 ;

[0028] K represents the product ion mobility, measured in cm. 2 / Vs;

[0029] E represents the electric field strength in the migration region, measured in V / cm.

[0030] [AH + [0] represents the number density of reactant ions, i.e., the number of particles per unit volume, expressed in cm³. -3 .

[0031] In a further preferred embodiment, B= ;

[0032] In the formula:

[0033] k is the reaction rate constant, in cm⁻¹. 3 / s;

[0034] t is the reaction time, measured in seconds (s).

[0035] p represents the pressure in the detection system, measured in Pa.

[0036] k B Boltzmann constant, 1.38 × 10⁻⁶ -23 J / K;

[0037] T represents the thermodynamic temperature in the detection system, measured in K.

[0038] In a preferred embodiment, it is used for the quantification of the target compound at a concentration greater than 10 ppbv.

[0039] In a further preferred embodiment, for the quantification of the target compound that generates dimer ions during detection, S M + The summation of the signal intensities of monomeric ions and dimeric ions obtained from the ionization of the target compound.

[0040] In a preferred embodiment, during detection, the IMS performs negative pressure sampling in positive mode.

[0041] In summary, the technical solution described in this invention has the following main beneficial effects:

[0042] Compared with the prior art, the technical solution of the present invention provides a chemical kinetic modeling method for fitting nonlinear quantitative curves over a wide range of analyte concentrations, which is particularly suitable for the detection and quantification of IMS.

[0043] Furthermore, this method is applicable not only to target compounds that produce only monomeric product ions, but also to target compounds that produce both monomeric and polymeric product ions, greatly enhancing the quantitative capabilities of analytical instruments, especially IMS, for target analytes of unknown concentrations.

[0044] Further or more detailed beneficial effects will be described in conjunction with specific embodiments in the detailed implementation. Attached Figure Description

[0045] Figure 1 This is the ion migration spectrum of 2-hexanone standard gas at a concentration of 10 ppb in the specific embodiment;

[0046] Figure 2 This is the trend of peak intensity variation of monomeric and dimer ions obtained from 2-hexanone standard gas within the concentration range of 1~80 ppb in the specific implementation method.

[0047] Figure 3 The nonlinear quantitative curve obtained from 2-hexanone standard gas within the concentration range of 1~80 ppb in the specific implementation method is shown. Detailed Implementation

[0048] The present invention will be further explained in conjunction with the embodiments:

[0049] The core technical problem faced by the technical solutions of this application's embodiments stems from the inventor's accurate understanding of the prior art. Therefore, how to obtain a quantitative method suitable for target compounds at higher concentrations, especially for target compounds that can generate polymer product ions, is a technical problem that the inventor urgently needs to solve.

[0050] It should be noted that the embodiments do not constitute a limitation on the scope of protection of the claims of this invention. All technical solutions that can be reasonably expected by those skilled in the art based on the technical concepts provided / proved by the embodiments should be covered within the scope of protection of the claims of this invention.

[0051] The implementation method is detailed below:

[0052] This embodiment uses IMS detection as an example to provide a quantitative method for high-concentration target compounds based on IMS:

[0053] First, the IMS was set to operate in positive ion mode, with a high voltage of 5000 V, a drift gas flow rate of 200 mL / min, and a migration tube temperature of 100℃. A high-energy vacuum ultraviolet photoionization source was used. An external sampling pump was connected to the IMS exhaust port to achieve negative pressure sampling of the target compound, 2-hexanone, as a standard sample.

[0054] First, a 2-hexanone standard gas with a parent gas concentration of 1 ppmv was diluted with pure compressed air to obtain a gradient concentration standard gas within the range of 1–80 ppbv. During the detection process, the 2-hexanone molecule first undergoes a proton transfer reaction with RIP ions to obtain a protonated monomeric ion, which then clusters with a second 2-hexanone molecule to obtain a protonated dimer ion. The ion migration spectrum is shown in the reference diagram. Figure 1 After ionization of 2-hexanone samples at gradient concentrations, the peak intensities of the monomeric and dimer ions were calculated, and their trends with sample concentration were obtained, as shown below. Figure 2 As shown, the correlation between the concentration of the target analyte and the intensity of the ion signal response can be obtained, which can be used to fit the quantitative model. The fitted curve is shown in the figure. Figure 3 As shown.

[0055] Subsequently, a quantitative model was established based on the first-order reaction kinetic model, and the signal response intensity data obtained from the target compound at gradient concentrations were fitted.

[0056] Specifically, the chemical kinetic model on which this implementation method is based is as follows:

[0057] (1)

[0058] (2)

[0059] Due to monomeric ion M + and dimer ion M2 + During the formation process, only one reactive ion, RIP, is consumed. + Therefore, the total product ion S M + The rate of formation is equal to the rate of consumption of reacting ions, resulting in the chemical reaction rate equation:

[0060] (3)

[0061] Because the ionization efficiency of analytical instruments is generally low, in IMS, the ionization efficiency is only 10. -9 Therefore, the number density of neutral molecules of the analyte in the ionization region ([M], cm⁻¹) can be approximated. -3 The ionization remains unchanged. Solving the indefinite integral of equation (3) yields equation (4):

[0062] (4)

[0063] The expression for the relationship between ion signal intensity and target analyte concentration can be obtained by reorganization, as shown in equation (5):

[0064] (5)

[0065] make , Equation (5) can be simplified to equation (6):

[0066] (6)

[0067] In the above formula:

[0068] S M + The summation of the signal intensities of the product ions obtained from the ionization of the target compound is expressed in mV.

[0069] c M The injection concentration of the target compound is expressed in ppbv.

[0070] a represents the product ion signal intensity S M + With product ion number density [S M + The converted value between ] is a=qsKE;

[0071] q is the elementary charge, 1.6 * 10⁻⁶. -19 C;

[0072] s is the cross-sectional area of ​​the Faraday disk detector, in cm². 2 ;

[0073] K represents the product ion mobility, measured in cm. 2 / Vs;

[0074] E represents the electric field strength in the migration region, measured in V / cm.

[0075] [AH + [0] represents the number density of reactant ions, i.e., the number of particles per unit volume, expressed in cm³. -3 .

[0076] k is the reaction rate constant, in cm⁻¹. 3 / s;

[0077] t is the reaction time, measured in seconds (s).

[0078] p represents the pressure in the detection system, measured in Pa.

[0079] k B Boltzmann constant, 1.38 × 10⁻⁶ -23 J / K;

[0080] T represents the thermodynamic temperature in the detection system, measured in K.

[0081] Both A and B are constants. In this embodiment, A = 4840 and B = 0.11.

[0082] Further calculations were performed to determine the summation of the intensities of each product ion peak as a function of concentration, and the result was fitted to equation (6). Figure 3 As shown, after adjustment R 2 The value is 0.997, proving that the theoretical model and experimental results are highly consistent.

[0083] Subsequently, by actually detecting the target substance at an unknown concentration, the concentration of the target substance can be accurately calculated by substituting its peak intensity into the formula.

[0084] In the description of this specification, the references to terms such as "embodiment," "basic embodiment," "preferred embodiment," "other embodiment," "example," "specific example," or "some examples," etc., indicate that a specific feature, structure, material, or characteristic described in connection with that embodiment or example is included in at least one embodiment or example of the present invention. In this specification, the illustrative expressions of the above terms do not necessarily refer to the same embodiment or example. Furthermore, the specific features, structures, materials, or characteristics described may be combined in any suitable manner in one or more embodiments or examples.

[0085] Although preferred embodiments of the invention have been described, those skilled in the art, upon learning the basic inventive concept, can make other changes and modifications to these embodiments. Therefore, the appended claims are intended to be interpreted as including both the preferred embodiments and all changes and modifications falling within the scope of the invention.

[0086] Obviously, those skilled in the art can make various modifications and variations to this invention without departing from its spirit and scope. Therefore, if these modifications and variations fall within the scope of the claims of this invention and their equivalents, this invention also intends to include these modifications and variations.

Claims

1. A quantitative method for high-concentration target compounds, characterized in that: The steps include the following: (S.1) The step of obtaining the correspondence between the concentration of the target analyte and the intensity of the ion signal response, which is used to fit and obtain a quantitative model; (S.2) The steps of obtaining a quantitative model based on first-order reaction kinetics and by fitting the signal response intensity data obtained from the target compound at gradient concentrations; (S.3) The step of obtaining the concentration parameter by detecting and substituting the sum of the signal intensities of all product ions obtained by ionization of the target compound into the quantitative model to achieve quantification.

2. The quantitative method according to claim 1, characterized in that: In (S.1), firstly, standard gas samples with gradient concentrations are prepared, and then the corresponding signal response intensity is obtained by detection to obtain the corresponding relationship.

3. The quantitative method according to claim 2, characterized in that: In (S.1), a gradient concentration standard gas is prepared in the concentration range of 1 to 80 ppbv.

4. The quantitative method according to claim 1, characterized in that: The detection instrument is IMS, and the quantitative model is: ； In the formula: S M + The summation of the signal intensities of the product ions obtained from the ionization of the target compound is expressed in mV. c M The injection concentration of the target compound is expressed in ppbv. A and B are both constants.

5. The quantitative method according to claim 4, characterized in that: A= ； In the formula: a represents the product ion signal intensity S M + With product ion number density [S M + The converted value between ]; According to the definition of current, S M + =[S M + ]qsKE, therefore a is qsKE; Where q is the elementary charge, 1.6 * 10⁻⁶ -19 C; s is the cross-sectional area of ​​the Faraday disk detector, in cm². 2 ; K represents the product ion mobility, measured in cm. 2 / Vs; E represents the electric field strength in the migration region, measured in V / cm. [AH + [0] represents the number density of reactant ions, i.e., the number of particles per unit volume, expressed in cm³. -3 .

6. The quantitative method according to claim 5, characterized in that: B= ； In the formula: k is the reaction rate constant, in cm⁻¹. 3 / s; t is the reaction time, measured in seconds (s). p represents the pressure in the detection system, measured in Pa. k B Boltzmann constant, 1.38 × 10⁻⁶ -23 J / K; T represents the thermodynamic temperature in the detection system, measured in K.

7. The quantitative method according to claim 4, characterized in that: Used for the quantification of target compounds at concentrations greater than 10 ppbv.

8. The quantitative method according to claim 4 or 7, characterized in that: Used for the quantification of target compounds that generate dimer or polymeric ions during detection.

9. The quantitative method according to claim 8, characterized in that: S M + The summation of the signal intensities of monomeric ions and dimeric ions obtained from the ionization of the target compound.

10. The quantitative method according to claim 4, characterized in that: During testing, IMS performs negative pressure sampling in positive mode.

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