Biomaterial viscoelasticity measuring system based on stimulated Brillouin scattering

Abstract

The invention discloses a biological material viscoelasticity measurement system based on stimulated Brillouin scattering, and relates to the field of optical measurement and biomechanical characterization, the system comprises: a stimulated Brillouin scattering light source module for generating laser; the first optical fiber collimator is arranged on an output light path of the stimulated Brillouin scattering light source module; the beam splitter is arranged on an output light path of the first optical fiber collimator; the objective lens is arranged on a transmission light path of the beam splitter; the objective lens is also arranged on a back scattering light path of a to-be-detected area of the biological material sample; the beam splitter is also arranged on an output light path of the objective lens; the second optical fiber collimator is arranged on a reflection light path of the beam splitter; the output end of the second optical fiber collimator is connected with the input end of the viscoelasticity measurement module through a third optical fiber; the viscoelasticity measuring module is used for measuring the viscoelasticity of the to-be-measured area of the biological material sample according to the light transmitted by the third optical fiber. The method and the device are suitable for living biological samples.

Description

Technical Field

[0001] This application relates to the fields of optical measurement and biomechanical characterization, and in particular to a viscoelastic measurement system for biomaterials based on stimulated Brillouin scattering. Background Technology

[0002] The viscoelastic properties of biomaterials reflect their internal microstructure and mechanical response behavior, and are of great significance in disease diagnosis, tissue engineering, biomaterial design, and basic life science research. Existing biomechanical measurement methods, such as atomic force microscopy, microrheological testing, and macroscopic mechanical tensile and compression experiments, usually require contact with the sample or are difficult to achieve high spatial resolution and in-situ measurements, which limits their application in living samples and microscale structures.

[0003] Optical techniques, such as Brillouin scattering, can reflect the mechanical properties of materials by detecting spontaneous thermoacoustic waves inside the material, but the signals are usually extremely weak, making it difficult to obtain high-quality spectral information, especially in weakly scattering biological samples.

[0004] Stimulated Brillouin scattering (SBS) can significantly enhance the Brillouin scattering signal by inducing acoustic waves with a strong laser. However, existing biomaterial viscoelasticity measurement systems based on SBS can only perform elastic imaging on relatively thin samples such as cells, limiting their application in in vivo biological sample studies.

[0005] Therefore, there is an urgent need for a biomaterial viscoelasticity measurement system suitable for live biological samples. Summary of the Invention

[0006] The purpose of this application is to provide a biomaterial viscoelasticity measurement system based on stimulated Brillouin scattering, suitable for live biological samples.

[0007] To achieve the above objectives, this application provides the following solution: This application provides a biomaterial viscoelasticity measurement system based on stimulated Brillouin scattering, comprising: a stimulated Brillouin scattering light source module, a first fiber collimator, a beam splitter, an objective lens, a second fiber collimator, a third fiber, and a viscoelasticity measurement module.

[0008] A stimulated Brillouin scattering (SBS) light source module is used to generate laser light; a first fiber collimator is positioned in the output optical path of the SBS light source module; a beam splitter is positioned in the output optical path of the first fiber collimator. The objective lens is positioned in the transmission optical path of the beam splitter; the beam splitter processes the output optical path of the first fiber collimator to generate transmitted light, and the objective lens focuses the transmitted light onto the test area of ​​the biological material sample to generate stimulated Brillouin backscattered light.

[0009] The objective lens is also positioned in the backscattered light path of the test area of ​​the biological material sample; the beam splitter is also positioned in the output light path of the objective lens; the second fiber collimator is positioned in the reflected light path of the beam splitter; the stimulated Brillouin backscattered light is transmitted to the objective lens through the backscattered light path, and the objective lens is also used to focus the stimulated Brillouin backscattered light onto the beam splitter, and the beam splitter is also used to process the stimulated Brillouin backscattered light output from the objective lens to generate reflected light, and the second fiber collimator is used to collimate the reflected light.

[0010] The output of the second fiber collimator is connected to the input of the viscoelastic measurement module via a third fiber. The viscoelastic measurement module is used to measure the viscoelasticity of the test area of ​​the biomaterial sample based on the light transmitted from the third fiber.

[0011] According to the specific embodiments provided in this application, this application has the following technical effects: This application provides a biomaterial viscoelasticity measurement system based on stimulated Brillouin scattering. A first fiber collimator is disposed in the output optical path of the stimulated Brillouin scattering light source module; a beam splitter is disposed in the output optical path of the first fiber collimator; an objective lens is disposed in the transmission optical path of the beam splitter; the objective lens is also disposed in the backscattering optical path of the test area of ​​the biomaterial sample; the beam splitter is also disposed in the output optical path of the objective lens; a second fiber collimator is disposed in the reflection optical path of the beam splitter; the output end of the second fiber collimator is connected to the input end of the viscoelasticity measurement module via a first fiber collimator. The three optical fibers are connected; the beam splitter processes the light output from the first fiber collimator to generate transmitted light, the objective lens focuses the transmitted light onto the test area of ​​the biological material sample to generate stimulated Brillouin backscattered light; the objective lens also focuses the stimulated Brillouin backscattered light onto the beam splitter, the beam splitter also processes the stimulated Brillouin backscattered light output from the objective lens to generate reflected light, the second fiber collimator collimates the reflected light to form a confocal system, and the input end face of the third fiber acts as a spatial filter aperture of the confocal system to form effective spatial filtering, realize confocal detection, and significantly suppress stray light interference from the non-focal plane. Attached Figure Description

[0012] To more clearly illustrate the technical solutions in the embodiments of this application or the prior art, the drawings used in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of this application. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0013] Figure 1 This is a schematic diagram of the overall structure of the biomaterial viscoelasticity measurement system based on stimulated Brillouin scattering provided in the embodiments of this application.

[0014] Figure reference numerals: 1-Laser, 2-First fiber, 3-Modulator, 4-Second fiber, 5-First fiber collimator, 6-Beam splitter, 7-Objective lens, 8-Biomaterial sample, 9-Second fiber collimator, 10-Third fiber, 11-Brillouin spectrometer, 12-Imaging device, 13-Data processing unit. Detailed Implementation

[0015] The technical solutions of the embodiments of this application will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of this application, and not all embodiments. Based on the embodiments of this application, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of this application.

[0016] To make the above-mentioned objectives, features and advantages of this application more apparent and understandable, the application will be further described in detail below with reference to the accompanying drawings and specific embodiments.

[0017] In one exemplary embodiment, such as Figure 1 As shown, a biomaterial viscoelasticity measurement system based on stimulated Brillouin scattering is provided, comprising: a stimulated Brillouin scattering light source module, a first fiber collimator 5, a beam splitter 6, an objective lens 7, a second fiber collimator 9, a third fiber 10, and a viscoelasticity measurement module.

[0018] The stimulated Brillouin scattering (SBS) light source module is used to generate laser light; the first fiber collimator 5 is disposed in the output optical path of the SBS light source module; the beam splitter 6 is disposed in the output optical path of the first fiber collimator 5; the objective lens 7 is disposed in the transmission optical path of the beam splitter 6; the beam splitter 6 is used to process the optical path output by the first fiber collimator 5 to generate transmitted light, and the objective lens 7 is used to focus the transmitted light onto the test area of ​​the biological material sample 8 to generate stimulated Brillouin backscattered light.

[0019] The objective lens 7 is also disposed in the backscattered light path of the test area of ​​the biological material sample 8; the beam splitter 6 is also disposed in the output light path of the objective lens 7; the second fiber collimator 9 is disposed in the reflected light path of the beam splitter 6; the stimulated Brillouin backscattered light is transmitted to the objective lens 7 through the backscattered light path, and the objective lens 7 is also used to focus the stimulated Brillouin backscattered light onto the beam splitter 6, and the beam splitter 6 is also used to process the stimulated Brillouin backscattered light output from the objective lens 7 to generate reflected light, and the second fiber collimator 9 is used to collimate the reflected light.

[0020] The output of the second fiber collimator 9 is connected to the input of the viscoelasticity measurement module via a third fiber 10; the viscoelasticity measurement module is used to measure the viscoelasticity of the test area of ​​the biomaterial sample 8 based on the light transmitted from the third fiber 10.

[0021] The stimulated Brillouin scattering (SBS) light source module is used to generate pulsed lasers with precisely modulated frequency and intensity. Specifically, in another exemplary embodiment of this application, the SBS light source module includes: a laser 1, a first optical fiber 2, a modulator 3, and a second optical fiber 4; the output end of the laser 1 is connected to the input end of the modulator 3 through the first optical fiber 2, and the output end of the modulator 3 is connected to the input end of the first optical fiber collimator 5 through the second optical fiber 4. In related technologies, biomaterial viscoelasticity measurement systems are typically complex in structure and require high optical path stability. This application, by setting up an optical fiber structure, simplifies the process and reduces the requirement for optical path stability.

[0022] The viscoelasticity measurement module is used to analyze the mechanical information carried in the signal light. In another exemplary embodiment of this application, the viscoelasticity measurement module includes: a Brillouin spectrometer 11, an imaging device 12, and a data processing unit 13.

[0023] The output of the second fiber collimator 9 is connected to the Brillouin spectrometer 11 via the third fiber 10; the imaging device 12 is set on the image plane of the Brillouin spectrometer 11 and is used to acquire and record the spectral images generated by the Brillouin spectrometer 11; the data processing unit 13 is used to measure the viscoelasticity of the test area of ​​the biological material sample 8 based on the spectral images.

[0024] In another exemplary embodiment of this application, the laser 1 is a narrow linewidth continuous laser. The narrow linewidth continuous laser emits narrow linewidth continuous laser light.

[0025] In another exemplary embodiment of this application, the modulator 3 is an acousto-optic modulator. The acousto-optic modulator is driven by a radio frequency driver (external radio frequency signal) to convert continuous laser into pulsed laser (a pulse sequence with high peak power) and simultaneously apply an offset (fixed frequency shift) related to the driving radio frequency to the laser frequency.

[0026] In another exemplary embodiment of this application, both the first optical fiber 2 and the second optical fiber 4 are single-mode polarization-maintaining optical fibers.

[0027] In another exemplary embodiment of this application, the Brillouin spectrometer 11 is a Fabry-Perot interferometer or a virtual imaging phase array spectrometer.

[0028] In practical applications, the Brillouin spectrometer 11 is preferably a tandem scanning Fabry-Perot interferometer or a static spectrometer based on a virtual imaging phase array.

[0029] In another exemplary embodiment of this application, the imaging device 12 is a camera.

[0030] In practical applications, the system can be mounted on a conventional optical microscope. The objective lens 7 is a component of the microscope, and the stimulated Brillouin scattering source module and confocal excitation and collection unit (including the first fiber collimator 5, beam splitter 6, objective lens 7, second fiber collimator 9 and third fiber 10) are coupled to the microscope through an optical interface.

[0031] The working process of the biomaterial viscoelasticity measurement system based on stimulated Brillouin scattering provided in this application embodiment is as follows: Laser 1 emits a narrow-linewidth laser beam, the first fiber 2 transmits the laser beam to modulator 3, modulator 3 modulates the laser beam to obtain a pulse pump laser, the second fiber 4 transmits the pulse pump laser beam to the first fiber collimator 5, the first fiber collimator 5 collimates the pulse pump laser beam into high-quality spatial light; beam splitter 6 is used to split the spatial light beam to obtain a transmitted pump beam (the transmitted light mentioned above) and a reflected reference beam (which can be used for optical path monitoring or balance detection); objective lens 7 focuses the transmitted light onto the test area of ​​biomaterial sample 8 to excite stimulated Brillouin scattering to generate stimulated Brillouin backscattered light, objective lens 7 focuses the stimulated Brillouin backscattered light onto beam splitter 6, beam splitter 6 reflects the stimulated Brillouin backscattered light to obtain reflected light, the reflected light is precisely coupled into the third fiber 10 by the second fiber collimator 9, the third fiber 10 transmits the reflected light to Brillouin spectrometer 11.

[0032] The Brillouin spectrometer 11 can spatially disperse signal light containing different frequency components with high precision, allowing light of different frequencies to disperse spatially. An imaging device 12 is placed on the image plane of the spectrometer, recording the spatial distribution of light intensity to reconstruct the spectrum and obtain a dispersed spectral image. The spectral image obtained by the imaging device 12 is processed by a data processing unit 13. The data processing unit 13 is used to control the spectrometer scanning, acquire spectral data, and measure the viscoelasticity of the test area of ​​the biological material sample based on the spectral image.

[0033] This application can be applied to non-contact mechanical characterization of cells, biological tissues, biogels, biomimetic materials, and other biological samples. Its core lies in employing an all-fiber optical path, achieving a compact structure, easy integration, and high stability. Through a confocal design, it enhances spatial resolution and signal-to-noise ratio, and boasts strong practicality, enabling rapid measurement of the viscoelasticity (elastic modulus and viscous dissipation properties) of biomaterials, allowing for simultaneous and quantitative measurement of these properties.

[0034] This application has strong applicability to basic research. It directly addresses the intrinsic mechanical properties (high-frequency elasticity and viscosity) of biomaterials, providing a physical method for quantitative measurement at the microscale. The measurement results can be correlated with macroscopic rheology at the corresponding frequency scale, providing a powerful tool for understanding fundamental issues such as cell mechanics and biopolymer physics.

[0035] This application presents a highly stable and easily integrated system. The use of fiber optic transmission as the core optical path significantly enhances the system's resistance to environmental interference and its long-term stability. By coupling the fiber optic collimator to the microscope interface, this application can be easily loaded as a module onto commercial inverted or upright microscopes, utilizing their existing sample stage, illumination, and imaging functions, greatly reducing the barrier to entry for users.

[0036] This application features high spatial resolution and signal-to-noise ratio. By combining objective focusing and confocal fiber collection, sub-micron level lateral and axial spatial resolution is achieved. The confocal design effectively suppresses off-focal background noise, and combined with the signal enhancement effect of stimulated scattering, it is possible to obtain high-quality spectra within an integration time on the order of milliseconds to seconds, enabling high-precision measurement of viscoelastic parameters of biological materials, suitable for dynamic observation of living biological samples.

[0037] The technical features of the above embodiments can be combined in any way. For the sake of brevity, not all possible combinations of the technical features in the above embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0038] This document uses specific examples to illustrate the principles and implementation methods of this application. The descriptions of the above embodiments are only for the purpose of helping to understand the methods and core ideas of this application. Furthermore, those skilled in the art will recognize that, based on the ideas of this application, there will be changes in the specific implementation methods and application scope. Therefore, the content of this specification should not be construed as a limitation of this application.

Claims

1. A biomaterial viscoelasticity measurement system based on stimulated Brillouin scattering, characterized in that, The biomaterial viscoelasticity measurement system based on stimulated Brillouin scattering includes: Stimulated Brillouin scattering source module, first fiber collimator, beam splitter, objective lens, second fiber collimator, third fiber and viscoelastic measurement module; The stimulated Brillouin scattering (SBS) light source module is used to generate laser light; a first fiber collimator is set in the output optical path of the SBS light source module; a beam splitter is set in the output optical path of the first fiber collimator; the objective lens is set in the transmission optical path of the beam splitter; the beam splitter is used to process the optical path output by the first fiber collimator to generate transmitted light, and the objective lens is used to focus the transmitted light onto the test area of ​​the biological material sample to generate stimulated Brillouin backscattered light. The objective lens is also positioned in the backscattered light path of the test area of ​​the biological material sample; the beam splitter is also positioned in the output light path of the objective lens; the second fiber collimator is positioned in the reflected light path of the beam splitter; the stimulated Brillouin backscattered light is transmitted to the objective lens through the backscattered light path, the objective lens is also used to focus the stimulated Brillouin backscattered light onto the beam splitter, the beam splitter is also used to process the stimulated Brillouin backscattered light output from the objective lens to generate reflected light, and the second fiber collimator is used to collimate the reflected light; The output of the second fiber collimator is connected to the input of the viscoelastic measurement module via a third fiber. The viscoelastic measurement module is used to measure the viscoelasticity of the test area of ​​the biomaterial sample based on the light transmitted from the third fiber.

2. The biomaterial viscoelasticity measurement system based on stimulated Brillouin scattering according to claim 1, characterized in that, The stimulated Brillouin scattering light source module includes: The system comprises a laser, a first optical fiber, a modulator, and a second optical fiber; the output of the laser is connected to the input of the modulator via the first optical fiber, and the output of the modulator is connected to the input of the first optical fiber collimator via the second optical fiber.

3. The biomaterial viscoelasticity measurement system based on stimulated Brillouin scattering according to claim 2, characterized in that, The laser is a narrow linewidth continuous laser.

4. The biomaterial viscoelasticity measurement system based on stimulated Brillouin scattering according to claim 3, characterized in that, The modulator is an acousto-optic modulator.

5. The biomaterial viscoelasticity measurement system based on stimulated Brillouin scattering according to claim 2, characterized in that, Both the first optical fiber and the second optical fiber are single-mode polarization-maintaining fibers.

6. The biomaterial viscoelasticity measurement system based on stimulated Brillouin scattering according to claim 2, characterized in that, The viscoelasticity measurement module includes: a Brillouin spectrometer, an imaging device, and a data processing unit; The output of the second fiber collimator is connected to the Brillouin spectrometer via a third fiber; the imaging device is set on the image plane of the Brillouin spectrometer to acquire and record the spectral images generated by the Brillouin spectrometer, and the data processing unit is used to measure the viscoelasticity of the test area of ​​the biological material sample based on the spectral images.

7. The biomaterial viscoelasticity measurement system based on stimulated Brillouin scattering according to claim 6, characterized in that, The Brillouin spectrometer is a Fabry-Perot interferometer or a virtual imaging phase array spectrometer.

8. The biomaterial viscoelasticity measurement system based on stimulated Brillouin scattering according to claim 6, characterized in that, The imaging device is a camera.

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