A method for eliminating inconsistency in gas content measurement of glass medicine bottles in TDLAS

Abstract

The present invention discloses a method for eliminating inconsistency in TDLAS for measuring gas content in glass medicine bottles, comprising the following steps: S1, measuring the temperature T and pressure P of the environment to be measured, selecting the central wavelength λ0, and calculating the current spectral line width Δν c , calculate the control voltage value v0 when the laser outputs the laser with the central wavelength λ0, and calculate the spectral line broadening Δν c Corresponding voltage value v1; S2, the laser control mode is a low-frequency ramp signal plus a high-frequency sine modulation signal, the low-frequency ramp signal period is set to f1, the scanning range is set to [v0-3v1, v0+3v1], and the scanning range is defined as three segments; the application obtains a virtual background signal under the TDLAS detection mode through segmented operation of spectral signals, and eliminates multiple types of background noise caused by the inconsistency of packaged medicine bottles through background subtraction. The method is simple and effective, with a wide range of applications, and can be used for different working conditions, different detection gases, and glass medicine bottles of different specifications.

Description

Technical Field

[0001] The present invention relates to the field of gas measurement, and in particular to a method for eliminating inconsistency in gas content measurement of glass medicine bottles in TDLAS. Background Art

[0002] In the pharmaceutical industry, glass vials, ampoules, and other bottles are widely used for drug filling to ensure the sterility of pharmaceuticals. During the filling process, the bottles are either evacuated or filled with nitrogen to isolate the drug from the air. If the sealing properties of the drugs do not meet production requirements, there is a risk of drug deterioration. To ensure the quality of drug packaging, sealing testing of glass vials, ampoules, and other bottles is crucial.

[0003] Currently, the quality of sealing is often assessed by measuring the oxygen content in the headspace of glass medicine bottles. Tunable diode laser absorption spectroscopy (TDLAS) technology has been widely used in the field of non-contact gas detection. Its high sensitivity and rapid detection speed make it an ideal spectral method for detecting gas concentrations. However, due to optical phenomena such as laser absorption, reflection, and refraction in glass containers, optical noise in the detection system increases. Furthermore, due to significant inconsistencies in the manufacturing process between different containers, accurate and stable measurement of oxygen content in the headspace of the bottle presents significant challenges.

[0004] In response to the problem of inconsistent light intensity caused by the absorption of laser by glass medicine bottles, patent CN110006598A proposes a light intensity compensation method based on the average value of the second harmonic / first harmonic, which can eliminate the measurement error caused by the different light intensities, but cannot eliminate other noises such as optical interference, and still faces the problem of the inconsistency of glass medicine bottles. Patent CN109596568B proposes a method for eliminating background gas errors in the TDLAS system. By changing the optical path and performing two sets of experiments, the influence of the background gas in the laser and detector on the measurement results is eliminated. This background elimination method can effectively remove the background noise caused by the inconsistency problem, but the implementation method of changing the optical path is complex and time-consuming, which is not conducive to rapid detection. Furthermore, patent CN113607686A proposes a background elimination method for constructing a historical database of second harmonic background signals, but the database construction process is too cumbersome, and the database needs to be reconstructed for glass containers of different types and specifications, and the algorithm flexibility is poor. Summary of the Invention

[0005] In view of the above, the object of the present invention is to provide a method for eliminating inconsistency in measuring oxygen content in the headspace of glass medicine bottles, eliminating the noise effects caused by the absorption, refraction, reflection and related optical interference of laser light by the glass bottle wall, while ensuring the accuracy, reliability and rapidity of detection;

[0006] To achieve the above object, the present invention provides the following solution: a method for eliminating inconsistency in measuring gas content in glass medicine bottles in TDLAS, comprising the following steps:

[0007] S1. Measure the temperature T and pressure P of the environment to be measured, select the central wavelength λ0, and calculate the current spectral line width Δν c , calculate the control voltage value v0 when the laser outputs the laser with the central wavelength λ0, and calculate the spectral line broadening Δν c Corresponding voltage value v1;

[0008] S2. The laser control mode is a low-frequency ramp signal plus a high-frequency sinusoidal modulation signal. The period of the low-frequency ramp signal is set to f1, and the scanning range is set to [v0-3v1, v0+3v1]. The scanning range is defined as three segments: the non-absorption lower spectrum segment [v0-3v1, v0-v1], the absorption spectrum segment [v0-v1, v0+v1], and the non-absorption upper spectrum segment [v0+v1, v0+3v1]. The period of the high-frequency sinusoidal modulation signal is set to f2, and the amplitude is set to amp. Let amp = 1.1v1, so that the modulation index m = 2.2;

[0009] Under the control mode described in S3 and S2, a glass medicine bottle containing a gas amount of N0 is first detected to obtain a spectral signal after gas absorption corresponding to the laser control voltage. Since the spectral signal is in a positive linear relationship with the laser control signal, according to the scanning range of the control signal, the spectral signal range is [I0-3I1, I0+3I1], wherein the spectral signal is divided into three segments, [I0-3I1, I0-I1] corresponds to the lower spectral line segment without absorption, [I0-I1, I0+I1] corresponds to the absorption spectral line segment, and [I0+I1, I0+3I1] corresponds to the upper spectral line segment without absorption;

[0010] Perform Fourier transform on the three defined spectral signals to perform spectral analysis, and obtain the Fourier spectrum intensity A1 of the spectral signal corresponding to the spectrum line segment without absorption at the frequency 2f2, the Fourier spectrum intensity A2 of the spectral signal corresponding to the absorption spectrum line segment at the frequency 2f2, and the Fourier spectrum intensity A3 of the spectral signal corresponding to the spectrum line segment without absorption at the frequency 2f2;

[0011] The Fourier spectrum intensity A1 of the spectrum signal corresponding to the non-absorption lower spectrum segment obtained in S4 and S3 at the frequency 2f2 and the Fourier spectrum intensity A3 of the spectrum signal corresponding to the non-absorption upper spectrum segment at the frequency 2f2 can be used to construct the Fourier spectrum intensity fitting value of the spectrum signal corresponding to the absorption spectrum segment at the frequency 2f2 when there is no gas absorption.

[0012] Fitting values obtained from S5 and S4 As the background signal of the absorption spectrum line segment, the Fourier spectrum intensity at the spectral signal 2f2 corresponding to the absorption spectrum segment without background noise is obtained by background subtraction.

[0013] S6. Take the complete spectrum signal [I0-3I1, I0+3I1], perform low-pass filtering on it, eliminate the sinusoidal component, and obtain the ramp DC quantity I ramp , calculate the peak-to-peak value P of the DC quantity and use it as the representative value of the light intensity;

[0014] The Fourier spectrum intensity A at the spectral signal 2f2 corresponding to the absorption spectrum without background noise obtained by S7 and S5 s Divide by the light intensity representation value P in S6, and finally get the gas content representation value after removing the influence of the inconsistency of the glass medicine bottle

[0015] S8. Further, measure different gas contents N i (i=1,2,3,) glass medicine bottles, get different oxygen content characterization values Q i (i=1,2,3,), use N i (i=0,1,2,3,) / Q i (i=0,1,2,3,) is linearly fitted to obtain N=kQ+p, where k and p are linear coefficients. Based on the fitting line and the current oxygen content characterization value Q, the oxygen content N in the headspace of the glass medicine bottle to be tested can be calculated.

[0016] Optionally, in step S1 , the central wavelength λ0 is selected from corresponding gas spectral lines according to the HITRAN spectrum database.

[0017] Optionally, in step S1, the spectral line is broadened Δν c Calculated by querying the spectral line parameters at the central wavelength.

[0018] Optionally, in step S1 , v0 and v1 are calculated based on the current-wavelength coefficient of the laser and the voltage-current conversion coefficient of the laser controller.

[0019] Optionally, the spectral line parameters and control parameters in steps S1 and S2 are adapted according to the type of the detected gas.

[0020] Optionally, the specifications of the glass vials to be tested can be variable.

[0021] In summary, due to the adoption of the above technical solution, the beneficial effects of the present invention are:

[0022] 1. The present invention provides a method for eliminating inconsistencies in TDLAS for measuring the oxygen content in the headspace of packaged medicine bottles. By performing segmented calculations on spectral signals, a virtual background signal is obtained under the TDLAS detection mode. Then, through background subtraction, multiple types of background noise caused by the inconsistency of the packaged medicine bottles are eliminated. The method is simple and effective.

[0023] 2. The present invention provides a method for eliminating inconsistencies in measuring the oxygen content in the headspace of packaged medicine bottles in TDLAS, which has a wide range of applications and can be used for different working conditions, different detection gases, and glass medicine bottles of different specifications. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the following briefly introduces the drawings required for use in the embodiments. It should be understood that the following drawings only illustrate certain embodiments of the present invention and should not be considered as limiting the scope. A person of ordinary skill in the art can also derive other relevant drawings based on these drawings without inventive effort.

[0025] Figure 1 This is the algorithm flow chart of this application;

[0026] Figure 2 This is a schematic diagram of the spectral signal segmentation processing of this application;

[0027] Figure 3 This is a schematic diagram of calculating the light intensity characterization value of this application;

[0028] Figure 4 It is the QN fitting line of this application. DETAILED DESCRIPTION

[0029] In order to make the objectives, technical solutions, and advantages of the present invention more clearly understood, the present invention is further described in detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are only intended to explain the present invention and are not intended to limit the present invention. That is, the embodiments described herein are only some embodiments of the present invention, not all embodiments. Generally, the components of the embodiments of the present invention described and illustrated in the drawings herein may be arranged and designed in various different configurations.

[0030] Therefore, the following detailed description of the embodiments of the present invention provided in the accompanying drawings is not intended to limit the scope of the invention as claimed, but is merely intended to represent selected embodiments of the present invention. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative work are within the scope of protection of the present invention.

[0031] It should be noted that relational terms such as "first" and "second" are used only to distinguish one entity or operation from another entity or operation, and do not necessarily require or imply any actual relationship or order between these entities or operations. Moreover, the terms "comprises," "comprising," or any other variations thereof are intended to cover non-exclusive inclusion, such that a process, method, article, or apparatus comprising a series of elements includes not only those elements, but also other elements not explicitly listed, or elements inherent to such process, method, article, or apparatus. In the absence of further limitations, an element defined by the phrase "comprising a ..." does not exclude the presence of additional identical elements in the process, method, article, or apparatus comprising the element.

[0032] Example 1

[0033] This embodiment provides a method for eliminating inconsistency in measuring oxygen content in the headspace of a 10 mL vial in TDLAS. The algorithm flow chart is shown in FIG. Figure 1 , the specific steps are as follows:

[0034] S1. Measure the temperature of the test environment T = 25 ° C and the pressure P = 1 atm. Select the appropriate central wavelength λ0 = 760.88 nm in the oxygen spectrum. Calculate the current spectrum line width Δν based on the oxygen spectrum line parameters at 760.88 nm. c =0.05cm -1 .

[0035] The oxygen laser uses VCSEL and the laser controller uses VITC002. At this time, the control voltage value v0 of the laser output at 760.88nm is 180mV. The spectrum line width Δν is calculated. c =0.05cm -1 The corresponding voltage value is v1=5mV.

[0036] S2. Set the period of the low-frequency ramp signal in the control signal of the laser to 10 Hz, set the scanning range to [v0-3v1, v0+3v1]=[165mV, 195mV], and divide the scanning range into three sections: the non-absorption lower spectrum segment [v0-3v1, v0-v1]=[165mV, 175mV], the absorption spectrum segment [v0-v1, v0+v1]=[175mV, 185mV], and the non-absorption upper spectrum segment [v0+v1, i0+3i1]=[185mV, 195mV].

[0037] The period of the high-frequency sinusoidal signal in the control signal of the laser is set to f2 = 14 kHz, and the amplitude is set to amp = 5.5 mV, thereby achieving a modulation index m = 2.2.

[0038] Under the control mode described in S3 and S2, the vial with an oxygen content of N0=0% is first tested to obtain the corresponding spectral signal after oxygen absorption. According to the scanning range of the control signal, the spectral signal is [I0-3I1, I0+3I1]. Among them, the spectral signal is divided into three segments, [I0-3I1, I0-I1] corresponds to the lower spectral line segment without absorption, [I0-I1, I0+I1] corresponds to the absorption spectral line segment, and [I0+I1, I0+3I1] corresponds to the upper spectral line segment without absorption. Specifically, I0=0.73+0.053cos(2f2πt), I1=0.01, as shown in the schematic diagram. Figure 2 .

[0039] Perform Fourier transform on the three defined spectral signals for spectrum analysis. The Fourier spectrum intensity A1 = 2.4V at the frequency 2f2 = 28kHz corresponding to the spectrum line segment without absorption, the Fourier spectrum intensity A2 = 4.25V at the frequency 2f2 = 28kHz corresponding to the spectrum line segment without absorption, and the Fourier spectrum intensity A3 = 2.51V at the frequency 2f2 = 28kHz corresponding to the spectrum line segment without absorption. See the schematic diagram. Figure 2 .

[0040] The Fourier spectrum intensity A1 of the spectrum signal corresponding to the non-absorption lower spectrum segment obtained in S4 and S3 at a frequency of 28kHz and the Fourier spectrum intensity A3 of the spectrum signal corresponding to the non-absorption upper spectrum segment at a frequency of 28kHz can be approximately calculated to obtain the Fourier spectrum intensity of the spectrum signal corresponding to the absorption spectrum segment at a frequency of 28kHz when there is no oxygen absorption.

[0041] Fitting values obtained from S5 and S4 As the background signal of the absorption spectrum segment, the Fourier spectrum intensity of the absorption spectrum segment without background noise at 28kHz is obtained by background subtraction.

[0042] S6. Further, in order to eliminate the influence of the bottle wall on the attenuation of the laser, the complete spectrum signal [I0-3I1, I0+3I1] is taken and low-pass filtered to eliminate the sinusoidal component to obtain the ramp DC quantity I ramp , calculate the peak-to-peak value of the DC value P = 0.053V, and use it as the representative value of the light intensity, such as Figure 3 shown.

[0043] The Fourier spectrum intensity A of the absorption spectrum without background noise obtained by S7 and S5 corresponds to the light intensity signal at 28kHz s Divide by the light intensity value P in step 8) to obtain the oxygen content value after removing the influence of the inconsistency of the glass medicine bottle.

[0044] S8 further measures the oxygen content of the packaged medicine bottles with 5%, 10%, and 21%, respectively, and obtains different oxygen content characterization values Q1=39.64, Q2=45.96, and Q3=54.12. The oxygen content N of the packaged medicine bottles and the characterization value Q i Doing linear fitting, we get N = 1.025Q-35.47, such as Figure 4 As shown in the figure, the headspace oxygen content N in different packaged vials can be calculated based on the fitting line and the current oxygen content characterization value Q.

[0045] Example 2

[0046] This example provides a method for eliminating inconsistencies in measuring the headspace oxygen content of 2 mL vials in TDLAS. This method differs from Example 1 in that the specifications of the vials to be measured are changed in this example, but the calculation method remains unchanged. This method can eliminate the effects of inconsistencies on vials of any specifications.

[0047] Example 3

[0048] This example provides a method for eliminating inconsistencies in the measurement of other gas contents in the headspace of a 10mL vial of penicillin using TDLAS. This method differs from Example 1 in that the penicillin vial headspace gas content can optionally measure multiple gases, such as oxygen, water vapor, and carbon dioxide. Simply calibrate the laser scanning range and control parameters for the different detection gases in S1 and S2.

[0049] Specifically, this embodiment provides a method for eliminating inconsistencies in the headspace water vapor content measurement of 10 mL of penicillin using TDLAS. The water vapor laser uses a 1392.5 nm Eblana laser, and the laser controller uses an ITC4001. The calculations in S1 state that v0 = 925 mV, v1 = 40 mV, and f1 = 10 Hz. In S2, amp = 45 mV, and f2 = 6 kHz. The remaining calculations remain unchanged. Finally, based on the water vapor concentration characterization value obtained in S7 and the fitted line in S8, the water vapor content in the current glass vial can be calculated.

[0050] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions and improvements made within the spirit and principles of the present invention should be included in the scope of protection of the present invention.

Claims

1. A method for eliminating inconsistencies in gas content measurement of glass medicine bottles in TDLAS. The method comprises the following steps: characterized in that, S1. Measure the temperature of the environment to be tested T ,pressure P , select the center wavelength , calculate the current line broadening , calculate the laser output center wavelength as Laser control voltage value v 0, calculate line broadening Corresponding voltage value v 1; S2, the laser control mode is a low-frequency ramp signal plus a high-frequency sinusoidal modulation signal, and the low-frequency ramp signal period is set to f 1. Set the scanning range to [ v 0-3 v 1, v 0+3 v 1], the scanning range is divided into three segments: the spectrum line segment without absorption [ v 0-3 v 1, v 0- v 1], absorption spectrum segment [ v 0- v 1, v 0+ v 1], no absorption upper spectral line segment [ v 0+ v 1, v 0+3 v 1], the period of high-frequency sinusoidal modulation signal is set to f 2, the amplitude is set to amp ,make amp =1.1 v 1, so that the modulation system m =2.2; Under the control mode described in S3 and S2, firstly, the gas content is N 0 glass medicine bottle to detect, and obtain the spectrum signal after gas absorption corresponding to the laser control voltage, the spectrum signal range is [ I 0-3 I 1, I 0+3 I 1], where the spectral signal is divided into three segments, [ I 0-3 I 1, I 0- I 1] corresponds to the spectrum line segment without absorption, [ I 0- I 1, I 0+ I 1] corresponds to the absorption spectrum line segment, [ I 0+ I 1, I 0+3 I 1] corresponds to the non-absorption upper spectral line segment, where I 0 represents the central wavelength of the absorption line v The original light intensity value at 0, I 1 means that in S2 control mode, when the wave number change is v 1, the corresponding change in light intensity; Perform Fourier transform on the three defined spectral signals to perform spectrum analysis and obtain the spectrum signal corresponding to the spectrum line segment without absorption at frequency 2 f Fourier spectrum intensity at 2 A 1. The absorption spectrum line segment corresponds to the spectrum signal at frequency 2 f Fourier spectrum intensity at 2 A 2. The spectrum line segment without absorption corresponds to the spectrum signal at frequency 2 f Fourier spectrum intensity at 2 A 3; Obtained from S4 and S3 A 1 and A 3. Construct the absorption spectrum line segment corresponding to the spectrum signal at frequency 2 when there is no gas absorption f Fourier spectrum intensity fitting value at 2 ; Fitting values obtained from S5 and S4 As the background signal of the absorption spectrum segment, the spectral signal corresponding to the absorption spectrum segment without background noise is obtained by background subtraction. f Fourier spectrum intensity at 2 ; S6, take the complete spectrum signal [ I 0-3 I 1, I 0+3 I 1], perform low-pass filtering on it to eliminate the sinusoidal component and obtain the ramp DC quantity I ramp , calculate the peak-to-peak value of the DC quantity P , which is used as the characterization value of the light intensity; The absorption spectrum without background noise obtained by S7 and S5 corresponds to spectral signal 2 f Fourier spectrum intensity at 2 Divide by the light intensity value in S6 P Finally, the gas content characterization value after removing the influence of the inconsistency of the glass bottle is obtained. ; S8. Further, measure different gas contents Ni,i =0,1,2,3... glass medicine bottles, get different oxygen content characterization values Qi, i =0,1,2,3…, use Ni / Qi,i =0,1,2,3… perform linear fitting to get the fitting line ;in k , p is the linear coefficient. Based on the fitting line and the current oxygen content characterization value Q, the oxygen content in the headspace of the glass bottle to be tested is calculated. N .

2. The method for eliminating inconsistency in measuring gas content in glass medicine bottles in TDLAS according to claim 1, characterized in that: In step S1, the central wavelength According to the HITRAN spectrum database, select the corresponding gas spectral line.

3. The method for eliminating inconsistency in measuring gas content in glass medicine bottles in TDLAS according to claim 2, characterized in that: In step S1, line broadening Calculated by querying the spectral line parameters at the central wavelength.

4. The method for eliminating inconsistency in measuring gas content in glass medicine bottles in TDLAS according to claim 3, characterized in that: In step S1, the current-wavelength coefficient of the laser and the voltage-current conversion coefficient of the laser controller are calculated. v 0. v 1.

5. The method for eliminating inconsistency in measuring gas content in glass medicine bottles in TDLAS according to claim 4, characterized in that: The spectral line parameters and control parameters in steps S1 and S2 are adapted according to the type of the detected gas.

6. The method for eliminating inconsistency in measuring gas content in glass medicine bottles in TDLAS according to any one of claims 1 to 5, characterized in that: The specifications of the glass vials to be tested can vary.

Images