Device and method for extracting substances in microfluid and device for extracting bacteria in blood

Abstract

The invention provides a device and a method for extracting substances in microfluid and a device for extracting bacteria in blood. In the application, a sound surface standing wave can be generated in the microchannel through which the microfluid flows through the transducer to form a sound field, the sound field generates a sound streaming effect in the flowing process of the microfluid, and one or more parameters of the size of the microchannel, the frequency of the transducer, the voltage and the flow of the microfluid can be adjusted according to the size of the target substance. Therefore, the submicron-level target substance is gathered at the center of a flow vortex generated by the acoustic streaming effect under the action of the acoustic streaming effect so as to be separated or extracted.

Description

[0001] This application claims priority to U.S. Provisional Patent No. US 63 / 530,345 filed in the U.S. Patent Office on August 2, 2023, the entire contents of which are incorporated by reference into this application. Technical Field

[0002] The present application relates to the field of microfluid extraction technology, and in particular to a device and method for extracting substances in microfluids and a device for extracting bacteria in blood. Background Art

[0003] Microfluidics refers to tiny fluids, such as fluids in tiny pipes. Research on microfluidics has gradually developed in the fields of biology, chemistry, materials, and medicine, and how to extract substances in microfluidics has received widespread attention. Summary of the invention

[0004] The embodiments of the present application provide a device and method for extracting substances in microfluids and a device for extracting bacteria in blood.

[0005] In a first aspect, an embodiment of the present application provides a device for extracting a substance in a microfluidic system, including an extraction module, wherein the extraction module includes:

[0006] A first microchannel, for a microfluid to flow through, wherein the microfluid includes a target substance to be extracted, and the size of the target substance is submicron level;

[0007] A first transducer is used to generate standing surface acoustic waves (SSAW) in the first microchannel to form a first acoustic field, wherein the first acoustic field is used to make the microfluid flow in the first microchannel along a first direction, and the first acoustic field generates an acoustic streaming effect (ASE) in the microfluid;

[0008] Among them, one or more parameters among the size of the first microchannel, the frequency of the first transducer, the voltage of the first transducer, the flow rate of the microfluid, and the size of the target substance satisfy a first relationship, and the first relationship is determined based on a first condition, and the first condition is that the target substance is gathered in the target streamline in the microfluid under the action of ASE, and the target streamline passes through the center of the flow vortex generated by ASE.

[0009] Optionally, the first condition also includes:

[0010] Under the action of ASE, substances other than the target substance in the microfluidic are gathered in the non-target streamlines in the microfluidic, and the non-target streamlines pass through the low flow velocity area outside the flow vortex generated by ASE.

[0011] Optionally, the device includes a plurality of extraction modules, the plurality of extraction modules are arranged sequentially along a first direction, the first microchannels in the plurality of extraction modules are connected sequentially along the first direction, and target substances of different extraction modules are different.

[0012] Optionally, the sizes of the target substances in different extraction modules decrease sequentially along the first direction.

[0013] In a second aspect, an embodiment of the present application provides a device for extracting bacteria from blood, comprising a first extraction module, a second extraction module, and a third extraction module, wherein the extraction modules are arranged in sequence along a first direction, and the blood flows in the first direction, and the extraction modules are used to extract target substances in the blood in sequence;

[0014] The extraction modules include:

[0015] A first microchannel, for blood to flow through, wherein the first microchannels in each extraction module are sequentially connected along a first direction;

[0016] A first transducer, used for generating SSAW in the first microchannel to form a first acoustic field, the first acoustic field is used for making the blood flow in the first microchannel along a first direction, and the first acoustic field generates ASE in the blood;

[0017] wherein one or more parameters among the size of the first microchannel, the frequency of the first transducer, the voltage of the first transducer, and the flow rate of the blood satisfy a first relationship with the size of the target substance, and the first relationship is determined based on the first condition;

[0018] The first extraction module is used to extract particles larger than 5 μm, and the particles larger than 5 μm include blood cells. The first condition of the first extraction module is that the particles larger than 5 μm are gathered at the pressure node of the SSAW under the action of the SSAW.

[0019] The second extraction module is used to extract submicron particles, which include platelets and bacteria. The first condition of the second extraction module is:

[0020] Submicron-sized particles are gathered in the target streamline in the blood under the action of ASE, and the target streamline passes through the center of the flow vortex generated by ASE;

[0021] And the rest of the substances in the blood are gathered in the non-target streamlines in the blood under the action of ASE, and the non-target streamlines pass through the low flow velocity area outside the flow vortex generated by ASE;

[0022] The third extraction module is used to extract bacteria from submicron particles. The first condition of the third extraction module is:

[0023] Under the action of ASE, bacteria gather in the target streamline in the blood, which passes through the center of the flow vortex generated by ASE;

[0024] And the remaining submicron particles are gathered in the non-target streamlines in the blood under the action of ASE, and the non-target streamlines pass through the low flow velocity area outside the flow vortex generated by ASE.

[0025] Optionally, the device further comprises a sample collector and a waste collector, wherein the sample collector is used to collect bacteria, and the waste collector is used to collect substances other than bacteria in the blood.

[0026] Optionally, the first microchannel is a cubic polydimethylsiloxane (PDMS) channel, and the first transducer is located on both sides of the first microchannel.

[0027] Optionally, the blood flow rates in the first, second and third extraction modules are 10ul / ml, 1ul / ml and 0.1ul / ml respectively, the widths of the first microchannels in the first, second and third extraction modules are 400μm, 200μm and 400μm respectively, and the heights of the first microchannels in the first, second and third extraction modules are 30μm, 70μm and 70μm respectively.

[0028] Optionally, the voltage and frequency of the first transducer are provided by a signal generator, with the voltage being 10 V and the frequency being 18.6 MHz.

[0029] In a third aspect, the present application provides a method for extracting a substance in a microfluidic system, comprising:

[0030] Based on the acoustic field formed by the surface acoustic standing wave (SSAW) in the microfluid, the acoustic streaming effect (ASE) is generated to enrich the target substance in the microfluid;

[0031] Separate and enrich the target substance;

[0032] Among them, the size of the microchannel through which the microfluid flows, the frequency and voltage of the transducer that generates the acoustic field, one or more parameters in the flow rate of the microfluid satisfy a first relationship with the size of the target substance, and the first relationship is determined based on a first condition, and the first condition is that the target substance is gathered in the target streamline in the microfluid under the action of ASE, and the target streamline passes through the center of the flow vortex generated by ASE.

[0033] In the present application, a transducer can be used to generate surface standing waves in a microchannel through which a microfluid flows to form a sound field. The sound field produces an acoustic streaming effect during the flow of the microfluid, and one or more parameters including the size of the microchannel, the frequency and voltage of the transducer, and the flow rate of the microfluid can be adjusted according to the size of the target substance, so that submicron-level target substances can be gathered in the center of the flow vortex generated by the acoustic streaming effect under the action of the acoustic streaming effect and thus be separated or extracted. BRIEF DESCRIPTION OF THE DRAWINGS

[0034] In order to more clearly illustrate the technical solutions in the embodiments of the present application, the drawings required for describing the embodiments are briefly introduced below.

[0035] Figure 1 Schematic diagram of the acoustic field in the microfluid provided in the embodiment of the present application.

[0036] Figure 2 It is a schematic diagram of the structure of the device for extracting substances in microfluidics provided in an embodiment of the present application.

[0037] Figure 3 This is a structural example diagram of the extraction module provided in an embodiment of the present application.

[0038] Figure 4 It is a schematic diagram of the structure of the device for extracting bacteria from blood provided in an embodiment of the present application.

[0039] Figure 5 This is a structural example diagram of the third microchannel provided in an embodiment of the present application.

[0040] Figure 6 It is a schematic diagram of the process of extracting bacteria from blood provided in one embodiment of the present application.

[0041] Figure 7 It is a schematic flow chart of a process for extracting bacteria from blood provided in another embodiment of the present application.

[0042] Figure 8A-8C This is an example diagram of the state of blood flowing through the extraction device provided in an embodiment of the present application.

[0043] Fig. 9 It is a schematic flow chart of the method for extracting substances in microfluidics provided in an embodiment of the present application.

[0044] Fig.10 It is a schematic diagram of the structure of an electronic device provided in an embodiment of the present application. DETAILED DESCRIPTION

[0045] The technical solution of the embodiment of the present invention will be described below in conjunction with the accompanying drawings in the embodiment of the present invention.

[0046] Microfluidics refers to tiny fluids, such as fluids in tiny pipes. Research on microfluidics has gradually developed in the fields of biology, chemistry, materials, and medicine, and how to extract substances in microfluidics has received widespread attention. The combination of acoustics and microfluidic control technology can accurately and quickly extract and separate substances in microfluidics, such as blood component separation, stem cell extraction, and cancer cell separation.

[0047] Most acoustofluidic separation devices generate an acoustic field in a fluid-filled microchannel and use acoustic radiation force (ARF) to control the trajectory of particles in the fluid. Figure 1 As shown, in the acoustic field of the microchannel, the acoustic wave propagates perpendicularly to the fluid flow direction, and a streaming vortex having a rotation axis parallel to the flow direction is formed in the microchannel.

[0048] Typically, the ARF drives particles with an acoustic contrast factor (ACF) to a pressure node in the acoustic field. The ACF is a parameter that takes into account the compressibility and density of the particle and fluid medium. The ARF varies with particle volume, and larger particles experience a stronger ARF, allowing them to reach the pressure node faster and be extracted or separated.

[0049] In addition to ARF, particles in the acoustic field are also subject to the Stokes drag force caused by ASE, which is a secondary effect of wave propagation and is proportional to the diameter of the particle. For small particles, the drag caused by ASE overcomes the ARF and drives the particles to circular streamlines, which poses a lower size limit for ARF-driven particle separation. Therefore, suppressing ASE has become a common goal to improve nanoparticle processing.

[0050] However, related studies have found that in some cases ASE can promote the aggregation of substances in microfluidics. Usually in a flow vortex, particles are affected by shear gradients and inertial forces. The explanation for ASE promoting the aggregation of substances is that there is a shear gradient near the center of the vortex and far away from the center of the vortex: the shear gradient of smaller particles (such as bacteria) can overcome the inertia force and diffuse from the high shear zone far away from the center of the vortex to the low shear zone in the center of the vortex; the inertia force of slightly larger particles can overcome the shear gradient and move away from the center of the vortex. Since the axis of rotation of the vortex is parallel to the lateral flow, the focused particles can move along the flow. However, the aggregation of substances in microfluidics based on ASE is affected by many factors, and how to better use ASE to aggregate substances in microfluidics remains to be studied.

[0051] Based on this, Figure 2 The device for extracting substances from microfluids provided in an embodiment of the present application is shown. It is worth noting that the type of microfluids applicable to the device is not limited, for example, it can be blood or water.

[0052] See also Figure 2The device 200 may include an extraction module 210, and the extraction module 210 may include a first microchannel 211 and a first transducer 212. As an example, the structure of the extraction module may be as follows: Figure 3 shown.

[0053] The first microchannel 211 can be used for a microfluid to flow through, and the microfluid includes a target substance to be extracted, and the size of the target substance is submicron level. In the present application, submicron level refers to a size of less than 5 μm and more than 100 nm. For example, the target substance can be bacteria. The material of the first microchannel 211 is not limited, for example, it can be PDMS.

[0054] The first transducer 212 can be used to generate SSAW in the first microchannel 211 to form a first acoustic field, and the first acoustic field can be used to make the microfluid flow in the first microchannel 211 along a first direction, and the first acoustic field can generate ASE in the microfluid. Figure 3 As shown, the first direction may be the extension direction of the first microchannel 211. The type of the first transducer is not limited, for example, it may be an interdigital transducer (IDTs). The number of the first transducers is also not limited, and usually two opposite transducers can generate an acoustic field in the microchannel.

[0055] Among them, one or more parameters among the size of the first microchannel 211, the frequency of the first transducer 212, the voltage of the first transducer 212, the flow rate of the microfluid, and the size of the target substance satisfy a first relationship, and the first relationship is determined based on a first condition, and the first condition is that the target substance is gathered in the target streamline in the microfluid under the action of ASE, and the target streamline passes through the center of the flow vortex generated by ASE. That is, one or more parameters among the size of the first microchannel 211, the frequency of the first transducer 212, the voltage of the first transducer 212, the flow rate of the microfluid, and the size of the target substance satisfy a certain quantitative relationship, so that the target substance can be gathered in the center of the flow vortex generated by ASE under the action of ASE.

[0056] As mentioned above, the aggregation process of substances in microfluids under the action of ASE is affected by different factors. The inventors of the present application found through further research that these factors include the flow rate of the microfluid (determined by the size and flow rate of the microchannel), the size of the substance, the excitation frequency and voltage of the acoustic field, the boundary of the fluid (i.e., the size of the microchannel), etc. And the magnitude relationship of these factors can be determined based on the calculation and experiment of the mechanical relationship of the substance in the fluid, where the mechanical relationship involves the wave equation, the fluid mechanics Navier-Stokes equations, etc.

[0057] Therefore Figure 2In the device shown, a transducer can be used to generate surface acoustic standing waves in a microchannel through which the microfluid flows to form an acoustic field. The acoustic field produces an acoustic flow effect during the flow of the microfluid, and one or more parameters including the size of the microchannel, the frequency and voltage of the transducer, and the flow rate of the microfluid can be adjusted according to the size of the target substance, so that submicron-level target substances can be gathered in the center of the flow vortex generated by ASE under the action of ASE and thus be separated or extracted.

[0058] Optionally, the first condition may also include: substances other than the target substance in the microfluid are gathered in non-target streamlines in the microfluid under the action of ASE, and the non-target streamlines pass through the low flow velocity area outside the flow vortex generated by ASE. For example, the size of substances other than the target substance in the microfluid may be larger than the size of the target substance. Then, one or more parameters of the size of the microchannel, the frequency and voltage of the transducer, and the flow rate of the microfluid may be adjusted according to the size of the target substance, so that substances in the microfluid with a size larger than the target substance are gathered in the low flow velocity area outside the flow vortex generated by ASE under the action of ASE, thereby maintaining a certain distance from the target substance at the center of the flow vortex. Based on this, the distance between the target substance and other substances in the microfluid can be increased, which is conducive to the separation of the target substance.

[0059] Optionally, the device may include a plurality of extraction modules, the plurality of extraction modules may be arranged in sequence along a first direction, the first microchannels 211 in the plurality of extraction modules may be connected in sequence along the first direction, and the target substances of different extraction modules are different. For example, the device may include three extraction modules, the first microchannels 211 in the three extraction modules are connected in sequence along the flow direction of the microfluid, so the microfluid may flow through the first microchannels 211 in the three extraction modules in sequence. The target substances of different extraction modules may be different, and one or more parameters of the size of the first microchannel 211 of different extraction modules, the frequency of the first transducer 212, the voltage of the first transducer 212, the flow rate of the microfluid, and the size of the target substance may be different. Based on this, the device can extract different substances in the microfluid in sequence.

[0060] Optionally, the sizes of target substances in different extraction modules can be reduced in sequence along the first direction. That is, along the flow direction of the microfluid, the device can extract substances in the microfluid in order from large to small according to the size of the target substances, which is conducive to the step-by-step extraction of different target substances in the microfluid.

[0061] It is worth noting that Figure 2 The extraction device shown can be used in conjunction with other devices during use, such as a pump (for controlling the flow of microfluids), a signal generator (for exciting the transducer), a microscope (for observing the state of microfluids), a computer (for analyzing the state of microfluids), etc.

[0062] As mentioned above, microfluidics research has also made some progress in fields such as medicine. In modern medicine, bloodstream infection (BSI) can be life-threatening if not treated in time. Traditionally. The bacteria causing the infection can usually be identified through blood culture tests, which usually take 3-5 days. However, due to the increase in mortality over time, patients are usually given a wide range of antibiotics before the test results are available. This may cause overuse of antibiotics, thereby accelerating the process of antibiotic resistance. To speed up the diagnosis of BSI, molecular methods have great potential and can give results within a few hours. However, its use is limited by variable sensitivity, sensitivity to contaminants, and small sample sizes. Running multiple molecular tests simultaneously may improve performance, but will significantly increase costs.

[0063] Based on this, Figure 4 As shown, the embodiment of the present application also provides a device for extracting bacteria from blood. It is worth noting that the extraction device can be used in conjunction with other devices during use, such as a pump (for controlling blood flow), a signal generator (for exciting the transducer), a microscope (for observing the state of blood), a computer (for analyzing the state of blood), etc.

[0064] See also Figure 4 The device 400 may include a first extraction module 410, a second extraction module 420, and a third extraction module 430. The extraction modules may be arranged sequentially along a first direction, the blood may flow along the first direction, and the extraction modules may be used to sequentially extract target substances in the blood.

[0065] Each extraction module may include a first microchannel 401 and a first transducer 402. The first microchannel 401 may be used for blood to flow through, and the first microchannels in each extraction module may be connected in sequence along a first direction. The material of the first microchannel 401 is not limited, and may be PDMS, for example. The first transducer 402 may be used to generate SSAW in the first microchannel to form a first acoustic field, and the first acoustic field may be used to make blood flow in the first microchannel along a first direction, and the first acoustic field generates ASE in the blood. The type of the first transducer 402 is not limited, and may be IDTs, for example. The number of first transducers 402 is also not limited, and for example, one first microchannel 401 may correspond to two first transducers 402.

[0066] Among them, one or more parameters among the size of the first microchannel 401, the frequency of the first transducer 402, the voltage of the first transducer 402, and the flow rate of blood may satisfy a first relationship with the size of the target substance, and the first relationship is determined based on the first condition.

[0067] The first extraction module 410 can be used to extract particles larger than 5 μm, including blood cells. The first condition of the first extraction module 410 can be that particles larger than 5 μm gather at the pressure node of SSAW under the action of SSAW. The pressure node of SSAW is the point where the amplitude is 0 in SSAW. That is, in the first extraction module, one or more parameters of the size of the first microchannel 401, the frequency of the first transducer 402, the voltage of the first transducer 402, and the flow rate of the blood can satisfy a certain quantitative relationship with the size of the target substance (larger than 5 μm), so that particles larger than 5 μm gather at the pressure node of SSAW under the action of SSAW and are separated.

[0068] The second extraction module 420 can be used to extract submicron particles, which may include platelets and bacteria. The first condition of the second extraction module 420 may be: submicron particles gather in the target streamline in the blood under the action of ASE, and the target streamline passes through the center of the flow vortex generated by ASE; and the remaining substances in the blood gather in the non-target streamline in the blood under the action of ASE, and the non-target streamline passes through the low flow velocity area outside the flow vortex generated by ASE. That is, in the second extraction module, one or more parameters of the size of the first microchannel 401, the frequency of the first transducer 402, the voltage of the first transducer 402, and the flow rate of the blood may satisfy a certain quantitative relationship with the size of the target substance (submicron level), so that the submicron particles can gather in the center of the flow vortex generated by ASE under the action of ASE, while the remaining substances in the blood can gather in the low flow velocity area outside the flow vortex generated by ASE under the action of ASE, so that the submicron particles can be separated from the remaining substances in the blood.

[0069] The third extraction module 430 can be used to extract bacteria from submicron particles. The first condition of the third extraction module 430 can be: bacteria gather in the target streamline in the blood under the action of ASE, and the target streamline passes through the center of the flow vortex generated by ASE; and the remaining submicron particles (such as platelets) gather in the non-target streamline in the blood under the action of ASE, and the non-target streamline passes through the low flow rate area outside the flow vortex generated by ASE. That is, in the third extraction module, one or more parameters of the size of the first microchannel 401, the frequency of the first transducer 402, the voltage of the first transducer 402, and the flow rate of the blood can satisfy a certain quantitative relationship with the size of the target substance (submicron level), so that bacteria can gather in the center of the flow vortex generated by ASE under the action of ASE, and the remaining submicron particles can gather in the low flow rate area outside the flow vortex generated by ASE under the action of ASE, so that bacteria can be separated from the remaining submicron particles.

[0070] exist Figure 4 In the device shown, SSAW can be generated by the transducer in the microchannel through which the blood flows to form an acoustic field. The acoustic field generates ASE during the blood flow process, and one or more parameters of the microchannel size, transducer frequency, voltage, and blood flow rate can be adjusted in different microchannels according to the size of the target substance. ASE is used to extract and separate the particles in the blood from large particles to small particles step by step, and finally the bacteria are gathered in the center of the flow vortex generated by ASE under the action of ASE, so as to be separated or extracted. Based on this device, bacteria in blood samples can be concentrated, thereby increasing the sample volume and the sensitivity of molecular detection. In addition, the device uses physical methods to separate bacteria, thereby producing less human cell fragments and reducing the risk of contamination.

[0071] Optionally, the device may further include a sample collector and a waste collector, wherein the sample collector is used to collect bacteria, and the waste collector is used to collect other substances in the blood, such as platelets, blood cells, etc. Therefore, the outlets of the first extraction module 410 and the second extraction module 420 may be connected to the waste collector, respectively, and the outlet of the third extraction module 430 may be connected to the sample collector (bacteria) and the waste collector (other submicron particles, such as platelets).

[0072] Optionally, the first microchannel 401 may be a cubic PDMS channel, and the first transducer may be located on both sides of the first microchannel.

[0073] Optionally, the blood flow rate in the first, second and third extraction modules can be 10ul / ml, 1ul / ml, and 0.1ul / ml respectively, the width of the first microchannel in the first, second and third extraction modules can be 400μm, 200μm, and 400μm respectively, and the height of the first microchannel in the first, second and third extraction modules can be 30μm, 70μm, and 70μm respectively.

[0074] Optionally, the voltage and frequency of the first transducer may be provided by a signal generator, the voltage may be 10 V, and the frequency may be 18.6 MHz.

[0075] Optionally, the end of the third microchannel 430 along the first direction may be in the shape of a nozzle. Figure 5 As shown, the nozzle-shaped microchannel can gradually increase the distance between the streamlines where the bacteria and other submicron particles gather along the first direction, which is conducive to more convenient separation of bacteria.

[0076] Combine the following Figure 6 and Figure 7 , an example is given of the device for extracting bacteria from blood according to an embodiment of the present application. Figure 6 and Figure 7The following examples illustrate the cooperation between the extraction device and other devices and the extraction device itself during the extraction process. It is worth noting that Figure 6 and Figure 7 It is only used for illustration and does not limit the embodiments of the present application.

[0077] See also Figure 6 During the extraction process, 10 ml of blood sample first passes through the sample container and enters the extraction device, and the flow rate of the blood sample is controlled by a pump. During the extraction process of the extraction device, the signal generator excites the transducer in the extraction device, thereby generating a surface acoustic standing wave and forming an acoustic field, so that the blood sample flows in the extraction device. After extraction by the extraction device, the bacteria in the blood enter the sample collector, and other substances in the blood enter the waste collector, and finally 1.5 ml of concentrated bacteria are obtained.

[0078] See also Figure 7 The extraction device is composed of three extraction modules, each of which includes a microchannel made of PDMS and two interdigital transducers. The three extraction modules are arranged in sequence along the direction of blood flow, and the microchannels in the three extraction modules are connected in sequence. In the extraction device, the first microchannel is a cubic channel. The blood flow rates in the first, second and third extraction modules are 10ul / ml, 1ul / ml and 0.1ul / ml respectively, the widths of the first microchannels in the first, second and third extraction modules are 400μm, 200μm and 400μm respectively, and the heights of the first microchannels in the first, second and third extraction modules are 30μm, 70μm and 70μm respectively. The voltage and frequency provided by the signal generator to the first transducer in each extraction module are fixed, the voltage is 10V, and the frequency is 18.6MHz.

[0079] When the blood sample flows through the first extraction module, particles larger than 5μm (including red / white blood cells, i.e., blood cells) in the blood sample will be extracted and enter the waste collector through the corresponding channels, and the remaining substances in the blood sample will flow to the second extraction module. In the second extraction module, submicron particles (including platelets and bacteria) in the blood sample are extracted and continue to flow to the third extraction module, and the remaining substances enter the waste collector through the corresponding channels, and the volume of the blood sample is reduced by 80% accordingly. In the third extraction module, bacteria and other submicron particles (such as platelets) are separated, and bacteria enter the sample collector through the corresponding channels, and the remaining submicron particles enter the waste collector through the corresponding channels, thereby achieving the separation of bacteria in the blood.

[0080] The states of blood flowing through each extraction module in the extraction device can be respectively as follows: Figures 8A-8C As shown. Fig. 8AIn the first extraction module, particles larger than 5 μm are aggregated, and red / white blood cells can move with the particles larger than 5 μm and enter the waste collector. Figure 8B In the second extraction module, submicron-sized particles are aggregated and enter the third extraction module, e.g. Figure 8B The remaining material in the blood enters the waste collector. Figure 8C In the third extraction module, particles of 0.49 μm (i.e., bacteria) are separated and enter the sample collector, and the remaining submicron particles (e.g., particles of 0.79 μm) enter the waste collector. In addition, the first microchannel in the third extraction module is in the shape of a nozzle at the end of the blood flow direction. The nozzle-shaped channel can increase the distance between the remaining submicron particles and bacteria, thereby facilitating the separation of bacteria.

[0081] like Fig. 9 As shown, the embodiment of the present application also provides a method for extracting substances in microfluidics, which includes steps S910-S920.

[0082] In step S910, the target substance is enriched in the microfluid based on ASE generated in the microfluid by the acoustic field formed by SSAW;

[0083] In step S920, the enriched target substance is separated.

[0084] Among them, the size of the microchannel through which the microfluid flows, the frequency and voltage of the transducer that generates the acoustic field, one or more parameters in the flow rate of the microfluid satisfy a first relationship with the size of the target substance, and the first relationship is determined based on a first condition, and the first condition is that the target substance is gathered in the target streamline in the microfluid under the action of ASE, and the target streamline passes through the center of the flow vortex generated by ASE.

[0085] Optionally, the first condition may also include: substances other than the target substance in the microfluid are gathered in non-target streamlines in the microfluid under the action of ASE, and the non-target streamlines pass through the low flow velocity area outside the flow vortex generated by ASE. Based on this, the distance between the target substance and other substances in the microfluid can be increased, thereby facilitating the separation of the target substance.

[0086] based on Fig. 9 The method shown can form an acoustic field by generating SSAW in the microfluidic, and the acoustic field produces an acoustic streaming effect during the flow of the microfluidic. The size of the microchannel, the frequency of the transducer, the voltage, and one or more parameters of the flow rate of the microfluidic can be adjusted according to the size of the target substance, so that the sub-micron-level target substance can be gathered in the target streamline in the microfluidic under the action of the acoustic streaming effect and thus be separated or extracted.

[0087] like Fig.10 As shown, an embodiment of the present application further provides an electronic device. The electronic device 1000 includes: at least one processor 1001, a memory 1002, and a computer program 1003 stored in the memory 1002 and executable on the at least one processor 1001, and when the processor 1001 executes the computer program 1003, the method for extracting substances in microfluids provided in the present application is implemented.

[0088] Exemplarily, the computer program 1003 may be divided into one or more modules / units, one or more modules / units are stored in the memory 1002, and are executed by the processor 1001 to complete the present application. One or more modules / units may be a series of computer program instruction segments capable of completing specific functions, and the instruction segments are used to describe the execution process of the computer program in the electronic device 1000.

[0089] Those skilled in the art will understand that Fig.10 It is only an example of the electronic device 1000 and does not constitute a limitation of the electronic device. It may include more or fewer components than shown in the figure, or a combination of certain components, or different components. For example, the electronic device 1000 may also include input and output devices, network access devices, buses, etc.

[0090] The processor 1001 may be a central processing unit (CPU), or other general-purpose processors, digital signal processors (DSP), application specific integrated circuits (ASIC), field-programmable gate arrays (FPGA) or other programmable logic devices, discrete gate or transistor logic devices, discrete hardware components, etc. A general-purpose processor may be a microprocessor or the processor may be any conventional processor, etc.

[0091] The memory 1002 may be an internal storage unit of the electronic device 1000, such as a hard disk or memory of the electronic device 1000. The memory 1002 may also be an external storage device of the electronic device 1000, such as a plug-in hard disk, a smart media card (SMC), a secure digital (SD) card, a flash card, etc. equipped on the electronic device 1000. Further, the memory 1002 may also include both an internal storage unit of the electronic device 1000 and an external storage device. The memory 1002 is used to store computer programs and other programs and data required by the electronic device 1000. The memory 1002 may also be used to temporarily store data that has been output or is to be output.

[0092] The electronic device 1000 provided in this embodiment can execute the above method embodiment, and its implementation principle and technical effect are similar, which will not be repeated here.

[0093] An embodiment of the present application further provides a computer-readable storage medium, which stores a computer program. When the computer program is executed by a processor, the steps in the above-mentioned method embodiments can be implemented.

[0094] An embodiment of the present application provides a computer program product. When the computer program product runs on an electronic device, the electronic device can implement the steps in the above-mentioned method embodiments when executing the computer program product.

[0095] If the integrated unit is implemented in the form of a software functional unit and sold or used as an independent product, it can be stored in a computer-readable storage medium. Based on this understanding, the present application implements all or part of the processes in the above method embodiments, which can be completed by instructing the relevant hardware through a computer program. The computer program can be stored in a computer-readable storage medium. When the computer program is executed by the processor, the steps of the above method embodiments can be implemented. Among them, the computer program includes computer program code, which can be in source code form, object code form, executable file or some intermediate form. The computer-readable medium may at least include: any entity or device that can carry the computer program code to the camera / electronic device, recording medium, computer memory, ROM (read-only memory), RAM (random access memory), CD-ROM (compact disc read-only memory), magnetic tape, floppy disk and optical data storage device. The computer-readable storage medium mentioned in the present application can be a non-volatile storage medium, in other words, a non-transient storage medium.

[0096] In the above embodiments, the description of each embodiment has its own emphasis. For parts that are not described or recorded in detail in a certain embodiment, reference can be made to the relevant descriptions of other embodiments.

[0097] Those of ordinary skill in the art will appreciate that the units and algorithm steps of each example described in conjunction with the embodiments disclosed herein can be implemented in electronic hardware, or a combination of computer software and electronic hardware. Whether these functions are performed in hardware or software depends on the specific application and design constraints of the technical solution. Professional and technical personnel can use different methods to implement the described functions for each specific application, but such implementation should not be considered to be beyond the scope of this application.

[0098] In the embodiments provided in the present application, it should be understood that the disclosed devices / equipment and methods can be implemented in other ways. For example, the device / equipment embodiments described above are only schematic, for example, the division of modules or units is only a logical function division, and there may be other division methods in actual implementation, such as multiple units or components can be combined or integrated into another system, or some features can be ignored or not executed. Another point is that the mutual coupling or direct coupling or communication connection shown or discussed can be through some interfaces, indirect coupling or communication connection of devices or units, which can be electrical, mechanical or other forms.

[0099] It should be understood that when used in the present specification and the appended claims, the term "comprising" indicates the presence of described features, wholes, steps, operations, elements and / or components, but does not exclude the presence or addition of one or more other features, wholes, steps, operations, elements, components and / or combinations thereof.

[0100] It should also be understood that the term “and / or” used in the specification and appended claims refers to any and all possible combinations of one or more of the associated listed items, and includes these combinations.

[0101] As used in the specification and appended claims of this application, the term "if" can be interpreted as "when" or "uponce" or "in response to determining" or "in response to detecting", depending on the context. Similarly, the phrase "if it is determined" or "if [described condition or event] is detected" can be interpreted as meaning "uponce it is determined" or "in response to determining" or "uponce [described condition or event] is detected" or "in response to detecting [described condition or event]", depending on the context.

[0102] In addition, in the description of the present application specification and the appended claims, the terms "first", "second", etc. are only used to distinguish the descriptions and cannot be understood as indicating or implying relative importance.

[0103] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present application, rather than to limit it. Although the present application has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the aforementioned embodiments, or replace some or all of the technical features therein with equivalents. However, these modifications or replacements do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present application.

Claims

1. A device for extracting substances in microfluidics, characterized in that: An extraction module is included, wherein the extraction module includes: A first microchannel, for a microfluid to flow through, wherein the microfluid includes a target substance to be extracted, and the size of the target substance is submicron level; A first transducer, configured to generate a surface acoustic standing wave (SSAW) in the first microchannel to form a first acoustic field, wherein the first acoustic field is configured to make the microfluid flow in a first direction in the first microchannel, and the first acoustic field generates an acoustic streaming effect (ASE) in the microfluid; Among them, one or more parameters among the size of the first microchannel, the frequency of the first transducer, the voltage of the first transducer, the flow rate of the microfluid, and the size of the target substance satisfy a first relationship, and the first relationship is determined based on a first condition, and the first condition is that the target substance is gathered in the target streamline in the microfluid under the action of the ASE, and the target streamline passes through the center of the flow vortex generated by the ASE.

2. The device according to claim 1, characterized in that The first condition also includes: The substances other than the target substance in the microfluid are gathered in non-target streamlines in the microfluid under the action of the ASE, and the non-target streamlines pass through a low flow velocity region outside the flow vortex generated by the ASE.

3. The device according to claim 2, characterized in that The device comprises a plurality of the extraction modules, the plurality of the extraction modules are arranged in sequence along the first direction, the first microchannels in the plurality of the extraction modules are connected in sequence along the first direction, and the target substances of different extraction modules are different.

4. The device according to claim 3, characterized in that The sizes of the target substances in different extraction modules decrease sequentially along the first direction.

5. A device for extracting bacteria from blood, characterized in that: It comprises a first extraction module, a second extraction module and a third extraction module, each extraction module is arranged in sequence along a first direction, blood flows along the first direction, and each extraction module is used to extract the target substance in the blood in sequence; Each extraction module comprises: a first microchannel, for the blood to flow through, the first microchannels in the extraction modules being connected in sequence along the first direction; A first transducer, configured to generate a surface acoustic standing wave (SSAW) in the first microchannel to form a first acoustic field, wherein the first acoustic field is configured to make the blood flow in the first microchannel along the first direction, and the first acoustic field generates an acoustic streaming effect (ASE) in the blood; wherein one or more parameters of the size of the first microchannel, the frequency of the first transducer, the voltage of the first transducer, the flow rate of the blood, and the size of the target substance satisfy a first relationship, and the first relationship is determined based on a first condition; The first extraction module is used to extract particles larger than 5 μm, and the particles larger than 5 μm include blood cells. The first condition of the first extraction module is that the particles larger than 5 μm are gathered at the pressure node of the SSAW under the action of the SSAW; The second extraction module is used to extract submicron particles, and the submicron particles include platelets and bacteria. The first condition of the second extraction module is: The submicron particles are gathered in a target streamline in the blood under the action of the ASE, and the target streamline passes through the center of the flow vortex generated by the ASE; and the remaining substances in the blood are gathered in non-target streamlines in the blood under the action of the ASE, and the non-target streamlines pass through a low flow velocity region outside the flow vortex generated by the ASE; The third extraction module is used to extract the bacteria from the submicron particles. The first condition of the third extraction module is: The bacteria are gathered in a target flow line in the blood under the action of the ASE, and the target flow line passes through the center of the flow vortex generated by the ASE; And the remaining submicron particles are gathered in the non-target streamlines in the blood under the action of the ASE, and the non-target streamlines pass through the low flow velocity area outside the flow vortex generated by the ASE.

6. The device according to claim 5, characterized in that The device further comprises a sample collector and a waste collector, wherein the sample collector is used to collect the bacteria, and the waste collector is used to collect substances other than the bacteria in the blood.

7. The device according to claim 6, characterized in that The first microchannel is a cubic polydimethylsiloxane (PDMS) channel, and the first transducer is located on both sides of the first microchannel.

8. The device according to claim 7, characterized in that The flow rates of the blood in the first, second and third extraction modules are 10ul / ml, 1ul / ml and 0.1ul / ml respectively, the widths of the first microchannels in the first, second and third extraction modules are 400μm, 200μm and 400μm respectively, and the heights of the first microchannels in the first, second and third extraction modules are 30μm, 70μm and 70μm respectively.

9. The device according to claim 8, characterized in that The voltage and frequency of the first transducer are provided by a signal generator, the voltage is 10V, and the frequency is 18.6MHz.

10. A method for extracting substances in microfluids, characterized in that: include: Based on the acoustic field formed by the surface standing acoustic wave (SSAW) and the acoustic streaming effect (ASE) in the microfluid, the target substance is enriched in the microfluid; separating and enriching the target substance; Among them, a first relationship is satisfied between the size of the microchannel through which the microfluid flows, the frequency and voltage of the transducer generating the acoustic field, one or more parameters of the flow rate of the microfluid, and the size of the target substance, and the first relationship is determined based on a first condition, which is that the target substance is gathered in the target streamline in the microfluid under the action of the ASE, and the target streamline passes through the center of the flow vortex generated by the ASE.

Images