Device and method for measuring micro-nano particles

Abstract

The embodiment of the present application discloses a device and method for measuring micro-nano particles, the device comprising: a first chamber, a microporous membrane, an electrophoresis tank, and a second chamber, wherein the microporous membrane is located between the first chamber and the electrophoresis tank, and the microporous membrane has micropores, and the first chamber is connected to the electrophoresis tank through the micropores; the second chamber is adjacent to the electrophoresis tank, and has a first side wall located between the second chamber and the electrophoresis tank, and the first side wall has a first opening for connecting the second chamber and the electrophoresis tank; the inner diameter of the micropore is smaller than the inner diameter of the electrophoresis tank, and the inner diameter of the electrophoresis tank is smaller than the inner diameter of the second chamber; the first chamber has a first electrode, and the second chamber has a second electrode. The technical solution of the embodiment of the present application can measure the properties of a single micro-nano particle in a solution.

Description

Technical Field

[0001] The present application relates to the technical field of micro-nano particle measurement, and in particular, to a device and method for measuring micro-nano particles. Background Art

[0002] Due to the special properties of particulate matter, particulate matter is widely used in the fields of medicine, chemical industry, materials, etc. Therefore, in the application of particulate matter, the measurement of the properties of particulate matter (hereinafter referred to as particles) is very important.

[0003] At present, commonly used particle measurement equipment includes optical microscopes, scanning electron microscopes and transmission electron microscopes. However, due to the low resolution of optical microscopes, it is difficult to observe particles smaller than 300 nanometers using optical microscopes, which is not suitable for the measurement of micro-nano particles. Although scanning electron microscopes and transmission electron microscopes have ultra-high resolution, their detection environment must be in a vacuum state, and they cannot measure the properties of particles in solution, and thus cannot measure the properties of micro-nano particles under living conditions. Commonly used particle measurement methods include dynamic light scattering, which can quickly perform large-scale particle detection, but cannot extract the characteristics of individual particles.

[0004] Therefore, the existing technology still has the problem of being unable to measure the properties of a single micro-nano particle under living conditions. Summary of the invention

[0005] To solve the above technical problems, the embodiments of the present application provide a device for measuring micro-nano particles, and also provide a method for measuring micro-nano particles, so as to detect the properties of a single micro-nano particle under living conditions.

[0006] Among them, the technical solution adopted in this application is:

[0007] A device for measuring micro-nanoparticles comprises a first chamber, a microporous membrane, an electrophoresis tank and a second chamber, wherein the microporous membrane is located between the first chamber and the electrophoresis tank, and the microporous membrane has micropores, and the first chamber is connected to the electrophoresis tank through the micropores; the second chamber is adjacent to the electrophoresis tank and has a first side wall located between the second chamber and the electrophoresis tank, and the first side wall has a first opening for connecting the second chamber and the electrophoresis tank; the inner diameter of the micropore is smaller than the inner diameter of the electrophoresis tank, and the inner diameter of the electrophoresis tank is smaller than the inner diameter of the second chamber; the first chamber has a first electrode, and the second chamber has a second electrode.

[0008] In another exemplary embodiment, the inner diameter of the electrophoresis tank is 2 times or more than the inner diameter of the micropore, and the length of the electrophoresis tank is 2 times or more than the thickness of the microporous membrane.

[0009] In another exemplary embodiment, the inner diameter of the micropore is 1 nanometer to 10 micrometers, and the inner diameter of the electrophoresis tank is 2 nanometers to 20 micrometers.

[0010] In another exemplary embodiment, the thickness of the microporous membrane is 1 nanometer to 10 micrometers, and the length of the electrophoresis tank is 2 nanometers to 20 micrometers.

[0011] In another exemplary embodiment, an inner diameter of the first opening is equal to an inner diameter of the electrophoresis tank.

[0012] In another exemplary embodiment, in a measuring state, the first chamber, the electrophoresis tank, and the second chamber are filled with electrolyte, and the micro-nanoparticles to be measured pass through the micropores and the electrophoresis tank along with the electrolyte.

[0013] In another exemplary embodiment, the device further comprises a liquid driver, which is adjacent to the second chamber and located on a side wall adjacent to or opposite to the first side wall, and is used for driving the flow of liquid in the device.

[0014] In another exemplary embodiment, the microporous membrane is an inorganic membrane.

[0015] In another exemplary embodiment, the microporous membrane is integrally formed with the first chamber, the electrophoresis tank, and the second chamber.

[0016] In another exemplary embodiment, the center of the microhole and the center of the first opening are parallel to the length direction of the electrophoresis tank.

[0017] In another exemplary embodiment, the shape of the electrophoresis tank is any one of a cylinder, a cuboid, a conical table, and a trapezoidal table.

[0018] A method for measuring micro-nano particles, comprising: allowing the micro-nano particles to be measured to pass through the micropores and electrophoresis tank of the device according to any of the above embodiments along with the electrolyte; obtaining electrical signal data between a first electrode and a second electrode during the movement of the micro-nano particles through the micropores and the electrophoresis tank; and determining attribute data of the micro-nano particles according to the electrical signal data.

[0019] In another exemplary embodiment, determining the property data of the micro-nano particles according to the electrical signal data includes: determining a first time taken by the micro-nano particles to pass through the electrophoresis tank according to the electrical signal data; and determining an electromotive potential of the micro-nano particles according to the first time.

[0020] In another exemplary embodiment, determining the property data of the micro-nano particles according to the electrical signal data includes: determining the maximum amplitude of the electrical signal change when the micro-nano particles pass through the micropores according to the electrical signal data; and determining the equivalent volume and equivalent diameter of the micro-nano particles according to the maximum amplitude.

[0021] In another exemplary embodiment, determining the property data of the micro-nano particles according to the electrical signal data includes: determining a second time taken by the micro-nano particles to pass through the micropores according to the electrical signal data; determining the long diameter of the micro-nano particles according to the second time; and determining the aspect ratio of the micro-nano particles according to the long diameter and an equivalent diameter of the micro-nano particles.

[0022] In the above technical solution, the solution contains micro-nano particles to be measured, and the micro-nano particles pass through the micropores and the electrophoresis tank as the solution flows. By analyzing the electrical signal data between the first electrode and the second electrode in this process, the properties of the micro-nano particles to be measured in the solution can be obtained. Since the solution environment provides the basic conditions for the survival of micro-nano particles, the present application can achieve the acquisition of the properties of a single micro-nano particle under living conditions. It should be understood that the above general description and the detailed description below are only exemplary and explanatory, and cannot limit the present application. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate embodiments consistent with the present application and, together with the description, serve to explain the principles of the present application.

[0024] Figure 1 is a cross-sectional view of a device for measuring micro-nano particles according to an exemplary embodiment;

[0025] Figure 2 is a schematic diagram of electrical signal data recorded in an exemplary measurement scenario;

[0026] Figure 3 is a schematic diagram of electrical signal data recorded according to another exemplary measurement scenario.

[0027] Explanation of reference numerals: 100, device for measuring micro-nanoparticles; 101, first chamber; 102, microporous membrane; 1021, micropore; 103, electrophoresis tank; 104, second chamber; 1041, first side wall; 1042, second side wall; 105, first electrode; 106, second electrode; 107, liquid driver.

[0028] The above-mentioned drawings have shown clear embodiments of the present application, which will be described in more detail hereinafter. These drawings and textual descriptions are not intended to limit the scope of the concept of the present application in any way, but to illustrate the concept of the present application to those skilled in the art by referring to specific embodiments. DETAILED DESCRIPTION

[0029] Here, exemplary embodiments will be described in detail, examples of which are shown in the accompanying drawings. When the following description refers to the drawings, unless otherwise indicated, the same numbers in different drawings represent the same or similar elements. The implementations described in the following exemplary embodiments do not represent all implementations consistent with the present application. Instead, they are only examples of devices and methods consistent with some aspects of the present application as detailed in the attached claims.

[0030] See also Figure 1 , Figure 1 It is a cross-sectional view of a device for measuring micro-nano particles according to an exemplary embodiment. The device can be used to measure the electromotive potential (also known as Zeta potential, electromotive voltage, which refers to the potential of the shear surface of the micro-nano particles), volume, morphology and other properties of the micro-nano particles.

[0031] First of all, it should be noted that the inner diameter described in this embodiment refers to the distance in the direction perpendicular to the direction in which the micro-nano particles move through the device during the measurement process, and the length refers to the distance in the direction in which the micro-nano particles move through the device during the measurement process.

[0032] like Figure 1 As shown, in an exemplary embodiment, a device 100 for measuring micro-nanoparticles includes a first chamber 101 , a microporous membrane 102 , an electrophoresis tank 103 , a second chamber 104 and a liquid driver 107 .

[0033] The microporous membrane 102 is located between the first chamber 101 and the electrophoresis tank 103, and the microporous membrane 102 has a micropore 1021. The first chamber 101 is connected to the electrophoresis tank 103 through the micropore 1021. The second chamber 104 is adjacent to the electrophoresis tank 103 and has a first side wall 1041 located between the second chamber 104 and the electrophoresis tank 103. The first side wall 1041 has a first opening for connecting the second chamber 104 and the electrophoresis tank 103. Thus, the first chamber 101 and the second chamber 104 are connected in series with the electrophoresis tank 103 through the micropore 1021.

[0034] In the measurement state, the first chamber 101 , the electrophoresis tank 103 and the second chamber 104 are filled with electrolyte, the electrolyte contains micro-nano particles to be measured, and the micro-nano particles pass through the micropores 1021 and the electrophoresis tank 103 as the electrolyte flows.

[0035] The flow direction of the electrolyte can be from the first chamber 101 to the second chamber 104 via the micropores 1021 and the electrophoresis tank 103 in sequence, or from the second chamber 104 to the first chamber 101 via the electrophoresis tank 103 and the micropores 1021 in sequence. If the electrolyte flows from the first chamber 101 to the second chamber 104, the micro-nano particles pass through the micropores 1021 and the electrophoresis tank 103 in sequence with the flow of the electrolyte; if the electrolyte flows from the second chamber 104 to the first chamber 101, the micro-nano particles pass through the electrophoresis tank 103 and the micropores 1021 in sequence with the flow of the electrolyte.

[0036] The liquid driver 107 is used to drive the electrolyte to flow, so the flow direction of the electrolyte in the measurement state is determined by the driving direction of the liquid driver 107. The liquid driver 107 can be a device such as a liquid pump, a pneumatic device, a syringe, etc. that can provide a driving force for the electrolyte to flow.

[0037] The liquid driver 107 is located on the other sidewalls of the second chamber 104, adjacent to the second chamber 104, wherein the other sidewalls of the second chamber 104 include the second sidewall 1042 opposite to the first sidewall 1041, and also include the sidewall adjacent to the first sidewall, which is not limited here. In one embodiment, the liquid driver 107 is located on the second sidewall 1042, and when the second sidewall 1042 is a convex shape, the liquid driver 107 can be disposed at the convex end of the second sidewall 1042.

[0038] A first electrode 105 is disposed in the first chamber 101 , and a second electrode 106 is disposed in the second chamber 104 . In a measuring state, a constant voltage or a constant current is applied between the first electrode 105 and the second electrode 106 in advance, so that the micro-nano particles are charged and suspended in the electrolyte.

[0039] In the process of the micro-nano particles moving through the micropores 1021 and the electrophoresis tank 103 with the flow of the electrolyte, by acquiring the electrical signal data between the first electrode 105 and the second electrode 106, the electromotive potential, volume, morphology and other property data of the micro-nano particles can be analyzed based on the electrical signal data, thereby solving the problem in the prior art that the properties of a single micro-nano particle in the solution cannot be measured.

[0040] In one embodiment, the microporous membrane 102 is an inorganic membrane, that is, the microporous membrane 102 is made of inorganic materials, such as low-stress silicon nitride materials, silicon nitride materials or silicon wafers. Compared with organic membranes, inorganic membranes have better film-forming effects and better stretchability, which is conducive to the movement of micro-nano particles through micropores 1021 with the flow of electrolyte. The number of micropores 1021 on the microporous membrane 102 can be one or more. If the microporous membrane 102 has only one micropore 1021, the multiple micro-nano particles contained in the electrolyte will pass through the micropore 1021 in sequence under the measurement state; if the microporous membrane 102 has multiple micropores 1021, the multiple micro-nano particles can flow into or out of different micropores 1021 with the flow of electrolyte.

[0041] The inner diameter of the micropore 1021 is smaller than the inner diameter of the electrophoresis tank 103, and the inner diameter of the electrophoresis tank 103 is smaller than the inner diameter of the second chamber 104, so that the electrolyte slowly passes through the electrophoresis tank 103 under the drive of the liquid driver 107. Exemplarily, the inner diameter of the electrophoresis tank 103 is more than twice the inner diameter of the micropore 1021. For example, when the inner diameter of the micropore 1021 is 1 nanometer to 10 micrometers, the inner diameter of the electrophoresis tank 103 can be 2 nanometers to 20 micrometers.

[0042] The length of the electrophoresis tank 103 is more than twice the thickness of the microporous membrane 102, so that the time for the micro-nano particles to move in the electrophoresis tank 103 is longer than the time for the micro-nano particles to move in the micropores 1021, so as to effectively measure the movement state of the micro-nano particles in the electrophoresis tank 103. For example, when the thickness of the microporous membrane 102 is 1 nanometer to 10 micrometers, the length of the electrophoresis tank 103 is 2 nanometers to 20 micrometers.

[0043] The first chamber 101, the microporous membrane 102, the electrophoresis tank 103 and the second chamber 104 are integrally formed, so that the device 100 has a high stability. The micropore 1021 and the electrophoresis tank 103 can be any geometric shape such as a cylinder, a cuboid, a conical platform, a trapezoidal platform, etc., which are not limited here. The edges of the micropore 1021 and the electrophoresis tank 103 can be uneven.

[0044] In another embodiment, the microporous membrane 102 has a micropore 1021, the inner diameter of the first opening on the first side wall 1041 is equal to the inner diameter of the electrophoresis tank 103, and the line between the center of the micropore 1021 and the center of the first opening is parallel to the length direction of the electrophoresis tank 103, so that the micropore 1021 corresponds to the center position of the electrophoresis tank 103, and the route of movement of the micro-nanoparticles in the electrophoresis tank 103 is parallel to the length direction of the electrophoresis tank 103. In addition, the position of the liquid driver 107 can also be on the line between the center of the micropore 1021 and the center of the first opening.

[0045] Another exemplary embodiment of the present invention further provides a method for measuring micro-nano particles, which is implemented based on the device for measuring micro-nano particles described in the above embodiments to determine the property data of the micro-nano particles to be measured.

[0046] In this method, the micro-nano particles to be measured are first moved with the electrolyte through the micropores and the electrophoresis tank in the device described in the above embodiment. As mentioned above, the movement direction of the micro-nano particles is the same as the flow direction of the electrolyte, and the flow direction of the electrolyte is determined by the driving direction of the liquid driver. Then, the electrical signal data between the first electrode and the second electrode is obtained in the process of the micro-nano particles moving through the micropores and the electrophoresis tank, so as to determine the attribute data of the micro-nano particles based on the electrical signal data.

[0047] The electrical signal data between the first electrode and the second electrode reflects the changes in the voltage or current applied to the two electrodes during the movement of the micro-nano particles through the micropores and the electrophoresis tank. The properties of the micro-nano particles can be analyzed based on these changes.

[0048] As mentioned above, the electrolyte passes through the electrophoresis tank very slowly under the drive of the liquid driver, and the charged micro-nano particles move in the electrophoresis tank mainly by the force of the electric field formed between the first electrode and the second electrode. When the micro-nano particles enter the electrophoresis tank, the electrons between the first electrode and the second electrode become larger, the current will decrease slightly, and the duration of the current decrease is inversely proportional to the electromotive potential of the micro-nano particles, or the voltage on the two electrodes will increase slightly, and the duration of the voltage increase is inversely proportional to the electromotive potential of the micro-nano particles. Therefore, by measuring the duration of the continuous decrease in current or the duration of the voltage increase between the first electrode and the second electrode, the electromotive potential of the micro-nano particles can be calculated.

[0049] Obviously, the duration of the continuous decrease in current and the continuous increase in voltage is the time that the micro-nano particles move in the electrophoresis tank. Therefore, by measuring the duration of the continuous decrease in current and the continuous increase in voltage, the first time taken by the micro-nano particles to pass through the electrophoresis tank can be determined, and the electromotive potential of the micro-nano particles can be determined based on the first time.

[0050] Since the inner diameter of the micropore is smaller than the inner diameter of the electrophoresis tank, when the micro-nano particle enters the micropore, the current between the first electrode and the second electrode will be greatly reduced or the voltage will be greatly increased. According to the Coulter principle, the maximum value of the current reduction or the maximum value of the voltage increase is proportional to the equivalent volume of the micro-nano particle. Therefore, the maximum amplitude of the electrical signal change when the micro-nano particle passes through the micropore can be determined based on the electrical signal data, and the equivalent volume of the micro-nano particle can be determined based on the maximum amplitude, and the equivalent diameter of the micro-nano particle can also be determined.

[0051] It should be noted that the equivalent volume of a micro-nano particle refers to a sphere with the same volume as the irregularly shaped micro-nano particle that is equivalent to the micro-nano particle. The diameter of the sphere is the equivalent diameter of the micro-nano particle, which is used to describe the morphology of the micro-nano particle.

[0052] In addition, in the process of the micro-nano particles moving through the micropores, they are affected by the combined effect of the electrolyte flow and the electric field formed between the first electrode and the second electrode, so that the micro-nano particles move through the micropores very quickly. The flow rate of the electrolyte is proportional to the pressure formed by the driving of the liquid driver, and the force of the electric field formed between the first electrode and the second electrode is proportional to the charge carried by the micro-nano particles and the electric field strength.

[0053] Since the time it takes for the micro-nano particle to pass through the micropore is proportional to the long diameter of the micro-nano particle, the duration of a substantial decrease in current or a substantial increase in voltage is proportional to the long diameter of the micro-nano particle, the long diameter of the micro-nano particle can be determined based on the second time it takes for the micro-nano particle to pass through the micropore. It should be noted that the long diameter of the micro-nano particle refers to the length of the micro-nano particle.

[0054] Therefore, based on the determined equivalent diameter and long diameter of the micro-nano particles, the aspect ratio of the micro-nano particles can be determined, and the aspect ratio is used to reflect the morphology of the micro-nano particles.

[0055] The method for measuring micro-nano particles provided in the present application will be described in detail below with a specific measurement scenario, that is, a process of obtaining the property data of the micro-nano particles based on the electrical signal data between the first electrode and the second electrode in the process of the micro-nano particles moving through the micropores and the electrophoresis tank with the flow of the electrolyte will be described in detail.

[0056] Still Figure 1 As shown, in an exemplary measurement scenario, the micro-nano particle to be measured is an elliptical polyethylene microsphere with a diameter of 100 nanometers, an inner diameter of the micropore 1021 of 200 nanometers, a thickness of 50 nanometers, an inner diameter of the electrophoresis tank 103 of 600 nanometers, and a length of 1 micron. The electrolyte is 5% saline solution that fills the first chamber 101, the micropore 1021, the electrophoresis tank 103, and the second chamber 104. The first electrode 105 is used as the positive electrode and the second electrode 106 is used as the negative electrode. A constant voltage source of 2V is applied between the two electrodes. Driven by the liquid driver 107, the electrolyte flows from the second chamber 104 through the electrophoresis tank 103 and the micropore 1021 to the first chamber 101 in sequence. The movement direction of the micro-nano particle is the same as the flow direction of the electrolyte, and the electrical signal data between the first electrode 105 and the second electrode 106 is recorded in the process.

[0057] When the micro-nano particles sequentially pass through the electrophoresis tank 103 and the micropore 1021, the recorded electrical signal data between the first electrode 105 and the second electrode 106 is the change of the current, such as Figure 2 As shown, since the flow speed of the electrolyte in the electrophoresis tank 103 is very slow, the charged micro-nano particles mainly rely on the force of the electric field formed by the first electrode 105 and the second electrode 106 to move in the electrophoresis tank 103. In the process of the micro-nano particles entering the electrophoresis tank 103 from the second chamber 104, the current between the first electrode 105 and the second electrode 106 has a small decrease trend, and the duration T1 of the current decrease is inversely proportional to the electromotive potential of the micro-nano particles. Therefore, the electromotive potential ζ of the micro-nano particles can be calculated by measuring T1, and the calculation formula is as follows:

[0058] ζ=K / (U*T1);

[0059] Where K is a proportionality coefficient, which is related to the voltage U applied between the first electrode 105 and the second electrode 106, the size of the micropore 1021, and the size of the electrophoresis tank 103, and can be determined by experiments. In this measurement scenario, U is 2V, K is -3*10 -5 V 2 ·s, T1 is 0.4ms, and the electrokinetic potential of the micro-nano particles is calculated to be -37.5mV according to the above formula.

[0060] Before the micro-nano particles enter the electrophoresis tank 103, the current between the first electrode 105 and the second electrode 106 is a stable value H. When the micro-nano particles completely pass through the electrophoresis tank 103 and enter the micropores 1021, the current will be greatly reduced. According to the Coulter principle, the maximum value of the current reduction amplitude h is proportional to the equivalent volume of the micro-nano particles. Therefore, the equivalent volume V of the micro-nano particles can be calculated by the following formula:

[0061] V = a*h / H;

[0062] Where a is a proportionality factor, which is related to the size of the microhole 1021 and can be determined experimentally. In this measurement scenario, H is measured to be 10nA, h is 200pA, and a is 4.83*10 -2 um 3 According to the above formula, V = 0.966*10 - 3 um 3 , the equivalent diameter D is 98.8nm.

[0063] Since the inner diameter of the micropore 1021 is very small, the flow speed of the electrolyte in the micropore 1021 is very fast, and the movement of the micro-nano particles in the micropore 1021 is affected by the combined effect of the electrolyte flow and the electric field force. The flow speed of the electrolyte is proportional to the pressure P formed by the driving of the liquid driver 107, and the electric field force is proportional to the charge and electric field strength of the micro-nano particles. Since the time for the micro-nano particles to pass through the micropore 1021 is proportional to the long diameter of the micro-nano particles, the duration T2 of the significant reduction of the current between the first electrode 105 and the second electrode 106 is proportional to the long diameter of the micro-nano particles, the long diameter L of the micro-nano particles can be calculated by the following formula:

[0064] L = T2*(m*(-ζ)*U+n*P);

[0065] Or L = T2*(m*(-K / T1)+n*P);

[0066] Where m is the electric field force proportionality coefficient, and n is the fluid proportionality coefficient. Both coefficients can be obtained through experiments. In this measurement scenario, T2 is 0.1ms, P is 2000Pa, and n is 2.5*10 -7 (m / Pa), m is 1.33*10 -2 m / (V 2 ·s), the long diameter of the micro-nano particles can be calculated to be L=149.7nm, and the aspect ratio L / D of the micro-nano particles is obtained to be 1.5, which is close to the actual morphology of the micro-nano particles.

[0067] In the measurement scenario where the liquid driver 107 drives the electrolyte to flow in reverse, that is, the liquid driver 107 drives the electrolyte to flow from the first chamber 101 through the micropore 1021 and the electrophoresis tank 103 to the second chamber 104, after the micro-nano particles enter the micropore 1021, the current between the first electrode 105 and the second electrode 106 will be greatly reduced, and the current will increase slightly during the movement of the micro-nano particles in the electrophoresis tank 103, but it is still less than the current before the micro-nano particles enter the micropore 1021. The method of analyzing the properties of the micro-nano particles such as the electromotive potential, equivalent volume, equivalent diameter, major diameter, and aspect ratio according to the change of the current between the first electrode 105 and the second electrode is the same as the above embodiment, and will not be repeated here.

[0068] In another exemplary measurement scenario, Figure 1As shown, the inner diameter of the micropore 1021 is 100 nanometers, the thickness of the micropore 1021 is 20 nanometers, the inner diameter of the electrophoresis tank 103 is 200 nanometers, the length of the electrophoresis tank 103 is 400 nanometers, the electrolyte is 5% saline solution filling the first chamber 101, the micropore 1021, the electrophoresis tank 103 and the second chamber 104, a constant current source of 2uA is applied between the first electrode 105 and the second electrode 106, and the electrolyte flows from the second chamber 104 through the electrophoresis tank 103 and the micropore 1021 in sequence under the drive of the liquid driver 107 to reach the first chamber 101.

[0069] When the micro-nano particles flow through the electrophoresis tank 103 and the micropores 1021 in sequence with the flow of the electrolyte, the recorded electrical signal data between the first electrode 105 and the second electrode 106 is the change of the voltage, such as Figure 3 As shown, during the process of the micro-nano particles entering the electrophoresis tank 103 from the second chamber 104, the voltage between the first electrode 105 and the second electrode 106 has a small increase trend, and the duration T3 of the voltage increase is inversely proportional to the electromotive potential of the micro-nano particles. The formula for calculating the electromotive potential ζ of the micro-nano particles is as follows:

[0070] ζ=K / (I*T3);

[0071] Where K is a proportionality coefficient, which is related to the current I applied between the first electrode 105 and the second electrode 106, the size of the micropore 1021, and the size of the electrophoresis tank 103, and can be determined by experiments. In this measurement scenario, I is 2uA, K is -3.2*10 -12 VA·s, T3 is 0.5ms, and the electrokinetic potential of the micro-nano particles is calculated to be -32mV according to the above formula.

[0072] Before the micro-nano particles enter the electrophoresis tank 103, the voltage between the first electrode 105 and the second electrode 106 is a stable value Q. When the micro-nano particles completely pass through the electrophoresis tank 103 and enter the micropores 1021, the voltage will increase significantly. According to the Coulter principle, the maximum value of the voltage increase amplitude q is proportional to the equivalent volume of the micro-nano particles. Therefore, the equivalent volume V of the micro-nano particles can be calculated by the following formula:

[0073] V = a*q / Q;

[0074] Where a is the proportionality coefficient, which is related to the size of the microhole 1021 and can also be determined experimentally. In this measurement scenario, Q is measured to be 200mV, q is 0.56mV, and a is 4.26*10 -2 um 3 According to the above formula, we can get V = 0.12*10 -3 um 3 , the equivalent diameter is 49.3nm.

[0075] The movement of the micro-nano particles in the micropores 1021 is affected by the flow of the electrolyte and the electric field force. The flow rate of the electrolyte is proportional to the pressure P formed by the driving of the liquid driver 107. The electric field force is proportional to the charge carried by the micro-nano particles and the current between the first electrode 105 and the second electrode 106. The duration T4 of the voltage increase between the first electrode 105 and the second electrode 106 is proportional to the long diameter L of the micro-nano particles. Therefore, the long diameter L of the micro-nano particles can be calculated by the following formula:

[0076] L = T2*(m*(-ζ)*U+n*P); or

[0077] L = T2*(m*(-K / T1)+n*P);

[0078] Where m is the electric field force proportionality coefficient, and n is the fluid proportionality coefficient. Both coefficients can be obtained through experiments. In this measurement scenario, T4 is 0.05ms, P is 2000Pa, and n is 2.1*10 -7 (m / Pa), m is 4.37m / (V 2 ·s), the long diameter of the micro-nano particle can be calculated to be L=49nm, thus it can be determined that the aspect ratio L / D of the micro-nano particle is 1, and the shape of the micro-nano particle may be a sphere.

[0079] It should also be noted that in the test scenario where the liquid driver 107 reversely drives the electrolyte to flow, the method for analyzing the electromotive potential, equivalent volume, equivalent diameter, major diameter, aspect ratio and other attribute data of the micro-nano particles based on the voltage change between the first electrode 105 and the second electrode 106 is the same as the above embodiment and will not be repeated here.

[0080] In practical applications, for example, in the field of micro-nano medicine, exosomes and microvesicles are used as diagnostic and therapeutic agents. There is clinical evidence that the size, concentration and surface properties of micro-nano particles can provide relevant information for diagnosis and early screening, or for pharmaceutical products containing micro-nano particles, the size, concentration and surface electrical properties of micro-nano particles can directly affect the efficacy and safety performance of the micro-nano particles in the human body. Therefore, it is very necessary for the present application to provide a reliable, accurate and repeatable micro-nano particle measurement method to measure the relevant properties of micro-nano particles.

[0081] The device for measuring micro-nano particles provided in the present application comprises a first chamber, a microporous membrane, an electrophoresis tank, and a second chamber. In the measuring state, the first chamber, the electrophoresis tank, and the second chamber are filled with an electrolyte, and the electrolyte can provide the micro-nano particles to be measured with the environment required for survival, thereby ensuring that the micro-nano particles are in a living state during the measurement process. The various properties measured correspond to the properties of the micro-nano particles under living conditions, thereby effectively obtaining accurate characterization of various relevant characteristics of the micro-nano particles.

[0082] It should be understood that the device and method for measuring micro-nano particles provided in the present application can also be actually applied to other fields, which will not be described one by one here.

[0083] The above content is only a preferred exemplary embodiment of the present application and is not intended to limit the implementation scheme of the present application. A person skilled in the art can easily make corresponding changes or modifications based on the main concept and spirit of the present application. Therefore, the scope of protection of the present application shall be based on the scope of protection required by the claims.

Claims

1. A device for measuring micro-nano particles, characterized in that: The invention comprises a first chamber, a microporous membrane, an electrophoresis tank, a liquid driver and a second chamber, wherein: The microporous membrane is located between the first chamber and the electrophoresis tank, and the microporous membrane has micropores, and the first chamber and the electrophoresis tank are connected through the micropores; The second chamber is adjacent to the electrophoresis tank and has a first side wall located between the second chamber and the electrophoresis tank, and the first side wall has a first opening for connecting the second chamber and the electrophoresis tank; The liquid driver is adjacent to the second chamber and is located on a side wall opposite to or adjacent to the first side wall, and is used to drive the liquid in the device to flow; The inner diameter of the micropore is smaller than the inner diameter of the electrophoresis tank, the inner diameter of the micropore is 1 nanometer to 10 micrometers, the inner diameter of the electrophoresis tank is 2 nanometers to 20 micrometers, the length of the electrophoresis tank is 2 times or more of the thickness of the microporous membrane, and the inner diameter of the electrophoresis tank is smaller than the inner diameter of the second chamber; The first chamber has a first electrode, and the second chamber has a second electrode; In a measuring state, the first chamber, the electrophoresis tank and the second chamber are filled with electrolyte, and the micro-nanoparticles to be measured pass through the micropores and the electrophoresis tank along with the electrolyte; During the movement of the micro / nano particles through the electrophoresis tank, the micro / nano particles move in the electrophoresis tank mainly by relying on the electric field force formed between the first electrode and the second electrode; When the micro / nano particles move through the micropores, they are affected by the flow of the electrolyte and the electric field formed between the first electrode and the second electrode. The property data of the micro-nano particles are determined by the following steps: Acquiring electrical signal data between the first electrode and the second electrode during the movement of the micro-nano particles through the micropores and the electrophoresis tank; The electromotive potential of the micro-nano particle is determined according to the electrical signal data of the micro-nano particle moving through the electrophoresis tank; and the equivalent volume and aspect ratio of the micro-nano particle are determined according to the electrical signal data of the micro-nano particle moving through the micropore.

2. The device according to claim 1, characterized in that The thickness of the microporous membrane is 1 nanometer to 10 micrometers, and the length of the electrophoresis tank is 2 nanometers to 20 micrometers.

3. The device according to claim 1 or 2, characterized in that: The inner diameter of the first opening is equal to the inner diameter of the electrophoresis tank.

4. The device according to claim 1 or 2, characterized in that: The microporous membrane is an inorganic membrane.

5. The device according to claim 1 or 2, characterized in that: The microporous membrane is integrally formed with the first chamber, the electrophoresis tank and the second chamber.

6. The device according to claim 1 or 2, characterized in that: The center of the microhole and the center of the first opening are parallel to the length direction of the electrophoresis tank.

7. The device according to claim 1 or 2, characterized in that: The shape of the electrophoresis tank is any one of a cylinder, a cuboid, a conical platform, and a trapezoidal platform.

8. The device according to any one of claims 1 to 7, characterized in that: The step of determining the electromotive potential of the micro-nano particles according to the electrical signal data of the micro-nano particles moving through the electrophoresis tank comprises: Determining a first time taken by the micro / nano particles to pass through the electrophoresis tank according to the electrical signal data; The electromotive potential of the micro-nano particle is determined according to the first time and the electric signal applied between the first electrode and the second electrode; the first time and the electric signal applied between the first electrode and the second electrode are both inversely proportional to the electromotive potential.

9. The device according to any one of claims 1 to 7, characterized in that: The step of determining the equivalent volume and aspect ratio of the micro-nano particles according to the electrical signal data of the micro-nano particles moving through the micropores comprises: Determine, according to the electrical signal data, a maximum amplitude of the electrical signal change between the first electrode and the second electrode when the micro-nano particle passes through the micropore, and a stable value of the electrical signal between the first electrode and the second electrode before the micro-nano particle enters the electrophoresis tank; The equivalent volume and equivalent diameter of the micro / nano particle are determined according to the maximum amplitude and the stable value; the stable value is inversely proportional to the equivalent volume, and the maximum amplitude is proportional to the equivalent volume.

10. The device according to any one of claims 1 to 7, characterized in that: The step of determining the equivalent volume and aspect ratio of the micro-nano particles according to the electrical signal data of the micro-nano particles moving through the micropores comprises: Determining a second time taken by the micro-nanoparticle to pass through the micropore according to the electrical signal data; Determining the long diameter of the micro-nano particle according to the second time and the pressure of the electrolyte under the driving of the liquid driver; the second time and the pressure are both proportional to the long diameter; The aspect ratio of the micro-nano particles is determined according to the long diameter and the equivalent diameter of the micro-nano particles.

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