Method and device for separating, regulating and controlling target particles in liquid sample

Abstract

The invention discloses a method and a device for separating, regulating and controlling target particles in a liquid sample, and the method comprises the following steps: constructing a product particle concentration prediction model according to unit volume sample purification time and product particle concentration data; according to the sample volume of each round of purification and the sample time consumption of each round of purification, carrying out purification time characteristic value calculation; inputting the purification time characteristic value into the product particle concentration prediction model to obtain a product particle concentration prediction result; and adjusting the operation duty ratio of a first filter membrane and a second filter membrane in the separation chip assembly by using the product particle concentration prediction result, so that the product particle concentration of the purified liquid sample reaches an expected interval. According to the length of sample purification time and data of purification identification results, the equipment can automatically generate better control parameters in the purification process; the purified product can reach a balance point of purity and yield, and downstream application and research are facilitated.

Description

Technical Field

[0001] The present invention belongs to the technical field of liquid sample purification, and in particular relates to a method and device for separating and controlling target particles in a liquid sample. Background Art

[0002] Exosomes (EVs) are small vesicles released by cells into the surrounding environment, with diameters ranging from 30 to 1000 nanometers. Exosomes can carry a variety of biomolecules, such as proteins, nucleic acids, and lipids, and through the transport and information transfer of these biomolecules, they play a vital role in intercellular communication and signal transduction.

[0003] At present, the main obstacle to achieving membrane purification and separation of exosomes for clinical application is the regulation of transmembrane mass transfer: using a filter membrane with a single pore size smaller than the target particle will result in insufficient purity and low flux; using a filter membrane with a single pore size larger than the target particle will result in insufficient yield. Summary of the Invention

[0004] To this end, the present invention provides a method and device for separating and controlling target particles in a liquid sample to solve the problems of insufficient purity, low flux or insufficient yield of filter membranes in traditional technologies.

[0005] To achieve the above objectives, the present invention provides the following technical solution: a method for separating and controlling target particles in a liquid sample, comprising: Based on the sample purification time per unit volume and the product particle concentration data, a product particle concentration prediction model is constructed; The purification time characteristic value is calculated based on the sample volume and the time consumed in each round of purification; Inputting the purification time characteristic value into the product particle concentration prediction model to obtain a product particle concentration prediction result; The product particle concentration prediction result is used to adjust the operating duty cycle of the first filter membrane and the second filter membrane in the separation chip assembly so that the product particle concentration of the purified liquid sample reaches the expected range.

[0006] As a preferred solution for the method of controlling the separation of target particles in a liquid sample, the expression of the product particle concentration prediction model constructed is: ; Where, Predict product particle concentration, S is the membrane area, is the measured particle concentration of the original solution; k is the characteristic value of the purification time; ~ is the sample volume for each round of purification.

[0007] As a preferred solution for the method of regulating the separation of target particles in liquid samples, the formula for calculating the purification time characteristic value is as follows based on the sample volume and the time required for each round of purification: ; Where, ~ is the sample volume for each round of purification; ~ The time taken for each round of sample purification is as follows: As a preferred embodiment of the method for controlling the separation of target particles in a liquid sample, after obtaining the predicted result of the product particle concentration, the method further includes correcting the predicted result of the product particle concentration to obtain a product particle concentration correction coefficient, wherein the product particle concentration correction coefficient is: ; Where, To predict the product particle concentration, is the target product particle concentration; is the product particle concentration correction factor.

[0008] As a preferred solution for the method for regulating the separation of target particles in a liquid sample, the formula for regulating the operating duty cycle of the first filter membrane and the second filter membrane in the separation chip assembly is: ; 1- ; Where, is the operating duty cycle of the first filter membrane; is the operating duty cycle of the second filter membrane; , are the operating duty cycle adjustment coefficients respectively.

[0009] The present invention also provides a device for controlling the separation of target particles in a liquid sample, comprising: A product particle concentration prediction model building module is used to build a product particle concentration prediction model based on the unit volume sample purification time and product particle concentration data; A purification time characteristic calculation module is used to calculate the purification time characteristic value based on the sample volume and the sample purification time of each round; a product particle concentration prediction module, configured to input the purification time characteristic value into the product particle concentration prediction model to obtain a product particle concentration prediction result; The filter membrane operation duty cycle adjustment module is used to adjust the operation duty cycle of the first filter membrane and the second filter membrane in the separation chip assembly using the product particle concentration prediction result, so that the product particle concentration of the purified liquid sample reaches the expected range.

[0010] As a preferred solution of the target particle separation and control device in the liquid sample, in the product particle concentration prediction model construction module, the expression of the product particle concentration prediction model constructed is: ; Where, Predict product particle concentration, S is the membrane area, is the measured particle concentration of the original solution; k is the characteristic value of the purification time; ~ is the sample volume for each round of purification.

[0011] As a preferred embodiment of the target particle separation and control device in a liquid sample, in the purification time characteristic calculation module, the formula for calculating the purification time characteristic value is as follows based on the sample volume and the sample time consumed in each round of purification: ; Where, ~ is the sample volume for each round of purification; ~ The time taken for each round of sample purification.

[0012] As a preferred solution of the target particle separation and control device in the liquid sample, it also includes: The product particle concentration correction module is used to correct the product particle concentration prediction result to obtain a product particle concentration correction coefficient. The product particle concentration correction coefficient is: ; Where, To predict the product particle concentration, is the target product particle concentration; is the product particle concentration correction factor.

[0013] As a preferred embodiment of the target particle separation control device in the liquid sample, in the filter membrane operation duty cycle adjustment module, the formula for adjusting the operation duty cycle of the first filter membrane and the second filter membrane in the separation chip assembly is: ; 1- ; Where, is the operating duty cycle of the first filter membrane; is the operating duty cycle of the second filter membrane; , are the operating duty cycle adjustment coefficients respectively.

[0014] The present invention has the following advantages: a product particle concentration prediction model is constructed based on the sample purification time per unit volume and product particle concentration data; a purification time characteristic value is calculated based on the sample volume and the sample purification time required for each round of purification; the purification time characteristic value is input into the product particle concentration prediction model to obtain a product particle concentration prediction result; and the product particle concentration prediction result is used to adjust the operating duty cycle of the first and second filter membranes in the separation chip assembly so that the product particle concentration of the purified liquid sample reaches the expected range. Based on the length of the sample purification time and the purification identification data, the present invention can automatically generate more optimal control parameters during the purification process; the purified product can achieve a balance between purity and yield, which is beneficial for downstream applications and research. BRIEF DESCRIPTION OF THE DRAWINGS

[0015] To more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the following briefly introduces the drawings required for the embodiments or the description of the prior art. Obviously, the drawings described below are merely exemplary, and those skilled in the art can, without inventive effort, derive other implementation drawings based on the provided drawings.

[0016] Figure 1 Schematic diagram of a separation chip assembly used in the method for regulating and separating target particles in a liquid sample provided in an embodiment of the present invention; Figure 2 Schematic diagram of the process of the method for separating and controlling target particles in a liquid sample provided in an embodiment of the present invention; Figure 3 Comparison of electron micrographs of the purified products provided in the examples of the present invention; Figure 4 This is a Western blot detection diagram of exosomes in the purified product provided in the examples of the present invention; Figure 5 Schematic diagram of a target particle separation and control device in a liquid sample provided in an embodiment of the present invention. DETAILED DESCRIPTION

[0017] The following describes the implementation of the present invention using specific embodiments. Those skilled in the art will readily understand the other advantages and benefits of the present invention from the disclosure herein. Obviously, the embodiments described are only a portion of the present invention, not all of it. All other embodiments derived by persons of ordinary skill in the art based on the embodiments of the present invention without inventive effort are intended to fall within the scope of protection of the present invention.

[0018] Traditional technologies can only choose between the yield and purity of purified products. The specific reasons are as follows: See also Figure 1 The existing solution one adopts a combination of a first filter membrane (a filter membrane with a pore size smaller than that of the target particles) and a second filter membrane (a filter membrane with a pore size smaller than that of the target particles), wherein the pore size of the first filter membrane and the second filter membrane is 20% to 150% smaller than that of the target particles.

[0019] Early stage of purification: a11) Target particle retention: Both the first filter membrane (the filter membrane with a pore size smaller than the target particles) and the second filter membrane (the filter membrane with a pore size smaller than the target particles) can effectively retain the target particles; a12) Membrane status: Filter cake layers quickly form on the first filter membrane (the membrane with a pore size smaller than the target particles) and the second filter membrane (the membrane with a pore size smaller than the target particles), and the membrane flux and membrane effective pore size decrease rapidly; a13) Impurity removal: The efficiency of impurities passing through the first filter membrane (a filter membrane with a pore size smaller than that of the target particles) and the second filter membrane (a filter membrane with a pore size smaller than that of the target particles) to reach the first chamber and the second chamber decreases as the filter cake layer is formed.

[0020] Late stage of purification: b11) Target particle retention: Both the first filter membrane (the filter membrane with a pore size smaller than the target particles) and the second filter membrane (the filter membrane with a pore size smaller than the target particles) can effectively retain the target particles; b12) Membrane status: The first filter membrane (the membrane with a pore size smaller than the target particles) and the second filter membrane (the membrane with a pore size smaller than the target particles) form a thick filter cake layer, and the membrane flux and effective pore size are far lower than the design expectations; b13) Impurity removal: Impurities cannot pass through the first filter membrane (a filter membrane with a pore size smaller than that of the target particles) and the second filter membrane (a filter membrane with a pore size smaller than that of the target particles) to reach the first chamber and the second chamber.

[0021] Existing solution 1: target particle retention: excellent; flux: poor; impurity removal: poor.

[0022] Again, see Figure 1 The existing solution two adopts a combination of a first filter membrane (a filter membrane with a pore size larger than the target particles) and a second filter membrane (a filter membrane with a pore size larger than the target particles); wherein the pore size of the first filter membrane and the second filter membrane is 20% to 50% larger than that of the target particles.

[0023] Early stage of purification: a21) Target particle retention: Due to the formation of a filter cake layer on the first filter membrane (a filter membrane with a pore size larger than that of the target particles) and the second filter membrane (a filter membrane with a pore size larger than that of the target particles), and the low concentration of target particles, the amount of target particles that pass through the first filter membrane (a filter membrane with a pore size larger than that of the target particles) and the second filter membrane (a filter membrane with a pore size larger than that of the target particles) and reach the first chamber and the second chamber is relatively small; a22) Membrane status: The filter cake layer on the first filter membrane (the membrane with a pore size larger than the target particles) and the second filter membrane (the membrane with a pore size larger than the target particles) forms rapidly and slowly, and the membrane flux and membrane effective pore size decrease slowly; a23) Impurity removal: Impurities pass through the first filter membrane (a filter membrane with a pore size larger than the target particles) and the second filter membrane (a filter membrane with a pore size larger than the target particles) to reach the first chamber and the efficiency of the second chamber is maintained at a high level.

[0024] Late stage of purification: b21) Target particle retention: Because the filter cake layers on the first filter membrane (the filter membrane with a pore size larger than the target particles) and the second filter membrane (the filter membrane with a pore size larger than the target particles) are relatively thin, and the target particles have already been enriched in the sample loading chamber, there is a serious loss of target particles in the later stages of purification;

[0025] b22) Membrane status: No thick filter cake layer formed on the first filter membrane (the membrane with a pore size larger than the target particles) and the second filter membrane (the membrane with a pore size larger than the target particles). The membrane flux and effective pore size remained close to the previous level. b23) Impurity removal: Impurities pass through the first filter membrane (a filter membrane with a pore size larger than the target particles) and the second filter membrane (a filter membrane with a pore size larger than the target particles) to reach the first chamber and the efficiency of the second chamber is maintained at a high level.

[0026] Existing option 2: target particle retention: poor; flux: excellent; impurity removal: excellent.

[0027] The above existing solutions 1 and 2 use filter membranes with the same pore size to work in a cycle until purification is completed.

[0028] The main obstacle to membrane purification and separation for clinical application of exosomes is the regulation of transmembrane mass transfer: solving the problem of insufficient purity and low flux when using a single filter membrane with a pore size smaller than the target particle; solving the problem of insufficient yield when using a single filter membrane with a pore size larger than the target particle. Figure 2 , an embodiment of the present invention provides a method for separating and controlling target particles in a liquid sample, comprising the following steps: S1. Construct a product particle concentration prediction model based on the sample purification time and product particle concentration data per unit volume; S2. Calculate the purification time characteristic value based on the sample volume and purification time of each round of purification; S3, inputting the purification time characteristic value into the product particle concentration prediction model to obtain a product particle concentration prediction result; S4. Using the product particle concentration prediction result, adjust the operating duty cycle of the first filter membrane and the second filter membrane in the separation chip assembly so that the product particle concentration of the purified liquid sample reaches the expected range.

[0029] In this embodiment, in step S1, the expression of the product particle concentration prediction model constructed is: ; Where, Predict product particle concentration, S is the membrane area, is the measured particle concentration of the original solution; k is the characteristic value of the purification time; ~ is the sample volume for each round of purification.

[0030] In this embodiment, in step S2, the formula for calculating the purification time characteristic value is as follows based on the sample volume and the sample purification time of each round of purification: ; Where, ~ is the sample volume for each round of purification; ~ The time taken for each round of sample purification.

[0031] In this embodiment, after obtaining the product particle concentration prediction result, step S3 further includes correcting the product particle concentration prediction result to obtain a product particle concentration correction coefficient. The product particle concentration correction coefficient is: ; Where, To predict the product particle concentration, is the target product particle concentration; is the product particle concentration correction factor.

[0032] In this embodiment, in step S4, the formula for adjusting the operating duty cycle of the first filter membrane and the second filter membrane in the separation chip assembly is: ; 1- ; Where, is the operating duty cycle of the first filter membrane; is the operating duty cycle of the second filter membrane; , are the operating duty cycle adjustment coefficients respectively.

[0033] Under the method for controlling the separation of target particles in a liquid sample according to an embodiment of the present invention, a third separation scheme is formed: In the early stage of purification, the first filter membrane (the filter membrane with a pore size larger than the target particles) is mainly used: a31) Target particle retention: Due to the formation of a filter cake layer on the first filter membrane (a filter membrane with a pore size larger than that of the target particles) and the low concentration of target particles, the loss of target particles through the first filter membrane (a filter membrane with a pore size larger than that of the target particles) to the first chamber is relatively small; the target particles are effectively retained on the second filter membrane (a filter membrane with a pore size smaller than that of the target particles); a32) Membrane status: The filter cake layer on the first filter membrane (the membrane with a pore size larger than the target particles) forms rapidly, and the membrane flux and membrane effective pore size decrease slowly. Because the impurity load is concentrated on the side of the first filter membrane (the membrane with a pore size larger than the target particles), the filter cake layer on the side of the second filter membrane (the membrane with a pore size smaller than the target particles) forms slowly, and the membrane flux and membrane effective pore size decrease slowly. a33) Impurity removal: Impurity removal efficiency is maintained at a high level.

[0034] In the later stage of purification, the second filter membrane (the filter membrane with a pore size smaller than the target particles) is mainly used: b31) Target particle retention: This stage mainly uses the second filter membrane (a filter membrane with a pore size smaller than the target particles)16 to effectively retain the target particles; b32) Membrane status: Because the impurity load is concentrated on the first filter membrane (the filter membrane with a pore size larger than the target particles), the filter cake layer of the second filter membrane (the filter membrane with a pore size smaller than the target particles) forms slowly, and the membrane flux and membrane effective pore size decrease slowly; b33) Impurity removal: Impurity removal efficiency is maintained at a high level.

[0035] Separation scheme three: Target particle retention: good; efficiency: good; impurity removal: excellent.

[0036] Taking the purification of exosomes from cell supernatant as an example, the multi-membrane separation chip design is compared with the existing chip design.

[0037] like Figure 3 Transmission electron microscopy images show that the product of the multi-membrane separation chip contains a large number of exosomes and low background impurities. The product of the large-pore membrane separation chip contains fewer exosomes, while the product of the small-pore membrane separation chip contains more background impurities.

[0038] like Figure 4 Western blot analysis revealed that the number of exosomes in the product from the multi-membrane separation chip was intermediate between that of the large-pore and small-pore filter separation chips. This identification indicates that the product from the multi-membrane separation chip using the method described in this embodiment achieves a balance between purity and yield, facilitating downstream applications and research.

[0039] In summary, the embodiments of the present invention construct a product particle concentration prediction model based on the sample purification time per unit volume and the product particle concentration data; calculate the purification time characteristic value based on the sample volume and the sample purification time of each round; input the purification time characteristic value into the product particle concentration prediction model to obtain a product particle concentration prediction result; and use the product particle concentration prediction result to adjust the operating duty cycle of the first filter membrane and the second filter membrane in the separation chip assembly so that the product particle concentration of the purified liquid sample reaches the expected range. According to the present invention, the device can automatically generate more optimal control parameters during the purification process based on the length of the sample purification time and the purification identification result data; the purified product can reach a balance between purity and yield, which is beneficial for downstream applications and research.

[0040] It should be noted that the method of the embodiment of the present invention can be performed by a single device, such as a computer or server. The method of this embodiment can also be applied in a distributed scenario, where multiple devices cooperate to perform the method. In such a distributed scenario, one of the multiple devices may only perform one or more steps of the method of the embodiment of the present invention, and the multiple devices will interact with each other to complete the method.

[0041] It should be noted that the above description is of some embodiments of the present invention. In some cases, the actions or steps described can be performed in a different order than those in the above embodiments and still achieve the desired results. In addition, the processes depicted in the accompanying drawings do not necessarily require the specific order or sequential order shown to achieve the desired results. In some embodiments, multitasking and parallel processing are also possible or may be advantageous.

[0042] See also Figure 5 Based on the same inventive concept, corresponding to any of the above-mentioned embodiments and methods, an embodiment of the present invention further provides a device for controlling the separation of target particles in a liquid sample, comprising: A product particle concentration prediction model building module 100 is used to build a product particle concentration prediction model based on the sample purification time per unit volume and the product particle concentration data; The purification time characteristic calculation module 200 is used to calculate the purification time characteristic value according to the sample volume and the sample purification time of each round; a product particle concentration prediction module 300, configured to input the purification time characteristic value into the product particle concentration prediction model to obtain a product particle concentration prediction result; The filter membrane operation duty cycle adjustment module 400 is used to adjust the operation duty cycles of the first filter membrane and the second filter membrane in the separation chip assembly using the product particle concentration prediction result, so that the product particle concentration of the purified liquid sample reaches the expected range.

[0043] In this embodiment, in the product particle concentration prediction model construction module 100, the expression of the product particle concentration prediction model constructed is: ; Where, Predict product particle concentration, S is the membrane area, is the measured particle concentration of the original solution; k is the characteristic value of the purification time; ~ is the sample volume for each round of purification.

[0044] In this embodiment, the purification time characteristic calculation module 200 calculates the purification time characteristic value according to the sample volume and the sample time consumed in each round of purification: ; Where, ~ is the sample volume for each round of purification; ~ The time taken for each round of sample purification.

[0045] In this embodiment, it also includes: The product particle concentration correction module 500 is used to correct the product particle concentration prediction result to obtain a product particle concentration correction coefficient. The product particle concentration correction coefficient is: ; Where, To predict the product particle concentration, is the target product particle concentration; is the product particle concentration correction factor.

[0046] In this embodiment, in the filter membrane operation duty cycle adjustment module 400, the formula for adjusting the operation duty cycle of the first filter membrane and the second filter membrane in the separation chip assembly is: ; 1- ; Where, is the operating duty cycle of the first filter membrane; is the operating duty cycle of the second filter membrane; , are the operating duty cycle adjustment coefficients respectively.

[0047] The device of the above embodiment is used to implement a corresponding method for separating and controlling target particles in a liquid sample in any of the above embodiments, and has the beneficial effects of the corresponding method embodiment, which will not be described in detail here.

[0048] An embodiment of the present invention also provides a non-transitory computer-readable storage medium, in which a program code for a method for separating and controlling target particles in a liquid sample is stored. The program code includes instructions for executing the above-mentioned method embodiment or any possible implementation thereof.

[0049] Computer-readable storage media can be any available medium that can be accessed by a computer, or a data storage device such as a server or data center that includes one or more available media. The available media can be magnetic media (e.g., floppy disks, hard disks, magnetic tapes), optical media (e.g., DVDs), or semiconductor media (e.g., solid-state drives (SSDs)).

[0050] An embodiment of the present invention further provides an electronic device, comprising: a memory and a processor; The processor and the memory communicate with each other via a bus; the memory stores program instructions that can be executed by the processor, and the processor calls the program instructions to execute a method for separating and regulating target particles in a liquid sample according to the above-mentioned method embodiment or any possible implementation thereof.

[0051] Specifically, the processor can be implemented by hardware or by software. When implemented by hardware, the processor can be a logic circuit, an integrated circuit, etc.; when implemented by software, the processor can be a general-purpose processor, which is implemented by reading software code stored in a memory. The memory can be integrated into the processor or located outside the processor and exist independently.

[0052] In the above embodiments, it can be implemented in whole or in part by software, hardware, firmware or any combination thereof. When implemented using software, it can be implemented in whole or in part in the form of a computer program product. The computer program product includes one or more computer instructions. When the computer program instructions are loaded and executed on a computer, the process or function described in the embodiment of the present invention is generated in whole or in part. The computer can be a general-purpose computer, a special-purpose computer, a computer network, or other programmable systems. The computer instructions can be stored in a computer-readable storage medium, or transmitted from one computer-readable storage medium to another computer-readable storage medium. For example, the computer instructions can be transmitted from a website, computer, server or data center to another website, computer, server or data center via a wired (e.g., coaxial cable, optical fiber, digital subscriber line (DSL)) or wireless (e.g., infrared, wireless, microwave, etc.) mode.

[0053] Obviously, those skilled in the art will appreciate that the various modules or steps of the present invention described above can be implemented using a general-purpose computing system. They can be centralized on a single computing system or distributed across a network of multiple computing systems. Alternatively, they can be implemented using program code executable by a computing system, and thus, they can be stored in a storage system and executed by the computing system. In some cases, the steps shown or described herein can be performed in a different order than that shown, or they can be fabricated into separate integrated circuit modules, or multiple modules or steps can be fabricated into a single integrated circuit module. Thus, the present invention is not limited to any particular combination of hardware and software.

[0054] Although the present invention has been described in detail above using general descriptions and specific embodiments, it will be apparent to those skilled in the art that modifications and improvements may be made thereto. Therefore, such modifications and improvements, without departing from the spirit of the present invention, are intended to be within the scope of protection claimed herein.

Claims

1. A method for separating and controlling target particles in a liquid sample, characterized in that: include: Based on the sample purification time per unit volume and the product particle concentration data, a product particle concentration prediction model is constructed; The purification time characteristic value is calculated based on the sample volume and the time consumed in each round of purification; Inputting the purification time characteristic value into the product particle concentration prediction model to obtain a product particle concentration prediction result; The product particle concentration prediction result is used to adjust the operating duty cycle of the first filter membrane and the second filter membrane in the separation chip assembly so that the product particle concentration of the purified liquid sample reaches the expected range.

2. The method for separating and controlling target particles in a liquid sample according to claim 1, wherein: The expression of the product particle concentration prediction model constructed is: ； Where, Predict product particle concentration, S is the membrane area, is the measured particle concentration of the original solution; k is the characteristic value of the purification time; ~ is the sample volume for each round of purification.

3. The method for separating and controlling target particles in a liquid sample according to claim 2, wherein: According to the sample volume and time consumed in each round of purification, the formula for calculating the purification time characteristic value is: ； Where, ~ is the sample volume for each round of purification; ~ The time taken for each round of sample purification.

4. The method for separating and controlling target particles in a liquid sample according to claim 3, wherein: After obtaining the product particle concentration prediction result, the method further includes correcting the product particle concentration prediction result to obtain a product particle concentration correction coefficient, where the product particle concentration correction coefficient is: ； Where, To predict the product particle concentration, is the target product particle concentration; is the product particle concentration correction factor.

5. The method for separating and controlling target particles in a liquid sample according to claim 3, wherein: The formula for adjusting the operating duty cycle of the first filter membrane and the second filter membrane in the separation chip assembly is: ； 1- ； Where, is the operating duty cycle of the first filter membrane; is the operating duty cycle of the second filter membrane; , are the operating duty cycle adjustment coefficients respectively.

6. A device for separating and controlling target particles in a liquid sample, characterized in that: include: A product particle concentration prediction model building module is used to build a product particle concentration prediction model based on the unit volume sample purification time and product particle concentration data; A purification time characteristic calculation module is used to calculate the purification time characteristic value based on the sample volume and the sample purification time of each round; a product particle concentration prediction module, configured to input the purification time characteristic value into the product particle concentration prediction model to obtain a product particle concentration prediction result; The filter membrane operation duty cycle adjustment module is used to adjust the operation duty cycle of the first filter membrane and the second filter membrane in the separation chip assembly using the product particle concentration prediction result, so that the product particle concentration of the purified liquid sample reaches the expected range.

7. The device for separating and controlling target particles in a liquid sample according to claim 6, characterized in that: In the product particle concentration prediction model construction module, the expression of the product particle concentration prediction model constructed is: ； Where, Predict product particle concentration, S is the membrane area, is the measured particle concentration of the original solution; k is the characteristic value of the purification time; ~ is the sample volume for each round of purification.

8. The device for separating and controlling target particles in a liquid sample according to claim 7, characterized in that: In the purification time characteristic calculation module, the formula for calculating the purification time characteristic value is as follows based on the sample volume of each round of purification and the sample time consumed in each round of purification: ； Where, ~ is the sample volume for each round of purification; ~ The time taken for each round of sample purification.

9. The device for controlling separation of target particles in a liquid sample according to claim 8, characterized in that: Also includes: The product particle concentration correction module is used to correct the product particle concentration prediction result to obtain a product particle concentration correction coefficient. The product particle concentration correction coefficient is: ； Where, To predict the product particle concentration, is the target product particle concentration; is the product particle concentration correction factor.

10. The device for separating and controlling target particles in a liquid sample according to claim 8, characterized in that: In the filter membrane operation duty cycle adjustment module, the formula for adjusting the operation duty cycle of the first filter membrane and the second filter membrane in the separation chip assembly is: ； 1- ； Where, is the operating duty cycle of the first filter membrane; is the operating duty cycle of the second filter membrane; , are the operating duty cycle adjustment coefficients respectively.

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