Optical detection device and system for online Raman analysis

Abstract

The present disclosure relates to an optical detection device and system for online Raman analysis. An optical detection device for online Raman analysis comprises: a light source assembly configured to generate an incident light beam for irradiating a sample; and an imaging lens assembly configured to collect an outgoing light beam from the sample, wherein: the outgoing light beam is incident on a Raman spectrum assembly to generate a Raman spectrum of the sample, and the incident light beam is shaped to have a predetermined cross-sectional shape, and the predetermined cross-sectional shape matches the slit shape of the Raman spectrum assembly.

Description

Technical Field

[0001] The present disclosure relates to an optical detection device and system for online Raman analysis, and in particular, to an optical detection device and system for improving the efficiency of collecting Raman scattering signals. Background Art

[0002] As the technology of using mammalian cell expression systems to produce antibodies, therapeutic proteins and various growth factors becomes more and more common, more attention is paid to metabolic monitoring and analysis during the entire cell culture process. In the biopharmaceutical industry, the concept of process analysis (PAT) is a system used to design, analyze, control R&D and production. The system ensures the quality and efficiency of the final product by measuring the key quality and performance attributes of the process in real time.

[0003] The online Raman analysis system has the advantages of real-time, continuity, and multi-data collection. It is used as a PAT tool for rapid and lower-cost quality inspection, and has become an important research method in the fields of analytical chemistry, biomedicine, and pharmacy. Raman spectroscopy technology is also widely used in the research and development and production of biopharmaceuticals, almost throughout the entire production process of biopharmaceuticals.

[0004] Traditional Raman detection systems are mainly used for offline analysis: detecting a single uniform compound with high concentration and strong Raman signal; however, they cannot cope with complex mixtures in bioreactors, low concentrations of target compounds, and interference from background fluorescence, and online Raman detection systems are needed. Therefore, in order to cope with the complex mixture environment of biological fermentation and achieve low-concentration monitoring of target substances (glucose, lactic acid, ammonia, glutamic acid, etc.), it is necessary to improve the detection device for online Raman analysis. Summary of the invention

[0005] The present application proposes an optical detection device and system for online Raman analysis.

[0006] According to a first aspect of an embodiment of the present disclosure, an optical detection device for online Raman analysis is provided, comprising: a light source assembly configured to generate an incident light beam for irradiating a sample; and an imaging lens assembly configured to collect an outgoing light beam from the sample, wherein: the outgoing light beam is emitted into a Raman spectrum assembly to generate a Raman spectrum of the sample, and the incident light beam is shaped to have a predetermined cross-sectional shape, which matches the slit shape of the Raman spectrum assembly.

[0007] In some embodiments, the light source assembly includes a laser configured to generate a first light beam.

[0008] In some embodiments, the light source assembly includes a first shaping lens group, which is configured to be disposed on an output light path of the laser and to shape the first light beam to generate an incident light beam.

[0009] In some embodiments, the light source assembly includes a beam expander lens assembly, which is configured to be disposed on an output light path of the laser and to expand the first light beam.

[0010] In some embodiments, the light source assembly includes a first filter element, which is configured to be disposed on an output light path of the laser and filter the first light beam to filter out components of the first light beam that are outside a preset wavelength range.

[0011] In some embodiments, the imaging lens assembly includes a first objective lens configured to collect the outgoing light beam.

[0012] In some embodiments, the first objective lens is an objective lens with a high numerical aperture, wherein the high numerical aperture ranges from 0.5 to 0.75.

[0013] In some embodiments, the imaging lens assembly includes a dichroic mirror, which is configured to be disposed on an optical path of the outgoing light beam and to cause one of at least a portion of the incident light beam and the outgoing light beam to be reflected and the other to be transmitted.

[0014] In some embodiments, the imaging lens assembly includes a second filter element, which is configured to be disposed on the optical path of the outgoing light beam and filter the outgoing light beam to filter out components in the outgoing light beam with a wavelength less than or equal to a preset wavelength.

[0015] In some embodiments, the optical detection device is configured to transmit the input light beam or the output light beam via an optical fiber.

[0016] In some embodiments, the optical detection device is configured as a probe having an infinite structure, wherein the probe is immersed in the sample for online detection.

[0017] According to a second aspect of an embodiment of the present disclosure, there is provided an optical detection system for online Raman analysis, comprising: a light source assembly configured to generate an incident light beam for irradiating a sample; an imaging lens assembly configured to collect an outgoing light beam from the sample; and a Raman spectrum assembly configured to generate a Raman spectrum of the sample based on the outgoing light beam, wherein: the incident light beam is shaped to have a predetermined cross-sectional shape, which matches a slit shape of the Raman spectrum assembly.

[0018] In some embodiments, the light source assembly includes a laser configured to generate a first light beam.

[0019] In some embodiments, the light source assembly further includes at least one of the following: a first shaping lens group, which is configured to be disposed on the output light path of the laser and to shape the first light beam to produce an incident light beam; a beam expanding lens group, which is configured to be disposed on the output light path of the laser and to expand the first light beam; and a first filter element, which is configured to be disposed on the output light path of the laser and to filter the first light beam to filter out components in the first light beam that are outside a preset wavelength range.

[0020] In some embodiments, the imaging lens group includes: a first objective lens, which is configured to collect an outgoing light beam; a dichroic mirror, which is configured to be disposed on the optical path of the outgoing light beam and causes one of the incident light beam and at least a portion of the outgoing light beam to be reflected and the other to be transmitted; and a second filter, which is configured to be disposed on the optical path of the outgoing light beam and filters the outgoing light beam to filter out components in the outgoing light beam whose wavelength is less than or equal to a preset wavelength.

[0021] In some embodiments, the Raman spectroscopy component includes: a reflector configured to reflect an outgoing light beam incident on the Raman spectroscopy component; a grating configured to be disposed on an outgoing light path of the reflector, and to receive the outgoing light beam reflected by the reflector and to split the outgoing light beam; a condenser configured to be disposed on an outgoing light path of the grating, and to converge the split outgoing light beam from the grating; and a photodetector configured to be disposed on an outgoing light path of the condenser, and to receive the outgoing light beam from the condenser and generate a Raman spectrum.

[0022] In some embodiments, the Raman spectroscopy assembly further includes a second shaping lens group, which is configured to be disposed on the output light path of the condenser and to shape the output light beam from the condenser so that the shaped output light beam matches the size of the light detector and irradiates the light detector.

[0023] In some embodiments, the Raman spectroscopy component is configured to detect Raman spectra with wavelengths in the range of 700-1000 nm.

[0024] The advantage of the embodiments of the present disclosure is that the collection efficiency of Raman scattering signals can be improved as much as possible without reducing the resolution too much, and the interference of background noise signals such as stray light can be effectively reduced.

[0025] Another advantage of the embodiments of the present disclosure is that a laser power that does not damage biologically active substances is selected, thereby achieving a rapid, real-time, continuous, non-destructive, long-term dynamic monitoring function of the metabolic conditions in the biological fermentation process.

[0026] It should be appreciated that the above advantages do not need to be all realized in one or some specific embodiments, but may be partially dispersed in different embodiments according to the present disclosure. The embodiments according to the present disclosure may have one or some of the above advantages, or may have other advantages alternatively or additionally.

[0027] Other features and advantages of the present invention will become more apparent from the following detailed description of exemplary embodiments of the present invention with reference to the accompanying drawings. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] The accompanying drawings, which constitute a part of the specification, describe embodiments of the present disclosure and, together with the specification, are used to explain the principles of the present disclosure. With reference to the accompanying drawings, the present disclosure can be more clearly understood according to the following detailed description, in which:

[0029] Figure 1 is a schematic diagram showing an optical detection system for online Raman analysis according to an embodiment of the present disclosure.

[0030] Figure 2 is a schematic structural diagram showing an optical detection device for online Raman analysis according to an embodiment of the present disclosure.

[0031] Figure 3 is a schematic diagram showing a cross-sectional shape of an incident light beam being shaped according to an embodiment of the present disclosure.

[0032] Figure 4 Schematic diagram showing the structure of a Raman spectroscopy component in an optical detection system for online Raman analysis according to an embodiment of the present disclosure.

[0033] Note that in the embodiments described below, the same reference numerals are sometimes used in common between different drawings to represent the same parts or parts with the same functions, and their repeated descriptions are omitted. In this specification, similar reference numerals and letters are used to represent similar items, so once an item is defined in one drawing, it does not need to be further discussed in subsequent drawings.

[0034] For ease of understanding, the positions, sizes, and ranges of various structures shown in the drawings and the like sometimes do not represent actual positions, sizes, and ranges, etc. Therefore, the disclosed invention is not limited to the positions, sizes, and ranges, etc. disclosed in the drawings and the like. In addition, the drawings are not necessarily drawn to scale, and some features may be exaggerated to show details of specific components. DETAILED DESCRIPTION

[0035] Various exemplary embodiments of the present disclosure will be described in detail below with reference to the accompanying drawings. It should be noted that unless otherwise specifically stated, the relative arrangement of components and steps, numerical expressions and numerical values ​​set forth in these embodiments do not limit the scope of the present disclosure.

[0036] The following description of at least one exemplary embodiment is in fact merely illustrative and is in no way intended to limit the present disclosure and its application or use. That is, the structures and methods herein are shown in an exemplary manner to illustrate different embodiments of the structures and methods in the present disclosure. However, those skilled in the art will appreciate that they merely illustrate exemplary ways of the present disclosure that can be implemented, rather than exhaustive ways. In addition, the drawings need not be drawn to scale, and some features may be enlarged to illustrate the details of specific components.

[0037] Technologies, methods, and apparatus known to ordinary technicians in the relevant field may not be discussed in detail, but where appropriate, such technologies, methods, and apparatus should be considered part of the authorization specification.

[0038] In summary, the Raman analysis method and the Raman spectrometer are mainly based on the principle of Raman scattering, that is, the energy from the laser will cooperate with the covalent bond vibration of the material molecules to produce elastic scattering or inelastic scattering, wherein the outgoing light of the elastic scattering has the same energy as the incident light, while the inelastic scattering releases less light than the excitation energy that causes the molecular vibration due to the absorption of some laser energy by the molecules, that is, the wavelength of the inelastic scattered light changes relative to the wavelength of the incident light. Some of the inelastic scattered light will return to the inside of the optical detection device and be detected by the optical detector to produce a Raman spectrum. Generally, in order to realize a real-time and continuous online Raman analysis process, an invasive probe signal acquisition method is used, such as immersing the probe directly in a bioreactor to detect low-concentration targets in a complex mixture environment. The probe transmits the collected Raman scattering signal to a spectrometer with Raman analysis function (hereinafter also referred to as a "Raman spectrum component") via an optical fiber, and finally produces a Raman spectrum of the target.

[0039] In a non-limiting embodiment, current biopharmaceutical research requires real-time monitoring of low-concentration reaction products, such as in the field of monoclonal antibodies (mAbs). When implementing the Quality by Design (QbD) concept in the production of mAbs, one of the key parameters that need to be monitored is the glycosylation process during the formulation process. Glycosylation is one of the main factors of monoclonal antibody heterogeneity, which affects important properties such as stability and immunogenicity, and is therefore of great significance to the function of antibodies in vivo. In order to obtain approval from drug regulatory authorities, glycosylation is also a critical quality attribute (Critical Quality Attributes, CQA) to ensure the safety and efficacy of biopharmaceutical products. One of the biggest challenges in mAb production is monitoring quality attributes such as glycosylation, so seamlessly integrating data monitoring into bioprocessing based on online Raman analysis methods is crucial to understanding the process and overcoming production challenges.

[0040] In actual detection, the Raman scattering signal is very weak and the background fluorescence interference is large. Usually, the total amount of collected Raman scattering signals is increased by increasing the excitation light power or increasing the integration time of signal acquisition. However, high-power or long-term excitation light irradiation will kill cells or destroy the structure of active substances such as proteins; and increasing the integration time method also increases the accumulation of noise signals. How to improve the Raman scattering signal without damaging active substances such as cells has become a difficulty. In addition, the balance between the resolution and signal amount of Raman spectroscopy is another major difficulty. Generally, the higher the resolution, the longer the spectral range, and the smaller the signal that can be collected by the collection unit of each detector. In order to solve such technical problems, the technical solution disclosed in the present invention improves the internal structure of the probe and the spectrometer, and improves the collection efficiency of the Raman scattering signal as much as possible (such as increasing the intensity and total amount) without reducing the resolution too much, while effectively reducing the interference of background noise signals such as stray light, improving the signal-to-noise ratio, and shortening the signal acquisition time, thereby realizing online Raman analysis of complex mixtures in bioreactors.

[0041] The optical detection system for online Raman analysis according to an embodiment of the present disclosure will be described in detail below with reference to the accompanying drawings. The optical detection system includes a light source assembly, an imaging lens group, and a Raman spectrum assembly, wherein the light source assembly is configured to generate an incident light beam for irradiating a sample, the imaging lens group is configured to collect an outgoing light beam from the sample, and the Raman spectrum assembly is configured to generate a Raman spectrum of the sample based on the outgoing light beam. It should be understood that in an actual optical detection system, the above three components can realize their respective functions with independent hardware structures, or they can be combined or packaged together to realize the overall function.

[0042] like Figure 1As shown, the optical detection system includes a probe 130 and a laser 140 and a spectrometer 150 connected to the probe 130 via an optical fiber. The probe 130 is immersed in the bioreactor 110 to perform real-time monitoring of the target compound stirred by the reactor stirring paddle 120. The laser 140 and the spectrometer 150 are respectively connected to a computer 160 for data analysis and processing of the optical signal. In some embodiments, the probe 130 and the laser 140 can be combined into an optical detection device for online Raman analysis, which is mainly used to generate an incident light beam for irradiating the sample and collect an outgoing light beam scattered from the sample, and can be connected to the spectrometer 150 as a Raman spectroscopy component and / or other optical signal processing devices (such as image sensors, etc.) for use. Additionally or alternatively, the laser 140 and the spectrometer 150 can be encapsulated in the same housing, and the probe 130 is independent of the housing and is respectively connected to the laser 140 and the spectrometer 150 in the housing via optical fibers.

[0043] Generally, in an optical detection system for online Raman analysis, the light source assembly can be configured to generate an incident light beam, which forms a preset light path via an imaging lens group to irradiate the sample to be detected to excite the Raman signal of the sample. In some embodiments, the light source assembly includes a laser 140, which can be configured to generate a first light beam, which can generate an incident light beam after passing through the optical assembly. Since the incident light beam is directly irradiated into the complex compound in the reaction via a probe immersed in the bioreactor 110, the laser generated by the laser 140 should be selected with a suitable wavelength, especially not to unnecessarily damage the active substances in the bioreactor 110. In a non-limiting embodiment, the laser 140 can use a laser with a wavelength of about 785 nm, which can reduce the interference of background excitation fluorescence while reducing damage to biologically active substances.

[0044] Additionally, in the optical detection system for online Raman analysis, the imaging lens group is configured to collect an outgoing light beam from the sample, which includes a Raman scattering signal excited by the sample. In some embodiments, the optical system in the probe 130 converges the incident light beam onto the sample to generate Raman scattering; the Raman scattering signal from the sample is then collected by the probe 130, and is injected into the slit of the spectrometer 150 via the optical fiber, and is diffracted into a spectral band by the grating in the spectrometer 150, so that it is collected by the detector, and finally a Raman spectrum of the sample is generated.

[0045] The following will be combined Figure 2 The specific structure and configuration of the light source assembly and the imaging lens assembly are described in detail. Figure 2The optical detection device for online Raman analysis composed of a light source assembly and an imaging lens group according to an embodiment of the present disclosure is shown, wherein the light source assembly mainly includes a laser 210, a first filter 220, a beam expander lens group 230 and a first shaping lens group 240, and the imaging lens group mainly includes a reflector 250, a dichroic mirror 260, a first objective lens 270 and a second filter 280. Figure 2 As shown, the incident light beam generated by the laser 210 passes through a plurality of optical elements in sequence, is emitted from the first objective lens 270 to the sample, and is collected by the first objective lens 270 again, and is transmitted to the Raman spectroscopy component ( Figure 2 for subsequent analysis.

[0046] In some embodiments, the laser 210 in the light source assembly is configured to generate a first light beam. The first filter 220 is configured to be disposed on the outgoing light path of the laser 210 and filter the first light beam to filter out components in the first light beam that are outside a preset wavelength range. In this way, the wavelength of the incident light beam that is finally irradiated onto the sample can be within a desired range to avoid unnecessary interference of light of other wavelengths on subsequent Raman analysis.

[0047] In some embodiments, the beam expander 230 and the first shaping lens 240 in the light source assembly expand and shape the first light beam after filtering. The conventional excitation spot is a circular spot, and when the light source assembly generates the first light beam with a laser, the cross-sectional shape of the incident light beam will be a circle with a small radius. Such a cross-sectional shape has poor matching with the incident slit of the spectrometer, which can easily cause problems such as stray light influx or low excitation efficiency. Therefore, it is necessary to shape the incident light beam so that it has a cross-sectional shape (excitation spot) that matches the slit shape.

[0048] The following combination Figure 3 The process of shaping the cross-sectional shape of the incident light beam is described in detail. The left and right parts of the figure show the shape relationship between the cross-sectional shape 3110 of the traditional incident light beam and the slit 2130, and the cross-sectional shape 3210 of the incident light beam after shaping and the slit 3220. Generally, the radius r of the traditional cross-sectional shape 3110 is about 5μm, while the length h of the slit is 100μm, and the width w1 usually has two specifications of 10μm and 25μm. In other words, when the first light beam emitted by the laser 210 is used directly, the cross-sectional diameter formed by it at most matches the slit width, but there is a large gap in the direction of the slit length, which is easy to flood in stray light from the surrounding environment. Taking this into account, the embodiment of the present disclosure proposes a scheme for shaping the first light beam into an elliptical spot. In a non-limiting embodiment, the shaped light beam has the following characteristics: Figure 3The cross-sectional shape 3210 has dimensions that satisfy the major axis 2a>h and the minor axis 2b≥w2. At this time, the cross-sectional shape 3210 matches the direction of the slit length while maintaining the correspondence in the slit width, covering the entire slit 3220 as much as possible, reducing the influx of stray light and improving the excitation efficiency.

[0049] Return to Figure 2 In some embodiments, the beam expander 230 is configured to be disposed on the output light path of the laser 210 and expand the first light beam to increase the cross-sectional shape of the first light beam. In particular, the first light beam is expanded to a radius of Figure 3 The semi-major axis a of the beam expander assembly 230 is a circle. In a non-limiting embodiment, the beam expander assembly 230 can be composed of two groups of positive lenses and a pinhole aperture located at their common focal position, wherein the focal length of the positive lens close to the laser 210 is smaller than the focal length of the positive lens far from the laser 210. Alternatively, the beam expander assembly 230 can also be composed of two groups of confocal lenses, one positive and one negative, wherein the focal length of the plano-concave lens is smaller than the focal length of the positive lens. It should be understood that the beam expander assembly 230 can also be arranged in other ways to meet the needs of the optical detection device.

[0050] In some embodiments, the first shaping lens group 240 is configured to be disposed on the output light path of the laser 210 and to shape the first light beam to generate an incident light beam. The incident light beam is shaped to have a predetermined cross-sectional shape, which can match the slit shape of the Raman spectroscopy component as described above. Figure 2 The light source assembly shown in FIG. 1 is provided with a first optical filter 220, a beam expander lens group 230 and a first shaping lens group 240 in sequence on the outgoing optical path of the laser 210. It should be understood that in other embodiments, the components inside the light source assembly may also be arranged in other orders, such as arranging the beam expander lens group 230 between the laser 210 and the first optical filter 220, or arranging the first shaping lens group 240 between the first optical filter 220 and the beam expander lens group 230. That is, the first optical filter 220, the beam expander lens group 230 and the first shaping lens group 240 may be modified in order as required. Alternatively, the light source assembly includes at least one of the first optical filter 220, the beam expander lens group 230 and the first shaping lens group 240, such as excluding the beam expander lens group 230, so as to perform shaping of the first light beam only without beam expansion.

[0051] In some embodiments, the first shaping lens group 240 may include a cylindrical lens, which mainly realizes the function of compressing the light beam in one direction, such as compressing a circular light spot into an ellipse. In a non-limiting embodiment, for a light source assembly including both the beam expansion lens group 230 and the first shaping lens group 240, the circle with a radius a after beam expansion is compressed to form a short axis with a length of 2b in one direction, that is, the shaping is obtained. Figure 3 It should be understood that the first shaping lens group 240 may also be implemented in other ways to generate an incident light beam having a desired cross-sectional shape.

[0052] like Figure 2 As shown, the optical detection device also includes an imaging lens group for collecting an outgoing light beam from the sample, which irradiates the incident light beam generated and shaped by the light source assembly onto the sample, and collects the Raman scattering signal from the sample at the same time. The dichroic mirror 260 is configured to make one of the incident light beam from the reflector 250 and at least a portion of the outgoing light beam from the first objective lens 270 be reflected and the other be transmitted. Specifically, as Figure 2 As shown, the dichroic mirror 260 reflects the incident light beam to the direction of the first objective lens 270, and irradiates the incident light beam outwardly to the sample through the first objective lens 270. Further, after the sample is excited, Raman scattering occurs, and the first objective lens 270 collects the outgoing light beam containing the Raman scattering signal from the sample, and the outgoing light beam reaches the dichroic mirror 260 along the optical path and is transmitted by the dichroic mirror 260, and reaches the optical fiber 290 output to the Raman spectroscopy component after being filtered by the second filter 280.

[0053] In some embodiments, the reflector 250 reflects the incident light beam from the light source assembly to the dichroic mirror 260 which is also disposed on the optical path of the outgoing light beam. The reflector 250 may be a plane reflector, which is mainly used to adjust the optical path direction of the incident light beam, thereby helping to reasonably arrange the components in the optical detection device, such as reducing the size of the optical detection device in the direction perpendicular to the optical path of the outgoing light beam. It should be understood that the reflector 250 may also include other types of reflective optical components, and may have other suitable numbers and be disposed at other suitable positions.

[0054] In some embodiments, the first objective lens 270 is configured to collect an outgoing light beam from the sample. Generally, the intensity I of the Raman signal is positively correlated with the spatial angle of the numerical aperture NA of the objective lens, satisfying I∝NA 2 . The numerical aperture NA of the traditional Raman collection objective lens is <0.3, and the Raman signal collection efficiency is less than 2.7%. It should be understood that the traditional Raman analysis device is mainly used for offline analysis. At this time, the objective lens is placed outside the container containing the sample, that is, the objective lens has a large working distance, and only increasing the numerical aperture NA cannot produce a significant improvement effect. Correspondingly, in the online Raman analysis system disclosed in the present invention, the first objective lens 270 is in direct contact with the sample, that is, the working distance is close to 0, so the optical signal flux can be increased by increasing the numerical aperture NA of the first objective lens 270, thereby improving the Raman signal collection efficiency. In a non-limiting embodiment, the first objective lens 270 is a high numerical aperture objective lens, wherein the high numerical aperture NA ranges from 0.5 to 0.75, and the Raman signal collection efficiency is increased to 4.2% to 20%.

[0055] In some embodiments, the second filter 280 in the imaging lens group is configured to be disposed on the optical path of the outgoing light beam and filter the outgoing light beam to filter out the components in the outgoing light beam whose wavelength is less than or equal to the preset wavelength. The preset wavelength can be set to be greater than or equal to the maximum wavelength of the incident light beam and less than the minimum wavelength of the Raman signal of the target object, or can be set to other wavelength values ​​that meet the analysis requirements to avoid the impact of the components in the incident light beam and the outgoing light beam with the same wavelength as the incident light beam on the Raman analysis process.

[0056] In some embodiments, the optical fiber 290 in the imaging lens assembly is configured to transmit the outgoing light beam collected by the first objective lens 270. The optical detection device transmits the input light beam or the outgoing light beam respectively via a plurality of optical fibers including the optical fiber 290. In particular, the arrangement and number of the optical fibers 290 can also be adjusted so that the outgoing light beam matches the incident slit of the Raman spectroscopy component.

[0057] Additionally or alternatively, the optical detection device adopts an infinite distance structure. As mentioned above, since the light path from the first objective lens 270 to the optical fiber 290 via the two-way color mirror 260 and the second color filter 280 is parallel light, the distance 2020 shown in the figure can be increased or decreased as needed. The hardware structure of the distance 2020 is such as Figure 1 The probe 130 shown in the figure is immersed in the sample for online detection, and the length of the probe 130 can be customized according to different application scenarios. In addition, in the optical system of the present disclosure, the tube lens adopts an achromatic design, which mainly corrects the dispersion in the wavelength range of 700nm to 1000nm, and can achieve a more efficient and economical structure and material selection.

[0058] Next, combine Figure 4 A Raman spectroscopy component 40 in an optical detection system for online Raman analysis is described. Generally, the Raman spectroscopy component 40 may include a reflector 420, a grating 430, a condenser 440, and a light detector 460. In particular, the Raman spectroscopy component 40 according to an embodiment of the present disclosure further includes a second shaping lens group 450. In addition, in other embodiments, the Raman spectroscopy component 40 further includes a housing, on which a light hole 410 is provided to collect and filter the outgoing light beam from the sample and inject it into the Raman spectroscopy component 40. The reflector 420, the grating 430, the condenser 440, the light detector 460, etc. may be arranged in the housing to prevent stray light in the environment from interfering with Raman scattering. Additionally, the Raman spectroscopy component 40 is configured to detect Raman spectra with a wavelength in the range of 700 to 1000 nm.

[0059] In some embodiments, the light hole 410 is used as an entrance slit of the Raman spectroscopy component 40. Figure 3In particular, since the incident light beam from the light source assembly can obtain a desired cross-sectional shape through beam expansion and shaping, the size of the slit 3220 can be further adjusted, such as increasing the width w2 of the slit 3220 to increase the amount of light entering. In a non-limiting embodiment, w2 can be set within a range of 25 to 80 μm, such as w2 = 30 μm, so that the Raman spectrometer assembly 40 obtains a greater signal strength.

[0060] In some embodiments, the reflector 420 is configured to reflect the outgoing light beam incident on the Raman spectroscopy component 40. Specifically, the outgoing light beam can be reflected onto the grating 430, thereby helping to adjust the component layout and occupied space of the Raman spectroscopy component 40. Additionally, the reflector 420 can include a concave reflector.

[0061] In some embodiments, the grating 430 is configured to be disposed on the outgoing light path of the reflector 420, and receives the outgoing light beam reflected by the reflector 420 and splits the outgoing light beam to distinguish signals of different wavelengths in the outgoing light beam. Additionally, the grating 430 may be a planar reflective grating.

[0062] In some embodiments, the condenser 440 is configured to be disposed on the outgoing light path of the grating 430 and to condense the split outgoing light beam from the grating 430 so that the split outgoing light beam changes its light path and is incident on the light detector 460. Additionally, the condenser 440 may include a concave reflective mirror.

[0063] In some embodiments, the light detector 460 is configured to be disposed on the outgoing light path of the condenser 440 , receive the outgoing light beam from the condenser 440 , and generate a Raman spectrum.

[0064] In particular, the Raman spectrum assembly 40 further includes a second shaping lens group 450, which is configured to be disposed on the outgoing light path of the condenser 440, and to shape the outgoing light beam from the condenser 440 so that the shaped outgoing light beam matches the size of the light detector 460 and is irradiated on the light detector 460. The second shaping lens group 450 may include a cylindrical lens for realizing the function of compressing the light beam in one direction, such as reducing the size of the incident spectral band in width or height. In the aforementioned embodiment of increasing the incident slit (light hole 410), the height of the spectral band after diffraction by the grating 430 increases. Adding the second shaping lens group 450 in front of the light detector 460 can make the height of the spectral band consistent with the height of the detection element of the light detector 460, that is, avoid the loss of light that exceeds the detection element due to the increase in the spectral band height. As a result, the Raman spectrum assembly 40 can obtain a greater Raman signal intensity without reducing the resolution.

[0065] The optical detection system and device disclosed in the present invention improve the structural composition of the imaging lens group and the Raman spectrum component, so that the Raman scattering signal from the sample can be increased as much as possible. Specifically, in some embodiments, a laser with a wavelength of 785nm is used to irradiate the sample, which can reduce the damage to the biologically active substance while reducing the interference of the background excitation fluorescence that may be produced. Compared with the traditional Raman optical detection device, the optical detection system disclosed in the present invention adds an optical component (such as a concave lens for beam expansion and a cylindrical lens for shaping) for beam expansion and shaping of the light beam from the laser, and additionally or alternatively increases the incident slit of the Raman spectrum component so that the cross-sectional shape of the incident light beam matches the incident slit. In addition, in the Raman spectrum component, the spectral band height is matched with the height of the detection element in the light detector by adding an optical component (such as a cylindrical lens) for shaping before the light detector. As a result, the optical detection system disclosed in the present invention can improve the collection efficiency of the Raman scattering signal as much as possible without reducing the resolution too much, and effectively reduce the interference of background noise signals such as stray light.

[0066] The terms used herein are only for describing specific exemplary embodiments and are not intended to limit the present disclosure. Unless the context clearly indicates otherwise, the singular forms of "one" and "the" used herein are intended to include plural forms as well. It should also be understood that when the word "including" is used in this article, it indicates the existence of the indicated features, wholes, steps, operations, units and / or components, but does not exclude the existence or increase of one or more other features, wholes, steps, operations, units and / or components and / or their combinations. In addition, in the description of the present disclosure, the terms "first", "second", etc. are only used for descriptive purposes and cannot be understood as indicating or implying relative importance or order. In addition, in the description of the present disclosure, unless otherwise specified, the meaning of "multiple" is two or more.

[0067] References to "an embodiment" or similar expressions in this specification refer to specific features, structures, or characteristics described in conjunction with the embodiment being included in at least one specific embodiment of the present disclosure. Therefore, the appearance of the phrase "in an embodiment of the present disclosure" and similar expressions in this specification does not necessarily refer to the same embodiment.

[0068] Those skilled in the art will appreciate that the present disclosure may be implemented in various forms, such as a complete hardware embodiment, a complete software embodiment (including firmware, resident software, microprogram code, etc.), or a combination of software and hardware, which will be referred to below as a "circuit," "module," "unit," or "system." In addition, the present disclosure may also be implemented in any tangible media form as a computer program product having a computer usable program code stored thereon.

[0069] The relevant description of the present disclosure is described with reference to the flowchart and / or block diagram of the system, device, method and computer program product according to the specific embodiment of the present disclosure. It can be understood that each block in each flowchart and / or block diagram, and any combination of blocks in the flowchart and / or block diagram, can be implemented using computer program instructions. These computer program instructions can be executed by a machine composed of a processor of a general-purpose computer or a special computer or other programmable data processing device, and the instructions are processed by a computer or other programmable data processing device to implement the functions or operations described in the flowchart and / or block diagram.

[0070] The accompanying drawings show the flowcharts and block diagrams of the architecture, functions and operations that can be implemented by the systems, devices, methods and computer program products according to various embodiments of the present disclosure. Therefore, each block in the flowchart or block diagram may represent a module, segment or part of the program code, which includes one or more executable instructions to implement the specified logical function. It should also be noted that in some other embodiments, the functions described in the blocks may not be performed in the order shown in the figure. For example, two blocks connected to each other in the figure may in fact be executed simultaneously, or in some cases according to the functions involved, they may also be executed in the opposite order of the icons. It should also be noted that each block of the block diagram and / or flowchart, as well as the combination of blocks in the block diagram and / or flowchart, can be implemented by a system based on dedicated hardware, or by a combination of dedicated hardware and computer instructions to perform specific functions or operations.

[0071] The embodiments of the present disclosure have been described above, and the above description is exemplary, not exhaustive, and is not limited to the disclosed embodiments. Many modifications and variations will be apparent to those of ordinary skill in the art without departing from the scope and spirit of the described embodiments. The selection of terms used herein is intended to best explain the principles of the embodiments, practical applications, or technical improvements to market technologies, or to enable other persons of ordinary skill in the art to understand the embodiments disclosed herein.

Claims

1. An optical detection device for online Raman analysis, comprising: a light source assembly configured to generate an incident light beam for illuminating a sample; as well as an imaging lens assembly configured to collect an outgoing light beam from the sample, in: The outgoing beam is injected into the Raman spectrometer to generate the Raman spectrum of the sample. The incident light beam is shaped to have a predetermined cross-sectional shape that matches the slit shape of the Raman spectroscopy component.

2. The optical detection device according to claim 1, wherein: The light source assembly includes a laser configured to generate a first light beam.

3. The optical detection device according to claim 2, wherein: The light source assembly includes a first shaping lens group, which is configured to be disposed on an outgoing light path of the laser and to shape a first light beam to generate an incident light beam.

4. The optical detection device according to claim 3, wherein: The light source assembly includes a beam expander lens group, which is configured to be disposed on an output light path of the laser and to expand the first light beam.

5. The optical detection device according to claim 3 or 4, wherein: The light source assembly includes a first filter, which is configured to be disposed on an outgoing light path of the laser and to filter the first light beam to filter out components in the first light beam that are outside a preset wavelength range.

6. The optical detection device according to claim 1, wherein: The imaging lens assembly includes a first objective lens, which is configured to collect an outgoing light beam.

7. The optical detection device according to claim 6, wherein: The first objective lens is an objective lens with a high numerical aperture, wherein the high numerical aperture ranges from 0.5 to 0.

75.

8. The optical detection device according to claim 6, wherein: The imaging lens group includes a dichroic mirror, which is configured to be disposed on an optical path of an outgoing light beam and to reflect one of at least a portion of the incident light beam and the outgoing light beam and transmit the other.

9. The optical detection device according to claim 1, wherein: The imaging lens assembly includes a second filter element, which is configured to be disposed on the optical path of the outgoing light beam and filter the outgoing light beam to filter out components in the outgoing light beam whose wavelength is less than or equal to a preset wavelength.

10. The optical detection device according to claim 1, wherein: The optical detection device is configured to transmit the input light beam or the output light beam via an optical fiber.

11. The optical detection device according to claim 1, wherein: The optical detection device is configured as a probe with an infinite structure, wherein the probe is immersed in a sample for online detection.

12. An optical detection system for online Raman analysis, comprising: a light source assembly configured to generate an incident light beam for illuminating a sample; an imaging lens assembly configured to collect an outgoing light beam from the sample; as well as A Raman spectroscopy component configured to generate a Raman spectrum of the sample based on the output light beam, wherein: The incident light beam is shaped to have a predetermined cross-sectional shape that matches the slit shape of the Raman spectroscopy component.

13. The optical detection system of claim 11, wherein: The light source assembly includes a laser configured to generate a first light beam.

14. The optical detection system of claim 13, wherein the light source assembly further comprises at least one of the following: a first shaping lens group, the first shaping lens group being configured to be disposed on an outgoing light path of the laser and to shape the first light beam to generate an incident light beam; A beam expander lens group, wherein the beam expander lens group is configured to be disposed on an output light path of the laser and to expand the first light beam; as well as The first filter is configured to be disposed on an outgoing light path of the laser and to filter the first light beam to filter out components in the first light beam that are outside a preset wavelength range.

15. The optical detection system according to claim 12, wherein the imaging lens assembly comprises: a first objective lens configured to collect an outgoing light beam; a dichroic mirror configured to be disposed on an optical path of the outgoing light beam and to reflect one of at least a portion of the incident light beam and the outgoing light beam and transmit the other; as well as The second filter is configured to be disposed on the optical path of the outgoing light beam and to filter the outgoing light beam to filter out components in the outgoing light beam whose wavelength is less than or equal to a preset wavelength.

16. The optical detection system of claim 12, wherein the Raman spectroscopy component comprises: a reflector configured to reflect an outgoing light beam incident on the Raman spectroscopy component; A grating, the grating being configured to be disposed on an outgoing light path of the reflector, and receiving an outgoing light beam reflected by the reflector and splitting the outgoing light beam; A condenser lens, the condenser lens being configured to be disposed on an outgoing light path of the grating and to condense the split outgoing light beam from the grating; as well as The photodetector is configured to be disposed on the outgoing light path of the condenser, receive the outgoing light beam from the condenser, and generate a Raman spectrum.

17. The optical detection system of claim 16, wherein: The Raman spectroscopy component also includes a second shaping lens group, which is configured to be arranged on the output light path of the condenser and to shape the output light beam from the condenser so that the shaped output light beam matches the size of the light detector and is irradiated on the light detector.

18. The optical detection system of claim 12, wherein: The Raman spectroscopic component is configured to detect Raman spectra with a wavelength in the range of 700-1000 nm.

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