WO2020113726A1 - 一种手性化合物的检测系统 - Google Patents

一种手性化合物的检测系统 Download PDF

Info

Publication number
WO2020113726A1
WO2020113726A1 PCT/CN2018/124285 CN2018124285W WO2020113726A1 WO 2020113726 A1 WO2020113726 A1 WO 2020113726A1 CN 2018124285 W CN2018124285 W CN 2018124285W WO 2020113726 A1 WO2020113726 A1 WO 2020113726A1
Authority
WO
WIPO (PCT)
Prior art keywords
spectrum
chiral
detection
base material
sample
Prior art date
Application number
PCT/CN2018/124285
Other languages
English (en)
French (fr)
Inventor
车顺爱
刘泽栖
段瑛滢
Original Assignee
同济大学
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 同济大学 filed Critical 同济大学
Publication of WO2020113726A1 publication Critical patent/WO2020113726A1/zh

Links

Images

Classifications

    • 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
    • G01N21/658—Raman scattering enhancement Raman, e.g. surface plasmons
    • 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

Definitions

  • the invention relates to a detection system for chiral compounds.
  • Chiral compounds refer to a class of compounds that have the same molecular structure but mirror each other in configuration.
  • a mirror image of a chiral compound usually has different characteristics.
  • thalidomide has two mirror image enantiomer configurations, S and R, of which R type has central sedation. Function, S type has a strong teratogenic effect. Therefore, in the R&D and production process involving chiral compounds, the distinction between enantiomers and content detection are crucial steps.
  • the analysis and detection system for chiral compounds mainly includes two types, namely, spectrum type and chromatography type.
  • the detection of chiral compounds must be distinguished by matching chiral structures to chiral structures.
  • Spectroscopy uses chiral compounds to identify chiral circularly polarized light
  • chromatography uses chiral fixed relative chiral compounds.
  • Spectral detection systems mostly use the optical rotation and circular dichroism of chiral compounds (that is, the characteristics of deflecting polarized light and the interaction characteristics different from the left and right circularly polarized light), which cannot detect racemization.
  • Chromatography detection systems mainly rely on the adsorption capacity of chromatographic column packings for different configurations of chiral compounds for separation and content detection.
  • the range of chromatographic systems that can be applied is limited, and commonly used chiral chromatography columns can only be applied to a part Chiral compounds that match their adsorption characteristics cannot detect compounds with too large a molecular weight, too small a molecular weight, or no polarity.
  • the equipment of the spectrum detection system is relatively complex and hardly portable.
  • the equipment of the chromatography system needs to include mobile phase devices and detection devices, etc., and is not portable. Therefore, the existing Chiral compound testing needs to be carried out in the laboratory, and the on-site testing of the samples to be tested cannot be achieved.
  • chiral recognition and detection have the following characteristics:
  • materials with chiral characteristics interact with chiral compounds, due to their electromagnetic fields, Chiral traits, single-chiral materials have different strengths for the interaction of different enantiomers of chiral compounds.
  • this difference in interaction strength can be characterized by the optical properties of the materials and compounds, and its interaction strength and the ratio of the enantiomer content (ee value) in the tested chiral compound system ) Linear correlation. Therefore, based on the performance of the optical properties of the interaction between the chiral material and the chiral compound, the content ratio can be deduced, thereby realizing the detection of the chiral compound.
  • a detection system capable of detecting the chiral compound can be formed.
  • the inventors proposed a chiral compound detection system based on the above-mentioned materials with chiral traits, and specifically proposed the following technical solutions.
  • the present invention provides a chiral compound detection system, characterized in that it includes: a base material; and a spectrometer, wherein the base material is made of a material with chiral characteristics and is used to place a hand The sample of the test compound; the light source and detection light of the spectrometer are both unpolarized light.
  • the detection system of the chiral compound of the first embodiment described above may also have a technical feature in which the material having chiral characteristics is a micro-nano powder or a micro-nano film material having a chiral structure.
  • the chiral compound detection system of the first embodiment described above may also have the technical feature that the material having chiral characteristics is composed of an inorganic material, an organic material, or an organic-inorganic composite material.
  • the inorganic material is a plasmon resonance material
  • the plasmon resonance material is a metal, a metal oxide, or a mixture of both
  • the chiral structure is any one of spiral fiber structure, flower-shaped structure, fan-shaped structure, and propeller-shaped structure
  • the spectrometer is a Raman spectrometer.
  • the detection system of the chiral compound of the first embodiment above may also have such technical characteristics, wherein the metal is one or a combination of gold, silver, copper and platinum, and the metal oxide is A combination of one or more of copper oxide, titanium oxide, zinc oxide, tin oxide, iron oxide, and cobalt oxide.
  • the technical characteristics may also be provided, in which the spectrometer has: a light source section for generating a light source; and a sample placement section for placing a substrate material carrying the sample ; Detection light receiving section, used to receive the detection light formed by the base material carrying the sample irradiated by the light source and generating the corresponding electrical signal; and Spectrum output section, used to receive the electrical signal and form the corresponding characteristic spectrum as the detection spectrum .
  • the chiral compound detection system of the first embodiment described above may also have such technical characteristics, and further includes a data analysis device, which is in communication with the Raman spectrometer and is used to receive the detection spectrum and perform data analysis on the detection spectrum The ratio of the enantiomeric content of the chiral compound in the sample to be tested is analyzed.
  • a data analysis device which is in communication with the Raman spectrometer and is used to receive the detection spectrum and perform data analysis on the detection spectrum The ratio of the enantiomeric content of the chiral compound in the sample to be tested is analyzed.
  • the present invention provides another chiral compound detection system for qualitative quantification of chiral compounds and enantiomeric content ratio detection, which is characterized by comprising: a first base material for When the chiral compound is qualitatively quantified, it is used as the base material to mount the test sample of the chiral compound; the second base material is used to mount the test sample as the base material when the content ratio of the chiral compound is detected; and the spectrometer is used To detect the first base material on which the sample to be tested is mounted to obtain a first detection spectrum for qualitative and quantitative determination, and to detect the second base material on which the sample to be tested is mounted to obtain The second detection spectrum for the detection of the enantiomeric content ratio, wherein the first base material is composed of a material without chiral characteristics, and the second base material is composed of a material with chiral characteristics.
  • the chiral compound detection system of the first embodiment described above may also have such technical characteristics, and further includes: a data analysis device having: a first spectrum storage unit for storing a plurality of first standard spectra ,
  • the first standard spectrum is a spectrum obtained by using spectrometers and the first base material to detect the standards of the chiral compound respectively;
  • the second spectrum storage unit is used to store a plurality of second standard spectra, the first
  • the second standard spectrum is a spectrum obtained by using a spectrometer and a second base material to separately detect the chiral compound standard;
  • the spectrum matching unit is used to match the first detection spectrum from the first spectrum storage unit
  • the corresponding first standard spectrum is used as the first matching spectrum, and the corresponding second standard spectrum is matched from the second spectrum storage unit according to the second detection spectrum as the second matching spectrum;
  • the spectrum analysis unit It is used to perform qualitative and quantitative analysis on the sample to be tested according to the first detection spectrum and the first matching spectrum, and to perform enantiomeric content ratio analysis
  • the detection system for chiral compounds since materials with chiral characteristics are used as base materials in conjunction with spectrometers, the materials with chiral characteristics can produce different strength interactions of different enantiomers of chiral compounds Therefore, the detection of this effect can be obtained by spectrometer to obtain the content ratio of the enantiomers to achieve the detection of chiral compounds.
  • the detection system of the present invention has the advantages of simple operation and accurate results.
  • FIG. 1 is a schematic structural diagram of a detection system according to Embodiment 1 of the present invention.
  • FIG. 2 is a Raman spectrum diagram for detecting a mixed sample of R-limonene and S-limonene by using the detection system according to Embodiment 1 of the present invention
  • FIG. 3 is a linear fitting diagram of the characteristic peak intensity and the percentage of chiral molecular content obtained by detecting the mixture of R-limonene and S-limonene using the detection system according to Embodiment 1 of the present invention
  • Example 4 is a characteristic spectrum diagram obtained by detecting the mixture of L-cyclohexylglycine and D-cyclohexylglycine by using the detection system of Example 1 of the present invention
  • FIG. 5 is a linear fitting diagram of the characteristic peak intensity and the percentage of chiral enantiomer content obtained by performing characteristic spectrum detection on a mixture of L-cyclohexylglycine and D-cyclohexylglycine by using the detection system according to Embodiment 1 of the present invention;
  • Example 6 is a detection system using flower-shaped nano-sized titanium oxide powder as a base material in Example 3 of the present invention to detect N-acetyl-L-cysteine and N-acetyl-D-cysteine at the same concentration respectively.
  • FIG. 7 is obtained by detecting the same concentration of N-acetyl-L-cysteine and N-acetyl-D-cysteine in the detection system using fan-shaped nano silver powder as the base material in Example 3 of the present invention Characteristic spectrum
  • FIG. 8 is a schematic diagram of the structure of a detection system according to Embodiment 4 of the present invention.
  • FIG. 1 is a schematic structural diagram of a detection system according to Embodiment 1 of the present invention.
  • the detection system 100 of this embodiment includes a base material 10, a spectrometer 20 and a data analysis device 30.
  • the base material 10 is a material having chiral characteristics.
  • the base material 10 is a gold nanospiral fiber array
  • the gold nanospiral fiber array has the following characteristics: 1) Gold is a metal-based plasmon resonance material, which is used as a base material in the Raman spectrum detection process It can enhance the Raman signal of the sample; 2)
  • the gold nanohelical fiber array is a film material formed on the silicon substrate through a growth method, which is composed of a plurality of neatly arranged single-strand gold spiral fibers.
  • the spiral fiber structure is A single-chiral structure.
  • this gold nanohelical fiber array is a material with chiral characteristics.
  • the detection system 100 of this embodiment realizes the detection of chiral compounds based on Raman spectroscopy detection.
  • the spectrometer 20 is an ordinary Raman spectrometer, and its light source and detection light are both unpolarized light. That is, the spectrometer 20 has a light source section 21 as a light source, a sample placement section 22 for placing the sample-carrying base material 10, and a Raman scattering generated when the sample-carrying base material 10 is irradiated by the light source.
  • the detection light receiving section 23 which generates light and generates a corresponding electrical signal and the spectrum output section 24 for receiving the electrical signal and forming a corresponding Raman spectrum as a detection spectrum, wherein the light generated by the light source section 21 is unpolarized light, and
  • the detection light receiving section 23 is also a general photodetector for unpolarized light.
  • the data analysis device 30 is a computer with data storage and data analysis calculation functions.
  • the computer is connected to the spectrometer 20 (for example, via a data cable), and can receive and store the spectrum output by the spectrum output unit. And analysis.
  • FIG. 2 is a Raman spectrum diagram for detecting a mixed sample of R-limonene and S-limonene by using the detection system of Embodiment 1 of the present invention.
  • the ratio of enantiomeric content in each sample is known, where -100% is a sample containing only R-limonene, 100% is a sample containing only S-limonene, -50% is R-limonene and S- A sample with a limonene content ratio of 75:25, 0% is a sample with an R-limonene to S-limonene content ratio of 50:50, and 50% is a sample with an R-limonene to S-limonene content ratio of 25:75. .
  • FIG. 3 is a linear fitting diagram of the characteristic peak intensity and the percentage of chiral molecular content obtained by detecting the mixture of R-limonene and S-limonene using the detection system according to Embodiment 1 of the present invention.
  • the abscissa is the percentage of chiral molecule content (ee value)
  • the ordinate is the characteristic peak intensity.
  • the detection system 100 of this embodiment when used to detect a sample of chiral compounds such as limonene, the signal intensity (ie, Raman signal intensity) is proportional to the chiral enantiomer in the sample. There is a linear relationship.
  • the detection system 100 of this embodiment is used to perform characteristic spectrum detection, and then the test result of the sample to be tested is compared with the test result of the standard product (for example Compare the characteristic peak intensity of the sample to be tested with the fitting curve between the characteristic peak intensity of each standard and the content ratio) to calculate the content ratio of S-limonene and R-limonene in the sample to be tested.
  • the specific operation of the detection system 100 in this embodiment for detecting the content ratio of chiral enantiomers is as follows:
  • the standards are mounted on the base material 10 respectively, and the base material 10 on which each standard is placed is sequentially detected by a spectrometer 20 to obtain the characteristic spectrum of each standard as a standard spectrum, and the data analysis device 30 is used Perform temporary storage and characteristic peak intensity analysis on these standard spectra, and then obtain a linear fitting graph of the characteristic peak intensity of each standard product and the percentage of chiral molecular content;
  • the sample to be tested is placed on the same base material 10, the sample to be tested is detected using a spectrometer 20 to obtain its characteristic spectrum as a sample spectrum, and the characteristic peak intensity analysis is performed on the sample spectrum using the data analysis device 30, Substituting the intensity value of the characteristic peak into the above linear fitting diagram, the enantiomeric content ratio of the chiral compound in the sample to be tested can be calculated.
  • cyclohexylglycine has two configurations, namely L-cyclohexylglycine and D-cyclohexylglycine.
  • FIG. 4 is a characteristic spectrum chart obtained by detecting the mixture of L-cyclohexylglycine and D-cyclohexylglycine by using the detection system of Example 1 of the present invention.
  • -100% is a sample containing only L-cyclohexylglycine
  • 100% is a sample containing only D-cyclohexylglycine
  • -50% is the content ratio of L-cyclohexylglycine to D-cyclohexylglycine is
  • 75:25 samples 0% is a sample with a 50:50 ratio of L-cyclohexylglycine and D-cyclohexylglycine
  • 50% is a 25:25 ratio with L-cyclohexylglycine and D-cyclohexylglycine: 75 samples.
  • FIG. 5 is a linear fitting diagram of the characteristic peak intensity and the percentage of chiral enantiomer content obtained by performing the characteristic spectrum detection on the mixture of L-cyclohexylglycine and D-cyclohexylglycine by using the detection system of Example 1 of the present invention.
  • the abscissa is the percentage of chiral molecule content (ee value), and the ordinate is the characteristic peak intensity.
  • the chiral compound cyclohexylglycine when the chiral compound cyclohexylglycine is detected by the detection system 100 of the first embodiment, it can also achieve the same detection effect as the limonene of the first embodiment. That is to say, by using the detection system 100 and following the same operation steps as in Embodiment 1, the enantiomeric content ratio of the test sample of cyclohexylglycine can be achieved.
  • the inventors also used the detection system 100 of the first embodiment to detect a variety of other chiral compounds, and found that this detection system 100 can achieve the enantiomeric content ratio of different chiral compounds. During the detection process, the sample The ee value of and the characteristic peak intensity both showed a linear relationship.
  • the chiral compounds verified by the inventors are shown in Table 1 below:
  • the chiral compounds that can be detected by the detection system 100 of the present invention in the ratio of enantiomeric content are close to one hundred pairs, and these chiral compounds have different characteristics.
  • Table 1 the number of chiral centers, single-chiral center compounds and multi-chiral center compounds are included in Table 1; by polar classification, polar compounds and non-polar compounds are included in Table 1; in addition, in Table 1 It also contains many different kinds of chiral compounds such as chromophore molecules, non-chromophore molecules, macromolecules, small molecules and biological molecules. It can be seen that, as long as the compound has Raman scattering properties, the enantiomeric content ratio can be detected by the detection system 100 including the base material 10, the spectrometer 20, and the data analysis device 30 in the first embodiment.
  • this embodiment replaces the base material 10 in Example 1 with other types of materials with chiral characteristics, and uses the detection system obtained after the replacement 100 samples of chiral compounds were tested.
  • the materials used to replace the base material 10 include the following types: gold-silver nano-spiral array, flower-shaped nano titanium oxide powder, and fan-shaped nano silver powder.
  • the gold-silver nanospiral fiber array is formed by attaching silver again on the basis of the gold nanospiral fiber array of the first embodiment.
  • the gold-silver nanospiral fiber array is composed of a plurality of neatly arranged single-strand gold-silver composite spiral fibers, and its characteristics are similar to those of the gold nanospiral fiber array of the first embodiment, and also belong to the plasmon resonance material, and also With chiral characteristics.
  • Flower-shaped nano titanium oxide powder is a material composed of nano-sized titanium oxide particles with a flower-shaped structure. Titanium oxide is a plasmon resonance material similar to gold and silver, and the flower-shaped structure is also a chiral structure. Thus, the flower-shaped nano titanium oxide powder also has chiral characteristics.
  • the fan-shaped nano silver powder is a material composed of nano-silver particles having a fan structure, which is also a material with chiral characteristics.
  • the base material 10 uses a gold-silver nanospiral fiber array
  • the characteristic spectrum obtained by detecting chiral compound samples with different ee values the characteristic peak intensity also exhibits a linear relationship with the ee value. It can be seen that the gold-silver nanospiral fiber array and the gold nanospiral fiber array have the same function in the detection system 100 of the present invention.
  • FIG. 7 is a detection system using fan-shaped nano-silver powder as a base material in Example 3 of the present invention for the same concentration of N-acetyl-L-cysteine and N-acetyl-D-cysteine The characteristic spectrum obtained by testing respectively.
  • the detection system 100 of 10 can make the two samples exhibit different signal intensities. Obviously, similar to the foregoing first embodiment, such a difference in signal intensity proves that the detection system 100 of this embodiment can also detect the enantiomeric content ratio in the chiral compound sample.
  • the detection system of the material with chiral characteristics and the Raman spectrometer of the present invention can detect hundreds of chiral compounds; 2. Even if other types are replaced For chiral materials, the detection system of the present invention can also detect chiral compounds.
  • the base material is a material with chiral characteristics (especially a plasmon resonance material with a chiral structure), it can be more or less carried out by the Raman signal of the chiral compound
  • the specificity is enhanced, so it can also be combined with Raman spectrometer to detect the enantiomeric content ratio of chiral compounds.
  • the detection system of the present invention containing chiral materials, spectrometer and data analysis device can detect the content ratio of chiral compounds.
  • the detection system of the present invention has a simple structure, It has the advantages of simple operation, low interference, accurate results and wide application.
  • FIG. 8 is a schematic diagram of the structure of a detection system according to Embodiment 4 of the present invention.
  • the detection system 200 of the fourth embodiment includes a spectrometer 20, a first base material 40, a second base material 50 and a data analysis device 60.
  • the spectrometer 20 and the data analysis device 60 can be communicatively connected through a data cable or a communication network, and the communication unit in the spectrometer 20 and the data analysis device 60 is omitted in FIG. 8.
  • the second base material 50 is the same as the base material 10 described in the first embodiment to the third embodiment, and is composed of a material with chiral characteristics, which will not be repeated here.
  • the first base material 40 is a surface plasma material that does not have chiral qualities. Such materials are used as substrates in conventional surface-enhanced Raman spectroscopy, such as round nano-gold powders without chiral structure Powder material composed of gold nanoparticles) and so on.
  • the detection process of the chiral compound test sample using the detection system 200 of this embodiment mainly includes: using the first base material 40 and the spectrometer 20 to test the sample to be tested, to obtain the first detection spectrum; using the second base material 50 and The spectrometer 20 detects the sample to be tested to obtain the second detection spectrum; the data analysis device 60 is used to analyze the first detection spectrum and the second detection spectrum, and the first detection spectrum is used for qualitative and quantitative analysis, while the second The detection spectrum determines the ratio of the enantiomeric content, and the chiral compound structure, total content and enantiomeric content of the sample to be tested can be obtained.
  • the data analysis device 60 includes a first spectrum storage unit 61, a second spectrum storage unit 62, a spectrum matching unit 63, and a spectrum analysis unit 64.
  • the first spectrum storage unit 61 is used to store a plurality of first standard spectra, which are obtained by separately detecting the standards of the chiral compound using the spectrometer 20 or other similar spectrometers and the first base material 40.
  • Raman spectrum That is, the first base material 40 is combined with the spectrometer 20 to detect a certain content of a plurality of chiral compounds, thereby obtaining a Raman spectrum of these chiral compounds as the first standard spectrum. Since the first base material 40 is a plasmon resonance material that does not have chiral properties, the fingerprint features in these first standard spectra can reflect the structure of the chiral compound, and at the same time, the intensity of the characteristic peak corresponds to the content of the chiral compound .
  • the second spectrum storage unit 62 is used to store a plurality of second standard spectra obtained by separately detecting the enantiomeric content standards of the chiral compound using the spectrometer 20 and the second base material 50.
  • Raman spectrum That is to say, the second standard spectrum can be used to reflect the proportion of the enantiomeric content in a certain chiral compound sample whose content is determined.
  • the spectrum matching unit 63 is configured to match the corresponding first standard spectrum from the first spectrum storage unit 61 as the first matching spectrum according to the first detection spectrum, and from the second spectrum according to the second detection spectrum
  • the storage unit 62 matches the corresponding second standard spectrum as the second matching spectrum.
  • the spectrogram analysis part 64 is used to perform qualitative and quantitative analysis on the sample to be tested according to the first detection spectrum and the first matching spectrum, and to perform enantiomeric content ratio analysis on the sample to be tested according to the second detection spectrum and the second matching spectrum. .
  • the spectrum matching unit 53 integrates the fingerprint characteristics of the two detection spectra, so as to find the standard spectrum matching the fingerprint characteristics from the first spectrum storage unit 61 and the second spectrum storage unit 62, respectively.
  • the second detection spectrum may not be due to the low signal intensity It has clear fingerprint characteristics.
  • the spectrum matching unit 53 cannot match the corresponding second standard spectrum according to the second detection spectrum, the first detection spectrum is used to match the second standard spectrum.
  • the spectrum matching unit 53 may use some spectrum matching methods in the prior art to use the standard spectrum with the highest matching degree as the matching result. Since the structure of the compound and its fingerprint feature are in one-to-one correspondence, the first standard spectrum and the second standard spectrum obtained should correspond to the same chiral compound, which is also the one in the sample to be tested. Chiral compounds. Thus, the matching process of the spectrum matching unit 63 realizes the qualitative analysis of the chiral compound in the sample to be tested.
  • the spectrum analysis unit 64 is based on the characteristic peak intensity ratio between the first detection spectrum and the first standard spectrum and the content of the standard product corresponding to the first detection spectrum Perform analytical calculations to obtain the total content of chiral compounds in the sample to be tested.
  • the spectrum analysis section 64 adaptively adjusts the second detection spectrum according to the ratio of the total content of the chiral compound in the sample to be tested and the total content of the chiral compound corresponding to the second standard spectrum (that is, according to the two The ratio of the total content of is adjusted to the intensity of the characteristic peak in the second detection spectrum, so that the total content of the chiral compound reflected by the adjustment of the second detection spectrum can be the same as the total content of the standard corresponding to the second standard spectrum) Then, the adjusted second detection spectrum is compared with the second standard spectrum to obtain the ratio of enantiomeric content (ee value) in the sample to be tested.
  • the spectrum analysis part 64 first adjusts the characteristic peak intensity value of the second detection spectrum according to the content ratio, when comparing with the second standard spectrum, the adjusted characteristic peak intensity in the second detection spectrum can be It directly reflects the proportion of the enantiomer content of the sample to be tested.
  • the tester when the sample to be tested needs to be detected, the tester only needs to detect the two Raman spectra of the sample to be tested using two kinds of base materials, so that the data analysis device can match and Analysis to complete qualitative and quantitative detection and content ratio detection at the same time.
  • the spectrometer can be in the form of a handheld Raman spectrometer
  • the data analysis device can be in the form of a cloud server.
  • the tester can carry the handheld Raman spectrometer and two kinds of substrate materials on the spot to test the sample on site Complete the detection and get the analysis results, the operation is simpler, and the on-site detection of chiral compounds in complex environments can be easily achieved.
  • the material with chiral characteristics is a nano metal film material having a single chiral structure, a nano metal powder material, a nano metal oxide powder material and the like.
  • the material with chiral characteristics can also be other types of materials, including micro-nano material powders or micro-materials with chiral structure composed of other types of organic substances, inorganic substances, or organic substance-inorganic substance mixtures. Nano film material.
  • the inorganic substance may include a metal and a metal oxide
  • the metal may be one or a combination of gold, silver, copper, platinum
  • the metal oxide may be copper oxide, titanium oxide, zinc oxide, tin oxide, One or a combination of iron oxide and cobalt oxide
  • the chiral structure may also be a variety of chiral structures such as a propeller-shaped structure.
  • the spectrometer used in the examples is a Raman spectrometer.
  • it can also be another kind of spectrometer as long as it can detect the interaction between the base material and the compound to be tested.
  • the detection results of the compounds of other types of spectrometers have qualitative characteristics (such as fingerprint characteristics similar to Raman spectroscopy) and quantitative characteristics (such as characteristic peak intensity and content are in a linear relationship)
  • the data analysis device is provided with a corresponding standard spectrum storage part, a spectrum matching part, a spectrum analysis part, etc., so as to realize qualitative and quantitative analysis of the sample to be tested and analysis of the enantiomeric content ratio.

Landscapes

  • Health & Medical Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Physics & Mathematics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Investigating, Analyzing Materials By Fluorescence Or Luminescence (AREA)

Abstract

涉及一种基于具有手性特质的材料的手性化合物检测系统，包括：基底材料；以及光谱仪，其中，基底材料由具有手性特质的材料构成，用于载置手性化合物的待测样品；光谱仪的光源和检测光均为非偏振光。还涉及一种同样基于具有手性特质的材料的手性化合物检测系统，包括：第一基底材料，用于进行定性定量时作为基底材料；第二基底材料，用于进行含量比例检测时作为基底材料；以及光谱仪，用于对载置了待测样品的第一基底材料进行检测从而得到用于进行定性定量的第一检测谱图，以及对载置了待测样品的第二基底材料进行检测从而得到用于进行对映体含量比例检测的第二检测谱图，其中，第二基底材料由具有手性特质的材料构成。

Description

一种手性化合物的检测系统 技术领域
本发明涉及一种手性化合物的检测系统。
背景技术
手性化合物是指分子结构相同，但构型上互为镜像的一类化合物。在医药化工领域中，互为镜像的一对手性化合物之间通常具有不同的特性，例如，沙利度胺具有S和R两种互为镜像的对映体构型，其中R型具有中枢镇静作用，S型却具有强烈的致畸作用。因此，在涉及手性化合物的研发生产过程中，对映体之间的区分及含量检测是至关重要的步骤。
现有技术中，手性化合物的分析检测系统主要包括两类，即光谱类和色谱类。手性化合物的检测必须通过手性结构对手性结构的匹配来进行识别性区别。光谱法采用的是手性化合物对手性圆偏振光的识别，色谱法采用的是手性固定相对手性化合物的识别。光谱类检测系统多利用手性化合物的旋光性和圆二色性(即，分别为让偏振光发生偏转的特性和与左右圆偏振光发生不同的相互作用特性)实现，其无法检测外消旋体，且后者容易受到左右圆偏振光切换过程中所产生的线偏振光的干扰，无法检测无发色基团的分子。色谱类检测系统主要依赖于色谱柱填料对不同构型手性化合物吸附能力的不同而进行分离及含量检测，然而，色谱类系统能够应用的范围有限，常用的手性色谱柱仅能应用于一部分符合其吸附特性的手性化合物，对分子量过大、分子量过小或没有极性的化合物都无法进行检测。
另外，上述现有检测系统中，光谱类检测系统的设备较复杂，几乎不具便携性，而色谱类系统的设备需要包含流动相装置和检测装置等，也不具有便携性，因此，现有的手性化合物检测需要在实验室进行，无法实现待测样品的现场检测。
发明内容
为解决上述问题，本发明的发明人针对手性识别的特性进行了研究，发现手性识别和检测具有如下特性：具有手性特质的材料与手性化合物发生相互作用时，由于其电磁场具有的手性特质，单手性材料对不同对映异构体的手性化合物产生的相互作用具有不同的强度。不仅如此，发明人还发现，这种相互作用强度的不同可以通过材料和化合物的光学性质进行表征，并且其相互作用强度与被测手性化合物体系中对映异构体的含量比例(ee值)线性相关。因此，根据手性材料与手性化合物的相互作用在光学性质上的表现即可推算出其含量比例，从而实现手性化合物的检测。
相应地，将具有手性特质的材料以及能够对该材料与手性化合物的相互作用进行测定的光谱仪组合，即可形成能够对手性化合物进行检测的检测系统。
基于上述发现，发明人提出了基于上述具有手性特质的材料的手性化合物检测系统，具体提出了如下技术方案。
作为第一种实施形态，本发明提供了一种手性化合物的检测系统，其特征在于，包括：基底材料；以及光谱仪，其中，基底材料由具有手性特质的材料构成，用于载置手性化合物的待测样品；光谱仪的光源和检测光均为非偏振光。
在上述第一种实施形态的手性化合物的检测系统中，还可以具有这样的技术特征，其中，具有手性特质的材料为具有手性结构的微纳米粉末或微纳米膜材料。
在上述第一种实施形态的手性化合物的检测系统中，还可以具有这样的技术特征，其中，具有手性特质的材料由无机材料、有机材料或有机-无机复合材料构成。
在上述第一种实施形态的手性化合物的检测系统中，还可以具有这样的技术特征，其中，无机材料为等离子体共振材料，该等离子体共振材料为金属、金属氧化物或二者的混合物，手性结构为螺旋纤维结构、花形结构、扇形结构、螺旋桨形结构中的任意一种，光谱仪为拉曼光谱仪。
在上述第一种实施形态的手性化合物的检测系统中，还可以具有这样的技术特征，其中，金属为金、银、铜、铂中的一种或几种的组合物，金属氧化物为氧化铜、氧化钛、氧化锌、氧化锡、氧化铁、氧化钴中的一种或几种的组合物。
在上述第一种实施形态的手性化合物的检测系统中，还可以具有这样的技术特征，其中，光谱仪具有：光源部，用于产生光源；样品放置部，用于放置载有样品的基底材料；检测光接收部，用于接收载有样品的基底材料被光源照射而形成的检测光并产生对应的电信号；以及光谱输出部，用于接收电信号并形成对应的特征光谱作为检测谱图。
在上述第一种实施形态的手性化合物的检测系统中，还可以具有这样的技术特征，还包括数据分析装置，与拉曼光谱仪通信连接，用于接收检测谱图并对检测谱图进行数据分析得到待测样品中的手性化合物的对映体含量比例。
作为第二种实施形态，本发明提供了另一种手性化合物的检测系统，用于对手性化合物进行定性定量以及对映体含量比例检测，其特征在于，包括：第一基底材料，用于在对手性化合物进行定性定量时作为基底材料载置手性化合物的待测样品；第二基底材料，用于在对手性化合物进行含量比例检测时作为基底材料载置待测样品；以及光谱仪，用于对载置了待测样品的第一基底材料进行检测从而得到用于进行定性定量的第一检测谱图，以及对载置了待测样品的第二基底材料进行检测从而得到用于进行对映体含量比例检测的第二检测谱图，其中，第一基底材料由不具有手性特质的材料构成，第二基底材料由具有手性特质的材料构成。
在上述第一种实施形态的手性化合物的检测系统中，还可以具有这样的技术特征，还包括：数据分析装置，具有：第一谱图存储部，用于存储多个第一标准谱图，该第一标准谱 图是采用光谱仪以及第一基底材料对手性化合物的标准品分别进行检测而得到的光谱图；第二谱图存储部，用于存储多个第二标准谱图，该第二标准谱图是采用光谱仪以及第二基底材料对手性化合物的标准品分别进行检测而得到的光谱图；谱图匹配部，用于根据第一检测谱图从第一谱图存储部中匹配出对应的第一标准谱图作为第一匹配谱图，以及根据第二检测谱图从第二谱图存储部中匹配出对应的第二标准谱图作为第二匹配谱图；以及谱图分析部，用于根据第一检测谱图及第一匹配谱图对待测样品进行定性定量分析，并根据第二检测谱图及第二匹配谱图对待测样品进行对映体含量比例分析。
发明作用与效果
根据本发明提供的手性化合物的检测系统，由于采用具有手性特质的材料作为基底材料与光谱仪配合使用，该具有手性特质的材料能够对手性化合物的不同对映体产生不同强度的相互作用，因此，通过光谱仪对这种作用效果进行检测即可得出对映体的含量比例从而实现手性化合物的检测。与现有技术中的手性化合物检测系统相比，本发明的检测系统具有操作简单、结果准确等优点。
附图说明
图1为本发明实施例一的检测系统的构成示意图；
图2是采用本发明实施例一的检测系统对R-柠檬烯和S-柠檬烯混合的样品进行检测的拉曼光谱图；
图3是采用本发明实施例一的检测系统对R-柠檬烯和S-柠檬烯的混合物进行检测得到的特征峰强度与手性分子含量百分比的线性拟合图；
图4是采用本发明实施例一的检测系统对L-环己基甘氨酸和D-环己基甘氨酸的混合物进行检测得到的特征光谱图；
图5是采用本发明实施例一的检测系统对L-环己基甘氨酸和D-环己基甘氨酸的混合物进行特征光谱检测得到的特征峰强度与手性对映体含量百分比的线性拟合图；
图6是本发明实施例三的采用花形纳米氧化钛粉末作为基底材料的检测系统对相同浓度的N-乙酰-L-半胱氨酸和N-乙酰-D-半胱氨酸分别进行检测得到的特征光谱图；
图7是本发明实施例三的采用扇形纳米银粉末作为基底材料的检测系统对相同浓度的N-乙酰-L-半胱氨酸和N-乙酰-D-半胱氨酸分别进行检测得到的特征光谱图；
图8是本发明实施例四的检测系统的构成示意图。
具体实施方式
以下结合附图来说明本发明的具体实施方式。
<实施例一>
图1为本发明实施例一的检测系统的构成示意图。
如图1所示，本实施例的检测系统100包括基底材料10、光谱仪20以及数据分析装置30。其中，基底材料10为具有手性特质的材料。
具体地，基底材料10为金纳米螺旋纤维阵列，该金纳米螺旋纤维阵列具有这样的特点：1)金是一种金属类的等离子体共振材料，其在拉曼光谱检测过程中作为基底材料时能够对样品的拉曼信号进行增强；2)金纳米螺旋纤维阵列是一种经由生长方法形成在硅基板上的膜材料，由多根整齐排列的单股金螺旋纤维构成，该螺旋纤维结构是一种单手性结构，相应地，这种金纳米螺旋纤维阵列是具有手性特质的材料。
本实施例的检测系统100基于拉曼光谱检测实现手性化合物的检测。
具体地，本实施例中，光谱仪20为普通拉曼光谱仪，其光源和检测光均为非偏振光。即，该光谱仪20具有用于作为光源的光源部21、用于放置载有样品的基底材料10的样品放置部22、用于接收载有样品的基底材料10经光源照射而产生的拉曼散射光并产生对应的电信号的检测光接收部23以及用于接收电信号并形成对应的拉曼光谱作为检测谱图的光谱输出部24，其中光源部21所产生的光为非偏振光，并且检测光接收部23也是针对非偏振光的普通的光电探测器。
另外，数据分析装置30为具有数据存储和数据分析计算功能的计算机，该计算机与光谱仪20通信连接(例如通过数据线缆连接)，能够接收光谱输出部输出的谱图并对该谱图进行存储及分析。
图2是采用本发明实施例一的检测系统对R-柠檬烯和S-柠檬烯混合的样品进行检测的拉曼光谱图。
图2中，各个样品中的对映体含量比例已知，其中-100％是仅含有R-柠檬烯的样品，100％是仅含有S-柠檬烯的样品，-50％是R-柠檬烯与S-柠檬烯的含量比为75:25的样品，0％是R-柠檬烯与S-柠檬烯的含量比为50:50的样品，50％是R-柠檬烯与S-柠檬烯的含量比为25:75的样品。
图3是采用本发明实施例一的检测系统对R-柠檬烯和S-柠檬烯的混合物进行检测得到的特征峰强度与手性分子含量百分比的线性拟合图。图3中，横坐标为手性分子含量百分比(ee值)，纵坐标为特征峰强度。
如图2和图3所示，当采用本实施例的检测系统100对柠檬烯这种手性化合物样品进行检测时，其信号强度(即拉曼信号强度)与样品中的手性对映体比例呈线性关系。也就是说，当需要对两种对映体含量未知的柠檬烯样品进行检测时，采用本实施例的检测系统100进行特征光谱检测，然后将待测样品检测结果与标准品检测结果进行对比(例如将待测样品的特征峰强度与各个标准品特征峰强度与含量比例之间的拟合曲线进行对比)，即可计算得到待 测样品中S-柠檬烯和R-柠檬烯的含量比例。
也就是说，本实施例中的检测系统100对手性对映体的含量比例进行检测的具体操作如下：
首先，配制多个手性化合物的标准品，每个标准品中含有不同比例的手性化合物的对映体；
然后，分别将标准品载置在基底材料10上，采用光谱仪20依次对载置有各个标准品的基底材料10进行检测从而得到各个标准品的特征光谱作为标准谱图，并利用数据分析装置30对这些标准谱图进行暂存以及特征峰强度分析，进而得到各个标准品的特征峰强度与手性分子含量百分比的线性拟合图；
最后，将待测样品载置在相同的基底材料10上，采用光谱仪20对待测样品进行检测从而得到其特征光谱作为样品谱图，并利用数据分析装置30对样品谱图进行特征峰强度分析，将该特征峰强度值代入上述线性拟合图，即可计算得到待测样品中的手性化合物的对映体含量比例。
<实施例二>
本实施例采用与实施例一相同的检测系统100对环己基甘氨酸这种手性化合物进行检测。其中，环己基甘氨酸具有两种构型，即L-环己基甘氨酸和D-环己基甘氨酸。
图4是采用本发明实施例一的检测系统对L-环己基甘氨酸和D-环己基甘氨酸的混合物进行检测得到的特征光谱图。
图4中，-100％是仅含有L-环己基甘氨酸的样品，100％是仅含有D-环己基甘氨酸的样品，-50％是L-环己基甘氨酸与D-环己基甘氨酸的含量比为75:25的样品，0％是L-环己基甘氨酸与D-环己基甘氨酸的含量比为50:50的样品，50％是L-环己基甘氨酸与D-环己基甘氨酸的含量比为25:75的样品。
图5是采用本发明实施例一的检测系统对L-环己基甘氨酸和D-环己基甘氨酸的混合物进行特征光谱检测得到的特征峰强度与手性对映体含量百分比的线性拟合图。图5中，横坐标为手性分子含量百分比(ee值)，纵坐标为特征峰强度。
如图4和图5所示，当采用实施例一的检测系统100对环己基甘氨酸这种手性化合物进行检测时，其也能够达到与实施例一的柠檬烯相同的检测效果。也就是说，采用该检测系统100，按照与实施例一相同的操作步骤进行操作，即可实现环己基甘氨酸的待测样品的对映体含量比例检测。
另外，发明人还采用实施例一的检测系统100对其他多种手性化合物进行了检测，发现这种检测系统100能够实现不同手性化合物的对映体含量比例检测，并且检测过程中，样品 的ee值和其特征峰强度均呈现线性关系。发明人验证过的手性化合物如下表1所示：
表1经验证能够通过本发明实施例一的检测系统100进行手性对映体比例检测的手性化合物
Figure PCTCN2018124285-appb-000001
Figure PCTCN2018124285-appb-000002
Figure PCTCN2018124285-appb-000003
根据表1可知，能够通过本发明的检测系统100进行对映体含量比例检测的手性化合物接近百对，并且这些手性化合物特性各异。例如，以手性中心数量分类，表1中包含了单手性中心化合物和多手性中心化合物；以极性分类，表1中包含了极性化合物和非极性化合物；另外，表1中还包含了有发色基团分子、无发色基团分子、大分子、小分子和生物分子等多种不同种类的手性化合物。可见，只要是具有拉曼散射特性的化合物，均可通过实施例一的含有基底材料10、光谱仪20以及数据分析装置30的检测系统100来进行对映体含量比例检测。
<实施例三>
为验证其他具有手性特质的材料是否也能用于手性化合物检测，本实施例将实施例一中的基底材料10用其他种类的具有手性特质的材料替换，并用替换后得到的检测系统100对手性化合物样品进行了检测。
本实施例中，用于替换基底材料10的材料包括这几种：金-银纳米螺旋线阵列、花形纳米氧化钛粉末以及扇形纳米银粉末。
其中，金-银纳米螺旋纤维阵列是在实施例一的金纳米螺旋纤维阵列的基础上再次进行银附着而形成的。由此，该金-银纳米螺旋纤维阵列由多根整齐排列的单股金-银复合螺旋纤维构成，其特性与实施例一的金纳米螺旋纤维阵列类似，也属于等离子体共振材料，并且也具有手性特质。
花形纳米氧化钛粉末是一种由具有花形结构的纳米氧化钛颗粒构成的材料。氧化钛是与金和银类似的等离子体共振材料，花形结构也是一种手性结构。由此，花形纳米氧化钛粉末也具有手性特质。
类似地，扇形纳米银粉末是由具有扇形结构的纳米银颗粒构成的材料，其也是一种具有手性特质的材料。
经试验，当基底材料10采用金-银纳米螺旋纤维阵列时，对ee值不同的手性化合物样品进行检测得到的特征光谱中，特征峰强度也表现出了与ee值呈线性关系的特性。可见，金-银纳米螺旋纤维阵列与金纳米螺旋纤维阵列在本发明的检测系统100中具有相同的作用。
另外两种材料的检测结果如下：
图6是本发明实施例三的采用花形纳米氧化钛粉末作为基底材料的检测系统对相同浓度的N-乙酰-L-半胱氨酸和N-乙酰-D-半胱氨酸分别进行检测得到的特征光谱图，图7是本发明实施例三的采用扇形纳米银粉末作为基底材料的检测系统对相同浓度的N-乙酰-L-半胱氨酸和N-乙酰-D-半胱氨酸分别进行检测得到的特征光谱图。
如图6及图7所示，当N-乙酰-L-半胱氨酸和N-乙酰-D-半胱氨酸的浓度相同时，采用花形纳米氧化钛粉末或扇形纳米银粉末作为基底材料10的检测系统100均能够让该两种样品呈现出不同的信号强度。显然，与前述实施例一类似，这样的信号强度差异证明本实施例的检测系统100也能够检测出手性化合物样品中的对映体含量比例。
实施例的作用与效果
从实施例一～实施例三中可以看出，当采用具有手性特质的材料作为基底材料对手性化合物进行拉曼光谱检测时，其对手性化合物不同对映体的表面增强作用有明显区别，这样的区别反映到光谱图上就使得不同对映体的特征峰强度有明显差异。因此，通过特征峰强度即 可推算得出对映体含量比例。
另外，从上述实施例还可以得出如下结果：1、本发明的具有手性特质的材料和拉曼光谱仪的检测系统能够对上百种手性化合物实现检测；2、即使更换其他种类的具有手性特质的材料，本发明的检测系统也能够实现手性化合物的检测。
结合检测原理方面的推断可以得知，只要基底材料是具有手性特质的材料(尤其是具有手性结构的等离子体共振材料)，其都能够或多或少地对手性化合物的拉曼信号进行特异性增强，因而也能够结合拉曼光谱仪来实现手性化合物的对映体含量比例检测。
进一步，通过上述各实施例的检测过程可以得知，上述具有手性特质的材料与手性化合物发生相互作用时，其对不同对映异构体的手性化合物产生的信号增强作用不同，这种相互作用的不同可以通过材料和化合物的光学性质(在上述实施例中为拉曼检测)进行表征。
显然，当这类具有手性特质的材料与手性化合物发生其他相互作用时，其所产生的相互作用强度也将有所不同，并且能够被相应的光学检测手段表征(即，被相应的光谱仪检测时体现出信号强度等方面的差异)。所以，本发明的含有具有手性特质的材料、光谱仪和数据分析装置的检测系统可以对手性化合物进行含量比例检测，与现有技术中的检测手段相比，本发明的检测系统具有结构简单、操作简单、干扰小、结果准确且应用广泛等优点。
<实施例四>
本实施例中，对于与实施例一相同的结构，给与相同的标号并省略相同的说明。
图8是本发明实施例四的检测系统的构成示意图。
如图8所示，实施例四的检测系统200包括光谱仪20、第一基底材料40、第二基底材料50以及数据分析装置60。其中，光谱仪20与数据分析装置60可以通过数据线缆或通信网络通信连接，图8中省略了光谱仪20和数据分析装置60中的通信单元。
第二基底材料50与实施例一～实施例三所描述的基底材料10相同，由具有手性特质的材料构成，在此不再赘述。
第一基底材料40为不具有手性特质的表面等离子体材料，这类材料在常规的表面增强拉曼光谱检测中作为基底使用，例如不具有手性结构的圆形纳米金粉末(即由圆形纳米金颗粒构成的粉末材料)等。
采用本实施例的检测系统200对手性化合物待测样品进行检测的过程主要包括：采用第一基底材料40和光谱仪20对待测样品进行检测，得到第一检测谱图；采用第二基底材料50和光谱仪20对待测样品进行检测，得到第二检测谱图；采用数据分析装置60对第一检测谱图和第二检测谱图进行分析，利用第一检测谱图进行定性和定量，同时利用第二检测谱图确定对映体含量比例，即可得到待测样品的手性化合物结构、总含量及对映体含量比例。
数据分析装置60包括第一谱图存储部61、第二谱图存储部62、谱图匹配部63以及 谱图分析部64。
第一谱图存储部61用于存储多个第一标准谱图，该第一标准谱图是采用光谱仪20或其他相同的光谱仪以及第一基底材料40对手性化合物的标准品分别进行检测而得到的拉曼光谱图。即，采用第一基底材料40结合光谱仪20对一定含量的多个手性化合物进行检测，从而得到这些手性化合物的拉曼光谱图作为第一标准谱图。由于第一基底材料40为不具有手性特性的等离子体共振材料，因此这些第一标准谱图中的指纹特征能够反映手性化合物的结构，同时，特征峰的强度对应于手性化合物的含量。
第二谱图存储部62用于存储多个第二标准谱图，该第二标准谱图是采用光谱仪20以及第二基底材料50对手性化合物的对映体含量标准品分别进行检测而得到的拉曼光谱图。也就是说，第二标准谱图能够用于反映含量确定的某种手性化合物样品中的对映体含量比例。
谱图匹配部63用于根据第一检测谱图从第一谱图存储部61中匹配出对应的第一标准谱图作为第一匹配谱图，以及根据第二检测谱图从第二谱图存储部62中匹配出对应的第二标准谱图作为第二匹配谱图。
谱图分析部64用于根据第一检测谱图及第一匹配谱图对待测样品进行定性定量分析，并根据第二检测谱图及第二匹配谱图对待测样品进行对映体含量比例分析。
具体地，由于第一基底材料40和第二基底材料50均对于待测样品中的手性化合物具有拉曼信号增强的作用，因此实际上第一检测谱图和第二检测谱图的指纹特征是相同的，谱图匹配部53综合该两个检测谱图的指纹特征，从而分别从第一谱图存储部61和第二谱图存储部62中找出指纹特征匹配的标准谱图。
一些情况下(例如待测样品中某种对映体的含量较少而第二基底材料50刚好对该种对映体的作用较弱)，第二检测谱图中可能因信号强度低而不具有清晰的指纹特征，此时，谱图匹配部53根据第二检测谱图无法匹配出对应的第二标准谱图时，则利用第一检测谱图来匹配第二标准谱图。
上述匹配过程中，谱图匹配部53可以采用现有技术中的一些谱图匹配手段，将匹配程度最高的标准谱图作为匹配结果。由于化合物的结构与其指纹特征是一一对应的，因此得出的第一标准谱图和第二标准谱图应当对应于同一种手性化合物，该种手性化合物也正是待测样品中的手性化合物。由此，谱图匹配部63的匹配过程就实现了对待测样品中手性化合物的定性分析。
匹配得到第一标准谱图和第二标准谱图后，谱图分析部64基于第一检测谱图和第一标准谱图之间的特征峰强度比例以及第一检测谱图对应的标准品含量进行分析计算，从而得到待测样品中的手性化合物的总含量。
然后，谱图分析部64根据待测样品中的手性化合物总含量以及第二标准谱图所对应的 手性化合物总含量的比例对第二检测谱图进行适应性调整(即，按照二者的总含量比例对第二检测谱图中的特征峰强度进行调整，使得第二检测谱图调整后所反映的手性化合物总含量能够与第二标准谱图所对应的标准品总含量相同)，再将调整后的第二检测谱图与第二标准谱图进行比对分析，从而得到待测样品中的对映体含量比例(ee值)。由于谱图分析部64先按含量比例调整了第二检测谱图的特征峰强度值，因此，与第二标准谱图进行对比时，调整后的第二检测谱图中的特征峰强度就能够直接反映出待测样品的对映体含量比例了。
实施例作用与效果
根据实施例四提供的检测系统，当需要进行待测样品检测时，检测人员只需要用两种基底材料分别检测得到待测样品的两种拉曼光谱图，即可让数据分析装置进行匹配和分析，从而同时完成定性定量检测以及含量比例检测。
进一步，本实施例的检测系统中，光谱仪可以采用手持型拉曼光谱仪的形式，数据分析装置可以采用云端服务器的形式，检测人员携带手持型拉曼光谱仪和两种基底材料即可现场对待测样品完成检测并得到分析结果，操作更为简单，并且可以很容易地实现复杂环境下的手性化合物的现场检测。
上述实施例仅用于举例说明本发明的具体实施方式，本发明的手性化合物检测系统不限于上述实施例的描述范围。
实施例中，具有手性特质的材料为具有单手性结构的纳米金属膜材料、纳米金属粉末材料、纳米金属氧化物粉末材料等。然而，在本发明中，具有手性特质的材料还可以是其他种类的材料，包括由其他种类的有机物、无机物或有机物-无机物混合物所构成的具有手性结构的微纳米材料粉末或微纳米膜材料。其中，无机物可以包含金属和金属氧化物，金属可以是金、银、铜、铂中的一种或几种的组合物，金属氧化物可以是氧化铜、氧化钛、氧化锌、氧化锡、氧化铁、氧化钴中的一种或几种的组合物；手性结构除了实施例的螺旋纤维结构、花形结构、扇形结构以外，还可以是螺旋桨形结构等多种手性结构。
另外，实施例中所用的光谱仪为拉曼光谱仪，然而在本发明中，其还可以是其他种类的光谱仪，只要能够检测基底材料与待测化合物的相互作用即可。进一步，若该其他种类的光谱仪对化合物的检测结果具有定性特征(例如与拉曼光谱相似的指纹特征)和定量特征(例如特征峰强度与含量呈线性关系)，则可以参照实施例四的形式，数据分析装置中设置对应的标准谱图存储部、谱图匹配部和谱图分析部等，从而实现对待测样品的定性定量分析和对映体含量比例分析。

Claims (9)

  1. 一种手性化合物的检测系统，其特征在于，包括：
    基底材料；以及
    光谱仪，
    其中，基底材料由具有手性特质的材料构成，用于载置手性化合物的待测样品；
    所述光谱仪的光源和检测光均为非偏振光。
  2. 根据权利要求1所述的手性化合物的检测系统，其特征在于：
    其中，所述具有手性特质的材料为具有手性结构的微纳米粉末或微纳米膜材料。
  3. 根据权利要求2所述的手性化合物的检测系统，其特征在于：
    其中，所述具有手性特质的材料由无机材料、有机材料或有机-无机复合材料构成。
  4. 根据权利要求3所述的手性化合物的检测系统，其特征在于：
    其中，所述无机材料为等离子体共振材料，该等离子体共振材料为金属、金属氧化物或二者的混合物，
    所述手性结构为螺旋纤维结构、花形结构、扇形结构、螺旋桨形结构中的任意一种，
    所述光谱仪为拉曼光谱仪。
  5. 根据权利要求4所述的手性化合物的检测系统，其特征在于：
    其中，所述金属为金、银、铜、铂中的一种或几种的组合物，
    所述金属氧化物为氧化铜、氧化钛、氧化锌、氧化锡、氧化铁、氧化钴中的一种或几种的组合物。
  6. 根据权利要求1所述的手性化合物的检测系统，其特征在于：
    其中，所述光谱仪具有：
    光源部，用于产生所述光源；
    样品放置部，用于放置载有所述样品的所述基底材料；
    检测光接收部，用于接收载有所述样品的所述基底材料被所述光源照射而形成的检测光并产生对应的电信号；以及
    光谱输出部，用于接收所述电信号并形成对应的特征光谱作为检测谱图。
  7. 根据权利要求6所述的手性化合物的检测系统，其特征在于，还包括：
    数据分析装置，与所述拉曼光谱仪通信连接，用于接收所述检测谱图并对所述检测谱 图进行数据分析得到所述待测样品中的所述手性化合物的对映体含量比例。
  8. 一种手性化合物的检测系统，用于对所述手性化合物进行定性定量以及对映体含量比例检测，其特征在于，包括：
    第一基底材料，用于在对所述手性化合物进行定性定量时作为基底材料载置所述手性化合物的待测样品；
    第二基底材料，用于在对所述手性化合物进行含量比例检测时作为基底材料载置所述待测样品；以及
    光谱仪，用于对载置了所述待测样品的所述第一基底材料进行检测从而得到用于进行所述定性定量的第一检测谱图，以及对载置了所述待测样品的所述第二基底材料进行检测从而得到用于进行所述对映体含量比例检测的第二检测谱图，
    其中，所述第一基底材料由不具有手性特质的材料构成，
    所述第二基底材料由具有手性特质的材料构成。
  9. 根据权利要求8所述的手性化合物的检测系统，其特征在于，还包括：
    数据分析装置，具有：
    第一谱图存储部，用于存储多个第一标准谱图，该第一标准谱图是采用所述光谱仪以及所述第一基底材料对所述手性化合物的标准品分别进行检测而得到的光谱图；
    第二谱图存储部，用于存储多个第二标准谱图，该第二标准谱图是采用所述光谱仪以及所述第二基底材料对所述手性化合物的标准品分别进行检测而得到的光谱图；
    谱图匹配部，用于根据所述第一检测谱图从所述第一谱图存储部中匹配出对应的所述第一标准谱图作为第一匹配谱图，以及根据所述第二检测谱图从所述第二谱图存储部中匹配出对应的所述第二标准谱图作为第二匹配谱图；以及
    谱图分析部，用于根据所述第一检测谱图及所述第一匹配谱图对所述待测样品进行定性定量分析，并根据所述第二检测谱图及所述第二匹配谱图对所述待测样品进行对映体含量比例分析。
PCT/CN2018/124285 2018-12-05 2018-12-27 一种手性化合物的检测系统 WO2020113726A1 (zh)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN201811479374.0 2018-12-05
CN201811479374.0A CN111272729B (zh) 2018-12-05 2018-12-05 一种手性化合物的检测系统

Publications (1)

Publication Number Publication Date
WO2020113726A1 true WO2020113726A1 (zh) 2020-06-11

Family

ID=70975253

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2018/124285 WO2020113726A1 (zh) 2018-12-05 2018-12-27 一种手性化合物的检测系统

Country Status (2)

Country Link
CN (1) CN111272729B (zh)
WO (1) WO2020113726A1 (zh)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114088686A (zh) * 2021-11-23 2022-02-25 安徽星鑫材料科技股份有限公司 一种实时无损测定氯化石蜡中氯含量的方法

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111982823A (zh) * 2020-08-05 2020-11-24 电子科技大学 一种磁场偏置的手性分子传感器件

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007134446A1 (en) * 2006-05-23 2007-11-29 The University Of Western Ontario High-throughput screening of enantiomeric excess (ee)
CN101776604A (zh) * 2010-01-26 2010-07-14 中国科学院光电技术研究所 一种增强分子拉曼散射的基底制作方法
CN101865841A (zh) * 2010-06-28 2010-10-20 北京航空航天大学 一种高灵敏度表面等离子体共振传感器
CN105259157A (zh) * 2015-11-06 2016-01-20 合肥学院 一种热点可见的表面增强拉曼散射基底、制备方法及利用该基底检测分子的方法

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003029790A1 (en) * 2001-10-01 2003-04-10 Georgia Tech Research Corporation High-throughput chiral detector and methods for using same
US7191070B2 (en) * 2003-12-03 2007-03-13 Baylor University Methods for determining enantiomeric purity
CN102864493B (zh) * 2012-10-12 2015-03-18 江南大学 一种基于有机小分子盐的金纳米棒手性自组装材料的制备方法
CN103896846B (zh) * 2014-03-05 2016-05-25 上海师范大学 一种以壳聚糖修饰的金纳米通道膜分离组氨酸对映体的方法及其检测方法
CN106053810A (zh) * 2016-05-10 2016-10-26 江南大学 一种基于手性纳米组装体的循环肿瘤细胞检测新方法
EP3532812B1 (en) * 2016-10-26 2022-06-08 University Of Virginia Patent Foundation Cavity-enhanced fourier transform rotational spectroscopy for chiral analysis
CN107036971B (zh) * 2016-11-14 2019-06-25 四川大学 手性传感元件、设备，手性表征方法，浓度表征方法

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007134446A1 (en) * 2006-05-23 2007-11-29 The University Of Western Ontario High-throughput screening of enantiomeric excess (ee)
CN101776604A (zh) * 2010-01-26 2010-07-14 中国科学院光电技术研究所 一种增强分子拉曼散射的基底制作方法
CN101865841A (zh) * 2010-06-28 2010-10-20 北京航空航天大学 一种高灵敏度表面等离子体共振传感器
CN105259157A (zh) * 2015-11-06 2016-01-20 合肥学院 一种热点可见的表面增强拉曼散射基底、制备方法及利用该基底检测分子的方法

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
袁旭寒 (YUAN, XUHAN): "基于表面增强拉曼散射的手性传感器及其机理研究 (A Chiral Sensor Based on Surface Enhanced Raman Scattering and Its Mechanism Research)", 中国优秀硕士学位论文全文数据库(信息科技辑) (CHINESE MASTER’S THESES FULL-TEXT DATABASE, INFORMATION SCIENCE & TECHNOLOGY), no. 6, 15 June 2018 (2018-06-15), DOI: 20190823174815X *
钟桐生等 (ZHONG, TONGSHENG ET AL.): "基于纳米通道表面增强拉曼散射光谱分离检测组氨酸对映体的研究 (Chiral Separation and Identification of D, L-Histidine Based on Nanochannels Membrane Coupling with Surface Enhanced Raman Scattering Spectroscopy)", 分析化学 (CHINESE JOURNAL OF ANALYTICAL CHEMISTRY), vol. 11, no. 43, 30 November 2015 (2015-11-30), DOI: 20190826110533 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114088686A (zh) * 2021-11-23 2022-02-25 安徽星鑫材料科技股份有限公司 一种实时无损测定氯化石蜡中氯含量的方法
CN114088686B (zh) * 2021-11-23 2023-09-05 安徽星鑫材料科技股份有限公司 一种实时无损测定氯化石蜡中氯含量的方法

Also Published As

Publication number Publication date
CN111272729A (zh) 2020-06-12
CN111272729B (zh) 2021-11-09

Similar Documents

Publication Publication Date Title
CN104914089B (zh) 用表面增强拉曼光谱对痕量混合物进行半定量分析的方法
Garrell Surface-enhanced Raman spectroscopy
Vo-Dinh et al. Analysis of a workplace air particulate sample by synchronous luminescence and room-temperature phosphorescence
Ruan et al. Surface-enhanced Raman scattering for perchlorate detection using cystamine-modified gold nanoparticles
CN109557071B (zh) 一种危险液体混合物的拉曼光谱定性定量识别方法
Lang et al. Integration of colorimetric and SERS detection for rapid screening and validation of melamine in milk
Bauer et al. LA-ICP-TOF-MS for rapid, all-elemental and quantitative bioimaging, isotopic analysis and the investigation of plasma processes
WO2020113726A1 (zh) 一种手性化合物的检测系统
CN108398416A (zh) 一种基于激光拉曼光谱的混合物成分测定方法
Vandenabeele et al. Some ideas on the definition of Raman spectroscopic detection limits for the analysis of art and archaeological objects
Wang et al. Single point calibration for semi-quantitative screening based on an internal reference in thin layer chromatography-SERS: the case of Rhodamine B in chili oil
WO2019100231A1 (zh) 一种基于壳层隔绝纳米粒子的三维热点拉曼检测芯片
US20090273778A1 (en) Surface enhanced resonant raman spectroscopy
CN106814130A (zh) 一种用于质谱检测的新型纳米芯片及其制备与应用
Moya‐Riffo et al. A procedure for overlapping deconvolution and the determination of its confidence interval for arsenic and lead signals in TXRF spectral analysis
WO2020113725A1 (zh) 一种手性化合物的检测方法
CN108362677A (zh) 一种基于表面拉曼增强技术快速检测土壤水解氮的方法
CN105424677B (zh) 基于表面增强拉曼光谱检测火灾现场残留有机物的方法
Kiefer Quantitative enantioselective Raman spectroscopy
Belle et al. Correspondence. Direct Characterization of the Phtalic Acid Isomers in Mixtures Using Surface-Enhanced Raman Scattering
CN114441503A (zh) 一种基于表面增强拉曼光谱内标分析的三聚氰胺定量检测方法
WO2020113723A1 (zh) 用于对手性化合物进行检测的基底材料
CN104849392B (zh) 相对书写时间鉴定方法
RU2526584C2 (ru) Спектрально-селективный портативный раман-люминесцентный анализатор
Guenther et al. Trace-level detection of explosives using sputtered SERS substrates

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 18942361

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 18942361

Country of ref document: EP

Kind code of ref document: A1

122 Ep: pct application non-entry in european phase

Ref document number: 18942361

Country of ref document: EP

Kind code of ref document: A1

32PN Ep: public notification in the ep bulletin as address of the adressee cannot be established

Free format text: NOTING OF LOSS OF RIGHTS PURSUANT TO RULE 112(1) EPC (EPO FORM 1205A DATED 27/01/2022)

122 Ep: pct application non-entry in european phase

Ref document number: 18942361

Country of ref document: EP

Kind code of ref document: A1