WO2016177002A1 - 基于拉曼光谱的检测保健品中是否添加有西药的方法 - Google Patents

基于拉曼光谱的检测保健品中是否添加有西药的方法 Download PDF

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WO2016177002A1
WO2016177002A1 PCT/CN2015/098694 CN2015098694W WO2016177002A1 WO 2016177002 A1 WO2016177002 A1 WO 2016177002A1 CN 2015098694 W CN2015098694 W CN 2015098694W WO 2016177002 A1 WO2016177002 A1 WO 2016177002A1
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raman
sample
signal
tested
western medicine
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French (fr)
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张建红
张丽
王红球
姜丽
宁岩实
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Tsinghua University
Nuctech Co Ltd
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Tsinghua University
Nuctech Co Ltd
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Priority to RU2017132986A priority Critical patent/RU2675407C1/ru
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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/65—Raman scattering

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  • the invention relates to the field of safety detection technology, and in particular to a method for detecting foods such as health care products by using Raman spectroscopy technology to determine whether a western medicine is added to a health care product.
  • Some unscrupulous merchants illegally add western medicine ingredients in foods (such as health care products) for the purpose of improving efficacy or speeding up drug efficacy.
  • Western medicine ingredients often have side effects and need to be taken under the guidance of a doctor. If long-term use of such foods can endanger health, it is very important to regulate health products.
  • the detection of illegally added western medicine in health care products mainly adopts methods such as chromatography and mass spectrometry. These methods have long detection time and cannot meet the needs of rapid screening on site.
  • An object of the present invention is to provide a method for detecting whether or not a western medicine is added to a health care product based on Raman spectroscopy, which is capable of quickly, efficiently and accurately determining whether a sample to be tested (such as a sample of health care products) contains an illegal western medicine component.
  • Embodiments of the present invention provide a method for detecting whether a western medicine is added to a health care product based on Raman spectroscopy, comprising the following steps:
  • the raw Raman spectral signal of the sample to be tested is obtained by a single measurement of the Raman spectrum of the sample to be tested.
  • step (a) comprises:
  • step (a3) comprises:
  • the fluorescence interference signal is calculated in an iterative manner as follows:
  • the sequence of numerical sample points of the superposed signal is ⁇ y n ⁇ , where the i-th numerical sample point is y n (i), and after one iteration calculation, the sequence is ⁇ y n+1 ⁇ , and the sequence ⁇ y n+1 ⁇ The ith numerical point in the y n+1 (i), where
  • m is a positive integer
  • the above iterative process is repeated. Each time an iteration is performed, the value of m is increased by 1, and the initial value of m is 1, and the iterative process is repeated until the m value reaches a predetermined threshold.
  • step (a1) before step (a1), the step (a) further comprises:
  • step (a01) detecting the intensity of the Raman feature in the collected single Raman spectral signal, if the Raman feature intensity is sufficient to identify the Raman feature, directly using the single Raman spectral signal as the original Raman spectrum of the sample to be tested The signal is directly performed in step (b); and if the Raman feature strength is insufficient to identify the Raman feature, steps (a1)-(a3) are continued.
  • step (a01) the detection of the intensity of the Raman feature is achieved by searching for a Raman characteristic peak in the single Raman spectral signal, and if the Raman characteristic peak can be searched, determining to pull Strong man characteristics The degree is sufficient to identify the Raman feature; if the Raman feature peak cannot be searched, it is determined that the Raman feature strength is insufficient to identify the Raman feature.
  • the detection of the intensity of the Raman feature is achieved by searching for a Raman characteristic peak in the single Raman spectral signal, if the Raman characteristic peak can be searched and the Raman The ratio of the intensity of the characteristic peak to the average intensity of the Raman spectral signal is greater than a predetermined first threshold, determining that the Raman characteristic intensity is sufficient to identify the Raman feature; if the Raman characteristic peak cannot be searched or although the Raman can be searched The characteristic peak but the ratio of the intensity of the Raman characteristic peak to the average intensity of the Raman spectral signal does not exceed a predetermined first threshold, then it is determined that the Raman characteristic intensity is insufficient to identify the Raman feature.
  • the method further comprises:
  • step (ax) detecting the intensity of the Raman feature in the superimposed signal, if the Raman feature intensity is sufficient to identify the Raman feature, directly using the superimposed signal as the original Raman spectral signal of the sample to be tested and directly performing the step (b) And if the Raman feature strength is insufficient to identify the Raman feature, proceed to step (a3).
  • step (ax) the detection of the Raman feature intensity is achieved by searching for the Raman feature peak in the superimposed signal, and if the Raman feature peak can be searched, determining the Raman feature intensity. It is sufficient to identify the Raman feature; if the Raman feature peak cannot be searched, it is determined that the Raman feature strength is insufficient to identify the Raman feature.
  • step (ax) the detection of the intensity of the Raman feature is achieved by searching for a Raman characteristic peak in the superimposed signal, if a Raman characteristic peak can be searched for and the Raman characteristic peak is The ratio of the intensity to the average intensity of the superimposed signal is greater than a predetermined second threshold, determining that the Raman feature intensity is sufficient to identify the Raman feature; if the Raman feature peak cannot be searched or although the Raman feature peak can be searched, Raman The ratio of the intensity of the characteristic peak to the average intensity of the superimposed signal does not exceed a predetermined second threshold, and it is determined that the Raman characteristic intensity is insufficient to identify the Raman feature.
  • the comparison between the original Raman spectral signal of the sample to be tested and the reference original Raman spectral signal of one or more western medicine components is calculated
  • the raw Raman spectral signal of the sample is measured for similarity to the reference raw Raman spectral signal of each of the western drug components.
  • the contrast between the enhanced Raman spectral signal of the sample to be tested and the reference enhanced Raman spectral signal of one or more western medicine components is calculated by calculating the test
  • the enhanced Raman spectral signal of the sample is performed similar to the reference enhanced Raman spectral signal of each of the western drug components.
  • the method for detecting whether a western medicine is added to a health care product based on Raman spectroscopy further comprises: establishing a reference raw Raman spectral signal of one or more western medicine ingredients before performing step (b) a database; and prior to performing step (c), establishing a reference enhanced Raman spectral signal of one or more of the western medicine components Database.
  • the mixture of the sample to be tested and the enhancer is formed by directly mixing the sample to be tested and the enhancer or by mixing an aqueous solution or an organic solution of the sample to be tested with the enhancer.
  • At least one aspect of the above technical solution of the present invention can detect whether or not a western medicine component is added to a sample to be tested by combining raw Raman spectroscopy and enhanced Raman spectroscopy.
  • This kind of scheme can balance and optimize the accuracy of detection and improve the balance of detection efficiency, and can accurately and quickly screen whether or not the illegal western medicine ingredients are added to the food.
  • FIG. 1 shows a schematic flow chart of a Raman spectroscopy-based Western medicine detection method according to an embodiment of the present invention
  • FIG. 2 is a flow chart schematically showing a process of generating an original Raman spectral signal of a sample to be tested according to an embodiment of the present invention
  • FIG. 3 is a flow chart schematically illustrating filtering out a fluorescent interference signal from a superimposed signal, in accordance with an embodiment of the present invention
  • Figure 4 is a schematic representation of a reference raw Raman spectral signal of a sildenafil standard
  • Figure 5 schematically illustrates a single Raman spectral signal of a sample of sildenafil according to an example
  • 6-8 schematically illustrate a single Raman spectral signal of a sample of a health care product according to an example, and a superimposed signal after filtering out the fluorescent interference signal and filtering out the fluorescent interference signal;
  • Figure 9 schematically illustrates an enhanced Raman spectral signal of a sample of a health care product according to an example.
  • Raman spectroscopy is a molecular vibrational spectroscopy that reflects the fingerprint characteristics of molecules and can be used to detect substances and even detect trace substances. Raman spectroscopy can be used to quickly and effectively detect the presence of illegal Western medicine ingredients in food.
  • FIG. 1 shows a schematic flow chart of a method for detecting whether or not a western medicine is added to a health care product based on Raman spectroscopy according to an embodiment of the present invention.
  • the method includes the following steps:
  • Step 100 measuring a Raman spectrum of the sample to be tested to obtain a raw Raman spectrum signal of the sample to be tested;
  • Step 200 comparing the original Raman spectrum signal of the sample to be tested with a reference raw Raman spectrum signal of one or more western medicine components to determine a raw Raman spectrum signal of the sample to be tested and the western medicine Whether the reference raw Raman spectral signals of the components match;
  • Step 300 If the original Raman spectral signal of the sample to be tested matches the reference original Raman spectral signal of one or more of the western medicine components, determining that the sample to be tested contains the western medicine component; If the original Raman spectral signal of the sample to be tested does not match the reference raw Raman spectrum signal of all components in the western drug component, the sample to be tested is subjected to enhanced Raman spectroscopy.
  • the step of the enhanced Raman spectroscopy test may further include:
  • Step 301 measuring a mixture of the sample to be tested and the enhancer to obtain an enhanced Raman spectrum signal of the sample to be tested;
  • Step 302 Compare the enhanced Raman spectrum signal of the sample to be tested with a reference enhanced Raman spectrum signal of one or more western medicine components to determine whether the western medicine component is contained in the sample to be tested.
  • the original Raman spectrum refers to the Raman spectrum signal obtained by directly measuring the Raman spectrum of the sample to be measured, and the enhanced pull is performed.
  • Themanne spectrum refers to a Raman spectrum signal obtained by measuring a Raman spectrum of a mixture of a sample to be tested and a reinforcing agent.
  • the so-called “reference raw Raman spectral signal” and “reference enhanced Raman spectral signal” respectively represent the original Raman spectral signal and enhanced Raman obtained by measuring a sample of a certain western medicine component which is standard or available for reference. Spectral signal.
  • a sample in which the original Raman spectrum is not detected and the western medicine component is not detected is enhanced by Raman.
  • the spectrum was further tested. This ensures the accuracy of the test results.
  • the method of the embodiment of the present invention can improve the detection speed and save costs.
  • the original Raman spectral signal of the sample to be tested can be obtained by a single measurement of the Raman spectrum of the sample to be tested. This method is the easiest and quickest, especially for improving detection efficiency. rate.
  • the sample to be tested when the sample to be tested is detected by Raman spectroscopy, it may be interfered by fluorescence. This fluorescence may be generated by the sample to be tested itself or by other substances such as packaging. The fluorescence spectrum may cover the range of the Raman spectrum in the frequency band and the intensity is often much larger than the Raman spectrum. Therefore, when Raman spectroscopy is performed, if the Raman spectral signal collected from the sample to be tested contains a strong fluorescent signal, the characteristic peak may not be correctly extracted from the Raman spectral signal to complete the object to be tested (eg, Identification of Western medicines added to health supplements.
  • step 100 is a flow chart schematically showing a process of generating an original Raman spectral signal of a sample to be tested, in accordance with an embodiment of the present invention.
  • the above step 100 may include:
  • Step 110 continuously measuring a Raman spectrum of the sample to be measured to acquire a plurality of Raman spectral signals
  • Step 120 superimpose the plurality of Raman spectral signals to form a superimposed signal
  • Step 130 Filter out the fluorescence interference signal from the superimposed signal to obtain an original Raman spectrum signal of the sample to be tested.
  • the signal intensity of the Raman spectrum is generally increased by extending the exposure time, but in an actual Raman spectroscopy apparatus, the intensity of a single acquired Raman spectrum signal is limited to avoid optical power. Excessive damage to the detector.
  • the Raman spectrum of the sample to be tested is continuously measured and the collected Raman spectrum signals are superimposed to enhance the signal strength, thereby avoiding the above adverse effects.
  • the "plurality" may be, for example, two, three, four, five, ten, fifteen, fifty, and the like.
  • filtering the fluorescence interference signal from the superimposed signal may be performed by the following steps: Step 131, that is, acquiring a plurality of numerical sampling points of the superimposed signal, the number of sampling points satisfying the sampling law Requirement; step 132, that is, calculating the fluorescence interference signal by an iterative manner based on the plurality of numerical sample points of the superimposed signal; and step 133, that is, subtracting the fluorescence interference signal from the superimposed signal.
  • the superimposed signal In order to calculate the fluorescence interference signal, the superimposed signal needs to have a form of discrete values. If the superimposed signal is a continuous analog curve, it needs to be converted into discrete numerical forms by sampling. However, in practice, the superimposed signal is often in the form of discrete values. In this case, the numerical sampling point can be directly obtained. In order to ensure the fidelity of the discrete signal, the number of sampling points should meet the requirements of the sampling law. .
  • the fluorescence signal is relatively slow and smooth compared to the Raman signature signal.
  • the fluorescent interference signal Iterative calculations can be performed as follows:
  • the sequence of numerical sample points of the superposed signal is ⁇ y n ⁇ , where the i-th numerical sample point is y n (i), and after one iteration calculation, the sequence is ⁇ y n+1 ⁇ , and the sequence ⁇ y n+1 ⁇ The ith numerical point in the y n+1 (i), where
  • m is a positive integer
  • the above iterative process is repeated. Each time an iteration is performed, the value of m is increased by 1, and the initial value of m is 1, and the iterative process is repeated until the m value reaches a predetermined threshold.
  • the result of the iterative calculation is the fluorescence interference signal.
  • min[...,...] represents the minimum value operation.
  • sequence number of the numerical point participating in each iteration operation should satisfy that im is greater than zero and i+m does not exceed the sequence ⁇ y n ⁇ The total length. Value points that do not satisfy this condition can remain unchanged for the original value during the iterative operation.
  • the predetermined threshold of m is determined based on the degree of smoothing of the superimposed signal. For example, it may be desirable to consider that the value of m reaches the predetermined threshold when the wavenumber width of two points separated by 2 m in the sequence of iterative results is greater than the minimum peak width but less than the fluorescent envelope width.
  • the superposition signal may be subjected to natural logarithm or squared processing before performing the above iterative calculation.
  • the fluorescent interference signal in the original Raman spectral signal can be filtered to improve the detection accuracy, and is particularly effective for samples with strong fluorescence interference and weak Raman signal.
  • 6-8 illustrate examples of using the above exemplary methods to remove fluorescent interference signals.
  • Figure 6 shows a single Raman spectral signal obtained by directly measuring the Raman spectrum of a sample of a health supplement. Signal information with significant features is difficult to see from Figure 6.
  • Fig. 7 shows a signal obtained by superimposing a plurality of Raman spectral signals obtained after continuous measurement. Compared to Figure 6, Figure 7 has been able to show some signal characteristics.
  • FIG. 8 is the original Raman spectrum signal obtained after the superimposed signal is removed from the fluorescence interference signal. As can be seen from Figure 8, the signal has a clear characteristic intensity. It can be seen that the above method of removing fluorescence interference can effectively improve the characteristic intensity of the signal, and provides a good basis for comparing the reference Raman spectrum signals.
  • a fluorescence interference removing device may be used, and the device may include: a unit for acquiring a plurality of numerical sampling points of the superimposed signal, for A plurality of numerical sample points of the superimposed signal calculate a unit of the fluorescence interference signal in an iterative manner and a unit for subtracting the fluorescence interference signal from the superimposed signal.
  • the fluorescent interference removal device can be implemented, for example, in the form of circuit hardware, firmware or software.
  • step 100 may also include optional steps, as shown in the dashed line portion of FIG.
  • step 100 may further include:
  • Step 101 performing a prediction amount on a Raman spectrum of the sample to be measured to acquire a single Raman spectrum signal
  • Step 102 detecting the intensity of the Raman feature in the collected single Raman spectral signal. If the Raman feature intensity is sufficient to identify the Raman feature, directly using the single Raman spectral signal as the original Raman spectrum of the sample to be tested. The signal is directly performed in step 200, i.e., in comparison with a reference raw Raman spectral signal of one or more western medicine components; and if the Raman characteristic intensity is insufficient to identify the Raman feature, then steps 110-130 are continued. This is to skip the steps of subsequent continuous measurement and removal of fluorescence interference in the case where the fluorescence interference signal in the sample to be tested is weak without affecting the Raman spectroscopy measurement, so as to improve the detection efficiency.
  • the detection of the Raman feature intensity is achieved by searching for a Raman feature peak in the single Raman spectral signal, and if the Raman feature peak can be searched, determining that the Raman feature intensity is sufficient The Raman feature is identified; if the Raman feature peak cannot be searched, it is determined that the Raman feature strength is insufficient to identify the Raman feature.
  • the detection of the Raman feature intensity is achieved by searching for a Raman feature peak in the single Raman spectral signal, if the Raman feature peak can be searched and the pull The ratio of the intensity of the man characteristic peak to the average intensity of the Raman spectral signal is greater than a predetermined first threshold, determining that the Raman feature intensity is sufficient to identify the Raman feature; if the Raman feature peak cannot be searched or although the search can be performed The ratio of the intensity of the Mann characteristic peak but the intensity of the Raman characteristic peak to the average intensity of the Raman spectral signal does not exceed a predetermined first threshold, and it is determined that the intensity of the Raman feature is insufficient to identify the Raman feature.
  • the average intensity of the above Raman spectral signal characterizes the combination of the Raman spectral characteristic intensity and the intensity of the fluorescence interference signal, and thus, the ratio of the intensity of the Raman characteristic peak to the average intensity of the Raman spectral signal reflects the Raman characteristic peak
  • the first threshold may be determined based on instrument accuracy, calculation error, etc., for example, may be determined to be 0.5, 1, 3, or the like.
  • step 12x may also be included: Detecting the intensity of the Raman feature in the superimposed signal, if the Raman feature intensity is sufficient to identify the Raman feature, directly using the superimposed signal as the original Raman spectral signal of the sample to be tested and directly performing step 200; If the MANN characteristic strength is insufficient to identify the Raman feature, then step 130 is continued.
  • the Raman characteristic intensity and the fluorescence interference signal intensity are relatively weak, it is possible to correctly detect the Raman spectrum in the case where the total intensity of the Raman spectrum signal is enhanced by continuous measurement and signal superposition. Raman features in the signal, such as characteristic peaks.
  • the detection of the Raman feature intensity is achieved by searching for the Raman feature peak in the superimposed signal, and if the Raman feature peak can be searched, determining the Raman feature intensity is sufficient to identify the Raman feature. If the Raman characteristic peak cannot be searched, it is determined that the Raman characteristic intensity is insufficient to identify the Raman feature.
  • the detection of the Raman feature intensity is achieved by searching for a Raman feature peak in the superimposed signal, if a Raman feature peak can be searched for and the intensity of the Raman feature peak is If the ratio of the average intensity of the superimposed signal is greater than a predetermined second threshold, determining that the Raman characteristic intensity is sufficient to identify the Raman feature; if the Raman characteristic peak cannot be searched or the Raman characteristic peak is searchable, the Raman characteristic peak is It is determined that the intensity of the Raman feature is insufficient to identify the Raman feature if the ratio of the intensity of the superimposed signal to the average intensity of the superimposed signal does not exceed a predetermined second threshold.
  • the average intensity of the Raman spectral signal described above characterizes the combination of the Raman spectral characteristic intensity and the intensity of the fluorescence interference signal, and thus the ratio of the intensity of the Raman characteristic peak to the average intensity of the Raman spectral signal. It reflects the contrast between the intensity of the Raman characteristic peak and the intensity of the fluorescence interference signal.
  • the second threshold may be determined based on instrument accuracy, calculation error, etc., for example, may be determined to be 0.5, 1, 3, or the like.
  • the second threshold and the first threshold may be the same or different.
  • the average intensity in the above embodiment may be an arithmetic mean or a geometric mean of the signal strength or the like.
  • the comparing the original Raman spectral signal of the sample to be tested with the reference original Raman spectral signal of one or more of the western medicine components by calculating the sample to be tested Determining the original Raman spectral signal with the reference original Raman spectral signal of each of the western medicine components, and if the similarity exceeds the third threshold, determining the original Raman spectral signal of the sample to be tested and the The reference raw Raman spectral signal of the western medicine component is matched, and if the similarity does not exceed the third threshold, determining that the original Raman spectral signal of the sample to be tested does not match the reference original Raman spectral signal of the western medicine component .
  • Corr represents the similarity between the original Raman spectral signal of the western medicine component and the original Raman spectral signal of the sample to be tested, and " ⁇ " represents a dot product operation.
  • A(x) and B(x) can be sampled separately to obtain n sample points, denoted as A 1 , A 2 , . . . , A n and B 1 , B, respectively. 2 ,...,B n
  • the similarity of the original Raman spectral signal of a western medicine component to the original Raman spectral signal of the sample to be tested Corr can be calculated according to formula (3):
  • ⁇ also represents a dot product operation.
  • the above similarity calculation may be performed for the entire Raman spectral signal, or may be performed only for a portion having a characteristic portion in the Raman spectral signal.
  • the term "characteristic portion” refers to a key portion of a Raman spectral signal of a certain Western medicine component or a Raman spectral signal of a sample to be tested that is different from other material components.
  • the feature portion may be one or more feature peaks, feature valleys, phase inflection points, and the like.
  • the above similarity may be weighted based on the peak position, peak width, and/or peak height of the characteristic peak.
  • the similarity is calculated Previously, the feature peaks could also be searched and sorted.
  • the similarity calculation can be simplified even to search for the original Raman spectral signal or the enhanced pull of the sample to be tested. Whether the characteristic peak corresponding to the original Raman spectral signal of a certain western medicine component or the characteristic peak of the enhanced Raman spectral signal exists at one or more positions in the human spectral signal is directly determined.
  • the contrast between the enhanced Raman spectral signal of the sample to be tested and the reference enhanced Raman spectral signal of one or more western medicine components is calculated. Determining the similarity between the enhanced Raman spectral signal of the sample to be tested and the reference enhanced Raman spectral signal of each of the western medicine components, and if the similarity exceeds the fourth threshold, determining that the sample to be tested contains the western medicine The component, on the other hand, if the similarity does not exceed the fourth threshold, it is determined that the sample to be tested does not contain the western medicine component.
  • the third threshold and the fourth threshold may or may not be equal.
  • the third threshold and the fourth threshold may be given according to actual detection requirements, accuracy of the detection instrument, and the like.
  • the method of detecting whether a western medicine is added to a health care product according to a Raman spectrum of an embodiment of the present invention may further include: establishing a reference raw Raman spectral signal of one or more western medicine components before performing step 200 Database.
  • the method of detecting whether a western medicine is added to a health care product according to the Raman spectrum of the embodiment of the present invention may further include: establishing a reference enhanced Raman spectral signal of one or more western medicine components before performing step 300 Database.
  • Figure 4 shows a reference raw Raman spectral signal of an exemplary western medicine ingredient (sildenafil) standard.
  • Figure 5 shows the raw Raman spectral signal of a sample of a health supplement, where the arrow indicates the characteristic peak in the original Raman spectral signal.
  • the mixture of the sample to be tested and the enhancer is formed by directly mixing the sample to be tested and the enhancer or by mixing an aqueous solution or an organic solution of the sample to be tested with the enhancer.
  • Figure 9 shows an enhanced Raman spectral signal of an exemplary sample of a health care product, wherein the arrows indicate characteristic peaks in the enhanced Raman spectral signal. It can also be used to compare with the reference enhanced Raman spectroscopy signal of the western medicine component standard to determine whether the western medicine component is contained in the sample to be tested, and the specific process will not be described again.
  • the enhancer may include any one of metal nanoparticle materials, metal nanowires, metal nanoclusters, carbon nanotubes, and carbon nanoparticles having a size in the range of 1-1000 nm or The combination.
  • the enhancer may comprise a metal nanomaterial, or may also contain a chloride nanoparticle, a bromide ion, a sodium ion, a potassium ion, or a sulfate ion.
  • the metal may include, for example, any one of gold, silver, copper, magnesium, aluminum, iron, cobalt, nickel, palladium, or platinum, or a combination thereof.
  • particles of the western medicine component adhere to the surface of the enhancer material, and the electromagnetic field on the surface of the enhancer material enhances the Raman spectrum signal of the western medicine component.
  • the acquisition of Raman spectral data can be obtained by irradiating a sample to be tested with a laser emitted from a laser, extracting and performing spectral analysis on Raman scattered light generated by laser irradiation of the sample to be tested.
  • the sample to be tested may be a sample of a health supplement.

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Abstract

一种基于拉曼光谱的检测保健品中是否添加有西药的方法，包括：对待测样品的拉曼光谱进行测量以获得待测样品的原始拉曼光谱信号（100）；将所述待测样品的原始拉曼光谱信号与一种或更多种西药成分的参考原始拉曼光谱信号进行对比以判定所述待测样品的原始拉曼光谱信号与所述西药成分的参考原始拉曼光谱信号是否匹配（200）；以及如果所述待测样品的原始拉曼光谱信号与所述西药成分中的一种或更多种的参考原始拉曼光谱信号匹配，则确定待测样品中含有所述西药成分；而如果所述待测样品的原始拉曼光谱信号与所述西药成分中的所有成分的参考原始拉曼光谱信号均不匹配，则对所述待测样品进行增强拉曼光谱测试，以判断待测样品中是否添加有西药（300）。

Description

基于拉曼光谱的检测保健品中是否添加有西药的方法
本申请要求于2015年5月4日递交中国专利局的、申请号为201510221524.8的中国专利申请的权益，该申请的全部公开内容以引用方式并入本文。
技术领域
本发明涉及安全检测技术领域，尤其涉及一种利用拉曼光谱技术来对诸如保健品等食品进行检测以判断保健品中是否添加有西药的方法。
背景技术
一些不法商家为达到提升功效或加快药效的目的，在食品(如保健品)里违规添加西药成分。西药成分往往具有副作用，需要在医生指导下服用，如果长期服用这类食品会危害身体健康，因此，对保健品的监管非常重要。
目前对保健品中非法添加西药的检测主要采用色谱、质谱等方法，这些方法检测时间长，无法满足现场快速筛查的需要。
发明内容
本发明的目的是提供一种基于拉曼光谱的检测保健品中是否添加有西药的方法，其能够快速、高效、准确地确定待测样品(如保健品样品)中是否包含违规的西药成分。
为了实现上述发明目的，本发明的技术方案通过以下方式来实现：
本发明的实施例提供了一种基于拉曼光谱的检测保健品中是否添加有西药的方法，包括以下步骤：
(a)对待测样品的拉曼光谱进行测量以获得待测样品的原始拉曼光谱信号；
(b)将所述待测样品的原始拉曼光谱信号与一种或更多种西药成分的参考原始拉曼光谱信号进行对比以判定所述待测样品的原始拉曼光谱信号与所述西药成分的参考原始拉曼光谱信号是否匹配；以及
(c)如果所述待测样品的原始拉曼光谱信号与所述西药成分中的一种或更多种的参考原始拉曼光谱信号匹配，则确定待测样品中含有所述西药成分；而如果所述待测样品的原始拉曼光谱信号与所述西药成分中的所有成分的参考原始拉曼光谱信号均不 匹配，则对所述待测样品进行增强拉曼光谱测试，所述增强拉曼光谱测试的步骤包括：
(c1)对所述待测样品与增强剂的混合物进行测量以获得待测样品的增强拉曼光谱信号；及
(c2)将所述待测样品的增强拉曼光谱信号与一种或更多种西药成分的参考增强拉曼光谱信号进行对比以判定所述待测样品中是否含有所述西药成分。
在一实施例中，在所述步骤(a)中，所述待测样品的原始拉曼光谱信号通过对待测样品的拉曼光谱的单次测量而获得。
在一实施例中，所述步骤(a)包括：
(a1)连续地对待测样品的拉曼光谱进行测量以采集多个拉曼光谱信号；
(a2)对所述多个拉曼光谱信号进行叠加以形成叠加信号；以及
(a3)从该叠加信号中滤除荧光干扰信号以获得待测样品的原始拉曼光谱信号。
在一实施例中，所述步骤(a3)包括：
(a31)获取该叠加信号的多个数值采样点，采样点的个数满足采样定律的要求；
(a32)基于该叠加信号的多个数值采样点通过迭代方式计算荧光干扰信号；以及
(a33)从该叠加信号中减去荧光干扰信号。
在一实施例中，在所述步骤(a32)中，荧光干扰信号以如下迭代方式计算：
假定该叠加信号的数值采样点序列为{yn}，其中第i个数值采样点为yn(i)，经过一次迭代计算得到序列为{yn+1}，序列{yn+1}中的第i个数值点为yn+1(i)，其中
Figure PCTCN2015098694-appb-000001
其中m为正整数，上述迭代过程反复进行，每进行一次迭代，m的数值增加1，m的初始值为1，上述迭代过程反复进行直至m值达到预定的阈值为止。
在一实施例中，在步骤(a1)之前，所述步骤(a)还包括：
(a00)对待测样品的拉曼光谱进行预测量以采集单个拉曼光谱信号；以及
(a01)对采集到的单个拉曼光谱信号中的拉曼特征强度进行检测，如果拉曼特征强度足以识别拉曼特征，则直接将该单个拉曼光谱信号作为待测样品的原始拉曼光谱信号并直接执行步骤(b)；而如果拉曼特征强度不足以识别拉曼特征，则继续执行步骤(a1)-(a3)。
在一实施例中，在步骤(a01)中，对拉曼特征强度的检测通过在所述单个拉曼光谱信号中搜索拉曼特征峰来实现，如果能够搜索到拉曼特征峰，则确定拉曼特征强 度足以识别拉曼特征；如果不能搜索到拉曼特征峰，则确定拉曼特征强度不足以识别拉曼特征。
在一实施例中，在步骤(a01)中，对拉曼特征强度的检测通过在所述单个拉曼光谱信号中搜索拉曼特征峰来实现，如果能够搜索到拉曼特征峰且该拉曼特征峰的强度与所述拉曼光谱信号的平均强度之比大于预定的第一阈值，则确定拉曼特征强度足以识别拉曼特征；如果不能搜索到拉曼特征峰或虽然能够搜索到拉曼特征峰但拉曼特征峰的强度与所述拉曼光谱信号的平均强度之比不超过预定的第一阈值，则确定拉曼特征强度不足以识别拉曼特征。
在一实施例中，在步骤(a2)和(a3)之间，所述方法还包括：
(ax)对所述叠加信号中的拉曼特征强度进行检测，如果拉曼特征强度足以识别拉曼特征，则直接将该叠加信号作为待测样品的原始拉曼光谱信号并直接执行步骤(b)；而如果拉曼特征强度不足以识别拉曼特征，则继续执行步骤(a3)。
在一实施例中，在步骤(ax)中，对拉曼特征强度的检测通过在所述叠加信号中搜索拉曼特征峰来实现，如果能够搜索到拉曼特征峰，则确定拉曼特征强度足以识别拉曼特征；如果不能搜索到拉曼特征峰，则确定拉曼特征强度不足以识别拉曼特征。
在一实施例中，在步骤(ax)中，对拉曼特征强度的检测通过在所述叠加信号中搜索拉曼特征峰来实现，如果能够搜索到拉曼特征峰且该拉曼特征峰的强度与所述叠加信号的平均强度之比大于预定的第二阈值，则确定拉曼特征强度足以识别拉曼特征；如果不能搜索到拉曼特征峰或虽然能够搜索到拉曼特征峰但拉曼特征峰的强度与所述叠加信号的平均强度之比不超过预定的第二阈值，则确定拉曼特征强度不足以识别拉曼特征。
在一实施例中，在所述步骤(b)中，所述将所述待测样品的原始拉曼光谱信号与一种或更多种西药成分的参考原始拉曼光谱信号的对比通过计算待测样品的原始拉曼光谱信号与每种所述西药成分的参考原始拉曼光谱信号的相似度来进行。
在一实施例中，在所述步骤(c)中，所述待测样品的增强拉曼光谱信号与一种或更多种西药成分的参考增强拉曼光谱信号的对比通过计算所述待测样品的增强拉曼光谱信号与每种所述西药成分的参考增强拉曼光谱信号的相似度来进行。
在一实施例中，所述基于拉曼光谱的检测保健品中是否添加有西药的方法还包括：在执行步骤(b)之前，建立一种或更多种西药成分的参考原始拉曼光谱信号的数据库；以及在执行步骤(c)之前，建立一种或更多种所述西药成分的参考增强拉曼光谱信号 的数据库。
在一实施例中，所述待测样品与增强剂的混合物由待测样品与增强剂直接混合而成或由待测样品的水溶液或有机溶液与增强剂混合而成。
本发明的上述技术方案中的至少一个方面能够通过结合原始拉曼光谱和增强拉曼光谱检测待测样品中是否添加有西药成分。这种方案可以兼顾和优化检测的准确性与提高检测效率的平衡，可以实现对于食品中是否添加违规西药成分进行准确的快速筛查。
附图说明
图1示出根据本发明的实施例的基于拉曼光谱的西药检测方法的示意性流程图；
图2示意性地示出根据本发明一实施例的生成待测样品的原始拉曼光谱信号的过程的流程图；
图3示意性地示出根据本发明的实施例的从叠加信号中滤除荧光干扰信号的流程图；
图4示意性地示出西地那非标准品的参考原始拉曼光谱信号；
图5示意性地示出根据一示例的西地那非的样品的单个拉曼光谱信号；
图6-8示意性地示出根据一示例的某保健品的样品单个拉曼光谱信号以及滤除荧光干扰信号前和滤除荧光干扰信号后的叠加信号；以及
图9示意性地示出根据一示例的某保健品的样品的增强拉曼光谱信号。
具体实施方式
下面通过实施例，并结合附图，对本发明的技术方案作进一步具体的说明。在说明书中，相同或相似的附图标号表示相同或相似的部件。下述参照附图对本发明实施方式的说明旨在对本发明的总体发明构思进行解释，而不应当理解为对本发明的一种限制。
拉曼光谱是一种分子振动光谱，它可以反映分子的指纹特征，可用于对物质的检测，甚至可以实现对痕量物质的检测。利用拉曼光谱可以实现对于食品中是否存在违规的西药成分进行快速有效地检测。
图1示出根据本发明的实施例的基于拉曼光谱的检测保健品中是否添加有西药的方法的示意性流程图。该方法包括以下步骤：
步骤100：对待测样品的拉曼光谱进行测量以获得待测样品的原始拉曼光谱信号；
步骤200：将所述待测样品的原始拉曼光谱信号与一种或更多种西药成分的参考原始拉曼光谱信号进行对比以判定所述待测样品的原始拉曼光谱信号与所述西药成分的参考原始拉曼光谱信号是否匹配；
步骤300：如果所述待测样品的原始拉曼光谱信号与所述西药成分中的一种或更多种的参考原始拉曼光谱信号匹配，则确定待测样品中含有所述西药成分；而如果所述待测样品的原始拉曼光谱信号与所述西药成分中的所有成分的参考原始拉曼光谱信号均不匹配，则对所述待测样品进行增强拉曼光谱测试。
所述增强拉曼光谱测试的步骤还可以具体包括：
步骤301：对所述待测样品与增强剂的混合物进行测量以获得待测样品的增强拉曼光谱信号；以及
步骤302：将所述待测样品的增强拉曼光谱信号与一种或更多种西药成分的参考增强拉曼光谱信号进行对比以判定所述待测样品中是否含有所述西药成分。
在上述实施例中，采用了原始拉曼光谱和增强拉曼光谱相结合的方式，原始拉曼光谱是指通过直接对待测样品的拉曼光谱进行测量而得到的拉曼光谱信号，而增强拉曼光谱是指通过对待测样品与增强剂的混合物的拉曼光谱进行测量而得到的拉曼光谱信号。所谓“参考原始拉曼光谱信号”和“参考增强拉曼光谱信号”分别表示的是通过对标准的或可供参照的某种西药成分的样品进行测量得到的原始拉曼光谱信号和增强拉曼光谱信号。
采用以上方式，可以高效准确地检测待测样品中是否添加有西药。一方面，由于在实际中微量的添加西药无法达到提升功效或加快药效的目的，食品(如保健品)中违规添加的西药含量一般大于1％，所以往往采用对待测样品进行直接测量获取原始拉曼光谱进行光谱比对就可以得出结果，这可以使得对违规添加西药成分的检测能够迅速完成，尤其适于现场的快速筛查。另一方面，在一些情况下，仅借助于原始拉曼光谱难以获得准确的检测结果，因此，上述实施例中还采用了对于原始拉曼光谱比对没有检测出西药成分的样品通过增强拉曼光谱进行进一步检测。这可以保证检测结果的准确性。与仅采用增强拉曼光谱检测的方法相比，本发明的实施例的方法可以提高检测速度，节约成本。
作为示例，在上述步骤100中，所述待测样品的原始拉曼光谱信号可以通过对待测样品的拉曼光谱的单次测量而获得。这种方式最为简便快捷，尤其适于提高检测效 率。
然而，另一方面，在利用拉曼光谱对待测样品进行检测时，可能会受到荧光的干扰。该荧光可能由待测样品本身产生，也可能由包装物等其它物质产生。而荧光光谱在频带上可能覆盖拉曼光谱的范围且强度往往远大于拉曼光谱。因此，在进行拉曼光谱检测时，从待测样品收集到的拉曼光谱信号如果包含较强荧光信号时，可能无法正确地从拉曼光谱信号中提取特征峰来完成对待测物(如被添加到保健品中的西药)的识别。对于在食品(如保健品)中添加西药的情况，由于食品本身的成分非常复杂，除去主要成分外还可能含有某些添加剂，因而，某些样品难以避免地会存在荧光干扰。为了更全面地适应于多种食品(如保健品)的检测要求，去除这种干扰是有意义的。
图2示意性地示出根据本发明一实施例的生成待测样品的原始拉曼光谱信号的过程的流程图。作为示例，上述步骤100可以包括：
步骤110：连续地对待测样品的拉曼光谱进行测量以采集多个拉曼光谱信号；
步骤120：对所述多个拉曼光谱信号进行叠加以形成叠加信号；以及
步骤130：从该叠加信号中滤除荧光干扰信号以获得待测样品的原始拉曼光谱信号。
在现有技术中，一般通过延长曝光时间来提高拉曼光谱的信号强度，但是在实际的拉曼光谱检测仪器中，单次采集的拉曼光谱信号的强度是有限制的，以避免光功率过大对探测器的损坏。而在本申请的实施例中，采用了对待测样品的拉曼光谱进行连续测量并将采集到的多个拉曼光谱信号进行叠加以增强信号强度，能够避免上述不利影响。所述“多个”可以例如是2个、3个、4个、5个、10个、15个、50个等等。
通过将多个拉曼光谱信号叠加，可以提高信号强度，以更容易地去除荧光干扰信号。作为一示例，如图3所示，从叠加信号中滤除荧光干扰信号可以通过以下步骤来进行：步骤131，即获取该叠加信号的多个数值采样点，采样点的个数满足采样定律的要求；步骤132，即基于该叠加信号的多个数值采样点通过迭代方式计算荧光干扰信号；和步骤133，即从该叠加信号中减去荧光干扰信号。
为了计算荧光干扰信号，叠加信号需要具备离散数值的形式，如果叠加信号为连续的模拟曲线，则需要通过采样转换成离散的数值形式。但在实际中，该叠加信号往往已经为离散数值形式，在这种情况下，直接地获取数值采样点即可，为了保证离散信号的保真度，采样点的个数应当满足采样定律的要求。
荧光信号与拉曼特征信号相比，变化相对缓慢平滑。作为一示例，荧光干扰信号 可以按照如下方式进行迭代计算：
假定该叠加信号的数值采样点序列为{yn}，其中第i个数值采样点为yn(i)，经过一次迭代计算得到序列为{yn+1}，序列{yn+1}中的第i个数值点为yn+1(i)，其中
Figure PCTCN2015098694-appb-000002
   式(1)
其中m为正整数，上述迭代过程反复进行，每进行一次迭代，m的数值增加1，m的初始值为1，上述迭代过程反复进行直至m值达到预定的阈值为止。经过迭代计算得到的结果即为荧光干扰信号。
在上述式(1)中，“min[…,…]”表示取最小值运算，显然，参与每次迭代运算的数值点的序号应当满足i-m大于零且i+m不超过序列{yn}的总长度。不满足该条件的数值点在迭代运算过程中可以保持原值不变。
在一示例中，m的预定的阈值根据所述叠加信号的平滑程度来确定。例如，可以要求当迭代结果的序列中的相隔2m的两个点的波数宽度大于最小峰宽但小于荧光包络宽度时，认为该m值达到该预定的阈值。
在一示例中，如果为了进一步提高计算精度，还可以在进行上述迭代计算之前，先对该叠加信号进行求自然对数或求平方处理。
虽然在上述示例中以由式(1)和式(2)所示的迭代方法为例对计算荧光干扰信号进行了介绍，但是，应当理解，这不是必须的。本领域中的求解光滑谱信号的方法也可以用于求解上述荧光干扰信号，但方法可能更复杂，计算效率可能较低。
通过上述方式，可以将原始拉曼光谱信号中的荧光干扰信号滤除，以提高检测精度，对于荧光干扰强、拉曼信号弱的样品尤其有效。图6-图8示出了利用上述示例性方法来去除荧光干扰信号的示例。图6示出的是直接对某保健品的样品的拉曼光谱进行测量所得到的单个拉曼光谱信号。从图6中难以看出具有显著特征的信号信息。图7示出的是将经过连续测量后得到的多个拉曼光谱信号叠加后得到的信号。与图6相比，图7已经能够显现出一些信号特征。而图8则是将该叠加信号去除荧光干扰信号之后得到的原始拉曼光谱信号。从图8中可以看出，该信号具有清晰的特征强度。由此可见，上述去除荧光干扰的方式可以有效地提高信号的特征强度，为对参考的拉曼光谱信号进行比对提供良好的基础。
为了实现上述从叠加信号中滤除荧光干扰信号的过程，可以采用一种荧光干扰去除装置，该装置可以包括：用于获取该叠加信号的多个数值采样点的单元、用于基于 该叠加信号的多个数值采样点通过迭代方式计算荧光干扰信号的单元以及用于从该叠加信号中减去荧光干扰信号的单元。该荧光干扰去除装置例如可以由电路硬件、固件或软件等形式实现。
作为示例，上述步骤100还可以包括可选的步骤，如图2中虚线部分所示。例如，在步骤110之前，所述步骤100还可以包括：
步骤101：对待测样品的拉曼光谱进行预测量以采集单个拉曼光谱信号；和
步骤102：对采集到的单个拉曼光谱信号中的拉曼特征强度进行检测，如果拉曼特征强度足以识别拉曼特征，则直接将该单个拉曼光谱信号作为待测样品的原始拉曼光谱信号并直接执行步骤200，即，与一种或更多种西药成分的参考原始拉曼光谱信号进行对比；而如果拉曼特征强度不足以识别拉曼特征，则继续执行步骤110-130。这是为了在待测样品中的荧光干扰信号较弱而不影响拉曼光谱测量的情况下跳过后续连续测量和去除荧光干扰的步骤，以提高检测效率。
在本发明的上述实施例中，实际上综合了单个原始拉曼光谱信号检测、叠加的原始拉曼光谱信号检测和增强拉曼光谱信号检测三种方式。这三种检测方式层层递进，实现了检测效率和准确性的最佳平衡。
作为示例，在上述步骤102中，对拉曼特征强度的检测通过在所述单个拉曼光谱信号中搜索拉曼特征峰来实现，如果能够搜索到拉曼特征峰，则确定拉曼特征强度足以识别拉曼特征；如果不能搜索到拉曼特征峰，则确定拉曼特征强度不足以识别拉曼特征。
替代地，在一示例中，在上述步骤102中，对拉曼特征强度的检测通过在所述单个拉曼光谱信号中搜索拉曼特征峰来实现，如果能够搜索到拉曼特征峰且该拉曼特征峰的强度与所述拉曼光谱信号的平均强度之比大于预定的第一阈值，则确定拉曼特征强度足以识别拉曼特征；如果不能搜索到拉曼特征峰或虽然能够搜索到拉曼特征峰但拉曼特征峰的强度与所述拉曼光谱信号的平均强度之比不超过预定的第一阈值，则确定拉曼特征强度不足以识别拉曼特征。
上述拉曼光谱信号的平均强度表征了拉曼光谱特征强度和荧光干扰信号的强度的组合，因而，拉曼特征峰的强度与所述拉曼光谱信号的平均强度之比反映了拉曼特征峰的强度与荧光干扰信号的强度的对比关系。该第一阈值可以根据仪器精度、计算误差等来确定，例如可以确定为0.5、1、3等等。
在一示例中，如图2所示，在步骤120和步骤130之间，还可以包括步骤12x： 对所述叠加信号中的拉曼特征强度进行检测，如果拉曼特征强度足以识别拉曼特征，则直接将该叠加信号作为待测样品的原始拉曼光谱信号并直接执行步骤200；而如果拉曼特征强度不足以识别拉曼特征，则继续执行步骤130。在拉曼特征强度与荧光干扰信号强度都相对偏弱的情况下，有可能在通过连续测量和信号叠加对拉曼光谱信号的总强度进行增强的情况下，就能够正确的检测到拉曼光谱信号中的拉曼特征，如特征峰。这样，采用上述步骤12x，就能够避免对于荧光干扰信号的不必要的计算，以提高计算效率。
作为示例，在步骤12x中，对拉曼特征强度的检测通过在所述叠加信号中搜索拉曼特征峰来实现，如果能够搜索到拉曼特征峰，则确定拉曼特征强度足以识别拉曼特征；如果不能搜索到拉曼特征峰，则确定拉曼特征强度不足以识别拉曼特征。
在另一示例中，在步骤12x中，对拉曼特征强度的检测通过在所述叠加信号中搜索拉曼特征峰来实现，如果能够搜索到拉曼特征峰且该拉曼特征峰的强度与所述叠加信号的平均强度之比大于预定的第二阈值，则确定拉曼特征强度足以识别拉曼特征；如果不能搜索到拉曼特征峰或虽然能够搜索到拉曼特征峰但拉曼特征峰的强度与所述叠加信号的平均强度之比不超过预定的第二阈值，则确定拉曼特征强度不足以识别拉曼特征。
与上述步骤102相似，上述拉曼光谱信号的平均强度表征了拉曼光谱特征强度和荧光干扰信号的强度的组合，因而，拉曼特征峰的强度与所述拉曼光谱信号的平均强度之比反映了拉曼特征峰的强度与荧光干扰信号的强度的对比关系。该第二阈值可以根据仪器精度、计算误差等来确定，例如可以确定为0.5、1、3等等。上述第二阈值和第一阈值可以相同，也可以不同。
在上述实施例中的平均强度可以是信号强度的算术平均值或几何平均值等。
作为示例，在所述步骤200中，所述将所述待测样品的原始拉曼光谱信号与一种或更多种所述西药成分的参考原始拉曼光谱信号的对比通过计算待测样品的原始拉曼光谱信号与每种所述西药成分的参考原始拉曼光谱信号的相似度来进行，如果该相似度超过第三阈值，则判定所述待测样品的原始拉曼光谱信号与所述西药成分的参考原始拉曼光谱信号匹配，反之，如果该相似度没有超过第三阈值，则判定所述待测样品的原始拉曼光谱信号与所述西药成分的参考原始拉曼光谱信号不匹配。
相似度的计算有多种方法，比如相关算法、最大似然法、绝对值算法等等。例如，假定某种有可能被加入到保健品中的西药成分的原始拉曼光谱信号为A(x)，待测样 品的原始拉曼光谱信号为B(x)，在一示例中，采用最大似然算法，可以通过式(2)对两者的相似度进行计算：
Figure PCTCN2015098694-appb-000003
   式(2)
其中Corr表示该种西药成分的原始拉曼光谱信号和待测样品的原始拉曼光谱信号的相似度，“·”表示点积运算。
在另一示例中，采用相关算法，可以对A(x)和B(x)分别进行采样以各获得n个采样点，分别表示为A1,A2,…,An以及B1,B2,…,Bn，某种西药成分的原始拉曼光谱信号和待测样品的原始拉曼光谱信号的相似度Corr可以根据式(3)进行计算：
Figure PCTCN2015098694-appb-000004
   式(3)
其中，“·”也表示点积运算。
在另一示例中，还可以采用绝对值算法，亦可以对A(x)和B(x)分别进行采样以各获得n个采样点，分别表示为A1,A2,…,An以及B1,B2,…,Bn，某种西药成分的原始拉曼光谱信号和待测样品的原始拉曼光谱信号的相似度Corr可以根据式(4)进行计算：
Figure PCTCN2015098694-appb-000005
   (4)
上述相似度计算可以针对整个拉曼光谱信号进行，也可以仅针对于拉曼光谱信号中具有特征部分的局部进行。
在本申请中，术语“特征部分”是指某种西药成分或待测样品的拉曼光谱信号中有别于其它的物质成分的拉曼光谱信号的关键部分。例如，所述特征部分可以是一个或更多个特征峰、特征谷、相位拐点等等。
在某种西药成分的原始拉曼光谱信号包括特征峰的情况下，上述相似度可以基于所述特征峰的峰位、峰宽和/或峰高来进行加权计算。在一示例中，在计算所述相似度 之前，还可以对所述特征峰进行搜索和排序。在某种西药成分的原始拉曼光谱信号或增强拉曼光谱信号的特征峰比较明显的情况下，在实际中，相似度计算甚至可以简化成搜索待测样品的原始拉曼光谱信号或增强拉曼光谱信号中是否在某一个或多个位置上存在与某种西药成分的原始拉曼光谱信号或增强拉曼光谱信号的特征峰相对应的特征峰来直接进行确定。
作为示例，在所述步骤300中，所述待测样品的增强拉曼光谱信号与一种或更多种西药成分(在保健品中可能被添加)的参考增强拉曼光谱信号的对比通过计算所述待测样品的增强拉曼光谱信号与每种所述西药成分的参考增强拉曼光谱信号的相似度来进行，如果该相似度超过第四阈值，则判定待测样品中含有所述西药成分，反之，如果该相似度没有超过第四阈值，则判定待测样品中不含有所述西药成分。
第三阈值和第四阈值可以相等，也可以不相等。第三阈值和第四阈值可以根据实际的检测需要、检测仪器的精度等因素来给出。
对于待测样品的增强拉曼光谱信号与某种西药成分的增强拉曼光谱信号的相似度的计算，与上述待测样品的原始拉曼光谱信号与所述西药成分的原始拉曼光谱信号的相似度的计算基本相同，在此不再赘述。以上仅是给出了一些相似度计算的示例，本领域技术人员所知的一些其他的相似度计算方法也是可行的。
作为示例，根据本发明的实施例的拉曼光谱的检测保健品中是否添加有西药的方法还可以包括：在执行步骤200之前，建立一种或更多种西药成分的参考原始拉曼光谱信号的数据库。类似地，根据本发明的实施例的拉曼光谱的检测保健品中是否添加有西药的方法还可以包括：在执行步骤300之前，建立一种或更多种西药成分的参考增强拉曼光谱信号的数据库。
图4示出了一种示例性西药成分(西地那非)标准品的参考原始拉曼光谱信号。图5示出的是某保健品的样品的原始拉曼光谱信号，其中箭头所指示的是原始拉曼光谱信号中的特征峰。经过上述实施例所述的过程可以得出两者是相匹配的，也就是说，该保健品的样品含有这种西药成分(西地那非)，是违规的。
作为示例，所述待测样品与增强剂的混合物由待测样品与增强剂直接混合而成或由待测样品的水溶液或有机溶液与增强剂混合而成。图9示出了一种示例性的某保健品的样品的增强拉曼光谱信号，其中箭头所指示的是增强拉曼光谱信号中的特征峰。其也可以用于与西药成分标准品的参考增强拉曼光谱信号进行比对以判定是否在待测样品中含有该西药成分，具体过程不再赘述。
在本发明的实施例中，作为示例，增强剂可以包含尺度在1-1000nm范围内的金属纳米颗粒材料、金属纳米线、金属纳米团簇、碳纳米管和碳纳米颗粒中任一种或它们的组合。在另一示例中，增强剂可以包含金属纳米材料，也可在包含金属纳米材料的同时还包含氯离子、溴离子、钠离子、钾离子或硫酸根离子。所述金属例如可以包括金、银、铜、镁、铝、铁、钴、镍、钯或铂中的任一种或它们的组合。在待测样品与增强剂的混合物中，西药成分的粒子会附着于增强剂材料的表面，而增强剂材料表面的电磁场会使得西药成分的拉曼光谱信号得到增强。
作为示例，拉曼光谱数据的获取，可以通过利用激光器发出的激光照射待测样品，并对由激光照射待测样品产生的拉曼散射光进行提取并进行光谱分析而得出拉曼光谱信号。
在本发明的实施例中，所述待测样品可以为保健品的样品。
虽然结合附图对本发明进行了说明，但是附图中公开的实施例旨在对本发明优选实施方式进行示例性说明，而不能理解为对本发明的一种限制。
虽然本发明总体构思的一些实施例已被显示和说明，本领域普通技术人员将理解，在不背离本总体发明构思的原则和精神的情况下，可对这些实施例做出改变，本发明的范围以权利要求和它们的等同物限定。

Claims (15)

  1. 一种基于拉曼光谱的检测保健品中是否添加有西药的方法，包括以下步骤：
    (a)对待测样品的拉曼光谱进行测量以获得待测样品的原始拉曼光谱信号；
    (b)将所述待测样品的原始拉曼光谱信号与一种或更多种西药成分的参考原始拉曼光谱信号进行对比以判定所述待测样品的原始拉曼光谱信号与所述西药成分的参考原始拉曼光谱信号是否匹配；以及
    (c)如果所述待测样品的原始拉曼光谱信号与所述西药成分中的一种或更多种的参考原始拉曼光谱信号匹配，则确定待测样品中含有所述西药成分；而如果所述待测样品的原始拉曼光谱信号与所述西药成分中的所有成分的参考原始拉曼光谱信号均不匹配，则对所述待测样品进行增强拉曼光谱测试，所述增强拉曼光谱测试的步骤包括：
    (c1)对所述待测样品与增强剂的混合物进行测量以获得待测样品的增强拉曼光谱信号；及
    (c2)将所述待测样品的增强拉曼光谱信号与一种或更多种西药成分的参考增强拉曼光谱信号进行对比以判定所述待测样品中是否含有所述西药成分。
  2. 根据权利要求1所述的基于拉曼光谱的检测保健品中是否添加有西药的方法，其特征在于，在所述步骤(a)中，所述待测样品的原始拉曼光谱信号通过对待测样品的拉曼光谱的单次测量而获得。
  3. 根据权利要求1所述的基于拉曼光谱的检测保健品中是否添加有西药的方法，其特征在于，所述步骤(a)包括：
    (a1)连续地对待测样品的拉曼光谱进行测量以采集多个拉曼光谱信号；
    (a2)对所述多个拉曼光谱信号进行叠加以形成叠加信号；以及
    (a3)从该叠加信号中滤除荧光干扰信号以获得待测样品的原始拉曼光谱信号。
  4. 根据权利要求3所述的基于拉曼光谱的检测保健品中是否添加有西药的方法，其特征在于，所述步骤(a3)包括：
    (a31)获取该叠加信号的多个数值采样点，采样点的个数满足采样定律的要求；
    (a32)基于该叠加信号的多个数值采样点通过迭代方式计算荧光干扰信号；以及
    (a33)从该叠加信号中减去荧光干扰信号。
  5. 根据权利要求4所述的基于拉曼光谱的检测保健品中是否添加有西药的方法，其特征在于，在所述步骤(a32)中，荧光干扰信号以如下迭代方式计算：
    假定该叠加信号的数值采样点序列为{yn}，其中第i个数值采样点为yn(i)，经过一次迭代计算得到序列为{yn+1}，序列{yn+1}中的第i个数值点为yn+1(i)，其中
    Figure PCTCN2015098694-appb-100001
    其中m为正整数，上述迭代过程反复进行，每进行一次迭代，m的数值增加1，m的初始值为1，上述迭代过程反复进行直至m值达到预定的阈值为止。
  6. 根据权利要求3所述的基于拉曼光谱的检测保健品中是否添加有西药的方法，其特征在于，在步骤(a1)之前，所述步骤(a)还包括：
    (a00)对待测样品的拉曼光谱进行预测量以采集单个拉曼光谱信号；以及
    (a01)对采集到的单个拉曼光谱信号中的拉曼特征强度进行检测，如果拉曼特征强度足以识别拉曼特征，则直接将该单个拉曼光谱信号作为待测样品的原始拉曼光谱信号并直接执行步骤(b)；而如果拉曼特征强度不足以识别拉曼特征，则继续执行步骤(a1)-(a3)。
  7. 根据权利要求6所述的基于拉曼光谱的检测保健品中是否添加有西药的方法，其特征在于，在步骤(a01)中，对拉曼特征强度的检测通过在所述单个拉曼光谱信号中搜索拉曼特征峰来实现，如果能够搜索到拉曼特征峰，则确定拉曼特征强度足以识别拉曼特征；如果不能搜索到拉曼特征峰，则确定拉曼特征强度不足以识别拉曼特征。
  8. 根据权利要求6所述的基于拉曼光谱的检测保健品中是否添加有西药的方法，其特征在于，在步骤(a01)中，对拉曼特征强度的检测通过在所述单个拉曼光谱信号中搜索拉曼特征峰来实现，如果能够搜索到拉曼特征峰且该拉曼特征峰的强度与所述拉曼光谱信号的平均强度之比大于预定的第一阈值，则确定拉曼特征强度足以识别拉曼特征；如果不能搜索到拉曼特征峰或虽然能够搜索到拉曼特征峰但拉曼特征峰的强度与所述拉曼光谱信号的平均强度之比不超过预定的第一阈值，则确定拉曼特征强度 不足以识别拉曼特征。
  9. 根据权利要求3所述的基于拉曼光谱的检测保健品中是否添加有西药的方法，其特征在于，在步骤(a2)和(a3)之间，还包括：
    (ax)对所述叠加信号中的拉曼特征强度进行检测，如果拉曼特征强度足以识别拉曼特征，则直接将该叠加信号作为待测样品的原始拉曼光谱信号并直接执行步骤(b)；而如果拉曼特征强度不足以识别拉曼特征，则继续执行步骤(a3)。
  10. 根据权利要求9所述的基于拉曼光谱的检测保健品中是否添加有西药的方法，其特征在于，在步骤(ax)中，对拉曼特征强度的检测通过在所述叠加信号中搜索拉曼特征峰来实现，如果能够搜索到拉曼特征峰，则确定拉曼特征强度足以识别拉曼特征；如果不能搜索到拉曼特征峰，则确定拉曼特征强度不足以识别拉曼特征。
  11. 根据权利要求9所述的基于拉曼光谱的检测保健品中是否添加有西药的方法，其特征在于，在步骤(ax)中，对拉曼特征强度的检测通过在所述叠加信号中搜索拉曼特征峰来实现，如果能够搜索到拉曼特征峰且该拉曼特征峰的强度与所述叠加信号的平均强度之比大于预定的第二阈值，则确定拉曼特征强度足以识别拉曼特征；如果不能搜索到拉曼特征峰或虽然能够搜索到拉曼特征峰但拉曼特征峰的强度与所述叠加信号的平均强度之比不超过预定的第二阈值，则确定拉曼特征强度不足以识别拉曼特征。
  12. 根据权利要求1所述的基于拉曼光谱的检测保健品中是否添加有西药的方法，其特征在于，在所述步骤(b)中，所述待测样品的原始拉曼光谱信号与一种或更多种西药成分的参考原始拉曼光谱信号的对比通过计算待测样品的原始拉曼光谱信号与每种所述西药成分的参考原始拉曼光谱信号的相似度来进行。
  13. 根据权利要求1所述的基于拉曼光谱的检测保健品中是否添加有西药的方法，其特征在于，在所述步骤(c)中，所述待测样品的增强拉曼光谱信号与一种或更多种西药成分的参考增强拉曼光谱信号的对比通过计算所述待测样品的增强拉曼光谱信号与每种所述西药成分的参考增强拉曼光谱信号的相似度来进行。
  14. 根据权利要求1所述的基于拉曼光谱的检测保健品中是否添加有西药的方法，还包括：在执行步骤(b)之前，建立一种或更多种西药成分的参考原始拉曼光谱信号的数据库；以及在执行步骤(c)之前，建立一种或更多种所述西药成分的参考增强拉曼光谱信号的数据库。
  15. 根据权利要求1-14中任一项所述的基于拉曼光谱的检测保健品中是否添加有西药的方法，其特征在于，所述待测样品与增强剂的混合物由待测样品与增强剂直接混合而成或由待测样品的水溶液或有机溶液与增强剂混合而成。
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