Laser particle size analyzer based on microscope system

Abstract

The invention relates to the technical field of particle size measurement, and discloses a laser particle size analyzer based on a microscope system. The invention integrates a laser particle size analyzer and an imager, wherein the laser particle size analyzer is composed of a laser light source, a spatial filter, a first lens, a microscope objective lens, a microfluidic chip, a beam splitter prism, an imaging objective lens, and a first detector, and the imager is composed of a white light source, a microfluidic chip, a microscope objective lens, a beam splitter prism, an imaging objective lens, and a first detector. A sample to be measured is stored in the microfluidic chip, and the microfluidic chip can control the injection of the sample. The optical system of the invention is combined with two measuring instruments to perform measurement, and a small amount of medicine is required, and multiple types of parameters can be measured at the same time. The operation is simple and the measurement accuracy is improved.

Description

Technical Field

[0001] The invention relates to the technical field of particle size measurement, and in particular to a laser particle size analyzer based on a microscope system. Background Art

[0002] At present, in some application fields, such as the medical industry, there is a need to measure precious trace samples, which are usually measured using a laser particle size analyzer or an imager. If a laser particle size analyzer is used alone for measurement, a large amount of sample is required to obtain a sufficient signal-to-noise ratio for measurement, resulting in high testing costs. If an imager is used alone for measurement, the imaging resolution is insufficient and the observation field is small, the measurement time is long, and the time cost of drug research and development is increased. In addition, there are few types of measurement data for a single machine, and it is necessary to switch to multiple machines to complete the measurement, which is cumbersome. Summary of the invention

[0003] The present invention aims to solve at least one of the technical problems existing in the prior art. To this end, the present invention proposes a laser particle size analyzer based on a microscope system, which integrates the laser particle size analyzer with an imager, and can measure multiple types of parameters while requiring a small amount of medicine, thereby improving the accuracy of the measurement.

[0004] To achieve the above object, the technical solution of the present invention is:

[0005] The laser particle size analyzer based on the microscope system according to the embodiment of the present invention comprises a laser light source, a spatial filter, a first lens, a microscope objective lens, a microfluidic chip, a beam splitter prism, an imaging objective lens, a first detector, and a white light source; the laser light source is used to emit laser light; the spatial filter is used to filter the stray light of the laser light; the first lens is used to converge the laser light after filtering; the focused spot of the laser light after convergence and filtering coincides with the rear focal plane of the microscope objective lens, so that the laser light is emitted as parallel light after passing through the microscope objective lens; the microfluidic chip is used for sample injection, and the parallel light interacts with the sample in the microfluidic chip to generate backscattered light and forward scattered light; the backscattered light reaches the beam splitter prism after passing through the microscope objective lens; The beam splitting prism reflects the backscattered light to the imaging objective lens; the backscattered light forms an image on the first detector after passing through the imaging objective lens; the white light source is used to emit white light toward the microfluidic chip, and the white light generates refracted light after interacting with the sample, and the refracted light passes through the microscope objective lens, the beam splitting prism, and the imaging objective lens in sequence and reaches the first detector, and forms an image on the first detector; wherein the laser light source, the spatial filter, the first lens, the microscope objective lens, the microfluidic chip, the beam splitting prism, the imaging objective lens, and the first detector constitute a laser particle size analyzer; the white light source, the microfluidic chip, the microscope objective lens, the beam splitting prism, the imaging objective lens, and the first detector constitute an imager.

[0006] According to some embodiments of the present invention, after the parallel light interacts with the sample in the microfluidic chip, transmitted light is also generated.

[0007] According to some embodiments of the present invention, the laser particle size analyzer further comprises a zero-ring light detector, and the transmitted light of the laser is imaged on the zero-ring light detector, and the sample concentration is determined by using an extinction method.

[0008] According to some embodiments of the present invention, the laser particle size analyzer further includes a second lens and a second detector, and the forward scattered light is imaged on the second detector after passing through the second lens.

[0009] According to some embodiments of the present invention, the spatial filter includes a third lens and an aperture, the third lens is arranged between the laser light source and the first lens, and the aperture is arranged between the first lens and the third lens.

[0010] According to some embodiments of the present invention, the first detector is movably disposed on a side of the imaging objective lens away from the beam splitting prism.

[0011] According to some embodiments of the present invention, the microscope objective lens is an oil immersion objective lens with a preset aperture.

[0012] According to some embodiments of the present invention, the position of the first detector is conjugate with the back focal plane of the microscope objective lens, and the lateral position of the detection range of the first detector coincides with the center of the back focal plane of the microscope objective lens. In this case, it is a microscope system laser particle size analyzer.

[0013] According to some embodiments of the present invention, the first detector is located conjugate with the sample of the microfluidic chip, and in this case is an imager.

[0014] According to some embodiments of the present invention, a reflector is arranged between the first lens and the beam splitting prism, and the reflector is used to reflect the laser converged by the first lens to the microscope objective lens, and make the focusing spot of the laser coincide with the back focal plane of the microscope objective lens.

[0015] According to some embodiments of the present invention, the reflector uses a galvanometer system or an electrically deflectable reflector to confirm the refractive index of the dispersion medium of the sample through a total reflection formula, wherein the total reflection formula is n1=n2sinθ c , where n1 is the refractive index of the dispersion medium of the sample, n2 is the refractive index of the microscope objective oil, θ c It is the incident angle obtained by inferring the mirror reflected light received by the first detector through the position relationship.

[0016] The laser particle size analyzer based on a microscope system of the present invention has at least the following beneficial effects: by controlling the injection of samples through a microfluidic chip, the amount of samples required during measurement can be reduced, thereby reducing the measurement cost; by integrating the laser particle size analyzer and the imager together, the measurement process can measure a variety of data, reducing the tedious operations that need to replace different instruments, reducing the time cost of measurement, and being able to improve the measurement accuracy.

[0017] Additional aspects and advantages of the present invention will be given in part in the following description and in part will be obvious from the following description, or will be learned through practice of the present invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] The above and / or additional aspects and advantages of the present invention will become apparent and easily understood from the description of the embodiments in conjunction with the following drawings, in which:

[0019] Figure 1 is a schematic structural diagram of a laser particle size analyzer based on a microscope system according to an embodiment of the present invention;

[0020] Figure 2 It is a schematic diagram of the optical path of scattered light after parallel light acts on the sample in the microfluidic chip;

[0021] Figure 3 It is a schematic diagram of an infinite conjugate teleoptical system;

[0022] Figure 4 It is a schematic diagram of the distance relationship between the imaging point of the emitted light in the detection range of the first detector and the center point of the detection range of the first detector.

[0023] Figure numerals: laser light source 1, third lens 2, aperture 3, first lens 4, reflector 5, beam splitting prism 6, microscope objective 7, microfluidic chip 8, imaging objective 9, first detector 10, zero-ring light detector 11, second lens 12, second detector 13, white light source 14. DETAILED DESCRIPTION

[0024] This section will describe in detail the specific embodiments of the present invention. The preferred embodiments of the present invention are shown in the accompanying drawings. The purpose of the accompanying drawings is to supplement the description of the text part of the specification with graphics, so that people can intuitively and vividly understand each technical feature and the overall technical solution of the present invention, but it cannot be understood as a limitation on the scope of protection of the present invention.

[0025] In the description of the present invention, it should be understood that descriptions involving orientations, such as up, down, front, back, left, right, etc., and orientations or positional relationships indicated are based on the orientations or positional relationships shown in the accompanying drawings, and are only for the convenience of describing the present invention and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation, and therefore should not be understood as a limitation on the present invention.

[0026] In the description of the present invention, "several" means one or more, "more" means more than two, "greater than", "less than", "exceed" etc. are understood as not including the number itself, and "above", "below", "within" etc. are understood as including the number itself. If there is a description of the first, second, and third, it is only used for the purpose of distinguishing the technical features, and cannot be understood as indicating or implying the relative importance or implicitly indicating the number of the indicated technical features or implicitly indicating the order of the indicated technical features.

[0027] In the description of the present invention, unless otherwise clearly defined, terms such as setting, installing, connecting, etc. should be understood in a broad sense, and technicians in the relevant technical field can reasonably confirm the specific meanings of the above terms in the present invention in combination with the specific content of the technical solution.

[0028] Reference Figure 1According to an embodiment of the present invention, the laser particle size analyzer based on the microscope system includes a laser light source 1, a spatial filter, a first lens 4, a microscope objective lens 7, a microfluidic chip 8, a beam splitter prism 6, an imaging objective lens 9, a first detector 10, and a white light source 14; the laser light source 1 is used to emit laser light; the spatial filter is used to filter the stray light of the laser, and homogenize the light spot of the laser emitted by the laser light source 1 to reduce the interference of the stray light contained in the laser on the subsequent detection results; the spatial filter is composed of a third lens 2 and an aperture 3; the laser beam will expand after passing through the spatial filter, and the first lens 4 is used to converge the filtered and expanded laser; the focused light spot of the converged and filtered laser after passing through the beam splitter prism 6 coincides with the rear focal plane of the microscope objective lens 7, and the rear focal plane of the microscope objective lens 7 is between the beam splitter prism 6 and the microscope objective lens 7, so that the laser passes through the microscope objective lens 7 and is emitted as parallel light or approximately parallel light; the rear focal plane of the microscope objective lens 7 is located away from the microfluidic chip , and is located between the microscope objective 7 and the beam splitter prism 6; the microfluidic chip 8 is used for sample injection, and after the parallel light interacts with the sample of the microfluidic chip 8, backscattered light is generated, and after the backscattered light passes through the microscope objective 7, it reaches the beam splitter prism 6, and the beam splitter prism 6 reflects the backscattered light to the imaging objective 9, and after the backscattered light passes through the imaging objective 9, it is imaged on the first detector 10; the white light source 14 is used to emit white light toward the microfluidic chip 8, and after the white light interacts with the sample, refracted light is generated, and the refracted light passes through the microscope objective 7, the beam splitter prism 6, and the imaging objective 9 in sequence and reaches the first detector 10, and is imaged on the first detector 10; wherein, the laser light source 1, the spatial filter, the first lens 4, the microscope objective 7, the microfluidic chip 8, the beam splitter prism 6, the imaging objective 9, and the first detector 10 constitute a laser particle size analyzer; the white light source 14, the microfluidic chip 8, the microscope objective 7, the beam splitter prism 6, the imaging objective 9, and the first detector 10 constitute an imager.

[0029] Furthermore, the first lens 4 adopts but is not limited to a telephoto lens, the type of the laser light source 1 can be adjusted according to actual needs, and the laser band of the laser light source 1 can be selected or adjusted according to actual needs to meet the light source requirements of the measurement.

[0030] Furthermore, the microfluidic chip 8 includes a microchannel, a micropump, and a microvalve. The microchannel is used for the circulation of samples, the micropump is used to drive the samples to circulate in the microchannel, and the micropump and microvalve are used to control the circulation speed of the samples. The samples are not easy to settle in the microfluidic chip 8. The area where the parallel light acts on the sample is at or below the level of hundreds of microns. The intensity of the output light after the parallel light acts on the sample is improved, and the intensity of the imaging signal that can be received by the first detector 10, the second detector 13, and the zero-ring light detector 11 is increased, thereby enhancing the measurement accuracy.

[0031] Reference Figure 2According to some embodiments of the present invention, after the parallel light interacts with the sample of the microfluidic chip 8, transmitted light and forward scattered light are also generated. The transmitted light is emitted from the microfluidic chip 8 in a direction parallel to the light path of the parallel light; the forward scattered light is emitted from the microfluidic chip 8 in a direction away from the microscope objective 7.

[0032] Reference Figure 2 According to some embodiments of the present invention, the laser particle size analyzer also includes a zero-ring light detector 11. The isotropic scattered light is imaged on the zero-ring light detector 11. The zero-ring light detector 11 is used to measure the shading rate of the sample in the microfluidic chip 8. The concentration of the sample can be further inferred by the acquired shading rate data.

[0033] Reference Figure 2 According to some embodiments of the present invention, the laser particle size analyzer further includes a second lens 12 and a second detector 13. The second lens 12 is located on the side of the microfluidic chip 8 away from the microscope objective lens 7. When the second detector 13 is located on the side of the second lens 12 away from the microfluidic chip 8 and is located at the back focal plane of the second lens 12, the forward scattered light passes through the second lens 12 and is received by the second detector 13; when the sample flow rate is fast or contains large particles, the second detector 13 can be used to measure large particles; the second detector 13 uses any one of CCD or CMOS, and the focal length and size of the second lens 12 and the type of the second detector 13 can be selected or adjusted according to actual needs to meet the imaging and measurement requirements. When the microfluidic chip 8 and the second detector 13 are imaging conjugates, the microfluidic chip 8, the second lens 12 and the second detector 13 can also form dark field microscopic imaging, which is used to image samples with a smaller refractive index than the dispersion medium, increase image contrast, and improve measurement accuracy.

[0034] Reference Figure 1 According to some embodiments of the present invention, the third lens 2 is arranged between the laser light source 1 and the first lens 4, and the aperture 3 is movably arranged between the first lens 4 and the third lens 2. By adjusting the relative position of the aperture 3 between the first lens 4 and the third lens 2, the third lens 2 and the aperture 3 constitute a spatial filter, which can filter the stray light of the laser and homogenize the laser spot, thereby improving the measurement accuracy.

[0035] Reference Figure 1According to some embodiments of the present invention, the first detector 10 is movably arranged on a side of the imaging objective lens 9 away from the beam splitting prism 6, and the first detector 10 is imaged conjugate with the microfluidic chip 8 by adjusting the position of the first detector 10 relative to the imaging objective lens 9. In this way, the backscattered light can be imaged on the first detector 10. In practical applications, the first detector 10 can be any one of CCD or CMOS. The focal length and size of the imaging objective lens 9, the type of the first detector 10, and the position of the first detector 10 relative to the imaging objective lens 9 can be selected or adjusted according to actual needs to meet the needs of imaging and measurement, and can enhance the adjustability of the entire optical system.

[0036] Reference Figure 1 and Figure 2 According to some embodiments of the present invention, the microscope objective lens 7 adopts an oil-immersion objective lens with a large numerical aperture to reduce the interference of interface reflections existing at the sample on the measurement results, while increasing the detection angle range of backscattered light; it is conceivable that, according to actual needs, the microscope objective lens 7 can also be replaced by other objective lenses or optical lens groups that are functionally similar to the oil-immersion objective lens to meet the required imaging and measurement requirements.

[0037] According to some embodiments of the present invention, referring to Figure 2 ,Since the transmitted light intensity of the laser is generally strong, a zero ring detector is ,purposely set up to receive the transmitted light, and the ,concentration of the sample can be detected by the extinction method as a ,reference for the sample.

[0038] According to some embodiments of the present invention, the first detector 10 is located at the image plane of the imaging objective lens 9, the first detector 10 is conjugate with the back focal plane of the microscope objective lens 7, and the center of the detection range of the first detector 10 is located at the center of the back focal plane of the microscope objective lens 7, so that the backscattered light can be accurately received by the first detector 10 to meet the required imaging and measurement requirements.

[0039] Further, see Figure 3 and Figure 4 , the microscope objective 7 is an infinite conjugate optical system, and the emission angle of the scattered light is θ ′ The relationship between the object height h and the equivalent focal length f of the microscope objective lens 7 is h = fsinθ ′ , the equivalent focal length f can be detected by necessary optical means, and at the same time, the object height h satisfies the relationship: Wherein, L is the distance between the back focal plane of the microscope objective 7 and the center of the imaging objective 9, L ′ is the distance between the first detector 10 and the center of the imaging objective 9, h ′is the distance between the imaging point of the scattered light spot in the detection range of the first detector and the center point of the detection range of the first detector. By combining the above two equations, the emission angle θ can be obtained. ′ , the scattering angle is θ=π-(θ ′ +θ). Based on the scattering angle θ and the basic principle of the laser particle size analyzer and the inversion algorithm, the particle size distribution of the sample is obtained to achieve high-precision particle size measurement.

[0040] According to some embodiments of the present invention, a reflector 5 is provided between the first lens 4 and the beam splitting prism 6, and the reflector 5 is used to reflect the laser light converged by the first lens 4 to the microscope objective 7, and to make the focused spot of the laser light coincide with the rear focal plane of the microscope objective 7, so as to adjust the laser light path. The reflector 5 can be adjusted manually, by galvanometer control, or by any other electric reflector system, and can be selected or adjusted according to actual needs to meet the imaging and measurement requirements.

[0041] Reference Figure 3 and Figure 4 According to some embodiments of the present invention, the reflector 5 is controlled to move the spot position to change the incident angle θ. The mirror reflected light and the incident light are symmetrical about the central optical axis of the microscope objective 7. The incident angle θ is inferred from the position of the emitted mirror reflected light spot. When the incident angle θ is slowly changed so that the incident angle θ reaches the total internal reflection angle θ c When the intensity of the emitted light spot changes suddenly, the position h′ at this time is recorded and combined with H=fsinθ c 、n1=n2sinθ c The refractive index of the dispersion medium of the sample is inferred, where n1 is the refractive index of the dispersion medium of the sample, n2 is the refractive index of the lens oil of the microscope objective 7, L is the distance between the back focal plane of the microscope objective 7 and the center of the imaging objective 9, and L ′ is the distance between the first detector 10 and the center of the imaging objective lens 9 , and f is the equivalent focal length of the microscope objective lens 7 .

[0042] The laser particle size analyzer based on the microscope system of the present invention has at least the following beneficial effects: the injection of the sample is controlled by the microfluidic chip 8, and the sample is circulated and injected in the microfluidic chip 8, so that the sedimentation of the sample is not easy to occur, and the amount of sample required for the measurement process is small, thereby reducing the measurement cost; by integrating the laser particle size analyzer and the imager together, the measurement process can measure a variety of data, reducing the tedious operation of changing different instruments, and the operation is simple and the time cost of the measurement is reduced, and the measurement accuracy can be improved.

[0043] In the description of this specification, the description with reference to the terms "one embodiment", "some embodiments", "illustrative embodiments", "examples", "specific examples", or "some examples" means that the specific features, structures, materials or characteristics described in conjunction with the embodiment or example are included in at least one embodiment or example of the present invention. In this specification, the schematic representation of the above terms does not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described may be combined in any one or more embodiments or examples in a suitable manner.

[0044] Although embodiments of the present invention have been shown and described, those skilled in the art will appreciate that various changes, modifications, substitutions and variations may be made to the embodiments without departing from the principles and spirit of the present invention, and that the scope of the present invention is defined by the claims and their equivalents.

Claims

1. A laser particle size analyzer based on a microscope system, characterized in that: include: A laser light source, used for emitting laser light; A spatial filter for filtering stray light of the laser; A first lens, used for converging the filtered laser light; A microscope objective lens, which converges and filters the focused spot of the laser light and overlaps the rear focal plane of the microscope objective lens, so that the laser light is emitted as parallel light after passing through the microscope objective lens; A microfluidic chip is used for sample injection, wherein the parallel light interacts with the sample in the microfluidic chip to generate backscattered light and forward scattered light; A beam splitter prism, wherein the backscattered light reaches the beam splitter prism after passing through the microscope objective lens; An imaging objective lens, wherein the beam splitting prism reflects the backscattered light to the imaging objective lens; a first detector, wherein the backscattered light is received by the first detector after passing through the imaging objective lens; A white light source, used for emitting white light toward the microfluidic chip, wherein the white light generates refracted light after interacting with the sample, and the refracted light sequentially passes through the microscope objective lens, the beam splitting prism, and the imaging objective lens before reaching the first detector, and an image is formed on the first detector; Wherein, the laser light source, the spatial filter, the first lens, the microscope objective lens, the microfluidic chip, the beam splitter prism, the imaging objective lens, and the first detector constitute a laser particle size analyzer; the white light source, the microfluidic chip, the microscope objective lens, the beam splitter prism, the imaging objective lens, and the first detector constitute an imager; After the parallel light interacts with the sample of the microfluidic chip, transmitted light is also generated; The laser particle size analyzer also includes a zero-ring light detector, and the transmitted light is received by the zero-ring light detector; The laser particle size analyzer further comprises a second lens and a second detector, and the forward scattered light is received by the second detector after passing through the second lens.

2. The laser particle size analyzer based on a microscope system according to claim 1, characterized in that: The spatial filter includes a third lens and an aperture. The third lens is arranged between the laser light source and the first lens, and the aperture is arranged between the first lens and the third lens.

3. The laser particle size analyzer based on a microscope system according to claim 1, characterized in that: The first detector is movably arranged on a side of the imaging objective lens away from the beam splitting prism.

4. The laser particle size analyzer based on a microscope system according to claim 1, characterized in that: The microscope objective lens adopts an oil immersion objective lens with a preset aperture.

5. The laser particle size analyzer based on a microscope system according to claim 1, characterized in that: The first detector is located at the image plane of the imaging objective lens, the first detector is conjugate with the back focal plane of the microscope objective lens, and the lateral position of the detection range of the first detector coincides with the center of the back focal plane of the microscope objective lens.

6. The laser particle size analyzer based on a microscope system according to claim 1, characterized in that: A reflector is arranged between the first lens and the beam splitting prism, and the reflector is used to reflect the laser light converged by the first lens to the microscope objective lens, and make the focusing spot of the laser light coincide with the rear focal plane of the microscope objective lens.

7. The laser particle size analyzer based on a microscope system according to claim 6, characterized in that: The reflector uses a galvanometer system or an electrically deflectable reflector to confirm the refractive index of the dispersion medium of the sample through a total reflection formula, and the total reflection formula is: ,in, is the refractive index of the dispersion medium of the sample, is the refractive index of the microscope objective oil, It is the incident angle obtained by inferring the mirror reflected light received by the first detector through the position relationship.

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