Automated extraction device for biological samples

Abstract

The invention provides an automatic extraction device for a biological sample, and the device comprises a piezoelectric substrate which is made of a piezoelectric material and comprises a sample placement area used for storing a biological sample bearing container, and a biological sample solution to be enriched is placed in the biological sample bearing container; the transduction module is arranged on the piezoelectric substrate and is used for converting the electric signal into mechanical vibration so as to generate surface acoustic waves; the extraction module faces the sample placement area and is used for extracting the enriched target concentrated sample; the control module is used for controlling the transduction module to generate surface acoustic waves and enriching the biological sample in the biological sample solution in the biological sample bearing container under the action of the surface acoustic waves to form a target concentrated sample; and acquiring the vibration shape of the surface acoustic wave and the liquid level characteristic information of the biological sample solution, and determining the enrichment position information corresponding to the target concentrated sample in the biological sample bearing container according to the vibration shape and the liquid level characteristic information so as to complete the automatic extraction of the target concentrated sample.

Description

Technical Field

[0001] The invention belongs to the technical field of acoustofluidics, and in particular relates to an automatic extraction device for biological samples. Background Art

[0002] With the development of microfluidics and piezoelectric materials, the technology of using surface acoustic waves (SAW) to enrich biological samples has gradually attracted attention. Surface acoustic waves can precisely manipulate biological samples at a microscale through mechanical vibrations to achieve efficient and high-precision enrichment. However, most known surface acoustic wave automated extraction devices still require manual intervention, such as manually adjusting electrical signals, manually extracting enriched samples, etc., resulting in unstable enrichment effects. Summary of the invention

[0003] The present application provides an automated extraction device for biological samples, aiming to solve the problem that most conventional known surface acoustic wave automated extraction devices still require manual intervention, such as manual adjustment of electrical signals, manual extraction of enriched samples, etc., resulting in unstable enrichment effects.

[0004] The present application provides an automated extraction device for biological samples, comprising:

[0005] A piezoelectric substrate, wherein the piezoelectric substrate is made of a piezoelectric material and comprises a sample placement area, wherein the sample placement area is used to store a biological sample holding container, wherein a biological sample solution to be enriched is placed in the biological sample holding container;

[0006] A transducer module, which is disposed on the piezoelectric substrate and is used to convert an electrical signal into a mechanical vibration to generate a surface acoustic wave;

[0007] An extraction module, the extraction module is facing the sample placement area and is used to extract the enriched target concentrated sample;

[0008] A control module, wherein the control module controls the transducer module to generate the surface acoustic wave, so that the biological sample in the biological sample solution is enriched in the biological sample holding container under the action of the surface acoustic wave to form the target concentrated sample; the control module obtains the vibration shape of the surface acoustic wave and the liquid surface characteristic information of the biological sample solution, and confirms the enrichment position information corresponding to the target concentrated sample in the biological sample holding container according to the vibration shape and the liquid surface characteristic information, so as to control the extraction module to complete the automatic extraction of the target concentrated sample according to the enrichment position information.

[0009] This application provides an automated extraction device for biological samples, which aims to solve the problem that most conventional known surface acoustic wave automated extraction devices still require manual intervention, such as manual adjustment of electrical signals, manual extraction of enriched samples, etc., resulting in unstable enrichment effects. The technical content of the automated extraction device mainly includes the following parts:

[0010] The piezoelectric substrate is made of piezoelectric material and has a sample placement area for storing a biological sample holding container. The biological sample holding container is filled with a biological sample solution to be enriched. The transducer module is arranged on the piezoelectric substrate, and is used to convert the electrical signal into mechanical vibration, thereby generating a surface acoustic wave. The extraction module faces the sample placement area, and is used to extract the enriched target concentrated sample. The control module is responsible for controlling the transducer module to generate surface acoustic waves, so that the biological sample in the biological sample solution is enriched in the biological sample holding container under the action of the surface acoustic wave to form a target concentrated sample. The control module confirms the enrichment position of the target concentrated sample by obtaining the vibration shape of the surface acoustic wave and the liquid surface characteristic information of the biological sample solution, and then controls the extraction module to complete the automatic extraction.

[0011] The piezoelectric substrate provides a stable platform for placing biological sample containers. The transducer module converts electrical signals into mechanical vibrations to generate surface acoustic waves to enrich biological samples. The extraction module automatically extracts the enriched target concentrated sample. The control module integrates multiple sensors and control logic to ensure the stability and accuracy of the enrichment and extraction process.

[0012] Through automated control, the need for manual adjustment of electrical signals and manual extraction of enriched samples is reduced, reducing operational complexity and human errors. The control module can monitor and adjust the vibration shape and liquid surface characteristics of the surface acoustic wave in real time to ensure that the biological sample is enriched under optimal conditions and improve the stability and reliability of the enrichment effect. The automated extraction module can quickly extract the target concentrated sample after confirming the enrichment position, shortening the operation time and improving the processing efficiency. The device can adapt to different types of biological sample solutions and has good versatility and flexibility. Automated control makes the enrichment and extraction process highly repeatable, and the processing results are more consistent each time, which is suitable for large-scale biological sample processing and laboratory automation processes. Reducing manual operations reduces the risk of contamination and ensures the purity and safety of biological samples.

[0013] In summary, the device has important application value in the field of biological sample processing, and is especially suitable for modern laboratory environments that require efficient, stable enrichment and automated operations. BRIEF DESCRIPTION OF THE DRAWINGS

[0014] In order to more clearly illustrate the technical solutions of the embodiments of the present application, the drawings required for use in the description of the embodiments will be briefly introduced below. Obviously, the drawings described below are some embodiments of the present application. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.

[0015] Figure 1 It is a structural schematic diagram of an automated extraction device provided in an embodiment of the present application;

[0016] Figure 2 This is a schematic diagram of the effect of surface wave frequency on flow field provided in an embodiment of the present application;

[0017] Figure 3 This is a schematic diagram of the effect of particle size on enrichment position provided in an embodiment of the present application;

[0018] Figure 4 This is a schematic diagram of the use of an automated extraction device provided in an embodiment of the present application.

[0019] Description of main components and symbols:

[0020] 10. Automated extraction device; 11. Piezoelectric substrate; 111. Biological sample carrying container; 112. Biological sample solution; 12. Transducer module; 13. Control module; 14. Pressing module.

[0021] It should be understood that the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the present application. DETAILED DESCRIPTION

[0022] The following will be combined with the drawings in the embodiments of the present application to clearly and completely describe the technical solutions in the embodiments of the present application. Obviously, the described embodiments are part of the embodiments of the present application, not all of the embodiments. Based on the embodiments in the present application, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of this application.

[0023] The flowcharts shown in the accompanying drawings are only examples and do not necessarily include all the contents and operations / steps, nor must they be executed in the order described. For example, some operations / steps may also be decomposed, combined or partially merged, so the actual execution order may change according to actual conditions.

[0024] It should be understood that the terms used in this application specification are only for the purpose of describing specific embodiments and are not intended to limit the application. As used in this application specification and the appended claims, unless the context clearly indicates otherwise, the singular forms "a", "an" and "the" are intended to include plural forms.

[0025] It should be further understood that the term “and / or” used in the specification and appended claims refers to any combination and all possible combinations of one or more of the associated listed items, and includes these combinations.

[0026] In conjunction with the accompanying drawings, some embodiments of the present application are described in detail below. In the absence of conflict, the following embodiments and features in the embodiments can be combined with each other.

[0027] With the development of microfluidics and piezoelectric materials, the technology of using surface acoustic waves (SAW) to enrich biological samples has gradually attracted attention. Surface acoustic waves can precisely manipulate biological samples at a microscale through mechanical vibrations to achieve efficient and high-precision enrichment. However, most known surface acoustic wave automated extraction devices still require manual intervention, such as manually adjusting electrical signals, manually extracting enriched samples, etc., resulting in unstable enrichment effects.

[0028] To solve the above problems, please refer to Figure 1 The automatic extraction device 10 for biological samples provided in the embodiment of the present application includes: a piezoelectric substrate 11, which is made of piezoelectric material and includes a sample placement area, wherein the sample placement area is used to store a biological sample holding container 111, wherein the biological sample holding container 111 contains a biological sample solution 112 to be enriched; a transducer module 12, wherein the transducer module 12 is disposed on the piezoelectric substrate 11 and is used to convert an electrical signal into a mechanical vibration to generate an acoustic surface wave; an extraction module (not shown in the figure), wherein the extraction module faces the sample placement area and is used to extract the enriched target concentrated sample; a control module Block 13, the control module 13 controls the transducer module 12 to generate the surface acoustic wave, so that the biological sample in the biological sample solution 112 is enriched in the biological sample holding container 111 under the action of the surface acoustic wave to form the target concentrated sample; the control module 13 obtains the vibration shape of the surface acoustic wave and the liquid surface characteristic information of the biological sample solution 112, and confirms the enrichment position information corresponding to the target concentrated sample in the biological sample holding container 111 according to the vibration shape and the liquid surface characteristic information, so as to control the extraction module to complete the automatic extraction of the target concentrated sample according to the enrichment position information.

[0029] Specifically, the embodiment of the present application provides an automatic extraction device 10 for biological samples, the core components of which include a piezoelectric substrate 11, a transducer module 12, an extraction module and a control module 13. The main technical contents of the device are as follows:

[0030] Piezoelectric substrate 11: Made of piezoelectric material, it includes a sample placement area for storing biological sample holding containers 111, such as microfluidic chips or microplates. Biological sample solutions 112 are placed in these containers to be enriched.

[0031] Transducer module 12: It is arranged on the piezoelectric substrate 11 and can convert the electrical signal into mechanical vibration, thereby generating surface acoustic wave (SAW). By adjusting the frequency and amplitude of the electrical signal, the biological sample can be precisely manipulated on a microscale to achieve efficient enrichment.

[0032] Extraction module: facing the sample placement area, responsible for automatically extracting the enriched target concentrated sample under the instruction of the control module 13. This module can be a micro-needle, micro-pump or other forms of micro-extraction devices.

[0033] Control module 13: It is the intelligent core of the whole device, responsible for controlling the transducer module 12 to generate surface acoustic waves, determining the enrichment position information of the target concentrated sample by analyzing the vibration shape and liquid surface characteristic information, and controlling the extraction module to complete the automatic extraction accordingly. The control module 13 can use sensors and algorithms to monitor and adjust the enrichment process in real time to ensure the stability and efficiency of the enrichment effect.

[0034] Suppose we need to enrich a specific cell type, such as white blood cells, from a blood sample. The operation process can be:

[0035] Prepare the sample: place the blood sample solution in a biological sample holding container 111 (such as a microfluidic chip), and place the container in the sample placement area of ​​the piezoelectric substrate 11 .

[0036] Start-up device: The control module 13 is powered on and starts to send electrical signals to the transducer module 12. The transducer module 12 converts the electrical signals into mechanical vibrations to generate surface acoustic waves.

[0037] Enrichment process: The surface acoustic wave propagates in the microfluidic chip, and the white blood cells in the blood sample are enriched in a specific area through vibration. The control module 13 detects the vibration shape of the surface acoustic wave and the liquid surface characteristic information in real time through the sensor to ensure that the white blood cells are enriched in the predetermined position.

[0038] Confirming the enrichment position: The control module 13 determines the exact position of the target concentrated sample (enriched leukocytes) based on the detected vibration shape and liquid surface characteristic information.

[0039] Automated extraction: The control module 13 instructs the extraction module (such as a microneedle) to extract the target concentrated sample from the enrichment location and transfer it to another container or detection device for subsequent analysis or processing.

[0040] The entire enrichment and extraction process does not require human intervention, and the intelligent scheduling of the control module 13 realizes automated operation, reduces human errors, and improves the stability of the enrichment effect. Utilizing the precise manipulation ability of surface acoustic waves, biological samples can be efficiently enriched on a microscale, and the purity and concentration of the target concentrated samples are higher, which is conducive to subsequent high-precision analysis and detection. The control module 13 can monitor the vibration shape and liquid surface characteristic information of the surface acoustic wave in real time, and dynamically adjust the parameters of the electrical signal according to this information to ensure the optimal effect of the enrichment process. The device is not only suitable for the enrichment of cells, but also can be used for the enrichment of other biological samples, such as proteins, DNA, RNA, etc., and has broad application prospects. Compared with traditional manual enrichment methods, the device is easy to operate, has high enrichment efficiency, can greatly reduce experimental time and labor costs, and is suitable for large-scale production and clinical applications.

[0041] In summary, it can be seen that the automatic extraction device 10 for biological samples has significant technical advantages and application prospects, and can play an important role in the biomedical field.

[0042] Among them, the piezoelectric substrate 11 can be any one of quartz, lithium niobate and lead zirconate titanate (PZT) according to the needs. For example, quartz has good thermal stability, piezoelectric effect and high mechanical strength, and is often used in high-frequency surface acoustic wave devices. Lithium niobate has high sensitivity and good frequency stability, and is suitable for scenes requiring high-precision control. Lead zirconate titanate (PZT) has a large piezoelectric constant and a high electromechanical coupling coefficient, and is suitable for occasions requiring higher power output. The actual piezoelectric substrate 11 can be selected according to the use requirements, and the embodiments of the present application are not limited to this.

[0043] At the same time, the liquid surface characteristics formed during the sample addition process affect the enrichment efficiency and the final enrichment position. For example, if the liquid surface is high on one side and low on the other, the enrichment position is not at the center of the circle; because the liquid surface shakes and changes, the enrichment position will also change. Using visual recognition of liquid surface characteristics can be used as an indicator to determine whether particles can be enriched.

[0044] In some embodiments, the control module 13 also obtains the frequency corresponding to the surface acoustic wave, the sample volume corresponding to each addition of the biological sample carrying solution, and the size of the micro-nanoparticles contained in the biological sample solution 112; the control module 13 determines the enrichment position information based on the frequency, sample volume, micro-nanoparticle size, vibration shape and the liquid surface characteristic information.

[0045] The control module 13 not only obtains the vibration shape and liquid surface characteristic information of the surface acoustic wave, but also can monitor the frequency of the surface acoustic wave. Frequency is one of the key parameters that affect the characteristics of the surface acoustic wave and the enrichment effect of the biological sample. The control module 13 can obtain the volume of the biological sample solution 112 added each time. The added volume will affect the height of the liquid level and the propagation path of the surface acoustic wave, thereby affecting the enrichment effect. The control module 13 can also obtain the size of the micro-nano particles contained in the biological sample solution 112. Different particle sizes respond differently to the surface acoustic wave, so the particle size is an important parameter that affects the efficiency and accuracy of the enrichment.

[0046] The control module 13 comprehensively analyzes the influence of these parameters on the enrichment effect based on the acquired frequency, sample volume, micro-nano particle size, vibration shape and liquid surface characteristic information, thereby determining the accurate enrichment position of the target concentrated sample. The control module 13 integrates an intelligent algorithm, which can adjust the frequency and amplitude of the electrical signal in real time according to the above parameters to ensure that the surface acoustic wave works under the best conditions, thereby achieving high-efficiency and high-precision enrichment.

[0047] like Figure 2 As shown, Figure 2 The effect of different surface wave frequencies on the flow field. By monitoring and adjusting the frequency of the surface acoustic wave, it can be ensured that the surface acoustic wave works at the optimal frequency, thereby improving the enrichment effect of biological samples. The optimal frequency can make the vibration energy of the surface acoustic wave most effectively transmitted to the biological sample, achieving efficient enrichment. The monitoring and control of the sample volume ensures that the liquid level and shape of each sample are consistent, reducing the interference of the liquid level change on the propagation path of the surface acoustic wave, and improving the stability and accuracy of the enrichment. Figure 3 As shown, the control module 13 can adjust the parameters of the surface acoustic wave according to the size of the micro-nano particles in the biological sample solution 112, so that particles of different sizes can be effectively enriched. This adaptability improves the efficiency of enrichment, especially for complex samples. By real-time monitoring and adjusting the electrical signal, the control module 13 can dynamically optimize the enrichment process to avoid the problem of insufficient enrichment or unstable enrichment effect caused by parameter mismatch.

[0048] The multi-parameter monitoring and intelligent algorithm of the control module 13 make the entire enrichment process more automated, reducing the manual intervention process, thereby greatly reducing human errors. Due to the precise control of parameters and automated operation, the enrichment process of the device has high repeatability and is suitable for large-scale and high-throughput biological sample enrichment.

[0049] Through multi-parameter comprehensive analysis, the device can adapt to a variety of biological samples and different experimental conditions, with higher versatility and flexibility. It can handle micro-nanoparticles of different sizes, expanding the scope of application and being suitable for the enrichment of various biological samples such as cells, proteins, DNA, and RNA.

[0050] The user only needs to add the biological sample solution 112 into the carrying container and start the device to complete the enrichment and extraction process. The operation is simple and suitable for laboratory technicians and clinical applications. The enrichment and extraction process is completed in a short time, which improves the experimental efficiency and shortens the research and detection time.

[0051] Assuming that you need to enrich specific white blood cells from a blood sample, the following specific operations can be performed using the provided device:

[0052] A certain volume of blood sample solution is added to the biological sample holding container 111, and it is placed in the sample placement area of ​​the piezoelectric substrate 11. The control module 13 is powered on and starts to send electrical signals. The control module 13 monitors the frequency, vibration shape and liquid surface characteristic information of the surface acoustic wave in real time. The control module 13 simultaneously monitors the sample volume and the size of the white blood cell particles in the solution. The control module 13 comprehensively analyzes and adjusts the parameters of the electrical signal according to the frequency, sample volume, white blood cell particle size, vibration shape and liquid surface characteristic information. The surface acoustic wave enriches the white blood cells in the blood sample to a specific area, such as one side of the container or a specific micropore, through mechanical vibration. The control module 13 determines the specific location of the white blood cell enrichment through multi-parameter analysis and records it. The control module 13 instructs the extraction module (such as a microneedle or a micropump) to extract the target concentrated sample (enriched white blood cells) from the determined enrichment location and transfer it to another container or detection device.

[0053] By introducing the monitoring and control of frequency, sample volume, and micro / nanoparticle size, the accuracy and efficiency of biological sample enrichment are significantly improved, human errors are reduced, and the applicability and user experience of the device are enhanced. This multi-parameter comprehensive analysis method provides reliable technical support for biomedical research and clinical applications.

[0054] Exemplarily, the formula corresponding to the enriched position information may include:

[0055] x=a·f+b·V+c·D+d·φ+e·1 / h+g·R+i;

[0056] a is the coefficient of frequency f, which is used to describe the effect of frequency on the enrichment position. b is the coefficient of sample volume V, which describes the effect of sample volume on the enrichment position. c is the coefficient of micro-nanoparticle size D, which describes the effect of particle size on the enrichment position. d is the coefficient of vibration shape φ, which describes the effect of vibration shape on the enrichment position. e is the reciprocal coefficient of liquid level h, which describes the effect of the reciprocal of liquid level on the enrichment position. g is the coefficient of the curvature radius R of the liquid surface shape, which describes the effect of the liquid surface shape on the enrichment position. i is a constant term, which represents the default enrichment position when all parameters are zero.

[0057] High-frequency surface acoustic waves are usually beneficial for more precise manipulation, so a is usually a positive value, indicating that the frequency has a positive correlation with the enrichment position. The larger the sample volume, the higher the liquid level, and the propagation path and energy distribution of the surface acoustic wave change, so b is usually a negative value, indicating that the sample volume has a negative correlation with the enrichment position. Smaller micro-nanoparticles are more easily enriched by surface acoustic waves, so c is usually a negative value, indicating that the particle size has a negative correlation with the enrichment position. The vibration shape directly affects the propagation mode of the surface acoustic wave, so d is usually a positive value, indicating that the vibration shape has a positive correlation with the enrichment position. The reciprocal of the liquid level can better describe the effect of the liquid surface on the propagation of the surface acoustic wave, so e is usually a positive value, indicating that the reciprocal of the liquid level has a positive correlation with the enrichment position. The radius of curvature of the liquid surface shape affects the reflection and refraction of the surface acoustic wave on the liquid surface, so g is usually a negative value, indicating that the radius of curvature of the liquid surface shape has a negative correlation with the enrichment position. The constant term i represents the default enrichment position when all parameters are zero, which can be adjusted according to actual experimental conditions. The above formula is fitted by experimental data to determine the specific values ​​of each coefficient, and linear regression, nonlinear regression or machine learning algorithm can be used for fitting. The formula can more accurately predict the enrichment position information of the surface acoustic wave in the biological sample holding container 111 through comprehensive analysis of multiple parameters, thereby improving the enrichment accuracy and efficiency. Through fitting and verification of experimental data, the coefficients of the formula can be further optimized to make it more reliable and effective in practical applications.

[0058] Exemplarily, the control module 13 determines the flow field characteristics corresponding to the biological sample solution 112 according to the frequency and the sample volume, so as to determine the number of eddies in the biological sample solution 112 under the action of the surface acoustic wave according to the flow field characteristics; the control module 13 determines the enrichment position information according to the number of eddies, the size of micro-nanoparticles, the vibration shape and the liquid surface characteristic information.

[0059] The control module 13 further refines the method for determining the enriched position information through comprehensive analysis of multiple parameters. The specific technical content includes the following steps:

[0060] Frequency and sample volume: The control module 13 determines the flow field characteristics of the biological sample solution 112 according to the frequency of the surface acoustic wave and the sample volume of the biological sample solution 112. The frequency affects the propagation speed and energy distribution of the surface acoustic wave, while the sample volume affects the height and shape of the liquid surface, which together determine the flow field distribution in the solution.

[0061] The control module 13 calculates the number of eddies in the biological sample solution 112 under the action of the surface acoustic wave according to the determined flow field characteristics. The eddies are local vortices generated by the surface acoustic wave in the solution, which can promote the enrichment of the biological sample. The number and distribution pattern of the eddies have a significant impact on the enrichment effect.

[0062] The control module 13 comprehensively considers the number of eddies, the size of micro-nanoparticles, the vibration shape of the surface acoustic wave and the liquid surface characteristic information (such as the liquid level height and the curvature radius of the liquid surface shape), and determines the enrichment position information of the target concentrated sample through mathematical models and algorithms.

[0063] Determining the flow field characteristics by frequency and sample volume can more accurately describe the propagation and energy distribution of surface acoustic waves in the solution, thereby improving the accuracy of the enrichment position. The calculation of the eddy number provides a quantitative description of the local vortex in the solution, which helps to more accurately determine the enrichment position of the biological sample in the vortex.

[0064] By comprehensively considering the number of eddies, the size of micro-nano particles, vibration shape and liquid surface characteristic information, the control module 13 can dynamically adjust the parameters in the enrichment process to optimize the enrichment efficiency. In particular, under different particle sizes and different liquid surface conditions, this multi-parameter comprehensive method can provide a more flexible and efficient enrichment scheme. The control module 13 can monitor the changes of the above parameters in real time and adjust the electrical signal according to the changes to ensure that the enrichment process is always carried out under the best conditions.

[0065] The entire enrichment and extraction process is highly automated, reducing the number of manual operations, thereby significantly reducing human errors. The intelligent algorithm of the control module 13 can automatically optimize parameters to avoid unstable enrichment effects caused by improper manual settings.

[0066] This method is not only applicable to a single type of biological sample, but can also process a variety of micro-nanoparticles of different sizes, which enhances the adaptability and versatility of the device. Through the calculation of flow field characteristics and the number of eddy currents, this method can adapt to different experimental conditions, such as different sample volumes and liquid surface characteristics, and improves the applicability of the device in different environments. The user only needs to add the biological sample solution 112 to the carrying container and start the device to complete the enrichment and extraction process. It is easy to operate and suitable for laboratory technicians and clinical applications. The control module 13 can provide enrichment position information in real time, and the user can quickly obtain the enrichment results, shortening the time of experiments and detection.

[0067] In some embodiments, it also includes: an image acquisition module for acquiring liquid surface characteristic information of the biological sample carrying solution; wherein the liquid surface characteristic information also includes aggregated particle information corresponding to the micro-nano particles in the biological sample solution 112; the aggregated particle information includes at least aggregated particle color and aggregated particle shape.

[0068] like Figure 4As shown, the image acquisition module can capture the liquid surface characteristic information of the biological sample carrying solution, including the height and shape of the liquid surface and the aggregation information of the micro-nano particles in the solution. The module can use a high-resolution camera or imaging device, and can transmit image data to the control module 13 in real time for analysis. The image acquisition module can determine the height of the liquid surface, which has a direct impact on the propagation path and energy distribution of the surface acoustic wave. The radius of curvature of the liquid surface shape affects the reflection and refraction of the surface acoustic wave on the liquid surface, further affecting the enrichment effect. The image acquisition module can identify the aggregation color of micro-nano particles in the solution, and particles of different colors may have different properties and responses. The image acquisition module can identify the aggregation shape of micro-nano particles in the solution, and different shapes also respond differently to the surface acoustic wave.

[0069] The control module 13 receives the liquid surface characteristic information and aggregated particle information transmitted by the image acquisition module, combines the existing frequency, sample volume, micro-nano particle size and vibration shape, and determines the enrichment position information through complex algorithms and models.

[0070] In some embodiments, the surface acoustic wave includes a first-stage surface wave and a second-stage surface wave; the control module 13 controls the transducer module 12 to sequentially generate the first-stage surface wave and the second-stage surface wave; the first-stage surface acoustic wave is used to form a plurality of vortices in the biological sample solution 112, so that the micro-nanoparticles close to the side wall of the biological sample holding container 111 are gathered at a plurality of gathering points away from the side wall; the second-stage surface acoustic wave is used to form a single vortex in the biological sample solution 112, so as to gather the plurality of micro-nanoparticles at the center position of the biological sample holding container 111.

[0071] The surface acoustic wave includes two stages of surface waves: a first stage surface wave and a second stage surface wave. The control module 13 generates the two stages of surface waves in sequence through the energy conversion module 12 to achieve efficient enrichment of micro-nano particles.

[0072] The first-stage surface wave is used to form multiple vortices in the biological sample solution 112, so that the micro-nano particles close to the side wall of the biological sample holding container 111 are gathered at multiple gathering points away from the side wall. The control module 13 sends the first-stage electrical signal to the transducer module 12, and the transducer module 12 generates the first-stage surface wave according to the signal. The design of the first-stage surface wave causes multiple local vortices to be generated on the liquid surface, and these vortices are distributed at different positions of the container, gradually guiding the particles close to the side wall to multiple gathering points near the center of the container.

[0073] The second-stage surface wave is used to form a single vortex in the biological sample solution 112, further concentrating the micro-nano particles in the multiple aggregation points to the center of the biological sample holding container 111. After the first-stage surface wave is completed, the control module 13 sends the second-stage electrical signal to the transducer module 12, and the transducer module 12 generates the second-stage surface wave according to the signal. The design of the second-stage surface wave causes a central vortex to be generated on the liquid surface, which has a strong enrichment ability, and further concentrates the particles in the multiple aggregation points formed in the first stage to the center of the container.

[0074] Through two stages of surface waves, micro-nanoparticles can be more efficiently concentrated in the center of the container. In the first stage, multiple vortices are formed to initially guide the particles from the side walls to the middle. In the second stage, a single central vortex is used to further concentrate the particles. This multi-stage enrichment strategy significantly improves the enrichment efficiency. Compared with single-stage enrichment, multi-stage enrichment can complete the enrichment process in a shorter time, thereby speeding up experiments and detection.

[0075] The multiple vortices in the first stage initially concentrate the particles to multiple gathering points, reducing the uneven distribution of particles on the side walls. The single central vortex in the second stage concentrates the particles in these gathering points to a central point, improving the accuracy of enrichment. Through multi-stage enrichment, the process of particles gradually enriching from the side walls to the center reduces cross-contamination between different particles and ensures the purity of the enriched sample.

[0076] The surface waves in the first and second stages can be adjusted according to the size of different particles to adapt to different types of biological samples. The multi-stage enrichment strategy can adapt to biological sample carrying containers 111 of different shapes and sizes, thereby improving the versatility and flexibility of the device.

[0077] The entire enrichment process is automatically controlled by the control module 13, which reduces the number of manual operations and greatly reduces human errors. The control module 13 can dynamically adjust the parameters of the electrical signal according to actual conditions to ensure that the enrichment process is always carried out under optimal conditions.

[0078] The user only needs to add the biological sample solution 112 into the carrying container and start the device to complete the enrichment and extraction process. The operation is simple and suitable for laboratory technicians and clinical applications. The control module 13 can monitor the generation and enrichment process of the surface wave in real time. The user can intuitively see the process status through the display screen or software interface, which improves the transparency and operability of the experiment. The data in the enrichment process can be recorded and subsequently analyzed to provide data support for the verification and optimization of the experimental results.

[0079] Assuming that specific white blood cells need to be enriched from a blood sample, the device of Example 3 can be specifically operated as follows:

[0080] Prepare the sample:

[0081] A certain volume (eg, V=50 μL) of blood sample solution is added into the biological sample holding container 111 , and the biological sample holding container 111 is placed on the sample placing area of ​​the piezoelectric substrate 11 .

[0082] The control module 13 is powered on and starts to send electrical signals. The control module 13 first sends the first-stage electrical signals to the transducer module 12, and the transducer module 12 generates the first-stage surface waves.

[0083] The first-stage surface wave forms multiple vortices in the biological sample solution 112, so that the white blood cells close to the side wall of the container gradually gather at multiple aggregation points away from the side wall. For example, assuming that the frequency of the first-stage electrical signal is 100 MHz, the control module 13 confirms the multiple aggregation points formed in the first stage through the sensor or image acquisition module to ensure that the initial enrichment effect is good. The control module 13 sends the second-stage electrical signal to the transducer module 12, and the transducer module 12 generates the second-stage surface wave. The second-stage surface wave forms a single central vortex in the biological sample solution 112, further concentrating the white blood cells in the multiple aggregation points formed in the first stage to the center of the container. For example, assuming that the frequency of the second-stage electrical signal is 50 MHz, the central vortex formed has a higher energy density.

[0084] In some embodiments, the angle between the transducer module 12 and the vertical direction of the cut edge of the piezoelectric substrate 11 is a target angle; the control module 13 adjusts the control parameters corresponding to the surface acoustic wave according to the target angle to adjust the vibration mode of the surface acoustic wave.

[0085] The transducer module 12 is fixed on the surface of the piezoelectric substrate 11, and the angle between it and the vertical direction of the cut edge of the piezoelectric substrate 11 is a target angle (such as 45 degrees). The target angle can be adjusted according to experimental requirements. For example, different types of biological samples respond differently to surface acoustic waves, and a specific angle is required to optimize the enrichment effect.

[0086] The IDT electrode is usually composed of a group of parallel metal finger electrodes. The input electrical signal generates an alternating electric field between the electrodes, thereby generating surface acoustic waves on the surface of the piezoelectric substrate 11. It is also possible to design multiple electrodes with different frequencies to achieve the generation of multi-band surface acoustic waves, further improving the enrichment efficiency and purity. The design of the transducer needs to consider its frequency response, power output and thermal stability to ensure that it can continue to work efficiently during the experiment.

[0087] The device generates surface acoustic waves on the surface of the piezoelectric substrate 11 through mechanical vibration, and the frequency and intensity of the surface acoustic waves can be controlled by the parameters of the electrical signal. The surface acoustic waves propagate in the biological sample holding container 111, and the biological sample in the biological sample solution 112 is enriched through the acoustic tweezers technology.

[0088] The control module 13 is connected to the transducer module 12 through an interface, which can be a physical interface (such as a cable) or a wireless interface (such as Bluetooth, Wi-Fi). The user can input the target biological sample type (such as exosomes) and the required enrichment parameters (such as frequency, intensity and time) through the control module 13. The control module 13 generates a corresponding electrical signal based on the input parameters and transmits it to the transducer module 12. The control module 13 can monitor the generation and propagation of the surface acoustic wave in real time to ensure the stability and effectiveness of the enrichment process. At the same time, an automated program can also be designed to automatically adjust and optimize the enrichment parameters to improve the enrichment efficiency.

[0089] The device integrates multiple enrichment steps into one, reducing the number of operating steps and complexity in the experiment. Through the automation program of the control module 13, one-key operation can be achieved, further simplifying the experimental process. Surface acoustic wave technology can complete the enrichment of biological samples in a short time, greatly shortening the experimental time.

[0090] At the same time, surface acoustic wave technology causes less damage to biological samples and does not cause mechanical damage to biological samples like centrifugation and filtration. Biological sample enrichment can be carried out under relatively mild conditions to maintain the integrity and activity of biological samples. By optimizing the frequency and intensity of surface acoustic waves, the target biological samples can be better protected and the entrainment of non-target biological samples can be reduced.

[0091] Surface acoustic waves have high resolution and can accurately separate different types of biological samples. By adjusting the parameters of the surface acoustic wave, specific types of biological samples can be selectively enriched to improve the enrichment purity. The device provided does not require the use of markers (such as antibodies or magnetic beads), reducing additional processing steps and possible contamination. The device can be applied to different types of biological samples, such as exosomes. It can handle sample volumes from microliters to milliliters, suitable for different laboratory and clinical needs. The vibration mode, frequency and intensity of the surface acoustic wave can also be flexibly adjusted according to different experimental needs to optimize the enrichment effect.

[0092] The automated extraction device 10 provided in the present application achieves efficient and low-damage enrichment of biological samples through surface acoustic wave technology. The device has significant advantages in simplifying the operation steps, reducing experimental costs, and improving enrichment efficiency and purity. It is particularly suitable for occasions where a large number of samples need to be processed and specific biological sample types need to be enriched. Through detailed parameter adjustment and optimization, the device can be widely used in medical research, biotechnology, clinical diagnosis and other fields.

[0093] In some embodiments, the transducer module 12 includes multiple transducer units, which are arranged on the piezoelectric substrate 11 and surround the biological sample holding container 12; the automated extraction device 10 also includes: a clamping module 14, which is arranged on at least one transducer unit, and the transducer unit corresponding to the clamping module 14 is a target transducer unit, and the angle between the target transducer unit and the vertical direction of the cut edge of the piezoelectric substrate 11 is a target angle; wherein the control parameter is used to control the target transducer unit so that the target transducer unit transmits surface acoustic waves to the biological sample holding container 12.

[0094] In this embodiment, the transducer module 12 includes a plurality of transducer units, which are evenly arranged on the piezoelectric substrate 11 and surround the biological sample holding container 12. The surround design can realize multi-directional surface acoustic wave propagation, so that a transducer unit at an angle can be selected at will, or multiple transducer units can be selected at the same time for control, which greatly improves the flexibility of the device. At the same time, the transducer unit can be replaced very conveniently, reducing the maintenance cost of the device.

[0095] Multiple transducer units can generate surface acoustic waves in different directions, so that the biological sample in the biological sample solution 112 is enriched under the action of predetermined surface acoustic waves according to actual needs. According to different types of biological samples and experimental requirements, transducer units in different directions can be selected for control to achieve a more precise enrichment effect.

[0096] The compression module 14 is arranged on at least one transducer unit, which is called a target transducer unit. For example, the angle between the target transducer unit and the vertical direction of the cut edge of the piezoelectric substrate 11 is a target angle (such as 60 degrees) to optimize the propagation path of the surface acoustic wave.

[0097] The pressing module 14 can firmly press the target transducer unit onto the piezoelectric substrate 11 to ensure close contact between the transducer unit and the substrate surface. Through physical pressing, the energy loss during the propagation of the surface acoustic wave can be reduced, and the propagation efficiency and enrichment effect of the surface acoustic wave can be improved.

[0098] At the same time, by pressing the module 14, Figure 1 and Figure 2 The transducer unit corresponding to any angle is tested, and then the most suitable target angle for the current biological sample enrichment is selected, the corresponding target transducer unit is determined, and the control parameters of the target transducer unit at the target angle are further adjusted to improve the efficiency of biological sample enrichment.

[0099] The control module 13 is connected to multiple target transducer units through an interface, and can control these transducer units separately or simultaneously. The control module 13 is embedded with a control algorithm, and can generate specific control signals according to the input parameters. The control module 13 generates corresponding electrical signals according to the input parameters and transmits them to the target transducer unit. In addition, one or more target transducer units can be controlled simultaneously to generate surface acoustic waves of specific vibration modes in different directions, thereby improving the enrichment effect.

[0100] Since the multiple transducer units surround the biological sample holding container 12 , the surface acoustic wave can propagate from multiple directions, thereby improving the enrichment effect of the biological sample.

[0101] Multiple transducer units can work together to generate surface acoustic waves in different directions simultaneously or sequentially, greatly improving the enrichment efficiency. At the same time, the clamping module 14 ensures close contact between the target transducer unit and the surface of the piezoelectric substrate 11, reducing energy loss during the propagation of the surface acoustic wave and further improving the enrichment effect.

[0102] Surface acoustic wave technology causes less damage to biological samples. By optimizing the frequency and intensity of surface acoustic waves, biological samples can be enriched under relatively mild conditions, further protecting the integrity and activity of biological samples.

[0103] Accordingly, through the multi-unit control of the control module 13, specific types of biological samples can be selectively enriched according to the response characteristics of different biological sample types to the surface acoustic wave, thereby improving the enrichment purity. Multi-directional multi-mode surface acoustic waves can better separate target biological samples from non-target biological samples, reduce the entrainment of non-target biological samples, and improve the enrichment purity.

[0104] The control module 13 can flexibly adjust the frequency, intensity and direction of the surface acoustic wave, which is suitable for different types of biological samples and different experimental requirements. Through the built-in automatic control program, the enrichment parameters can be automatically optimized to improve the flexibility and repeatability of the experiment.

[0105] The above embodiment significantly improves the efficiency of biological sample enrichment by designing multiple transducer units surrounding the biological sample holding container 12 and the compression module 14, while reducing biological sample damage and improving enrichment purity. The device has obvious advantages in processing a large number of samples and specific biological sample types, and is suitable for a variety of experimental needs in the fields of medical research, biotechnology, clinical diagnosis, etc. Through flexible parameter adjustment and automated control procedures, the device can achieve efficient and low-damage biological sample enrichment and improve the reliability and repeatability of the experiment.

[0106] In some embodiments, the transducer module 12 is sputtered, evaporated or 3D printed on the piezoelectric substrate 11 .

[0107] In this embodiment, the transducer module 12 is not an independent unit, but is directly sputtered or evaporated on the surface of the piezoelectric substrate 11. This integrated design can improve the overall performance and reliability of the device. The transducer module 12 sputtered, evaporated or 3D printed on the piezoelectric substrate 11 usually includes interdigital transducers (IDT), which can accurately control the generation and propagation of surface acoustic waves.

[0108] When receiving an electrical signal, the sputtered or evaporated transducer module 12 can convert the electrical signal into mechanical vibration to generate a surface acoustic wave. Since the transducer module 12 is directly sputtered, evaporated or 3D printed on the piezoelectric substrate 11, the transducer module 12 is in close contact with the substrate, reducing energy loss.

[0109] By directly sputtering or evaporating the transducer module 12 on the piezoelectric substrate 11, the entire device is made more compact and integrated, reducing problems that may occur during assembly. The integrated design reduces poor contact between the transducer module 12 and the piezoelectric substrate 11, and improves the reliability and stability of the device.

[0110] By sputtering or evaporating the transducer module 12 on the piezoelectric substrate 11, an integrated design of the device is achieved, which improves the integration and stability. This design significantly reduces energy loss, improves enrichment accuracy and efficiency, and reduces manufacturing costs and maintenance costs of the device. The device has obvious advantages in processing a large number of samples and specific biological sample types, and is suitable for a variety of experimental needs in the fields of medical research, biotechnology, clinical diagnosis, etc. Through flexible parameter adjustment and automated control procedures, the device can achieve efficient and low-damage enrichment of biological samples and improve the reliability and repeatability of the experiment.

[0111] Exemplarily, the control parameters include at least frequency and power, and the frequency and power of the transducer module are determined according to the diameter, density, compression coefficient of the biological sample to be enriched in the biological sample solution and the target angle.

[0112] In this embodiment, the control parameters generated by the control module 13 include at least the frequency and power of the surface acoustic wave. These parameters are determined according to the diameter, density, compression coefficient and the target angle of the biological sample to be enriched. The frequency parameter determines the wavelength and propagation speed of the surface acoustic wave. By adjusting the frequency, the response of the surface acoustic wave to a specific biological sample can be optimized. The power parameter determines the intensity of the surface acoustic wave. By adjusting the power, the size of the acoustic field generated by the surface acoustic wave to the biological sample in the biological sample solution 112 can be controlled. Biological samples of different diameters and volumes respond differently to the surface acoustic wave. By adjusting the frequency and power, efficient enrichment of specific biological samples can be achieved.

[0113] By automatically adjusting the frequency and power according to the diameter, density, compression coefficient and target angle of the biological sample by the control module 13, the enrichment effect of the surface acoustic wave on the target biological sample can be significantly improved. At the same time, by accurately adjusting the frequency and power of the surface acoustic wave, the biological sample can be enriched under relatively mild conditions, reducing mechanical damage to the biological sample. Biological samples of different diameters and volumes respond differently to the surface acoustic wave. By optimizing the frequency and power, specific types of biological samples can be enriched more accurately. The optimized parameters can better separate the target biological sample and the non-target biological sample, reduce the entrainment of the non-target biological sample, and improve the enrichment purity.

[0114] In combination with the above embodiments, the device can adapt to a variety of biological sample types with different diameters and volumes, expanding its application range. It can also flexibly adjust the enrichment parameters by inputting different biological sample parameters to meet different experimental requirements.

[0115] In some embodiments, the transducer includes at least one IDT, and a ratio of a wavelength range of a surface acoustic wave emitted by the IDT to a finger width range of the IDT is within a preset ratio range.

[0116] In the present embodiment, the transducer module 12 includes at least one interdigital transducer. The interdigital transducer is composed of a series of interdigital electrodes, which can convert electrical signals into surface acoustic waves (SAW, Surface Acoustic Wave). The interdigital transducer is composed of a plurality of parallel comb-shaped electrodes, which are arranged in parallel to form an interdigital structure. The finger width of the interdigital transducer refers to the width of each electrode finger, which is usually at the micron level. When the interdigital transducer receives an electrical signal, the electrical signal generates an alternating electric field between the interdigital electrodes, thereby driving the mechanical vibration of the surface of the piezoelectric substrate 11 and generating a surface acoustic wave. The generated surface acoustic wave propagates along the substrate surface, and the target biological sample in the biological sample solution 112 is enriched to a specific area through the action of the surface acoustic wave.

[0117] According to specific application requirements, multiple IDTs can be set to achieve multi-directional surface acoustic wave propagation. After receiving the electrical signal, the IDT converts the electrical signal into mechanical vibration to generate surface acoustic waves. Multiple IDTs can generate surface acoustic waves from multiple directions simultaneously or individually, improving the enrichment efficiency.

[0118] The ratio of the wavelength range of the surface acoustic wave emitted by the IDT to the finger width range of the IDT is within a preset ratio range, and the specific ratio range can be adjusted according to experimental requirements and biological sample characteristics to optimize the enrichment effect.

[0119] By adjusting the finger width of the interdigital transducer, the wavelength of the generated surface acoustic wave can be controlled, thereby optimizing the response of the surface acoustic wave to a specific biological sample. A suitable wavelength to finger width ratio can ensure that the surface acoustic wave propagates more effectively in the biological sample solution 112, thereby improving the accuracy of biological sample enrichment.

[0120] For example, Figure 3 As shown, the shape of each interdigital transducer on the piezoelectric substrate 11 is a trapezoid.

[0121] Each interdigital transducer is in the shape of a trapezoid, that is, the length of the electrode fingers gradually changes on the surface of the substrate. The layout of the trapezoidal electrode can be an isosceles trapezoid, and the specific layout is designed according to the experimental requirements. The trapezoidal interdigital electrode can generate surface acoustic waves within a specific range through its length gradient design, thereby achieving efficient enrichment of different biological samples.

[0122] The design of the trapezoidal electrode can generate a more complex acoustic field, allowing biological samples to be more accurately enriched in the target area under the action of sound. The multi-mode surface acoustic wave field of the trapezoidal design can adapt to biological samples of different diameters, densities and compression coefficients, improving the versatility and adaptability of the device. At the same time, the length gradient design of the trapezoidal electrode can optimize the propagation of surface acoustic waves on the surface of the piezoelectric substrate and improve the enrichment efficiency.

[0123] Exemplarily, the preset ratio range is 1 / 8 to 1 / 2. The ratio of the wavelength range of the surface acoustic wave emitted by the interdigital transducer to the finger width range of the interdigital transducer is in the range of 1 / 8 to 1 / 2. According to the characteristics of the biological sample to be enriched, the finger width and the interval width of the interdigital transducer are adjusted to ensure that the ratio is within the preset range. By adjusting the finger width of the interdigital transducer, the wavelength of the generated surface acoustic wave can be accurately controlled to optimize the response of the surface acoustic wave to the target biological sample. The design with a ratio range of 1 / 8 to 1 / 2 can ensure that the propagation of the surface acoustic wave in the biological sample solution 112 is more efficient and improves the enrichment efficiency. The optimized wavelength to finger width ratio can reduce mechanical damage to the biological sample and protect the integrity and activity of the target biological sample. This ratio range is applicable to a variety of different types of biological samples, improving the versatility and adaptability of the device. By optimizing the ratio, the propagation efficiency of the surface acoustic wave can be improved, the energy loss can be reduced, and the enrichment effect can be improved.

[0124] Exemplarily, the wavelength of the surface acoustic wave is 20 to 1000 μm. The wavelength range of the surface acoustic wave emitted by the interdigital transducer is 20 to 1000 μm. According to the required wavelength range, the appropriate interdigital electrode finger width and electrical signal frequency are designed. The wavelength range of 20 to 1000 μm can cover a variety of biological samples of different sizes and is suitable for enrichment of different types of biological samples. By adjusting the frequency of the electrical signal, surface acoustic waves can be generated in different wavelength ranges to form a multi-mode surface acoustic wave field and improve the enrichment efficiency. By adjusting the wavelength range, the interference of background biological samples and impurities can be reduced and the enrichment purity can be improved.

[0125] In some embodiments, the control parameter includes at least frequency, and the frequency range corresponding to the frequency is between 10 MHz and 150 MHz. The frequency range of the surface acoustic wave emitted by the interdigital transducer is between 10 MHz and 150 MHz. According to the frequency range, the electrode finger width, electrode spacing and other parameters of the interdigital transducer are adjusted to ensure that the surface acoustic wave can be effectively generated within the frequency range. The frequency range of 10 MHz to 150 MHz can cover a variety of biological samples of different sizes and types to meet different enrichment requirements. For example, when the target angle is 0 degrees, the frequency is 19.8 MHz. When the target angle is 30 degrees, the frequency is 18.6 MHz. When the target angle is 60 degrees, the frequency is 32.2 MHz. When the target angle is 90 degrees, the frequency is 34.4 MHz.

[0126] By adjusting the frequency of the electrical signal, surface acoustic waves of different vibration modes can be generated to form a multi-mode acoustic field, thereby improving the diversity and flexibility of enrichment. In some embodiments, the control parameters include at least that the thickness of the piezoelectric substrate 11 is 0.1 to 10 mm; and / or that the material of the biological sample holding container 12 is polydimethylsiloxane, and the thickness of the side wall of the biological sample holding container 12 decreases upward along the piezoelectric substrate 11.

[0127] The piezoelectric substrate 11 is usually made of piezoelectric materials such as quartz, lithium niobate (LN), and lithium tantalate (LT). These materials have high electromechanical coupling coefficients and good surface acoustic wave propagation performance. The material of the biological sample holding container 12 is polydimethylsiloxane (PDMS). The side wall thickness of the biological sample holding container 12 decreases upward along the piezoelectric substrate 11. Since PDMS has good biocompatibility, transparency and softness, it is suitable for the cultivation and enrichment of biological samples. The design of the side wall thickness of the biological sample holding container 12 decreasing upward along the piezoelectric substrate 11 can optimize the propagation of surface acoustic waves in the container, reduce energy loss, and improve enrichment efficiency. At the same time, the decrease can be linear decrease or nonlinear decrease, and the present application preferably adopts nonlinear decrease.

[0128] In summary, the thickness of the piezoelectric substrate 11 and the design of the biological sample holding container 12 have a significant impact on the enrichment effect of the biological sample. Since the thickness of the piezoelectric substrate 11 ranges from 0.1 to 10 mm, the appropriate thickness can be selected according to the experimental requirements to optimize the propagation speed of the surface acoustic wave and improve the enrichment efficiency. The transparency and biocompatibility of the PDMS material, as well as the design of the biological sample holding container 12 with the side wall thickness decreasing upward along the piezoelectric substrate 11, can optimize the propagation of the surface acoustic wave in the container, reduce energy loss, and improve the enrichment efficiency. This design is particularly suitable for processing mixed samples containing multiple types of biological samples, and can achieve accurate enrichment of different biological samples at different frequencies and directions, thereby improving the reliability and repeatability of the experiment.

[0129] The serial numbers of the embodiments of the present application are for description only and do not represent the advantages and disadvantages of the embodiments. The above are only specific implementation methods of the present application, but the protection scope of the present application is not limited thereto. Any technician familiar with the technical field can easily think of various equivalent modifications or replacements within the technical scope disclosed in the present application, and these modifications or replacements should be included in the protection scope of the present application. Therefore, the protection scope of the present application shall be based on the protection scope of the claims.

Claims

1. An automated extraction device for biological samples, characterized in that: include: A piezoelectric substrate, wherein the piezoelectric substrate is made of a piezoelectric material and comprises a sample placement area, wherein the sample placement area is used to store a biological sample holding container, wherein a biological sample solution to be enriched is placed in the biological sample holding container; A transducer module, which is disposed on the piezoelectric substrate and is used to convert an electrical signal into a mechanical vibration to generate a surface acoustic wave; An extraction module, the extraction module is facing the sample placement area and is used to extract the enriched target concentrated sample; a control module, wherein the control module controls the transducer module to generate the surface acoustic wave, so that the biological sample in the biological sample solution is enriched in the biological sample holding container under the action of the surface acoustic wave to form the target concentrated sample; The control module obtains the vibration shape of the surface acoustic wave and the liquid surface characteristic information of the biological sample solution, and confirms the enrichment position information corresponding to the target concentrated sample in the biological sample holding container according to the vibration shape and the liquid surface characteristic information, so as to control the extraction module to complete the automatic extraction of the target concentrated sample according to the enrichment position information.

2. The device according to claim 1, characterized in that The control module also obtains the frequency corresponding to the surface acoustic wave, the sample volume corresponding to each sample addition of the biological sample carrying solution, and the size of the micro-nano particles contained in the biological sample solution; the control module determines the enrichment position information based on the frequency, sample volume, micro-nano particle size, vibration shape and the liquid surface characteristic information.

3. The device according to claim 2, characterized in that The control module determines the flow field characteristics corresponding to the biological sample solution according to the frequency and the sample volume, so as to determine the number of eddies in the biological sample solution under the action of the surface acoustic wave according to the flow field characteristics; the control module determines the enrichment position information according to the number of eddies, the size of micro-nano particles, the vibration shape and the liquid surface characteristic information.

4. The device according to claim 3, characterized in that The formula corresponding to the enriched position information may include: x=a·f+b·V+c·D+d·φ+e·1 / h+g·R+i; Among them, a is the coefficient of frequency f, b is the coefficient of sample volume V, c is the coefficient of micro-nanoparticle size D, d is the coefficient of vibration shape φ, e is the reciprocal coefficient of liquid level height h, g is the coefficient of curvature radius R of liquid surface shape, and i is a constant term, which indicates the default enrichment position when all parameters are zero.

5. The device according to claim 4, characterized in that a is usually positive, indicating that the effect of frequency on enrichment position is positively correlated; and / or, b is a negative value, indicating that the effect of sample volume on the enrichment position is negatively correlated; and / or, c is a negative value, indicating that the effect of particle size on the enrichment position is negatively correlated; and / or, A positive value of d indicates that the effect of the mode shape on the enrichment position is positively correlated; and / or, e is a positive value, indicating that the inverse of the liquid level has a positive correlation with the enrichment position; and / or, g is a negative value, indicating that the curvature radius of the liquid surface shape has a negative correlation with the enrichment position.

6. The device according to claim 1, characterized in that Also includes: An image acquisition module, used to acquire liquid surface characteristic information of the biological sample carrying solution; Wherein, the liquid surface characteristic information also includes aggregated particle information corresponding to the micro-nano particles in the biological sample solution; the aggregated particle information at least includes aggregated particle color and aggregated particle shape.

7. The device according to claim 1, characterized in that The surface acoustic wave includes a first-stage surface wave and a second-stage surface wave; the control module controls the transducer module to sequentially generate the first-stage surface wave and the second-stage surface wave; The first-stage surface acoustic wave is used to form a plurality of vortices in the biological sample solution, so that the micro-nanoparticles close to the side wall of the biological sample holding container are gathered at a plurality of gathering points away from the side wall; The second-stage surface acoustic wave is used to form a single vortex in the biological sample solution to gather the plurality of micro-nanoparticles at the center of the biological sample holding container.

8. The device according to claim 1, characterized in that The angle between the energy conversion module and the vertical direction of the cut edge of the piezoelectric substrate is a target angle; The control module adjusts a control parameter corresponding to the surface acoustic wave according to the target angle to adjust a vibration mode of the surface acoustic wave.

9. The device according to claim 8, characterized in that The transducer module includes a plurality of transducer units, which are arranged on the piezoelectric substrate and surround the biological sample carrying container; the automatic extraction device also includes: A pressing module, wherein the pressing module is arranged on at least one of the transducer units, the transducer unit corresponding to the pressing module is a target transducer unit, and an angle between the target transducer unit and a vertical direction of the cut edge of the piezoelectric substrate is the target angle; The control parameter is used to control the target transducer unit to generate a surface acoustic wave, so that the target transducer unit propagates the surface acoustic wave toward the biological sample holding container.

10. The device according to claim 8, characterized in that The control parameters include at least frequency and power. The frequency and power of the transducer module are determined according to the diameter, density, compression coefficient of the biological sample to be enriched in the biological sample solution and the target angle.

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