CN120369870A

CN120369870A - Organic sample analysis method and chromatograph based on micro gas chromatography

Info

Publication number: CN120369870A
Application number: CN202510846784.8A
Authority: CN
Inventors: 徐满满; 徐干干
Original assignee: Shanghai Zhensu Automation Technology Co ltd
Current assignee: Shanghai Zhensu Automation Technology Co ltd
Priority date: 2025-06-24
Filing date: 2025-06-24
Publication date: 2025-07-25
Anticipated expiration: 2045-06-24
Also published as: CN120369870B

Abstract

The invention discloses an organic sample analysis method and a chromatographic analyzer based on micro gas chromatography, and specifically relates to the technical field of micro gas chromatography analysis, and is used to solve the problems of unstable separation performance and low detection accuracy of complex samples caused by insufficient uniformity of stationary phase coating in existing micro chromatographic columns; the initial profile of stationary phase distribution is constructed by continuous pre-flushing of carrier gas, segmented temperature gradient, micro-negative pressure and directional pulse flow are alternately applied to reshape the uniform distribution layer, a correction factor set of temperature-resistance coupling relationship is generated by combining a correction mixture with a tracer gas pulse, the carrier gas flow rate and temperature program are dynamically adjusted to generate a matching operation curve, high-precision separation detection and quantitative analysis are achieved, and stable separation performance is maintained in a miniaturized structure by coordinated control of stationary phase distribution optimization and real-time parameter feedback correction, thereby improving the detection accuracy and reproducibility of wide boiling range organic mixtures.

Description

Organic sample analysis method and chromatograph based on micro gas chromatography

Technical Field

The invention relates to the technical field of micro gas chromatography, in particular to an organic sample analysis method and a chromatograph based on micro gas chromatography.

Background

The miniature gas chromatography can obviously improve the portability and the analysis speed of equipment by miniaturizing the traditional gas chromatography system, so that the miniature gas chromatography is suitable for the requirement of rapidly detecting organic samples on site. During miniaturization, the size reduction of the chromatographic column causes challenges to the internal stationary phase coating process, and the prior art generally adopts a micromachining means to realize the loading of the stationary phase in the miniature column. However, limited by the physical dimensions and processing accuracy of the miniature chromatographic column, uniformity control of the stationary phase coating can affect the separation performance of the system.

In the existing micro gas chromatography, contradiction exists between the uniformity of a stationary phase coating of a micro chromatographic column and the separation capacity, so that the separation efficiency of a multi-component sample is difficult to be considered while the high column efficiency is maintained, and the high-precision separation capability of a complex organic mixture is restricted.

Disclosure of Invention

In order to overcome the above-mentioned drawbacks of the prior art, embodiments of the present invention provide a micro-gas chromatography-based organic sample analysis method and chromatograph to solve the problems set forth in the background art.

In order to achieve the above purpose, the present invention provides the following technical solutions:

A method for analyzing an organic sample based on micro gas chromatography, comprising:

s1, continuously pre-flushing carrier gas to a micro chromatographic column and collecting pressure waveforms to construct a stationary phase distribution initial section;

S2, alternately applying a sectional temperature gradient, micro negative pressure and directional pulse flow on the basis of the initial section of stationary phase distribution, and reshaping to form a stationary phase uniform distribution layer;

s3, injecting correction mixture and trace inert trace gas pulse into the stationary phase uniform distribution layer, obtaining correction peak retention time and trace gas lag time difference, and generating correction factor sets;

S4, dynamically adjusting a carrier gas flow rate and temperature program according to the correction factor set, and establishing an operation curve matched with the stationary phase uniform distribution layer;

S5, loading an organic sample to be detected to a micro chromatographic column with a stationary phase uniform distribution layer under the condition of an operation curve, completing component separation and recording peak signals in real time;

and S6, outputting quantitative results of all components according to the corresponding relation between the peak signal and the peak retention time and the delay time difference of the trace gas.

In a preferred embodiment, continuously pre-flushing carrier gas to the micro chromatographic column and collecting pressure waveforms, constructing a stationary phase distribution initial profile, comprising:

stably introducing carrier gas into the micro chromatographic column and arranging a pressure sensor at an inlet end to acquire continuous pressure data;

Filtering the continuous pressure data to form a pressure waveform curve;

inverting the stationary phase axial resistance distribution according to the pressure waveform curve and generating a stationary phase distribution initial section.

In a preferred embodiment, the alternating application of a segmented temperature gradient, micro negative pressure and directed pulse flow based on the initial profile of the stationary phase distribution, the reshaping to form a stationary phase uniform distribution layer, comprises:

Dividing a plurality of independent temperature areas along the axial direction of the micro chromatographic column based on the stationary phase distribution initial section, wherein the temperature gradient difference value of each independent temperature area is in a preset range, and applying temperature in sections through a thin film heater attached to the outer wall of the chromatographic column;

After the temperature gradient is applied, connecting a vacuum pump at the outlet end of the micro chromatographic column to generate micro negative pressure, wherein the pressure range of the micro negative pressure is adapted to the structural strength of the micro chromatographic column;

injecting carrier gas into the inlet end of the micro chromatographic column in a pulse form during the action of micro negative pressure, wherein the pulse frequency and the duration are adapted to the hydrodynamic characteristics of carrier gas flow;

And alternately executing temperature gradient application, micro negative pressure generation and pulse carrier gas injection, wherein the circulation times are adapted to the uniformity variation trend of the stationary phase coating thickness distribution until the stationary phase coating thickness distribution meets the preset uniformity standard.

In a preferred embodiment, injecting a correction mixture and a trace of inert tracer gas pulses into the stationary phase uniformly distributed layer, obtaining a correction peak retention time and a tracer gas lag time difference and generating a correction factor set, comprising:

alternately injecting correction mixture and inert tracer gas pulses into the stationary phase uniform distribution layer;

synchronously capturing and correcting the separation peak shapes of different boiling point components in the mixture and the diffusion peak shapes of the trace gas by a thermal conductivity detector, and extracting the peak time of each separation peak shape and the trailing time of the diffusion peak shape;

Based on the time domain difference of the vertex time and the tailing time, combining the axial temperature distribution data of the stationary phase uniform distribution layer to construct a diffusion resistance compensation coefficient of each boiling point component;

And gradually matching the diffusion resistance compensation coefficient with a theoretical value in a standard retention time database to generate a correction factor set containing a temperature-resistance coupling relation, and sequencing the priority of the gradual matching according to the polarity difference of the boiling point components.

In a preferred embodiment, wherein the timing of injection of the correction mixture and the interval of the trace gas pulses are dynamically adjusted based on the porosity gradient of the stationary phase uniform distribution layer.

In a preferred embodiment, dynamically adjusting the carrier gas flow rate and temperature program according to the correction factor set to establish an operating curve matching the stationary phase uniform distribution layer comprises:

based on a temperature-resistance coupling relation in the correction factor set, splitting boiling point components of a sample to be detected into two types of high priority and low priority according to polarity priority;

For the high-priority components, according to the corresponding diffusion resistance compensation coefficient, the carrier gas flow velocity is gradually increased along the axial position of the stationary phase uniform distribution layer, and the flow velocity increasing amplitude is positively correlated with the compensation coefficient;

for the low-priority components, the axial temperature distribution data of the stationary phase uniform distribution layer are combined, and the temperature gradient of each section is taken as a median value, so that the temperature rising rate range of the temperature program is symmetrically expanded;

And recombining the adjusted carrier gas flow rate and temperature program according to the outflow sequence of boiling components to generate an operation curve containing a sectional flow rate control instruction and a nonlinear temperature gradient, wherein the recombination process ensures that the flow rate and the temperature change rate between adjacent sections are continuously conductive.

In a preferred embodiment, loading an organic sample to be tested onto a micro chromatographic column of a stationary phase uniform distribution layer under the condition of an operation curve, completing component separation and recording peak signals in real time, comprising:

Loading an organic sample to be tested to an inlet of a miniature chromatographic column through a microliter syringe, wherein the loading volume is adapted to the adsorption capacity of a stationary phase uniform distribution layer;

According to the sectional flow speed control instruction in the operation curve, switching the carrier gas flow speed to a target value section by section, wherein the time interval of the switching process is matched with the theoretical outflow time window of the boiling point component;

Synchronously running a nonlinear temperature gradient program in a curve, and controlling the temperature rise rate of a thin film heater on the outer wall of the miniature chromatographic column, wherein the rate of change is consistent with the temperature gradient difference value between adjacent sections;

Capturing the separated component peak signals through a thermal conductivity detector, recording the peak signals in real time in a time-voltage waveform, wherein the waveform sampling frequency is adapted to the minimum resolution of peak shape half peak width;

And (3) carrying out time sequence alignment on the recorded peak signals and theoretical retention time in the correction factor set, and generating a peak sequence to be analyzed after time axis calibration.

In a preferred embodiment, the outputting of the quantitative results of each component based on the peak signal versus peak retention time and trace gas lag time, comprises:

baseline correction is carried out on the peak sequence to be analyzed after the time axis calibration, and the peak areas of the corrected peak signals are calculated through an integral algorithm;

based on the temperature-resistance coupling relation in the correction factor set, matching theoretical retention time and diffusion resistance compensation coefficient corresponding to each peak to generate a conversion factor of peak area and concentration;

The time axis alignment error of the conversion factor is adjusted by combining the compensation quantity of the trace gas lag time difference to the peak retention time, and the compensation quantity is calculated by the product of the lag time difference and the carrier gas flow rate;

multiplying the adjusted conversion factors by peak areas to obtain concentration values of all components, sequencing the concentration values according to the outflow sequence of boiling components, and outputting a quantitative result table.

In another aspect, the present invention provides a chromatograph for analysis of an organic sample based on micro gas chromatography, comprising:

The carrier gas supply module is configured to continuously introduce carrier gas into the micro chromatographic column and is connected with the pressure sensor at the inlet end so as to collect continuous pressure waveform data;

The stationary phase regulating and controlling module is configured to alternately apply a sectional temperature gradient, a micro negative pressure and a pulse carrier gas flow on the basis of the initial section of stationary phase distribution of the micro chromatographic column so as to remodel to form a stationary phase uniform distribution layer;

The correction factor generation module is configured to inject correction mixture and trace inert trace gas pulse into the stationary phase uniform distribution layer, obtain correction peak retention time and trace gas lag time difference, and generate a correction factor set;

the dynamic parameter control module is configured to dynamically adjust a carrier gas flow rate and temperature program according to the correction factor set, and establish an operation curve matched with the stationary phase uniform distribution layer;

The separation detection module is configured to load an organic sample to be detected to the miniature chromatographic column under the condition of an operation curve, and record a separated peak signal in real time;

the quantitative output module is configured to output quantitative results of all components according to the corresponding relation between the peak signals and the retention time and the lag time difference in the correction factor set;

A processor and a memory storing a correction factor set and an operating curve generation algorithm.

In another aspect, the processor is configured to:

Generating a stationary phase distribution initial section according to continuous pressure waveform data acquired by a pressure sensor;

Controlling the stationary phase regulating and controlling module to execute alternate application operation;

Controlling a correction factor generation module to acquire retention time and lag time difference;

controlling a dynamic parameter control module to generate an operation curve;

Controlling a separation detection module to record peak signals;

And controlling the quantitative output module to generate a quantitative result.

Compared with the prior art, the invention has the following beneficial effects:

1. the invention obviously improves the separation precision and stability of the miniature gas chromatographic system by dynamically regulating and controlling the stationary phase coating distribution and the real-time feedback correction mechanism. Aiming at the difficult problem of uniformity control of the stationary phase coating of the miniature chromatographic column, the physical distribution characteristic of the stationary phase is directionally regulated in the carrier gas flowing process by adopting a mode of alternately acting the sectional temperature gradient and the micro negative pressure, so that the thickness of the coating tends to be consistent on a microscopic scale. Through the synergistic effect of pressure waveform inversion and dynamic parameter adjustment, the separation capacity of the chromatographic column is effectively expanded while the high column efficiency is ensured, so that components with different boiling points and polarities in a complex organic mixture can be separated with high resolution, and the problem of selectivity reduction caused by uneven coating distribution in the traditional microminiaturization process is solved.

2. The stationary phase thermodynamic response is dynamically associated with the hydrodynamic properties based on a correction factor set of temperature-drag coupling relationships. By feeding back the peak signal and the lag time difference data in real time, the system can adaptively adjust the carrier gas flow rate and the temperature control program, and maintain the stability of separation parameters under the conditions of temperature change and pressure change. The thermal expansion of the stationary phase coating in the micro column and the turbulent interference of carrier gas are effectively inhibited, so that the quantitative analysis result has higher reproducibility and accuracy, and the method is particularly suitable for rapid and accurate detection of trace components and wide boiling range samples.

Drawings

FIG. 1 is a flow chart of a micro gas chromatography based organic sample analysis method of the present invention;

Fig. 2 is a schematic structural diagram of a chromatograph based on micro gas chromatography of the present invention.

Detailed Description

The following description of the embodiments of the present invention will be made clearly and completely with reference to the accompanying drawings, in which it is apparent that the embodiments described are only some embodiments of the present invention, but not all embodiments. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.

Example 1 fig. 1 shows a micro gas chromatography based organic sample analysis method according to the invention, comprising the steps of:

S1, continuously pre-flushing carrier gas to a micro chromatographic column and collecting pressure waveforms to construct an initial profile of stationary phase distribution, wherein the method is specifically implemented as follows:

And stably introducing carrier gas into the micro chromatographic column and setting a pressure sensor at the inlet end to acquire continuous pressure data. The carrier gas is nitrogen or helium with purity not lower than 99.99%, the range of the inlet flow rate is calculated by poiseuille law, for example, the flow rate is controlled to be in the range of 0.5mL/min to 2.0mL/min according to the ratio of the square of the inner diameter of the micro chromatographic column to the viscosity of the carrier gas multiplied by the preset pressure difference. The preset pressure difference is, for example, 80% of the maximum allowable pressure difference between the inlet end and the outlet end of the micro chromatographic column, and the maximum allowable pressure difference is set according to the deformation resistance strength of the micro chromatographic column material and the bearing capacity of the sealing structure, for example, the elastic modulus of the stainless steel material is 200GPa, and the bearing strength of the fluororubber sealing structure is 10MPa. The pressure sensor is a piezoresistive micro-electromechanical system sensor, is arranged at the joint between the inlet end of the micro chromatographic column and the carrier gas conveying pipeline, and has a measuring range of 0kPa to 100kPa, for example, and the measuring range is selected according to the upper limit of the working pressure of the micro chromatographic column, for example, 1.5 times. The sampling frequency is set to be not lower than, for example, 200Hz, the setting is based on the Nyquist sampling theorem, and the sampling frequency is required to be greater than 40Hz when the highest frequency component of carrier gas pressure fluctuation is more than 2 times, for example, the mechanical pulsation fundamental frequency of a carrier gas pump is 20 Hz. The continuous pressure data is converted into digital signals by an analog-to-digital converter with time as an abscissa and a pressure value as an ordinate, the bit number of the analog-to-digital converter is 16 bits, the conversion rate is 1000 times per second, and the pressure fluctuation detail is ensured to be undistorted.

The continuous pressure data is filtered to form a pressure waveform curve. The filtering process uses a low pass digital filter with a cut-off frequency of, for example, 50Hz, which is set on the basis of, for example, 1.5 times the fundamental frequency of the mechanical pulsations of the carrier gas delivery pump, for example, when the fundamental frequency of the mechanical pulsations of the pump is 20Hz, the cut-off frequency is set to 30Hz to cover the harmonics. The filtered data is processed in a sliding window manner, the window length is set in such a way as to cover at least two complete pressure fluctuation periods, for example, the window length is set to 100ms, and the overlapping ratio of adjacent windows is adjusted to be 50% according to the ratio of the window length to the pressure fluctuation period. The data in the window is interpolated by cubic spline to generate a smooth curve, and the density of interpolation nodes is, for example, one data point per millisecond. The vertical axis of the pressure waveform curve is a normalized pressure value, the normalized method is to divide the original pressure data by the maximum pressure fluctuation amplitude after subtracting the initial steady-state pressure value, the initial steady-state pressure value is the average pressure value within 10 seconds to 20 seconds after carrier gas is introduced, and the selection basis of the time window is the shortest time required for the carrier gas flow to reach the steady state.

Inverting the stationary phase axial resistance distribution according to the pressure waveform curve and generating a stationary phase distribution initial section. The inversion process is based on a correction model of Darcy's law, and input parameters comprise a filtered pressure waveform curve, carrier gas flow rate, carrier gas viscosity and the inner diameter of the micro chromatographic column. The carrier gas viscosity is obtained through a table lookup method, for example, table lookup data are derived from a carrier gas physical property parameter database issued by the international standard chemical society, index parameters of the database are real-time monitoring of the temperature of the outer wall of the miniature chromatographic column, a temperature monitoring point is positioned on the surface of the outer wall of the axial center position of the chromatographic column, and the accuracy of a temperature sensor is +/-0.1 ℃ for example. The correction model divides the micro chromatographic column into, for example, 100 to 200 axial micro-segments with equal length, and the setting of the number of the micro-segments is based on the ratio of the total length of the chromatographic column to the minimum distinguishable coating thickness variation interval, for example, when the minimum distinguishable coating thickness interval is 10 μm, the number of the micro-segments corresponding to the total length 1m of the chromatographic column is 100 segments. The pressure drop of each micro-segment is determined by iterative calculation, and the iterative condition is that the difference value of resistance coefficients of two adjacent micro-segments is smaller than 0.01%, and the setting basis of the difference value threshold value is 1/10 of the measurement error range of the resistance coefficients. The output result of the axial resistance distribution of the stationary phase is a resistance coefficient corresponding to each axial position, wherein the resistance coefficient is defined as the product of the coating thickness of the stationary phase and the viscosity of the carrier gas divided by the product of the length of the micro-element section and the cross-sectional area of the column, and the dimension is Pa.s/m 2. The initial profile of stationary phase distribution takes axial position as abscissa and resistance coefficient as ordinate, discrete data points are generated and then form a continuous curve through linear interpolation, the resolution of the axial position is set to be 1% of the total length of the miniature chromatographic column, and the resolution value is calculated by dividing the total length of the chromatographic column by 100.

Obtaining stationary phase axial resistance coefficients of all axial positions in the miniature chromatographic column through inversion of a pressure waveform curve, wherein the axial resistance coefficients represent the resistance degree of stationary phase coating to carrier gas flow, and the dimension is Pa.s/m < 2 >;

the axial resistance coefficients are arranged according to the axial position sequence of the chromatographic column, an axial resistance coefficient distribution curve is generated, the axial position is taken as an abscissa (unit: m) of the curve, the resistance coefficient is taken as an ordinate (unit: pa.s/m < 2 >), and the data are stored as a two-dimensional array containing position-resistance coefficients;

The stationary phase distribution initial section is defined as discretized expression of an axial drag coefficient distribution curve and is used for guiding temperature zone division in the step S2 and porosity gradient calculation in the step S3.

S2, alternately applying a sectional temperature gradient, micro negative pressure and directional pulse flow on the basis of the initial section of stationary phase distribution, and reshaping to form a stationary phase uniform distribution layer, wherein the method is implemented as follows:

Based on the initial profile of stationary phase distribution, a plurality of independent temperature areas are divided along the axial direction of the micro chromatographic column, the temperature gradient difference value of each independent temperature area is in a preset range, and the temperature is applied in sections through a thin film heater attached to the outer wall of the chromatographic column. The number of independent temperature zones is determined according to the fluctuation interval of the resistance coefficient in the initial section of the stationary phase distribution, for example, when the fluctuation amplitude of the resistance coefficient at the axial position is larger than a preset threshold value, the corresponding section is divided into one independent temperature zone, and the preset threshold value is 20% of the average value of the resistance coefficient. The preset range of the temperature gradient difference is determined by the temperature resistance limit of the micro chromatographic column material and the thermal stability of the stationary phase, for example, when the stationary phase is polysiloxane, the upper limit of the temperature gradient difference is set to be 200 ℃ so as to avoid thermal decomposition of the material. The heating power of the film heater is calculated according to the difference value between the length of the temperature area and the target temperature gradient, for example, the heating power of the temperature area with the length of 10cm needs to be applied with 5W/cm < 2> to realize the gradient of 50 ℃/cm, the heating power is dynamically regulated by a PID controller, PID parameters are calibrated by a step response experiment, the step response experiment comprises the steps of applying step voltage to the film heater and recording a temperature change curve, and the proportional coefficient, the integral time and the differential time are regulated according to the overshoot and the stable time of the temperature change curve.

After the temperature gradient is applied, a vacuum pump is connected to the outlet end of the micro chromatographic column to generate micro negative pressure, and the pressure range of the micro negative pressure is adapted to the structural strength of the micro chromatographic column. The pressure range is determined by the elastic deformation limit of the micro chromatographic column material, for example, the maximum negative pressure allowed by the micro chromatographic column made of stainless steel is-5 kPa, and the actual working pressure is set to be-5 kPa to-0.1 kPa so as to avoid column collapse or sealing failure. The pumping rate of the vacuum pump is matched with the target pressure decay time constant according to the inner cavity volume of the micro chromatographic column, for example, when the inner cavity volume is 1mL, the pumping rate is set to be 10mL/min, and the time for reducing the pressure from normal pressure to minus 5kPa is 30 seconds. The operating state of the vacuum pump is monitored in real time through a pressure sensor, and when the fluctuation amplitude of the pressure exceeds a set threshold value, the pumping speed is automatically adjusted to maintain the pressure stability, and the set threshold value is, for example, +/-5% of the fluctuation amplitude of the pressure.

During the micro-negative pressure action, carrier gas is injected into the inlet end of the micro-chromatographic column in a pulse form, and the pulse frequency and duration are adapted to the hydrodynamic characteristics of the carrier gas flow. The pulse frequency is determined by Reynolds number calculation, for example, when the Reynolds number is less than 2000, the pulse frequency is set to 1Hz to 5Hz to avoid disruption of the laminar flow state. The Reynolds number is calculated based on the carrier gas density, flow rate, viscosity, and the inner diameter of the micro-chromatography column, for example, 150 when the carrier gas density is 1.164kg/m3, the flow rate is 2mL/min, the viscosity is 0.01 Pa.s, and the inner diameter is 0.25 mm. The pulse duration is adjusted according to the average residence time of the carrier gas within the miniature chromatographic column, for example, at a residence time of 10 seconds, the single pulse duration is set to 0.5 seconds to 1 second to ensure that the pulsed carrier gas covers at least 5% of the column space. The injection of carrier gas pulse is controlled by a high-speed electromagnetic valve, the response time of the electromagnetic valve is less than 10ms, the opening of the valve port is linearly regulated according to the target flow, and the flow calibration method is to measure the carrier gas volume change in unit time under normal pressure, for example, the flow of 1mL per minute is measured by a soap film flowmeter to correspond to the opening of the valve port to 30%.

And alternately executing temperature gradient application, micro negative pressure generation and pulse carrier gas injection, wherein the circulation times are adapted to the uniformity variation trend of the stationary phase coating thickness distribution until the stationary phase coating thickness distribution meets the preset uniformity standard. The number of cycles is adjusted based on the decay rate of the standard deviation of the coating thickness after each cycle, for example, the cycle is terminated when the standard deviation decay rate is less than 5%, and the maximum number of cycles is limited to 10 to avoid over-treatment. The uniformity standard is verified by an off-line detection result of the coating thickness by an optical interferometer or a scanning electron microscope, for example, when the thickness standard deviation is smaller than 1 μm, the standard is judged to be up to standard, the detection method of the optical interferometer comprises cutting the micro chromatographic column into a plurality of sections, each section has the length of 1cm, measuring the coating thickness of each section and calculating the standard deviation. When the temperature abnormality or the pressure overrun is detected in the circulation process, a protection mechanism is triggered to suspend the process and alarm, and the abnormal condition is that the temperature exceeds the decomposition temperature of the stationary phase by 10 ℃ or the pressure is lower than-5 kPa, for example, the protection mechanism comprises the steps of cutting off the power supply of the film heater and starting the pressure relief valve to release negative pressure.

S3, injecting correction mixture and trace inert trace gas pulse into the stationary phase uniform distribution layer, obtaining correction peak retention time and trace gas lag time difference, and generating correction factor sets, wherein the correction factor sets are implemented as follows:

Alternately injecting a correction mixture and inert tracer gas pulses into the stationary phase uniform distribution layer, wherein the timing of the injection of the correction mixture and the interval of the tracer gas pulses are dynamically adjusted based on the porosity gradient of the stationary phase uniform distribution layer. The porosity gradient is calculated by the axial resistance coefficient distribution curve generated in the step S1, and the calculation formula is that the porosity gradient is equal to the ratio of the difference value of the resistance coefficients of two adjacent axial positions to the position spacing, for example, the porosity gradient is 30 Pa.s/m 3 when the resistance coefficient is 1.2 Pa.s/m 2 at the position A, 1.5 Pa.s/m 2 at the position B and the spacing is 0.01 m. When the porosity gradient is greater than a preset threshold, the injection interval of the correction mixture and the trace gas pulse is shortened, for example, the interval time is reduced by 5% every 10 Pa.s/m 3 of the increase of the porosity gradient. The preset threshold is set according to the type of stationary phase material, for example, the threshold of a polysiloxane stationary phase is set to 20pa·s/m3, and the metal organic framework Material (MOF) is set to 50pa·s/m3.

When the porosity gradient is greater than a preset threshold, the injection interval of the correction mixture and the trace gas pulse is shortened, for example, the interval time is reduced by 10% every 0.1/mm of increase in the porosity gradient. The preset threshold is calculated by the average pore diameter of the stationary phase material in the micro chromatographic column, for example, when the average pore diameter is 100nm, the preset threshold is set to be 0.05/mm. The calibration mixture contains a target component with a boiling point range covering the sample to be analyzed, for example, the calibration mixture is a C8-C16 normal alkane mixture, and argon which is significantly different from the carrier gas type is selected as the inert trace gas so as to ensure the signal separation degree in the thermal conductivity detector. The injection of the correction mixture and the trace gas is controlled by a high-speed electromagnetic valve, the switching time of the electromagnetic valve is less than 10ms, the injection flow is regulated by a mass flow controller, and the flow error is less than +/-1%.

The separation peak shapes of different boiling point components in the mixture and the diffusion peak shapes of the trace gas are synchronously captured and corrected by a thermal conductivity detector, and the peak time of each separation peak shape and the trailing time of the diffusion peak shape are extracted. The time resolution of the thermal conductivity detector is set to 0.05 seconds to completely capture the details of the peak shape, the time resolution is determined by the bridge response time of the detector and the bandwidth of the signal amplifying circuit, and the bridge response time is calculated by the thermal conductivity coefficient and the heat capacity of the hot wire material, for example, when the thermal conductivity of the tungsten wire is 173W/(m.K) and the heat capacity is 0.13J/(g.K), the response time is 0.03 seconds. The peak time is defined as the time corresponding to the intersection point of the maximum slope point of the peak rising edge and the base line, and the maximum slope point is calculated by a three-point difference method, for example, when the slope difference between the adjacent three data points is smaller than 0.1%, the peak point is determined. The tailing time is defined as the time at which the peak shape falls to 10% of the peak height, and the position at 10% of the peak height is determined by linear interpolation. The difference between the vertex time and the tail time is calculated as the time domain difference, for example, the vertex time of a certain component is 100 seconds, the tail time is 110 seconds, and the time domain difference is 10 seconds. The baseline calibration method is to collect steady-state signal average values for 30 seconds when no sample is injected, baseline drift compensation is realized through sliding window average filtering, and the window length is 5 seconds.

Based on the time domain difference of the vertex time and the tailing time, the diffusion resistance compensation coefficient of each boiling point component is constructed by combining the axial temperature distribution data of the stationary phase uniform distribution layer. The axial temperature distribution data is recorded by a temperature control unit when the sectional temperature gradient is applied in the step S2, for example, the actual temperature value and the time-temperature change curve of each independent temperature zone, the time synchronization precision of the temperature data is 0.1 seconds, and the temperature data is synchronized with the signal acquisition clock of the thermal conductivity detector. The calculation formula of the diffusion resistance compensation coefficient is expressed as a ratio of a time domain difference to a temperature gradient of a corresponding axial position, for example, the time domain difference is 10 seconds, the temperature gradient of the section is 50 ℃ per m, and the diffusion resistance compensation coefficient is 0.2 seconds m/°c. The temperature gradient is calculated by dividing the temperature difference between two adjacent temperature zones by the temperature zone length, e.g. temperature zone a is 150 ℃, temperature zone B is 120 ℃, and temperature zone length is 0.1m, the temperature gradient is 300 ℃/m. When the temperature gradient change exceeds a set range, for example, the temperature difference of adjacent temperature areas exceeds 30 ℃, the abnormal mark pauses the correction flow and starts a temperature calibration program after triggering, and the calibration program comprises the steps of re-measuring the actual temperature of the temperature areas and updating the axial temperature distribution data.

And gradually matching the diffusion resistance compensation coefficient with a theoretical value in a standard retention time database to generate a correction factor set containing a temperature-resistance coupling relation, and sequencing the priority of the gradual matching according to the polarity difference of the boiling point components. The standard retention time database is a pre-established retention time data set containing a plurality of compounds under different temperatures and stationary phase conditions, for example, baseline data is generated by testing the retention time of C8-C16 alkane in the polysiloxane stationary phase, and the data acquisition conditions are carrier gas flow rate of 1mL/min and temperature gradient of 50 ℃/m. The step-wise matching process prioritizes higher polarity components, such as compounds containing hydroxyl or carboxylic acid groups, based on differences in adsorption energy of the components in the stationary phase, estimated by octanol-water partition coefficients (log P values) of the compounds, determined by shake flask experiments or obtained from PubChem databases. For example, when the log p value is less than 3, it is judged as a highly polar component, and matching is preferentially performed. The correction factor set is stored in the form of a two-dimensional matrix, the rows of the matrix corresponding to unique identifiers of boiling components, and the columns comprising diffusion resistance compensation coefficients, theoretical retention times and temperature-resistance coupling coefficients. The matrix data is stored in CSV format, and external software calling and visual analysis are supported.

When the diffusion resistance compensation coefficient of a component in the correction mixture deviates from the theoretical value of the database by more than an allowable threshold, for example 10% of the theoretical value, the calibration failure flag is triggered and the injection procedure is automatically repeated. The interval between repeated injection procedures is adjusted according to the thermal stability of the stationary phase uniform distribution layer, for example, the maximum number of repetitions of the polysiloxane stationary phase is 5 times, and each interval is at least 2 minutes to prevent degradation of the coating. The calibration failure flag is linked with the dynamic adjustment of the carrier gas flow rate in step S4, and the flow rate adjustment amplitude is calculated according to the deviation degree, for example, every time the deviation increases by 5%, the flow rate increases by 5%. In extreme cases, such as 3 consecutive triggers of calibration failure, the system automatically switches to a backup calibration mixture, which selects components of the same boiling point range but of lower polarity, such as a perfluoroalkane mixture, and sends a maintenance alarm.

S4, dynamically adjusting a carrier gas flow rate and temperature program according to the correction factor set, and establishing an operation curve matched with the stationary phase uniform distribution layer, wherein the operation curve is implemented as follows:

Based on the temperature-resistance coupling relation in the correction factor set, the boiling point components of the sample to be detected are divided into two types of high priority and low priority according to the polarity priority. The polarity priority is classified according to the octanol-water distribution coefficient threshold set at the time of correction factor set generation in step S3, for example, when the log p value of the component is less than 3, it is classified as a high priority component, and the rest is a low priority component. The temperature-resistance coupling relation in the correction factor set is derived from the mapping result of the diffusion resistance compensation coefficient and the theoretical retention time in the step S3, and is specifically expressed as the product of the temperature gradient optimization coefficient corresponding to each boiling point component and the resistance compensation value, and the product is used for quantifying the separation response characteristics of the components at different temperatures and coating resistances. And (2) applying experimental calibration to the temperature gradient optimization coefficient through the sectional temperature gradient in the step (S2), wherein the calibration method is to measure the retention time deviation of the reference component under different temperature gradients, and selecting the coefficient value corresponding to the minimum deviation.

For the high-priority components, the carrier gas flow velocity is gradually increased along the axial position of the stationary phase uniform distribution layer according to the corresponding diffusion resistance compensation coefficient, and the flow velocity increasing amplitude is positively correlated with the compensation coefficient. The diffusion resistance compensation coefficient is derived from the calculation result in the step S3, the dimension of the diffusion resistance compensation coefficient is second meter per degree celsius (s.m/° C), and the calculation formula is the time domain difference (seconds) divided by the temperature gradient (° C/m) of the corresponding axial position. For example, when the time domain difference is 10 seconds and the temperature gradient is 50 ℃ per m, the compensation coefficient is 0.2 s.m/° C. The flow rate rise is calculated by multiplying the compensation coefficient by the adjusted gain coefficient of the base flow rate, the gain coefficient is determined by a separation degree optimization experiment, for example, when the initial gain coefficient is 0.5, a mixture of benzene and toluene is injected, and when the separation degree reaches 1.5, the effective gain coefficient is recorded. The basic flow rate is the initial flow rate reference value of the carrier gas set in the step S1, for example, the initial flow rate is 0.5mL/min, and the adjusted upper flow rate limit does not exceed the maximum range (for example, 5 mL/min) of the mass flow controller.

And for the low-priority components, the axial temperature distribution data of the stationary phase uniform distribution layer are combined, and the temperature rising rate range of the temperature program is symmetrically expanded by taking each section of temperature gradient as a median value. The axial temperature distribution data is derived from the history of the sectional temperature control in the step S2, for example, the preset temperature gradient of a certain temperature zone is 50 ℃ per m, the temperature rising rate range after expansion is set to 40 ℃ per m to 60 ℃ per m, the expansion amplitude is determined based on the actual temperature control precision of the temperature zone, for example, the expansion amplitude is +/-20% when the temperature control precision is +/-1 ℃. The symmetrical expansion is realized through double-interval linear mapping, and the mapping formula is that the expansion lower limit is equal to the median minus the expansion amplitude, and the expansion upper limit is equal to the median plus the expansion amplitude. When the temperature gradient exceeds the glass transition point of the material, a temperature protection mechanism is triggered and the upper limit of the expansion amplitude is locked, for example, the upper limit of expansion is 280 ℃ when the glass transition temperature of the polysiloxane stationary phase is 300 ℃, and the locking logic is automatically replaced by the upper limit value if the current temperature gradient exceeds the upper limit.

And recombining the adjusted carrier gas flow rate and temperature program according to the outflow sequence of boiling components to generate an operation curve containing a sectional flow rate control instruction and a nonlinear temperature gradient, wherein the recombination process ensures that the flow rate and the temperature change rate between adjacent sections are continuously conductive. The outflow sequence is predicted from theoretical data from the standard retention time database in step S3, for example when the main peak retention time is known to be 10 minutes, the corresponding carrier gas flow rate adjustment segment start time is 9.5 minutes. The flow rate change rate between adjacent sections is constrained according to a fluid continuity equation, specifically, the flow rate difference of adjacent time nodes is not more than 20% of the flow rate of the front section, for example, when the flow rate of the front section is 1mL/min, the flow rate of the adjacent section is maximally adjusted to 1.2mL/min. The temperature change rate is limited by a derivative smoothing algorithm, for example, the temperature slope difference between adjacent temperature intervals is not more than 5 ℃ per minute, the slope difference is calculated by a three-point difference method, and the difference step length is 0.1 minute. The recombined operation curve takes time as a horizontal axis, synchronously stores a carrier gas flow speed target value and a temperature set value, has a data format of a multi-column CSV table, and supports the importing and executing of standard chromatographic control software (for example Agilent ChemStation).

When a parameter in the operating curve exceeds the hardware execution capability, an adaptive degradation mode is triggered. For example, when the applied flow rate exceeds the maximum range (e.g., 5 mL/min) of the mass flow controller, the adaptive degradation mode scales the flow rate of all segments by a scaling factor equal to the maximum range divided by the applied flow rate maximum, e.g., 5/6≡0.833 when the applied flow rate is 6mL/min maximum, and multiplies all segment flow rates by 0.833 and synchronously reduces the drain temperature time to maintain separation efficiency. The degraded running curve generates log marks and transmits the log marks to a user interface to prompt manual review. In extreme cases, for example, when the temperature program exceeds the upper tolerance limit (for example, 350 ℃) of the heating film, the system terminates the analysis flow and starts forced cooling, the cooling rate is 10 ℃ per minute until the temperature is recovered to a safe threshold (for example, 50 ℃), feedback data of the temperature sensor are monitored in real time in the cooling process, and if the cooling rate is insufficient, an auxiliary fan is started to dissipate heat.

S5, loading an organic sample to be detected to a micro chromatographic column with a stationary phase uniform distribution layer under the condition of an operation curve, completing component separation and recording peak signals in real time, wherein the method is specifically implemented as follows:

And loading the organic sample to be tested to the inlet of the miniature chromatographic column through a microliter syringe, wherein the loading volume is adapted to the adsorption capacity of the stationary phase uniform distribution layer. The adsorption capacity is calculated from the coating thickness and the surface area of the stationary phase uniform distribution layer in step S2, for example, when the coating thickness is 1 μm and the surface area is 0.5 square meter per gram, the adsorption capacity is 0.5 μl per mg, and the loading volume is set to 70% of the maximum adsorption capacity to avoid overload. The injection accuracy of the microliter injector is +/-0.1 microliter, the injection speed is adjusted through the fluid resistance of the inlet end of the miniature chromatographic column, the fluid resistance is derived from the inversion result of the pressure waveform curve in the step S1, for example, when the fluctuation amplitude of the inlet pressure is 5 kilopascals, the injection speed is controlled at 0.2 microliter per second so as to ensure that the sample is uniformly dispersed.

And according to the sectional flow speed control instruction in the operation curve, switching the carrier gas flow speed to the target value section by section, wherein the time interval of the switching process is matched with the theoretical outflow time window of the boiling point component. The theoretical outflow time window is derived from the time series prediction data in the operation curve generated in step S4, and the time series prediction data is generated by mapping the correction factor set in step S3 with the theoretical retention time. For example, when the theoretical retention time of a certain component is 10 minutes, the flow rate switching time window is set to 9.5 minutes to 10.5 minutes. The transition time of the flow rate switching is determined according to the step response characteristic of the carrier gas flow controller, which is calibrated by the scaling experiment in the adaptive degradation mode in step S4, for example, when the controller step response time is 0.5 seconds, the transition time is set to 2 seconds to avoid abrupt flow changes. The error range of the target value of the flow controller is smaller than +/-1%, the parameters of the proportional-integral-derivative control algorithm are calibrated in real time through a closed-loop proportional-integral-derivative control algorithm, and the parameters of the proportional-integral-derivative control algorithm are optimized through temperature control experimental data in the step S2.

And (3) synchronously running a nonlinear temperature gradient program in the curve, and controlling the temperature rise rate of the thin film heater on the outer wall of the miniature chromatographic column, wherein the rate of change is consistent with the temperature gradient difference value between adjacent sections. The temperature rise rate is calculated by the ratio of the difference in temperature gradient between adjacent segments to the time interval defined in step S4, for example, when the difference in temperature gradient between adjacent segments is 50 degrees celsius per meter and the time interval is 5 minutes, the temperature rise rate is set to 10 degrees celsius per meter per minute. The temperature control precision of the thin film heater is +/-0.5 ℃, the temperature feedback signal is acquired through a platinum resistance sensor, and the sampling frequency of the platinum resistance sensor is 10 Hz so as to ensure the detail capture of temperature fluctuation. When the deviation between the actual temperature and the target value exceeds 2 ℃, triggering a temperature compensation mechanism, wherein the compensation quantity is the integral accumulation quantity of the deviation value, and the integral time constant is calibrated to be 30 seconds through the sectional temperature gradient experiment in the step S2.

The separated component peak signals are captured by a thermal conductivity detector, the peak signals are recorded in real time in a time-voltage waveform, and the waveform sampling frequency is adapted to the minimum resolution of the peak shape half peak width. The bridge excitation voltage of the thermal conductivity detector is 5 volts, the signal amplification factor is 1000 times, the noise level is less than 1 microvolt, and the noise level is verified by the baseline calibration data of step S1. The minimum resolution of the half-peak width is determined by the nyquist sampling theorem, e.g. when the minimum half-peak width is 2 seconds, the sampling frequency is at least 10 hz to ensure that each peak shape contains 20 data points. The baseline calibration method is to collect steady-state signal average values for 60 seconds when no sample is injected, baseline drift compensation is realized through sliding window average filtering, the window length is 10 seconds, the overlapping rate is 50%, and the filtering parameters are optimized through the correction mixture peak shape data in the step S3.

And (3) carrying out time sequence alignment on the recorded peak signals and theoretical retention time in the correction factor set, and generating a peak sequence to be analyzed after time axis calibration. The timing alignment is achieved by a linear interpolation method in which the node pitch is adjusted according to the timing prediction accuracy in the operation curve of step S4, for example, when the theoretical retention time prediction error is 0.3 seconds, the node pitch is set to 0.1 seconds. The aligned peak sequence is stored as a time-voltage-temperature three-column data matrix, the data format is a comma separated value file, and the introduction of third-party analysis software is supported. If peak overlap or baseline drift is detected to exceed a threshold value in the alignment process, triggering peak splitting algorithm processing, wherein the peak splitting threshold value is set to be that the slope change rate at the position of 10% of the peak height exceeds 5% per second, the slope change rate is calculated through a three-point difference method, and the difference step length is 0.05 seconds.

When a carrier gas flow rate switching delay or temperature overrun is detected, an adaptive error correction mechanism is triggered. For example, when the flow rate switching delay exceeds 20% of the theoretical time window, the duration of the current flow rate segment is automatically prolonged to the starting point of the next window, the time sequence parameters of the subsequent segment are recalculated, and the calculation logic of the time sequence parameters is consistent with the operation curve generation algorithm of the step S4. If the temperature exceeds the limit, if the deviation duration exceeds 30 seconds, the analysis process is suspended and the gradient cooling program is started, the cooling rate is 5 ℃ per minute until the temperature is restored to the safe range, and the safe range is set according to the thermal stability of the stationary phase in the step S2, for example, the safe upper temperature limit of the polysiloxane stationary phase is 280 ℃. The error correction log is recorded in real time and transmitted to the user terminal, the log comprises a time stamp, an abnormal type and processing measures, and the log format is compatible with the operation curve data in the step S4.

S6, outputting quantitative results of all components according to the corresponding relation between the peak signal, the peak retention time and the trace gas lag time difference, wherein the quantitative results are implemented as follows:

And carrying out baseline correction on the peak sequence to be analyzed after the time axis calibration, and calculating the area of each peak by an integral algorithm through corrected peak signals. The baseline correction uses a sliding window averaging filter method, where the length of the sliding window is determined by twice the peak-to-peak width, for example, 10 seconds for a half-peak width of 5 seconds and a 50% overlap between windows. The filtered baseline is fitted to the peak valley points by least squares, which are defined as the locations where the signal values on both sides of the peak shape are 5% lower than the peak height for the first time, and the fit residual threshold is set to 1% of the peak height, for example, the residual threshold is 10mV when the peak height is 1000 mV. When the residual exceeds the threshold, the peak shape distortion flag is triggered and the peak signal recording procedure of step S5 is re-executed. The integration algorithm is a trapezoid method, the integration interval is from the peak start point to the peak end point, the judgment condition of the peak start point and the end point is that the signal value reaches 5% of the peak height, the integration result is stored as a peak area-time corresponding table, the data format is two lines of comma separated value files, and the integration algorithm is compatible with the output data of the step S5.

Based on the temperature-resistance coupling relation in the correction factor set, the theoretical retention time and the diffusion resistance compensation coefficient corresponding to each peak are matched, and the conversion factors of peak area and concentration are generated. The temperature-resistance coupling relation is derived from the mapping data of the diffusion resistance compensation coefficient and the theoretical retention time in the step S3, and the diffusion resistance compensation coefficient is calculated by the ratio of the time domain difference and the temperature gradient in the step S3, for example, when the time domain difference is 10 seconds and the temperature gradient is 50 degrees celsius per meter, the diffusion resistance compensation coefficient is 0.2 seconds per meter per celsius. The conversion factor is calculated by dividing the peak area by the product of the diffusion resistance compensation coefficient and the theoretical retention time, for example, when the peak area is 1000mv·s and the theoretical retention time is 600 seconds, the conversion factor is 1000/(0.2×600) =8.33. The matching process is controlled by the time axis alignment error margin, which is set to 0.5% of the theoretical retention time, for example, 3 seconds when the theoretical retention time is 600 seconds, and when the actual retention time deviation exceeds 3 seconds, it is determined that the matching is failed and the correction factor set updating flow of step S3 is triggered.

And (3) adjusting the time axis alignment error of the conversion factor by combining the compensation quantity of the trace gas lag time difference to the peak retention time, wherein the compensation quantity is calculated by the product of the lag time difference and the carrier gas flow rate. The lag time difference results from the time domain difference of the trace gas peak apex and the correction mixture peak apex in step S3, for example, the time domain difference is 2 seconds. The carrier gas flow rate is derived from a segmented flow rate target value in the operating curve generated in step S4, for example, a target value of 1 milliliter per minute. The compensation amount is calculated by a ratio of the lag time difference to the carrier gas flow rate, for example, 2 seconds/(1 mL/min) =120 seconds·min/mL, and is adjusted to a dimensionless scale factor by a unit conversion coefficient, for example, when the carrier gas flow rate is 1mL/min, the scale factor is 2 seconds/(1 mL/min×60 seconds/min) =0.033. The adjustment method of the time axis alignment error is to multiply the conversion factor by the inverse of the scale factor, for example, when the conversion factor is 8.33, the adjusted conversion factor is 8.33× (1/0.033) =252.4. When the scale factor exceeds a preset threshold, for example, 10% of the peak volume, it is determined that the flow rate control is abnormal and the operation curve regeneration flow of step S4 is triggered.

Multiplying the adjusted conversion factors by peak areas to obtain concentration values of all components, sequencing the concentration values according to the outflow sequence of boiling components, and outputting a quantitative result table. The concentration value is calculated by multiplying the peak area by a conversion factor, for example, the concentration is 1000×252.4= 252400ppm at a peak area of 1000mv·s and a conversion factor of 252.4. The sorting logic is based on the order of the component flows in the operation curve of step S4, for example, the low boiling point component flows out of the first row of the corresponding table. The quantitative result table contains the component names, retention times, concentration values, and error ranges calculated by confidence intervals of the correction factor set in step S3, the confidence intervals being determined according to standard deviations of a plurality of calibration experiments, for example, the error ranges of ±2.5% when the confidence is 95%. The result table is exported as comma separated value file, the format is compatible with the data matrix of step S5, and third party analysis software (for example Agilent MassHunter) is supported to directly import and generate a detection report.

When a conversion factor abnormality or a concentration value out of range is detected, a concentration calibration rollback mechanism is triggered. For example, when the conversion factor exceeds a preset upper limit (e.g. 500), the last valid correction factor set in step S3 is automatically invoked to recalculate, and if three consecutive rollbacks fail, the process is aborted and manual intervention is prompted. When the concentration value exceeds the measuring range, the dilution factor is dynamically adjusted according to the loading volume data in the step S5, for example, when the initial loading volume is 0.5 microliter, the dilution factor is set to 2, and the concentration is recalculated, so that the adjustment amplitude of the dilution factor is not more than 10 times of the initial value to avoid distortion. The calibration log records all abnormal events and processing measures, the log format is consistent with the error correction log in the step S5, the error correction log comprises a time stamp, an abnormal type, processing parameters and a result state, and the log file is stored in a standard JSON format so as to be convenient for traceability analysis.

The method breaks through the static regulation limitation of traditional chromatographic separation through a multi-step collaborative mechanism, overcomes nonlinear interference of coating distribution in a miniature chromatographic column through coupling design of pressure waveform inversion and dynamic application of temperature gradient in the initial section construction stage of a stationary phase, recombines a temperature-resistance coupling relation of a correction factor set, carrier gas flow rate and a temperature program into a nonlinear operation curve in the separation parameter optimization stage, realizes dynamic matching of stationary phase thermodynamic and hydrodynamic response, and solves the problem of accumulated error of signal drift and retention time offset in miniature equipment through linkage feedback of hysteresis time difference compensation and baseline drift correction in the real-time separation and quantification stage. The data transfer between the steps forms closed-loop logic, for example, a correction factor set is generated based on stationary phase distribution parameters, the dynamic adjustment range of an operation curve is reversely constrained, and a peak signal recorded in real time provides verification data for iterative updating of the correction factor set.

Example 2 fig. 2 shows a schematic structural diagram of a chromatograph for analyzing an organic sample based on micro gas chromatography according to the present invention, comprising:

a processor and a memory, the memory storing a correction factor set and an operating curve generation algorithm, the processor configured to:

controlling a dynamic parameter control module to generate an operation curve;

Controlling a separation detection module to record peak signals;

The carrier gas supply module continuously introduces nitrogen or helium into the micro chromatographic column through the mass flow controller, the flow range is 0.5-5mL/min, the pressure sensor adopts Honeywell ABP2 series, the measuring range is 0-100kPa, the sampling frequency is 200Hz, and the collected continuous pressure waveform data generates a stationary phase distribution initial section through a Darcy law inversion algorithm. The stationary phase regulating and controlling module comprises a Kapton film heater array attached to the outer wall of the chromatographic column, the temperature is controlled within 50-300 ℃, the precision is +/-0.5 ℃, a vacuum pump is connected to the outlet end of the chromatographic column to generate micro negative pressure of-5 kPa to-0.1 kPa, the pulse carrier gas flow is controlled by Lee Company LF series high-speed electromagnetic valves, and the single pulse duration is 0.1-1 second. The correction factor generation module injects a C8-C16 normal alkane correction mixture and helium tracing pulse into the stationary phase uniform distribution layer, and the thermal conductivity detector records the retention time of the correction peak and the lag time difference at a time resolution of 0.05 seconds to generate a correction factor set comprising a temperature-resistance coupling relation. The dynamic parameter control module adjusts the carrier gas flow rate and the temperature program according to the correction factor set to generate a segmented flow rate instruction (0.5-5 mL/min) and a nonlinear temperature gradient (the temperature difference of adjacent segments is less than or equal to 50 ℃). And loading a sample to be detected under the condition of an operation curve by the separation detection module, recording peak signals in real time, and eliminating baseline drift through sliding window average filtering. The quantitative output module multiplies the peak area and the conversion factor to generate a concentration value, and outputs a CSV format result table containing component names, retention time and error range (+ -2.5%). The processor executes control logic through STM32F7 series micro controller, the memory stores correction factor set and operation curve by FLASH, and the abnormal processing comprises temperature over-limit triggering gradient cooling (5 ℃ per min) and flow speed over-limit scaling instruction proportion.

The calculation in the embodiment is to take the dimension and take the numerical value, and the preset parameters and the threshold selection in the calculation are set by those skilled in the art according to the actual situation.

It should be noted that the present invention can be deployed on the device itself to implement embedded applications, and also can run on a PC end or other terminals with user interfaces, so as to satisfy various hardware environments and use requirements.

The above embodiments may be implemented in whole or in part by software, hardware, firmware, or any other combination. When implemented in software, the above-described embodiments may be implemented in whole or in part in the form of a computer program product. The computer program product comprises one or more computer instructions or computer programs. When the computer instructions or computer program are loaded or executed on a computer, the processes or functions described in accordance with embodiments of the present application are produced in whole or in part. The computer may be a general purpose computer, a special purpose computer, a network of computers, or other programmable devices. The computer instructions may be stored in a computer-readable storage medium or transmitted from one computer-readable storage medium to another computer-readable storage medium, for example, the computer instructions may be transmitted from one website site, computer, server, or data center to another website site, computer, server, or data center by wired (e.g., infrared, wireless, microwave, etc.). The computer readable storage medium may be any available medium that can be accessed by a computer or a data storage device such as a server, data center, etc. that contains one or more sets of available media. The usable medium may be a magnetic medium (e.g., floppy disk, hard disk, magnetic tape), an optical medium (e.g., DVD), or a semiconductor medium. The semiconductor medium may be a solid state disk.

It will be clearly understood by those skilled in the art that, for convenience and brevity of description, specific working procedures of the above-described system, apparatus and module may refer to corresponding procedures in the foregoing method embodiments, which are not repeated herein.

In the several embodiments provided in the present application, it should be understood that the disclosed system, apparatus and method may be implemented in other manners. For example, the apparatus embodiments described above are merely illustrative, and for example, the division of the modules is merely a logical function division, and there may be additional divisions when actually implemented, for example, multiple modules or components may be combined or integrated into another system, or some features may be omitted or not performed. Alternatively, the coupling or direct coupling or communication connection shown or discussed with each other may be an indirect coupling or communication connection via some interfaces, devices or modules, which may be in electrical, mechanical, or other forms.

The modules described as separate components may or may not be physically separate, and components shown as modules may or may not be physical modules, may be located in one place, or may be distributed over multiple network modules. Some or all of the modules may be selected according to actual needs to achieve the purpose of the solution of this embodiment.

In addition, each functional module in each embodiment of the present application may be integrated into one processing module, or each module may exist alone physically, or two or more modules may be integrated into one module.

The functions, if implemented in the form of software functional modules and sold or used as a stand-alone product, may be stored in a computer-readable storage medium. Based on this understanding, the technical solution of the present application may be embodied essentially or in a part contributing to the prior art or in the form of a software product stored in a storage medium, comprising several instructions for causing a computer device (which may be a personal computer, a server or a network device, etc.) to perform all or part of the steps of the method according to the embodiments of the present application. The storage medium includes a U disk, a removable hard disk, a read-only memory (ROM), a random access memory (random access memory, RAM), a magnetic disk, an optical disk, or other various media capable of storing program codes.

The foregoing is merely illustrative of the present application, and the present application is not limited thereto, and any person skilled in the art will readily recognize that variations or substitutions are within the scope of the present application. Therefore, the protection scope of the application is subject to the protection scope of the claims.

Finally, the foregoing description of the preferred embodiment of the invention is provided for the purpose of illustration only, and is not intended to limit the invention to the particular form disclosed, but on the contrary, the intention is to cover all modifications, equivalents, and alternatives falling within the spirit and scope of the invention.

Claims

1. An organic sample analysis method based on micro gas chromatography, characterized in that it comprises:

S1, continuously pre-flushing the carrier gas into the micro-chromatographic column and collecting the pressure waveform to construct the initial profile of the stationary phase distribution;

S2, on the basis of the initial profile of the stationary phase distribution, alternately applying segmented temperature gradient, slight negative pressure and directional pulse flow to reshape and form a uniformly distributed layer of the stationary phase;

S3, injecting a calibration mixture and a trace amount of inert tracer gas pulse into the stationary phase uniform distribution layer, obtaining the calibration peak retention time and the tracer gas lag time difference and generating a calibration factor set;

S4, dynamically adjusting the carrier gas flow rate and temperature program according to the correction factor set to establish an operation curve matching the uniform distribution layer of the stationary phase;

S5. Loading the organic sample to be tested into the micro-chromatographic column with the uniformly distributed stationary phase layer under the operating curve conditions, completing component separation and recording peak signals in real time;

S6. Output the quantitative results of each component according to the corresponding relationship between the peak signal, the peak retention time and the tracer gas lag time difference.

2. The method for analyzing organic samples based on micro gas chromatography according to claim 1, characterized in that the micro chromatographic column is continuously pre-flushed with carrier gas and pressure waveforms are collected to construct an initial profile of the stationary phase distribution, comprising:

The carrier gas is stably introduced into the micro-chromatographic column and a pressure sensor is arranged at the inlet end to obtain continuous pressure data;

The continuous pressure data is filtered to form a pressure waveform curve;

The stationary phase axial resistance distribution is inverted based on the pressure waveform curve and the initial stationary phase distribution profile is generated.

3. The method for analyzing organic samples based on micro gas chromatography according to claim 2, characterized in that segmented temperature gradient, slight negative pressure and directional pulse flow are alternately applied on the basis of the initial profile of the stationary phase distribution to reshape the stationary phase uniform distribution layer, comprising:

Based on the initial profile of the stationary phase distribution, a plurality of independent temperature zones are divided along the axial direction of the micro-chromatographic column, the temperature gradient difference of each independent temperature zone is within a preset range, and the temperature is applied in sections through a thin film heater attached to the outer wall of the chromatographic column;

After applying the temperature gradient, a vacuum pump is connected to the outlet of the micro-chromatographic column to generate a slight negative pressure, the pressure range of which is adapted to the structural strength of the micro-chromatographic column;

During the period of micro-negative pressure, carrier gas is injected into the inlet end of the micro-chromatographic column in the form of pulses, and the pulse frequency and duration are adapted to the fluid dynamics characteristics of the carrier gas flow;

The temperature gradient application, slight negative pressure generation and pulse carrier gas injection are performed alternately, and the number of cycles is adapted to the uniformity change trend of the stationary phase coating thickness distribution until the stationary phase coating thickness distribution meets the preset uniformity standard.

4. The method for analyzing organic samples based on micro gas chromatography according to claim 3 is characterized in that a calibration mixture and a trace amount of inert tracer gas pulse are injected into the uniformly distributed layer of the stationary phase to obtain the calibration peak retention time and the tracer gas lag time difference and generate a calibration factor set, comprising:

Alternately injecting a calibration mixture and pulses of an inert tracer gas into a uniformly distributed layer of the stationary phase;

The separation peaks of components with different boiling points in the calibration mixture and the diffusion peaks of the tracer gas are captured synchronously by a thermal conductivity detector, and the peak time of each separation peak and the tailing time of the diffusion peak are extracted;

Based on the time domain difference between the peak time and the tail time, combined with the axial temperature distribution data of the uniformly distributed layer of the stationary phase, the diffusion resistance compensation coefficient of each boiling point component is constructed;

The diffusion resistance compensation coefficients were matched step by step with the theoretical values in the standard retention time database to generate a correction factor set containing the temperature-resistance coupling relationship. The priority of the step-by-step matching was sorted according to the polarity differences of the boiling point components.

5. The method for analyzing organic samples based on micro gas chromatography according to claim 4, characterized in that the injection timing of the calibration mixture and the interval between the tracer gas pulses are dynamically adjusted based on the porosity gradient of the uniformly distributed layer of the stationary phase.

6. The method for analyzing organic samples based on micro gas chromatography according to claim 4 is characterized in that the carrier gas flow rate and temperature program are dynamically adjusted according to the correction factor set to establish an operation curve matching the uniform distribution layer of the stationary phase, comprising:

Based on the temperature-resistance coupling relationship in the correction factor set, the boiling point components of the sample to be tested are divided into two categories of high priority and low priority according to polarity priority;

For high-priority components, according to their corresponding diffusion resistance compensation coefficients, the carrier gas flow rate is increased step by step along the axial position of the stationary phase uniform distribution layer, and the flow rate increase is positively correlated with the compensation coefficient.

For low-priority components, combined with the axial temperature distribution data of the uniformly distributed layer of the stationary phase, the heating rate range of the temperature program is symmetrically expanded with each temperature gradient as the median value;

The adjusted carrier gas flow rate and temperature program are reorganized according to the outflow order of the boiling point components to generate an operation curve containing segmented flow rate control instructions and nonlinear temperature gradient. The reorganization process ensures that the flow rate and temperature change rate between adjacent segments are continuous and differentiable.

7. The method for analyzing organic samples based on micro gas chromatography according to claim 6, characterized in that the organic sample to be tested is loaded into a micro chromatographic column of a uniformly distributed stationary phase layer under the operating curve conditions, component separation is completed and peak signals are recorded in real time, comprising:

The organic sample to be tested is loaded into the inlet of the micro-chromatographic column through a microliter syringe, and the loading volume is adapted to the adsorption capacity of the uniformly distributed layer of the stationary phase;

According to the segmented flow rate control instructions in the operation curve, the carrier gas flow rate is switched to the target value segment by segment, and the time interval of the switching process matches the theoretical outflow time window of the boiling point component;

The nonlinear temperature gradient program in the synchronous operation curve controls the temperature rise rate of the thin film heater on the outer wall of the micro-chromatographic column, and the rate of change is consistent with the temperature gradient difference between adjacent sections;

The peak signals of the separated components are captured by a thermal conductivity detector, and the peak signals are recorded in real time as time-voltage waveforms, with the waveform sampling frequency adapted to the minimum resolution of the peak half-peak width;

The recorded peak signals are time-sequentially aligned with the theoretical retention times in the correction factor set to generate a peak sequence to be analyzed after time axis calibration.

8. The method for analyzing organic samples based on micro gas chromatography according to claim 7 is characterized in that, according to the corresponding relationship between the peak signal, the peak retention time and the tracer gas lag time difference, the quantitative results of each component are output, including:

Baseline correction is performed on the peak sequence to be analyzed after time axis calibration, and the peak area of each peak is calculated by the integration algorithm after correction of the peak signal;

Based on the temperature-resistance coupling relationship in the correction factor set, the theoretical retention time and diffusion resistance compensation coefficient corresponding to each peak are matched to generate the conversion factor between peak area and concentration;

The time axis alignment error of the conversion factor is adjusted by combining the compensation of the tracer gas lag time difference to the peak retention time. The compensation amount is calculated by multiplying the lag time difference by the carrier gas flow rate.

The adjusted conversion factor is multiplied by the peak area to obtain the concentration value of each component. The concentration values are sorted according to the elution order of the boiling point components and the quantitative result table is output.

9. A chromatographic analyzer for organic sample analysis based on micro gas chromatography, used to implement the organic sample analysis method based on micro gas chromatography according to any one of claims 1 to 8, characterized in that it comprises:

a carrier gas supply module, configured to continuously supply carrier gas to the micro-chromatographic column and connected to a pressure sensor at the inlet end to collect continuous pressure waveform data;

The stationary phase control module is configured to alternately apply segmented temperature gradient, slight negative pressure and pulsed carrier gas flow based on the initial stationary phase distribution profile of the micro-chromatographic column to reshape a uniformly distributed stationary phase layer;

A correction factor generation module is configured to inject a correction mixture and a trace amount of inert tracer gas pulse into the stationary phase uniform distribution layer, obtain the correction peak retention time and the tracer gas lag time difference, and generate a correction factor set;

a dynamic parameter control module configured to dynamically adjust the carrier gas flow rate and temperature program according to the correction factor set to establish an operating curve matching the uniform distribution layer of the stationary phase;

A separation and detection module, configured to load the organic sample to be tested into the micro-chromatographic column under the operating curve conditions, and record the peak signal after separation in real time;

A quantitative output module, configured to output the quantitative results of each component according to the corresponding relationship between the peak signal and the retention time and the lag time difference in the correction factor set;

A processor and a memory, wherein the memory stores a correction factor set and an operation curve generation algorithm.

10. The chromatograph for organic sample analysis based on micro gas chromatography according to claim 9, wherein the processor is configured to perform the following operations:

Generate an initial profile of the stationary phase distribution based on continuous pressure waveform data collected by the pressure sensor;

Controlling the stationary phase regulation module to perform an alternating application operation;

Control correction factor generation module to obtain retention time and lag time difference;

Control the dynamic parameter control module to generate an operation curve;

Control the separation detection module to record the peak signal;

Controls the quantitative output module to generate quantitative results.