Microfluidic chip for measuring multi-angle dynamic light scattering and application method thereof
By designing a microfluidic chip, adjusting the angle and position of the fiber optic sleeve, and combining it with a non-uniform width microfluidic channel, the problems of large size, high environmental sensitivity, and poor concentration adaptability of existing devices were solved, and efficient and stable multi-angle dynamic light scattering measurement was achieved.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- HUAZHONG UNIV OF SCI & TECH
- Filing Date
- 2024-01-29
- Publication Date
- 2026-05-19
AI Technical Summary
Existing multi-angle dynamic light scattering devices are large in size, poorly integrated, and their measurement results are easily affected by the external environment. They also have low concentration adaptability and cannot measure high-concentration samples.
A microfluidic chip was designed, including a microfluidic channel, an incident fiber sleeve, a receiving fiber sleeve, a fixed groove, and a fixed slider. By adjusting the rotation angle and position of the fiber sleeve, combined with the non-uniform width design of the microfluidic channel, the scattering angle and optical path can be adjusted, making it suitable for measuring samples of different concentrations.
It achieves miniaturized multi-angle dynamic light scattering measurement, reduces the influence of the external environment, adapts to a wide concentration range, can efficiently measure high-concentration samples, and improves the stability and accuracy of the measurement.
Smart Images
Figure CN117960262B_ABST
Abstract
Description
Technical Field
[0001] This application belongs to the field of optical measurement technology, and more specifically, relates to a microfluidic chip for measuring multi-angle dynamic light scattering and its application method. Background Technology
[0002] Dynamic light scattering (DLS) is an effective method for measuring the particle size distribution of nanoparticles and submicron particles. It obtains implicit particle size distribution information by calculating the autocorrelation function of light intensity, offering advantages such as simple sample preparation, non-destructive testing, high measurement accuracy, high speed, and non-contact operation. Multi-angle dynamic light scattering (DLS) is a technique that utilizes the different scattering characteristics of particles of different sizes at different scattering angles. It measures the autocorrelation function of light intensity from multiple different scattering angles and combines these measurements into a single data analysis using appropriate weighting coefficients to obtain the particle size distribution. Compared to single-angle DLS, multi-angle DLS can obtain more information about the scattered light from the particles, improving the robustness and accuracy of particle size distribution measurement.
[0003] Traditional multi-angle dynamic light scattering devices mostly operate by fixing the sample cell at the center of a rotating platform and rotating the detector 360° around the platform. These devices have drawbacks such as large size, poor integration, and susceptibility to external environmental influences. Furthermore, due to inherent limitations in their principle, traditional dynamic light scattering methods are only suitable for measuring dilute solutions to reduce the impact of multiple scattering on the measurement results. When dealing with high-concentration samples, dilution is required, but this process can easily disrupt the stability of the original particle system, causing the measurement results to deviate significantly from the true values and fail to reflect the actual situation. Summary of the Invention
[0004] In view of the above-mentioned defects or improvement needs of the prior art, this application provides a microfluidic chip for measuring multi-angle dynamic light scattering and its application method. The purpose is to solve the problems of existing multi-angle dynamic light scattering devices being large in size, poor in integration, easily affected by the external environment, low concentration adaptability, and unable to measure high-concentration samples.
[0005] To achieve the above objectives, in a first aspect, this application provides a microfluidic chip for measuring multi-angle dynamic light scattering, comprising a microfluidic channel, an incident fiber sleeve, a receiving fiber sleeve, a fixed groove, and a fixed slider, wherein:
[0006] The microfluidic channel is a straight channel, and the width of the microfluidic channel gradually narrows from one end to the other.
[0007] The fixed chute is arranged along the microfluidic channel, and the fixed chute restricts the fixed slider from moving back and forth along the fixed chute.
[0008] The top ends of the incident fiber sleeve and the receiving fiber sleeve are fixed on the fixed slider and are located on both sides of the microfluidic channel, respectively; the incident fiber sleeve and the receiving fiber sleeve rotate about the top end as the center.
[0009] Preferably, the fixed chute includes a first fixed chute and a second fixed chute, which are parallel to each other and arranged along the microfluidic channel, respectively located on both sides of the microfluidic channel; the fixed slider includes a first fixed slider and a second fixed slider, the first fixed chute restricts the first fixed slider from moving back and forth along the first fixed chute, and the second fixed chute restricts the second fixed slider from moving back and forth along the second fixed chute; the relative positions of the first fixed slider and the second fixed slider remain fixed.
[0010] Preferably, it further includes a solution injection channel and a solution outflow channel; the solution injection channel and the solution outflow channel are located at opposite ends of the microfluidic channel, the solution injection channel is used to inject the test solution into the microfluidic channel, and the solution outflow channel is used to discharge the test solution.
[0011] Preferably, it further includes an angle wheel scale, the center of which is fixed on a fixed slider, so that the angle wheel scale moves along a fixed groove with the fixed slider; the angle wheel scale is used to adjust and determine the rotation angle of the incident fiber sleeve and the receiving fiber sleeve.
[0012] Preferably, the scattering angle is changed by adjusting the rotation angle of the incident fiber sleeve and the receiving fiber sleeve.
[0013] Preferably, it also includes a position scale arranged next to a fixed slide groove, the position scale being used to adjust and determine the positions of the incident fiber sleeve and the receiving fiber sleeve.
[0014] Preferably, the scattered optical path is changed by adjusting the positions of the incident fiber sleeve and the receiving fiber sleeve.
[0015] Secondly, this application provides an application method for measuring multi-angle dynamic light scattering using a microfluidic chip, wherein the method is applied to any of the chips mentioned in the first aspect, specifically including:
[0016] The incident fiber and the receiving fiber are respectively embedded and fixed in the incident fiber sleeve and the receiving fiber sleeve;
[0017] Adjust the position of the fixed slider on the fixed groove according to the preset scattering optical path; adjust the rotation angle of the incident fiber sleeve and the receiving fiber sleeve according to the preset scattering angle.
[0018] The microfluidic channel is filled with the solution to be tested; a laser is incident on the solution to be tested and scatters, and the scattered light enters the receiving optical fiber and is transmitted to the optical measurement system to measure the change in the intensity of the scattered light;
[0019] By changing the rotation angles of the incident fiber sleeve and the receiving fiber sleeve, the intensity changes of scattered light at different angles are measured; the particle size distribution of the nanoparticles in the dissolved sample is then obtained through inversion.
[0020] Preferably, during the inversion process, the calculation process of the autocorrelation function of the scattered light intensity of the rod-shaped particles is as follows:
[0021] Second-order autocorrelation function of light intensity in the vertical direction and the second-order autocorrelation function of light intensity in the horizontal direction The expressions are as follows:
[0022]
[0023]
[0024] Where A is the light intensity autocorrelation function G (2) The baseline of (τ), B is the instrument factor, θ r The scattering angle is τ, the delay time is τ, and the normalized electric field autocorrelation function in the vertical direction is τ. and the autocorrelation function of the normalized electric field in the horizontal direction The ones are respectively:
[0025]
[0026]
[0027] Where exp() is an exponential function with base e; D t and D r These are the translational diffusion coefficient and the rotational diffusion coefficient, respectively; q is the amplitude of the scattering vector; k represents the order; S 2k Weighting coefficients:
[0028]
[0029] Where L is the length; P 2k (x) is a k-th order Legendre polynomial function, where x is the independent variable of the function; J0 is a 0-th order spherical Bessel function.
[0030] Preferably, during the inversion process, the calculation process of the autocorrelation function of the scattered light intensity of the spherical particles is as follows:
[0031] Second-order autocorrelation function of light intensity The expression is:
[0032]
[0033] Where A is the light intensity autocorrelation function G (2)The baseline of (τ), B is the instrument factor, θ r τ is the scattering angle, and τ is the delay time. It is in θ r The autocorrelation function of the normalized electric field at the angle.
[0034] Overall, the technical solutions conceived in this application have the following beneficial effects compared with the prior art:
[0035] (1) This application achieves the integration of scattering angle and incident optical path adjustment through the structural design of the flow control chip. The device of this application, in conjunction with optical fiber, realizes dynamic light scattering measurement, reduces system volume, avoids the influence of external environment, has a large concentration adaptation range, and realizes efficient measurement of high concentration samples by dynamic light scattering.
[0036] (2) In this application, the microfluidic channel is designed with non-uniform width. Its width gradually narrows from the injection channel to the outflow channel. The position of the incident light incident on the microfluidic channel is changed by the up-and-down moving slider, thereby controlling the size of the scattered light path. Different scattered light paths are suitable for samples of different concentrations, so that the system has a large concentration adaptability range.
[0037] (3) In this application, the incident fiber sleeve and the receiving fiber sleeve move together along the fixed slide groove and the rotation angle can be adjusted, thereby adjusting the rotation angle of the incident fiber and the receiving fiber, thereby realizing the detection of polarized scattered light at multiple angles.
[0038] (4) This application can measure the shape parameters of spherical and rod-shaped particles. It has fast measurement speed, good stability, high accuracy and high concentration adaptability. It can measure particle groups with a wide distribution of particle size from nanometer to micrometer. Attached Figure Description
[0039] Figure 1 This is a schematic diagram of the structure of a microfluidic chip for measuring multi-angle dynamic light scattering provided in an embodiment of this application;
[0040] In the attached diagram: 1. Angle wheel scale; 2. Fixed chute; 3. Solution outflow channel; 4. Solution channel; 5. Incident fiber sleeve; 6. Solution injection channel; 7. Position scale; 8. Receiving fiber sleeve; 9. Fixed slider. Detailed Implementation
[0041] To make the objectives, technical solutions, and advantages of this application clearer, the following detailed description is provided in conjunction with the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative and not intended to limit the scope of this application.
[0042] The technical solutions provided in the embodiments of this application are described below.
[0043] like Figure 1 The diagram shows the structure of a microfluidic chip for measuring dynamic light scattering from multiple angles, provided in an embodiment of this application. The chip includes a detection module and a microfluidic channel module.
[0044] The detection module includes an angle wheel scale 1, a fixed slide 2, an incident fiber sleeve 5, a position scale 7, a receiving fiber sleeve 8, and a fixed slider 9.
[0045] The fixed chute 2 includes two parallel chutes, the first chute and the second chute, which are distributed along the direction of the microfluidic channel 4 and located on both sides of the microfluidic channel 4.
[0046] Angle wheel scale 1, incident fiber sleeve 5 and receiving fiber sleeve 8 move together along fixed slide 2 to adjust and determine the rotation angle of the incident fiber and the receiving fiber.
[0047] The fixed slide 2 is used to restrict the movement of the fixed slider 9, which can move up and down along the fixed slide 2. The fixed slider 9 includes two relatively fixed sliders: a first slider and a second slider. The first slider moves up and down along the first slide 2, and the second slider moves up and down along the second slide 2.
[0048] The top ends of the incident fiber sleeve 5 and the receiving fiber sleeve 8 are respectively fixed on two sliders, so that the incident fiber sleeve 5 and the receiving fiber sleeve 8 can move up and down in the vertical direction along the fixed slide groove 2 or rotate around the top slider as the center.
[0049] The incident fiber sleeve 5 and the receiving fiber sleeve 8 are used to embed and fix the incident fiber and the receiving fiber. When the incident fiber sleeve 5 and the receiving fiber sleeve 8 move in the vertical direction, they change the position of the incident light incident on the microfluidic channel, thereby controlling the change in the size of the scattering volume. Different scattering optical paths are suitable for samples of different concentrations. When the incident fiber sleeve 5 and the receiving fiber sleeve 8 rotate around the slider at the top, they change the scattering angle, thereby realizing multi-angle detection of dynamic light scattering.
[0050] Position scale 7 is set next to the fixed slide 2 to adjust and determine the positions of the incident fiber sleeve 5 and the receiving fiber sleeve 8.
[0051] The microfluidic channel module includes a solution outflow channel 3, a microfluidic channel 4, and a solution injection channel 6.
[0052] The microfluidic channel 4 is set inside the microfluidic chip and is used to hold the solution to be tested. The microfluidic channel 4 is set as a straight channel with a non-uniform width design. Its width gradually narrows from the injection channel to the outflow channel. That is, the microfluidic channel 4 has different widths at different positions in the vertical direction and has different scattering optical paths.
[0053] The solution injection channel 6 and the solution outflow channel 3 are respectively located at both ends of the microfluidic channel 4, and are used to inject the test solution into the microfluidic channel 4 and to remove the test solution after measurement.
[0054] The working process of the microfluidic chip in the dynamic light scattering system is as follows:
[0055] (1) Using a laser to generate an incident laser beam;
[0056] The incident fiber is connected to the laser. The vertically polarized light emitted by the laser is coupled into the incident fiber and transmitted through the incident fiber. After the laser reaches the end face of the incident fiber, it is focused and collimated by the integrated self-focusing lens.
[0057] (2) Select the appropriate scattering angle and scattering optical path according to the sample being measured;
[0058] The incident fiber and the receiving fiber are respectively embedded and fixed in the incident fiber sleeve and the receiving fiber sleeve. Next, the vertical position of the sleeve is adjusted by using the fixed slider in front of the sleeve to change the scattered optical path, thereby selecting a scattered optical path size suitable for the current sample concentration. Then, the incident fiber sleeve and the receiving fiber sleeve are rotated around the fixed slider to adjust the scattered light receiving angle to the selected angle.
[0059] (3) Measurement of the scattered light intensity of the nanoparticle suspension to be tested;
[0060] The solution to be tested is injected into the solution injection channel to fill the microfluidic channel. Subsequently, a focused and collimated laser beam is incident on the solution. The laser beam is scattered, and the scattered light is coupled into the receiving fiber by a self-focusing lens integrated into the end face of the receiving fiber. The scattered light is then transmitted along the receiving fiber into the subsequent optical measurement system to obtain the time-domain signal of the light intensity change. The operation of adjusting the scattered light receiving angle in step (2) is repeated to measure the scattered light signal at other selected angles.
[0061] (4) Calculation of the autocorrelation function of scattered light intensity;
[0062] (41) Calculation of the autocorrelation function of the scattered light intensity of spherical particles;
[0063] Based on step (3), the information on the change of light intensity of the scattered light from the sample at different angles over time is obtained and transmitted to the subsequent digital correlator to calculate the second-order light intensity autocorrelation function. Second-order autocorrelation function of light intensity The expression is:
[0064]
[0065] Where A is the light intensity autocorrelation function G (2)The baseline of (θ), B is the instrument factor, θ r τ is the scattering angle, and τ is the delay time. It is in θ r The autocorrelation function of the normalized electric field at the angle.
[0066] (42) Calculation of the autocorrelation function of the scattered light intensity of rod-shaped particles;
[0067] Based on step (3), the intensity of the scattered light from the sample at different angles changes with time. The scattered light from the vertically polarized and horizontally polarized portions is received and transmitted to a subsequent digital correlator to calculate the second-order autocorrelation functions of the intensity in the vertical and horizontal directions. and The expressions for the second-order autocorrelation function of light intensity in the vertical direction and the second-order autocorrelation function of light intensity in the horizontal direction are as follows:
[0068]
[0069]
[0070] Normalized electric field autocorrelation function in the vertical direction and the autocorrelation function of the normalized electric field in the horizontal direction The expressions are as follows:
[0071]
[0072]
[0073] Among them, D t and D r These are the translational diffusion coefficient and the rotational diffusion coefficient, S. 2k The weighting coefficient is expressed as follows:
[0074]
[0075] Where L is the length, P 2k (x) is a k-th order Legendre polynomial function, and J0 is a 0-th order spherical Bessel function.
[0076] (5) The autocorrelation function of the electric field is sent to the subsequent calculation and processing unit, and the particle size distribution and particle shape information of the nanoparticles in the nanoparticle suspension to be measured are calculated using the trained neural network. According to the measured particle size distribution range of the sample particle group, the weight of the scattered light at each angle is adjusted. The initial weight of each angle is 1. For nano-sized particle groups, the weight of the scattered light at large angles (greater than 90°) is reduced to 0.5. For submicron-sized particle groups, the weight of the scattered light at large angles (greater than 90°) is reduced to 0.1. The above operation is repeated to retrieve a more accurate particle size distribution of the sample.
[0077] It should be understood that expressions such as “comprising” and “may include” used in this application indicate the existence of the disclosed functions, operations, or constituent elements, and do not limit one or more additional functions, operations, and constituent elements. In this application, terms such as “comprising” and / or “having” are to be interpreted as indicating a particular characteristic, number, operation, constituent element, component, or combination thereof, but not to exclude the existence or possibility of adding one or more other characteristics, numbers, operations, constituent elements, components, or combinations thereof.
[0078] In the description of the embodiments of this application, it should be noted that, unless otherwise explicitly specified and limited, the term "connection" should be interpreted broadly. For example, "connection" can be a detachable connection or a non-detachable connection; it can be a direct connection or an indirect connection through an intermediate medium. "Fixed connection" refers to a connection where the relative positional relationship remains unchanged after connection. "Rotary connection" refers to a connection where the components can rotate relative to each other after connection. "Sliding connection" refers to a connection where the components can slide relative to each other after connection. The directional terms mentioned in the embodiments of this application, such as "top," "bottom," "inner," "outer," "left," and "right," are only for reference to the directions in the accompanying drawings. Therefore, the directional terms used are for better and clearer explanation and understanding of the embodiments of this application, and are not intended to indicate or imply that the device or component referred to must have a specific orientation, or be constructed and operated in a specific orientation. Therefore, they should not be construed as limitations on the embodiments of this application.
[0079] Furthermore, the mathematical concepts mentioned in the embodiments of this application, such as symmetry, equality, parallelism, and perpendicularity, are limitations specific to the current technological level, rather than absolute and strict mathematical definitions. Slight deviations are permissible; approximations of symmetry, equality, parallelism, and perpendicularity are all acceptable. For example, "A and B are parallel" means that A and B are parallel or approximately parallel, and the angle between A and B can be between 0 and 10 degrees. "A and B are perpendicular" means that A and B are perpendicular or approximately perpendicular, and the angle between A and B can be between 80 and 100 degrees.
[0080] The above content is readily understood by those skilled in the art. The above description is merely a preferred embodiment of this application and is not intended to limit this application. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of this application should be included within the protection scope of this application.
Claims
1. A microfluidic chip for measuring multi-angle dynamic light scattering, characterized in that, It includes a microfluidic channel, an incident fiber sleeve, a receiving fiber sleeve, a fixed groove, and a fixed slider, wherein: The microfluidic channel is a straight channel, and the width of the microfluidic channel gradually narrows from one end to the other. The fixed chute is arranged along the microfluidic channel, and the fixed chute restricts the fixed slider from moving back and forth along the fixed chute. The top ends of the incident fiber sleeve and the receiving fiber sleeve are connected to the fixed slider and are located on both sides of the microfluidic channel, respectively; the incident fiber sleeve and the receiving fiber sleeve rotate about the top end as the center. The fixed chute includes a first fixed chute and a second fixed chute, which are parallel to each other and arranged along the microfluidic channel, respectively located on both sides of the microfluidic channel; the fixed slider includes a first fixed slider and a second fixed slider, the first fixed chute restricts the first fixed slider from moving back and forth along the first fixed chute, and the second fixed chute restricts the second fixed slider from moving back and forth along the second fixed chute; the relative positions of the first fixed slider and the second fixed slider remain fixed.
2. The chip according to claim 1, characterized in that, It also includes a solution injection channel and a solution outflow channel; the solution injection channel and the solution outflow channel are located at the two ends of the microfluidic channel, respectively. The solution injection channel is used to inject the test solution into the microfluidic channel, and the solution outflow channel is used to discharge the test solution.
3. The chip according to claim 1, characterized in that, It also includes an angle wheel scale, the center of which is fixed on a fixed slider, so that the angle wheel scale moves along a fixed groove with the fixed slider; the angle wheel scale is used to adjust and determine the rotation angle of the incident fiber sleeve and the receiving fiber sleeve.
4. The chip according to claim 3, characterized in that, The scattering angle is changed by adjusting the rotation angle of the incident fiber sleeve and the receiving fiber sleeve.
5. The chip according to claim 1, characterized in that, It also includes a position scale arranged next to a fixed slide, which is used to adjust and determine the positions of the incident fiber sleeve and the receiving fiber sleeve.
6. The chip according to claim 1, characterized in that, Adjusting the positions of the incident fiber sleeve and the receiving fiber sleeve changes the scattered optical path.
7. A method for applying a microfluidic chip to measure multi-angle dynamic light scattering, characterized in that, The method is applied to any one of the chips of claims 1-6, specifically including: The incident fiber and the receiving fiber are respectively embedded and fixed in the incident fiber sleeve and the receiving fiber sleeve; Adjust the position of the fixed slider on the fixed groove according to the preset scattering optical path; adjust the rotation angle of the incident fiber sleeve and the receiving fiber sleeve according to the preset scattering angle. The microfluidic channel is filled with the solution to be tested; a laser is incident on the solution to be tested and scatters, and the scattered light enters the receiving optical fiber and is transmitted to the optical measurement system to measure the change in the intensity of the scattered light; By changing the rotation angles of the incident fiber sleeve and the receiving fiber sleeve, the intensity changes of scattered light at different angles are measured; the particle size distribution of nanoparticles in the solution to be tested is obtained by inversion.