Sample purification device and sample purification method

Abstract

The invention discloses a sample purification device and a sample purification method, the sample purification device comprises a purification chip, a liquid injection assembly, an oscillation assembly and a purification loop, the chip comprises a sample pool and a first chamber and a second chamber respectively located at two opposite sides of the sample pool, and the liquid injection assembly is communicated with a material inlet and a material outlet at the bottom of the sample pool and is used for injecting a sample into the sample pool; the sample collector is also used for recovering a target sample in the sample pool; the oscillation assembly can abut against the outer side wall of the first cavity and the outer side wall of the second cavity so as to generate ultrasonic oscillation. The purification loop comprises a filtrate recovery container and a negative pressure driving assembly which are communicated with each other, the filtrate recovery container is respectively communicated with the first chamber and the second chamber, and the negative pressure driving assembly is used for providing negative pressure for the first chamber and the second chamber to realize separation and purification. The sample purification device can quickly and effectively purify a biological sample and improve the purity of the sample; the volume of liquid in the sample pool can be monitored in real time, so that different purification degrees can be selected according to actual requirements.

Description

Technical Field

[0001] This application relates to the field of sample processing technology, and in particular to a sample purification device and a sample purification method. Background Technology

[0002] Platelet-rich plasma (PRP) is a platelet concentrate prepared from autologous whole blood through centrifugation. Its platelet concentration can reach 4-8 times that of normal blood, and it contains various growth factors such as PDGF and TGF-β. These bioactive substances play a crucial role in tissue repair and regeneration, making PRP an important therapeutic tool in the field of regenerative medicine.

[0003] Currently, it is difficult to control the concentration of growth factors in the platelet-rich plasma obtained through activation, resulting in low concentrations and low purity of the platelet-rich plasma. Summary of the Invention

[0004] In view of this, in order to solve at least one of the above technical problems, it is necessary to propose a sample purification device and a sample purification method.

[0005] In a first aspect, this application provides a sample purification device for separating a target sample from a biological sample. The sample purification device includes: a purification chip comprising a sample pool and a first chamber and a second chamber located on opposite sides of the sample pool; the sample pool is connected to the first chamber via a first filter membrane, and the sample pool is also connected to the second chamber via a second filter membrane; the outer wall of the first chamber has a first negative pressure port, and the outer wall of the second chamber has a second negative pressure port; the bottom of the purification chip has an inlet / outlet port connected to the sample pool; and a liquid injection assembly connected to the inlet / outlet port, the liquid injection assembly being used to inject the biological sample into the sample pool via the inlet / outlet port. The injection assembly is also used to recover the target sample separated from the biological sample in the sample pool; the oscillation assembly includes two ultrasonic generators, which are respectively held against the outer walls of the first chamber and the second chamber; and the purification circuit includes a filtrate recovery container and a negative pressure drive assembly that are interconnected. The filtrate recovery container is also connected to the first negative pressure port and the second negative pressure port, respectively. The negative pressure drive assembly is used to simultaneously or alternately provide negative pressure to the first chamber and the second chamber, so that the filtrate of the biological sample in the sample pool, excluding the target sample, enters the filtrate recovery container through the first negative pressure port and the second negative pressure port under the negative pressure.

[0006] In some possible embodiments, the sample purification device further includes a volume monitoring module for real-time monitoring of the volume of biological samples in the sample pool.

[0007] In some possible embodiments, the volume monitoring module includes a light source component and an imaging component, wherein the light source component is used to emit light toward the sample pool, and the imaging component is used to take a picture of the sample pool when the light source component emits light toward the sample pool.

[0008] In some possible embodiments, the light emitted by the light source assembly can illuminate the entire range from the bottom to the top of the sample pool; or, the volume detection module further includes a moving mechanism, on which both the light source assembly and the imaging assembly are disposed, and the moving mechanism is used to move the light source assembly and the imaging assembly between the top and bottom of the purification chip.

[0009] In some possible embodiments, the sample purification device includes two sets of oscillation components with different frequencies, wherein the two ultrasound generators in each set of oscillation components have the same frequency, and both frequencies are 20~70KHz.

[0010] In some possible embodiments, the purification chip is a closed chip, which includes a first sidewall and a second sidewall disposed opposite to each other, and a bottom wall and a top wall connecting the first sidewall and the second sidewall. The first filter membrane is disposed inside the first sidewall and forms a first chamber with the first sidewall. The second filter membrane is disposed inside the second sidewall and forms a second chamber with the second sidewall. The first chamber and the second chamber are spaced apart from the bottom wall. The inlet and outlet are disposed through the first sidewall between the first chamber and the bottom wall.

[0011] In some possible embodiments, the injection assembly includes a syringe in communication with the inlet / outlet and a drive element for driving the syringe; and / or, The negative pressure drive assembly includes a vacuum chamber connected to the filtrate recovery container and a vacuum pump connected to the vacuum chamber. The vacuum chamber can also be connected to the outside.

[0012] Secondly, embodiments of this application provide a sample purification method using the sample purification device described above. The method includes: injecting a biological sample into the sample pool via the inlet / outlet through the injection assembly; simultaneously or alternately providing negative pressure to the first chamber and the second chamber, so that filtrate from the biological sample in the sample pool with particle sizes smaller than the pore sizes of the first and second filter membranes enters the filtrate recovery container via the first and second chambers under the negative pressure; stopping the negative pressure provided to the first chamber and / or the second chamber, and controlling the two ultrasonic generators to vibrate to generate ultrasonic vibration waves; and recovering the target sample retained in the sample pool via the inlet / outlet through the injection assembly.

[0013] In some possible embodiments, during the sample purification process, the method further includes: monitoring the volume of the sample in the sample pool in real time using a volume monitoring module, and controlling the injection assembly to perform the recovery of the target sample based on the monitoring results.

[0014] In some possible embodiments, the sample purification device includes two sets of oscillation components with different frequencies, and the two ultrasound generators in each set of oscillation components have the same frequency. The step of controlling the oscillation components to vibrate in order to apply ultrasound vibration waves to the biological samples in the sample pool includes: controlling the two sets of oscillation components to vibrate alternately, and alternately applying ultrasound vibration waves of different frequencies to the biological samples in the sample pool.

[0015] The sample purification device and method provided in this application can quickly and effectively purify biological samples (such as platelet-rich plasma) by combining a purification chip with alternating ultrasonic oscillation and negative pressure aspiration, resulting in higher purity platelet-rich plasma, which is beneficial for controlling the concentration of growth factors in platelet-rich plasma. Furthermore, the volume monitoring module can monitor the liquid volume in the sample pool in real time, allowing users to select different purification levels according to their actual needs. In addition, beneficial components may also be present in other filtrates besides the target sample in the biological sample; by setting up a filtrate recovery container, the filtrate can be easily recovered. Attached Figure Description

[0016] Figure 1 This is a hardware architecture diagram of a sample purification apparatus provided in an embodiment of this application.

[0017] Figure 2 This is a schematic diagram of the sample purification device provided in one embodiment of this application.

[0018] Figure 3 This is a schematic diagram of the structure of a purification chip provided in an embodiment of this application.

[0019] Figure 4 This is a schematic diagram of the structure of a purification chip with two sets of oscillation components provided in one embodiment of this application.

[0020] Figure 5 This is a schematic diagram of the volume monitoring module and purification chip provided in an embodiment of this application.

[0021] Figure 6 This is a schematic diagram of the volume monitoring module and purification chip provided in another embodiment of this application.

[0022] Figure 7 A flowchart of a sample purification method provided in an embodiment of this application.

[0023] Explanation of main component symbols Sample purification device 100; purification chip 1; sample pool 101; first chamber 102; second chamber 103; first filter membrane 11; second filter membrane 12; first negative pressure port 13; second negative pressure port 14; inlet / outlet 15; inlet / outlet pipeline 16; first side wall 111; second side wall 112; bottom wall 113; top wall 114; first support part 115; second support part 116; liquid injection assembly 2; syringe 21; drive component 22; oscillation assembly 3; ultrasonic generator 31; purification circuit 4; filtrate recovery container 5; negative pressure drive assembly 6; controller 7; volume monitoring module 8; light source assembly 81; imaging assembly 82; moving mechanism 83; user interface 9.

[0024] The following detailed description, in conjunction with the accompanying drawings, will further illustrate this application. Detailed Implementation

[0025] The technical solutions in the embodiments of this application will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of this application, and not all embodiments.

[0026] It should be noted that when a component is described as "fixed to" or "mounted to" another component, it can be directly on the other component or may be interspersed with an intermediate component. When a component is described as "set to" another component, it can be directly set on the other component or may be interspersed with an intermediate component. The term "and / or" as used herein includes all and any combination of one or more of the associated listed items.

[0027] It should be noted that although a logical order is shown in the flowchart, in some cases, the steps shown or described may be performed in a different order than that shown in the flowchart. The methods disclosed in the embodiments of this application include one or more steps or actions for implementing the method. Method steps and / or actions may be interchanged with each other without departing from the scope of the claims. Unless a specific order of steps or actions is specified, the order and / or use of specific steps and / or actions may be modified without departing from the scope of the claims.

[0028] Please see Figure 1 and Figure 2 As shown, one embodiment of this application provides a sample purification device 100 for separating a target sample from a biological sample to purify the biological sample. For example, it can be used to purify platelet-rich plasma to increase the concentration of platelets. The sample purification device 100 includes a purification chip 1, a liquid injection assembly 2, an oscillation assembly 3, and a purification circuit 4. In addition, the sample purification device 100 also includes a controller 7, which can control the coordinated operation between the various parts of the sample purification device 100 to complete the biological sample purification process.

[0029] The purification chip 1 includes a sample pool 101 and a first chamber 102 and a second chamber 103 located on opposite sides of the sample pool 101. The sample pool 101 is connected to the first chamber 102 via a first filter membrane 11 and to the second chamber 103 via a second filter membrane 12. The pore sizes of both the first filter membrane 11 and the second filter membrane 12 are smaller than the particle size of the target sample to be separated from the biological sample. The outer wall of the first chamber 102 is provided with a first negative pressure port 13, and the outer wall of the second chamber 103 is provided with a second negative pressure port 14. The bottom of the purification chip 1 is provided with an inlet / outlet port 15 connected to the sample pool 101. The liquid injection assembly 2 is connected to the inlet / outlet port 15 and is used to inject biological samples into the sample pool 101 through the inlet / outlet port 15. The liquid injection assembly 2 is also used to recover the target sample separated from the biological sample in the sample pool 101. The oscillation component 3 can be held against the outer wall of the purification chip 1 to cause the liquid in the sample pool 101 to oscillate, facilitating the separation and purification of biological samples. The purification circuit 4 is connected to the first negative pressure port 13 and the second negative pressure port 14 respectively, to provide alternating negative pressure drive for the separation and purification of biological samples.

[0030] Please see Figure 2 and Figure 3As shown, the purification chip 1 can be a closed chip. The purification chip 1 also includes a first sidewall 111 and a second sidewall 112 disposed opposite to each other, and a bottom wall 113 and a top wall 114 connecting the first sidewall 111 and the second sidewall 112. A first filter membrane 11 is disposed inside the first sidewall 111 and forms the first chamber 102 with the first sidewall 111. A second filter membrane 12 is disposed inside the second sidewall 112 and forms the second chamber 103 with the second sidewall 112. The first sidewall 111, the first filter membrane 11, the second sidewall 112, the second filter membrane 12, the bottom wall 113, and the top wall 114 together form a closed sample pool 101, which can reduce the risk of biological sample contamination. Furthermore, the closed chip is not completely sealed; an interface (not shown) for communication with the outside is provided on the top wall 114, and an air filtration device (not shown) is provided at the interface to prevent external air from contaminating the sample during negative pressure suction. Understandably, in other embodiments, for some biological samples that are not easily contaminated and are not sensitive to air, the purification chip can also be an open chip, that is, without a top wall.

[0031] In some embodiments, a first support portion 115 is provided on the inner wall of the first sidewall 111, and a first filter membrane 11 is attached to the first support portion 115. The thickness of the first support portion 115 defines the thickness of the first chamber 102. Similarly, a second support portion 116 is provided on the inner wall of the second sidewall 112, and a second filter membrane 12 is attached to the second support portion 116. The thickness of the second support portion 116 defines the thickness of the second chamber 103. In some embodiments, the first support portion 115 and the first sidewall 111 are integrally formed, and the second support portion 116 and the second sidewall 112 are integrally formed, which can improve the structural strength of the purification chip 1.

[0032] In some embodiments, the first chamber 102 and the second chamber 103 are spaced apart from the bottom wall 113, and the inlet / outlet 15 is disposed through the first side wall 111 between the first chamber 102 and the bottom wall 113. Specifically, the inlet / outlet 15 is disposed through the first side wall 111 between the first support portion 114 and the bottom wall 113. Distributing the inlet / outlet 15 at the bottom of the sample pool 101 facilitates sample injection from the bottom of the sample pool 101, reducing the generation of excessive air bubbles during injection, which could clog the filter membrane and affect the filtration effect. Furthermore, it facilitates the full recovery of the separated and purified target sample.

[0033] Please see Figure 2 As shown, the injection assembly 2 includes a syringe 21 connected to the inlet / outlet 15 and a drive component 22 that drives the syringe 21, which can realize automatic injection or recovery of target samples.

[0034] In some embodiments, the drive unit 22 may include a drive motor and a screw.

[0035] In some embodiments, the inlet / outlet 15 is connected to an inlet / outlet pipe 16, and the end of the inlet / outlet pipe 16 away from the inlet / outlet 15 is provided with a standard connector (e.g., a Luer connector) that can be connected to the interface of most syringes.

[0036] Please see Figure 1 and Figure 2 As shown, the oscillation assembly 3 includes two ultrasonic generators 31, which are respectively held against the outer walls of the first chamber 102 and the second chamber 103, and generate ultrasonic vibration waves to achieve liquid disturbance.

[0037] Two ultrasonic generators 31 are respectively pressed against the outer surfaces of the first sidewall 111 and the second sidewall 112, generating transverse (i.e., perpendicular to the first sidewall 111 and the second sidewall 112, or horizontal) ultrasonic vibration waves. These transverse ultrasonic vibration waves are transmitted to the entire purification chip 1 through the outer walls of the first chamber 102 and the second chamber 103, causing the purification chip 1 to vibrate at high frequency, which in turn drives the first filter membrane 11 and the second filter membrane 12 to vibrate at high frequency. The two ultrasonic vibration waves together disturb the biological sample and generate acoustic streaming, preventing the target sample from clogging the filter pores or agglomerating. This allows the target sample adsorbed in the membrane pores to quickly separate from the membrane pores and be resuspended in the returned biological sample, thereby preventing the membrane pores from becoming clogged and achieving efficient separation.

[0038] In some embodiments, to achieve the above objectives, the ultrasonic vibration waves generated by the two ultrasonic generators 31 have a vibration frequency of 20kHz-70kHz, a power of less than or equal to 60W, and a voltage of less than or equal to 10V. Within one ultrasonic vibration wave cycle, the duty cycle of both ultrasonic vibration waves is less than or equal to 100%. By controlling the above ultrasonic parameters, the ultrasonic vibration waves can effectively penetrate the shell of the purification chip 1 and be transmitted to the first filter membrane 11 and the second filter membrane 12 inside, so that the filter membranes vibrate with a certain amplitude, which facilitates the faster separation of the target sample adsorbed on the filter membrane. At the same time, the ultrasonic vibration waves can disturb the liquid sample to generate an acoustic flow effect, which disperses the aggregated particles, prevents clogging of the filter membrane, and improves filtration efficiency. More importantly, the ultrasonic vibration waves within the above parameter range are less likely to damage the biological sample, ensuring the quality of separation and purification.

[0039] In some embodiments, the two ultrasonic generators 31 are located on the same horizontal plane. That is, the two ultrasonic vibration waves propagate in opposite directions and can superimpose on each other, further preventing filter membrane clogging and improving separation efficiency. In addition, the ultrasonic vibration waves of the two ultrasonic generators 31 have the same frequency, and when they superimpose, they can generate resonance, further improving the anti-clogging and separation effects.

[0040] In some embodiments, the ultrasonic generator 31 is movably configured to adhere to the outer wall of the purification chip 1 during purification and to be removed after purification. This eliminates the need for a vibrating element on the purification chip 1, thereby reducing chip costs.

[0041] Please see Figure 4 As shown, the sample purification device 100 may include multiple sets of oscillation components 3 with different frequencies, for example, it may include two sets of oscillation components 3 with different frequencies. The two ultrasonic generators 31 in each set of oscillation components 3 have the same ultrasonic frequency. By setting two sets of oscillation components 3 with different frequencies, alternating high and low frequency vibrations can be achieved, which is more targeted. For example, when the filter membrane is severely clogged, high-frequency vibration can be used to detach the particles adsorbed on the filter membrane. When the filter membrane is not severely clogged, low-frequency vibration can be used to disturb the liquid flow, improve the separation effect, and further reduce damage to biological samples and reduce energy consumption.

[0042] Please see Figure 1 and Figure 2 As shown, the purification circuit 4 includes a filtrate recovery container 5 and a negative pressure drive assembly 6 that are interconnected. The filtrate recovery container 5 is also connected to a first negative pressure port 13 and a second negative pressure port 14, respectively. The negative pressure drive assembly 6 is used to provide negative pressure to the first chamber 102 and the second chamber 103 simultaneously or alternately, so that the filtrate of the biological sample in the sample pool 101, excluding the target sample, enters the filtrate recovery container 5 through the first filter membrane 11 and the first negative pressure port 13, or through the second filter membrane 12 and the second negative pressure port 14, under the negative pressure.

[0043] In some embodiments, the filtrate recovery container 5 may include a recovery bottle. The recovery bottle is simultaneously connected to a first negative pressure port 13 and a second negative pressure port 14 via two conduits. The recovery bottle is further connected to a negative pressure drive assembly 6, which simultaneously provides negative pressure to the first chamber 102 and the second chamber 103, allowing filtrate particles smaller than the pore sizes of the first and second filter membranes 11 and 12 in the biological sample within the sample pool 101 to be simultaneously recovered into the recovery bottle. Since the filtrate also contains beneficial components, this method achieves optimal filtrate recovery and avoids filtrate waste.

[0044] It is understandable that solenoid valves can be installed on the two pipelines connecting the first negative pressure port 13 and the second negative pressure port 14 to control the opening and closing of the corresponding pipelines. The negative pressure drive assembly 6 can alternately provide negative pressure to the first chamber 102 and the second chamber 103. Under the action of alternating negative pressure, the filtrate in the first chamber 102 and the second chamber 103 is alternately drawn into the recovery bottle.

[0045] Please see Figure 1 , Figure 2 and Figure 5 As shown, the sample purification device 100 also includes a volume monitoring module 8. The volume monitoring module 8 is used to monitor the volume of the biological sample in the sample pool 101 in real time. When the purification volume reaches the target requirement, the purification process can be stopped, and the purified target sample in the sample pool 101 can be recovered through the liquid injection component 2. The volume monitoring module 8 can be a camera module, capable of monitoring the liquid volume in the sample pool 101 in real time, and notifying the controller 7 to stop purification when the user-set value is reached.

[0046] In some embodiments, the volume monitoring module 8 includes a light source component 81 and an imaging component 82. The light source component 81 emits light toward the sample pool 101, and the imaging component 82 takes an image of the sample pool 101 when the light source component 81 emits light toward the sample pool 101. The housing of the purification chip 1 can be a transparent housing, so that the liquid level inside the sample pool 101 can be seen after taking an image of the sample pool 101. In addition, the housing of the purification chip 1 can also be provided with volume scales, so that the volume of liquid in the sample pool 101 can be directly identified through the image, which is simple, convenient, and accurate in volume identification without the need for complex calculations.

[0047] After the imaging component 82 acquires an image, it transmits it to the controller 7. The controller 7 can identify the image and obtain the liquid volume. When the obtained liquid volume reaches the preset value, it can control the negative pressure drive component 6 and the oscillation component 3 to stop the purification action, and control the liquid injection component 2 to recover the separated target sample.

[0048] In some embodiments, the light emitted by the light source assembly 81 can illuminate the entire range from the bottom to the top of the sample pool 101, which allows for more intuitive monitoring of the volume changes of the liquid in the sample pool 101.

[0049] In other embodiments, such as Figure 6 As shown, the volume monitoring module 8 also includes a moving mechanism 83. The light source assembly 81 and the imaging assembly 82 are both mounted on the moving mechanism 83. The moving mechanism 83 is used to move the light source assembly 81 and the imaging assembly 82 between the top and bottom of the purification chip 1 (i.e., move vertically). When the height of the purification chip 1 is high or the installation space of the volume monitoring module 8 is limited, making it difficult to capture the entire sample pool 101, the light source assembly 81 and the imaging assembly 82 can be moved vertically by the simple moving mechanism 83 to capture images of the liquid level position in the sample pool 101. Since the chip shell has scale lines, the liquid volume can also be obtained. Moreover, in this way, the imaging assembly 82 acquires a local image of the sample pool 101, which makes the liquid level acquisition more accurate and can further improve the accuracy of the reading.

[0050] Please see Figure 7As shown, combined Figures 1 to 6 This application also provides a sample purification method using the sample purification device 100 described above. Before purification, it is necessary to connect the various pipelines in the device, clamp the purification chip 1 from the left and right sides using two ultrasonic generators 31, and connect the first negative pressure port 13 and the second negative pressure port 14 to the filtrate recovery container 5 through pipelines. The filtrate recovery container 5 is connected to the first solenoid valve 63 through a quick-connect plug 64, and the inlet and outlet pipelines 16 are connected to the interface of the syringe 21 through a standard connector.

[0051] The sample purification method includes the following steps: In step S10, the biological sample is injected into the sample pool 101 through the inlet / outlet 15 via the injection component 2.

[0052] In step S20, negative pressure is simultaneously or alternately provided to the first chamber 102 and the second chamber 103, so that the filtrate of the biological sample in the sample pool 101 with a particle size smaller than the pore size of the first filter membrane 11 and the second filter membrane 12 enters the filtrate recovery container 5 through the first chamber 102 and the second chamber 103 under the action of the negative pressure.

[0053] Step S30: Stop providing negative pressure to the first chamber 102 and / or the second chamber 103, and control the two ultrasonic generators 31 to vibrate to generate ultrasonic vibration waves.

[0054] In step S40, the target sample retained in the sample pool 101 is recovered through the inlet / outlet 15 via the liquid injection component 2.

[0055] Steps S20 and S30 can be repeated multiple times until the desired target sample volume is reached, at which point the process can be stopped. Understandably, the order of negative pressure suction and ultrasonic vibration is not limited to the aforementioned steps and can be adjusted according to actual needs.

[0056] Ultrasonic vibration waves cause the biological sample, the first filter membrane 11, and the second filter membrane 12 to vibrate at high frequency. This allows particles adsorbed in the membrane pores to quickly separate from the pores and be resuspended in the reflux liquid, preventing membrane clogging and preventing the target sample from agglomerating and encapsulating small particles, thus reducing the purity of the target sample. The negative pressure drive assembly 6 simultaneously provides negative pressure to both the first chamber 102 and the second chamber 103, causing the filtrate in the sample pool 101 to be recycled into the same recovery bottle. Since the filtrate also contains beneficial components, this method achieves optimal filtrate recovery, avoids waste, and reduces the risk of filtrate contamination.

[0057] The sample purification device 100 may include two sets of oscillation components 3 with different frequencies. In steps S30 and S50, the two sets of oscillation components 3 can be controlled to vibrate alternately to apply ultrasonic vibration waves of different frequencies to the biological samples in the sample pool 101.

[0058] Furthermore, during sample purification, the method also includes: real-time monitoring of the sample volume in the sample pool 101 using the volume monitoring module 8, and controlling the injection assembly 2 to recover the target sample based on the monitoring results. For details on the volume monitoring method, please refer to the foregoing description.

[0059] Furthermore, the sample purification device 100 may also include a user interface 9, such as a display screen and keyboard, allowing the user to input the desired purification volume. This enables the sample purification device 100 to automatically control the purification process. When the volume monitoring module 8 detects that the liquid volume in the sample pool 101 has reached the required purification volume, purification can be stopped, and the purified sample in the sample pool 101 can be recovered via the injection component 2. For example, when the biological sample is platelet-rich plasma, the user can select different levels of purification of platelet-rich plasma based on the patient's condition.

[0060] When purification circuit 4 simultaneously provides negative pressure to the first chamber 102 and the second chamber 103, the sample purification method includes the following steps: In step S1a, the biological sample is injected into the sample pool 101 through the inlet / outlet 15 via the injection component 2.

[0061] Step S2a: Negative pressure is simultaneously provided to the first chamber 102 and the second chamber 103, so that the filtrate of the biological sample in the sample pool 101 with a particle size smaller than the pore size of the first filter membrane 11 and the second filter membrane 12 enters the filtrate recovery container 5 through the first chamber 102 and the second chamber 103 under the action of the negative pressure.

[0062] In step S3a, the negative pressure supplied to the first chamber 102 and the second chamber 103 is stopped, and the two ultrasonic generators 31 are controlled to vibrate to generate ultrasonic vibration waves.

[0063] Step S4a: The target sample retained in the sample pool 101 is recovered through the inlet / outlet 15 via the liquid injection component 2.

[0064] In addition, when purification circuit 4 alternately provides negative pressure to the first chamber 102 and the second chamber 103, the purification method specifically includes the following steps: In step S1b, the biological sample is injected into the sample pool 101 through the inlet / outlet 15 via the injection component 2.

[0065] In step S2b, a negative pressure is provided to the first chamber 102, so that the filtrate in the biological sample in the sample pool 101 with a particle size smaller than the pore size of the first filter membrane 11 enters the first chamber 102 under the action of the negative pressure, and further enters the filtrate recovery container 5.

[0066] In step S3b, the negative pressure supplied to the first chamber 102 is stopped, and the two ultrasonic generators 31 are controlled to vibrate to generate ultrasonic vibration waves.

[0067] Step S4b: Provide negative pressure to the second chamber 103, so that the filtrate from the biological sample in the sample pool 101 with a particle size smaller than the pore size of the second filter membrane 12 enters the second chamber 103 under the action of the negative pressure, and further enters the filtrate recovery container 5.

[0068] In step S5b, the negative pressure supplied to the second chamber 103 is stopped, and the two ultrasonic generators 31 are controlled to vibrate to generate ultrasonic vibration waves.

[0069] In step S6b, the target sample retained in the sample pool 101 is recovered through the inlet / outlet 15 via the liquid injection component 2.

[0070] Steps S2b to S5b can be repeated multiple times until the desired target sample volume is achieved, at which point the process can be stopped. The alternating aspiration time and frequency can be designed according to actual needs. Understandably, the sequence of negative pressure aspiration and ultrasonic vibration is not limited to the aforementioned steps and can be adjusted according to actual requirements.

[0071] In this embodiment, by alternately providing negative pressure to the first chamber 102 and the second chamber 103, when the negative pressure driving component 50 draws the first chamber 102 through the first negative pressure port 13, the components adhering to the surface of the second filter membrane 12 can return to the sample pool 101 with the airflow and / or liquid flow, thus preventing the second filter membrane 12 from becoming clogged. Similarly, when the second chamber 103 is drawn by negative pressure, it can also prevent the first filter membrane 11 from becoming clogged. This method can further reduce the risk of filter membrane clogging.

[0072] The sample purification device 100 and sample purification method provided in this application embodiment can quickly and effectively purify biological samples (such as platelet-rich plasma) by combining the purification chip 1 with alternating ultrasonic oscillation and negative pressure aspiration, resulting in higher purity platelet-rich plasma, which is beneficial for controlling the concentration of growth factors in platelet-rich plasma. Furthermore, the volume monitoring module 8 can monitor the liquid volume in the sample pool 101 in real time, allowing users to select different purification levels according to actual needs. In addition, beneficial components may also exist in other filtrates besides the target sample in the biological sample; by setting up the filtrate recovery container 5 in conjunction with the negative pressure drive component 6, the filtrate recovery is facilitated.

[0073] Using this sample purification device 100, platelet-rich plasma can be obtained by blood centrifugation and further purified after activation, thereby effectively controlling the concentration of growth factors in platelet-rich plasma.

[0074] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of this application and are not intended to limit it. Although this application has been described in detail with reference to preferred embodiments, those skilled in the art should understand that modifications or equivalent substitutions can be made to the technical solutions of this application without departing from the spirit and scope of the technical solutions of this application.

Claims

1. A sample purification apparatus for separating a target sample from a biological sample, characterized in that, The sample purification device includes: The purification chip includes a sample pool and a first chamber and a second chamber located on opposite sides of the sample pool. The sample pool is connected to the first chamber through a first filter membrane and to the second chamber through a second filter membrane. The outer wall of the first chamber is provided with a first negative pressure port and the outer wall of the second chamber is provided with a second negative pressure port. The bottom of the purification chip is provided with an inlet and outlet port connected to the sample pool. The liquid injection assembly is connected to the inlet and outlet. The liquid injection assembly is used to inject biological samples into the sample pool through the inlet and outlet. The liquid injection assembly is also used to recover the target samples separated from the biological samples in the sample pool. An oscillation assembly includes two ultrasonic generators, which are respectively abutted against the outer walls of the first chamber and the second chamber; and The purification circuit includes a filtrate recovery container and a negative pressure drive assembly that are interconnected. The filtrate recovery container is also connected to a first negative pressure port and a second negative pressure port, respectively. The negative pressure drive assembly is used to simultaneously or alternately provide negative pressure to the first chamber and the second chamber, so that the filtrate of the biological sample in the sample pool, excluding the target sample, enters the filtrate recovery container through the first negative pressure port and the second negative pressure port under the negative pressure.

2. The sample purification apparatus as described in claim 1, characterized in that, It also includes a volume monitoring module, which is used to monitor the volume of biological samples in the sample pool in real time.

3. The sample purification apparatus as described in claim 2, characterized in that, The volume monitoring module includes a light source component and an imaging component. The light source component is used to emit light toward the sample pool, and the imaging component is used to take pictures of the sample pool when the light source component emits light toward the sample pool.

4. The sample purification apparatus as described in claim 3, characterized in that, The light emitted by the light source assembly can illuminate the entire range from the bottom to the top of the sample pool; or The volume detection module also includes a moving mechanism, on which the light source component and the imaging component are both mounted. The moving mechanism is used to move the light source component and the imaging component between the top and bottom of the purification chip.

5. The sample purification apparatus as described in claim 1, characterized in that, It includes two sets of oscillation components with different frequencies. The two ultrasonic generators in each set of oscillation components have the same frequency, which is 20~70KHz.

6. The sample purification apparatus as described in claim 1, characterized in that, The purification chip is a closed chip, which includes a first sidewall and a second sidewall disposed opposite to each other, and a bottom wall and a top wall connecting the first sidewall and the second sidewall. The first filter membrane is disposed inside the first sidewall and forms a first chamber with the first sidewall. The second filter membrane is disposed inside the second sidewall and forms a second chamber with the second sidewall. The first chamber and the second chamber are spaced apart from the bottom wall. The inlet and outlet are disposed through the first sidewall between the first chamber and the bottom wall.

7. The sample purification apparatus as described in claim 1, characterized in that, The injection assembly includes a syringe connected to the inlet / outlet and a drive component for driving the syringe; and / or, The negative pressure drive assembly includes a vacuum chamber connected to the filtrate recovery container and a vacuum pump connected to the vacuum chamber. The vacuum chamber can also be connected to the outside.

8. A sample purification method using the sample purification apparatus as described in claim 1, characterized in that, include: Biological samples are injected into the sample pool via the inlet and outlet through the injection assembly; Negative pressure is simultaneously or alternately provided to the first chamber and the second chamber, so that the filtrate of the biological sample in the sample pool with a particle size smaller than the pore size of the first filter membrane and the second filter membrane enters the filtrate recovery container through the first chamber and the second chamber under the action of the negative pressure; Stop providing negative pressure to the first chamber and / or the second chamber, and control the vibration of both ultrasound generators to generate ultrasonic vibration waves; and The target sample retained in the sample pool is recovered via the inlet and outlet through the injection assembly.

9. The sample purification method as described in claim 8, characterized in that, The method further includes the following during sample purification: The volume monitoring module monitors the volume of the sample in the sample pool in real time, and controls the injection assembly to recover the target sample based on the monitoring results.

10. The sample purification method as described in claim 9, characterized in that, The sample purification device includes two sets of oscillation components with different frequencies, and the two ultrasound generators in each set of oscillation components have the same frequency. The step of controlling the oscillation components to vibrate in order to apply ultrasound vibration waves to the biological samples in the sample pool includes: The two sets of oscillation components are controlled to vibrate alternately, thereby applying ultrasonic vibration waves of different frequencies to the biological samples in the sample pool.

Images