Device and method for measuring micro/nano-sized particles

The device (100) comprises a cavity (101) and at least two microporous membranes (102), wherein the microporous membranes (102) are arranged in series in the cavity (101) and divide the cavity (101) into a plurality of chambers (1011); each of the microporous membranes (102) is provided with micropores (103), and two adjacent chambers (1011) are in communication via the micropores (103); and each of the chambers (1011) is provided with an electrode (1012).

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a 371 of International Application No.PCT/CN2020/128400, filed Nov. 12, 2020, which claims the priority of Chinese Patent Application No. 201911158297.3 filed on Nov. 22, 2019, the entire contents of which are hereby incorporated by reference.

TECHNICAL FIELD

The present application relates to the technical field of micro/nano-sized particle measurement, and in particular, to a device and method for measuring micro/nano-sized particles.

BACKGROUND

Based on the special attributes of particulate matter, particulate matter is widely used in medicine, chemical industry, materials and other fields. In the application of particulate matter, it is very important to measure the three-dimensional shape and other attributes of particulate matter (hereinafter referred to as particles).

The inventors realized that a particle measurement equipment currently used commonly includes optical microscopes, scanning electron microscopes and transmission electron microscopes, but due to the low resolution of optical microscopes, it is difficult to observe particles with a size less than 300 nanometers by optical microscopes, which is not suitable for micro/nano-sized particle measurement. Scanning electron microscopy and transmission electron microscopy can obtain the three-dimensional morphology of particles by tilting the particle samples at different angles under vacuum conditions, but cannot obtain real morphological information for particle samples that need to be measured in solution state or biological particle samples. Therefore, there is still a problem in tradition that the three-dimensional morphology of micro/nano-sized particles in solution cannot be measured.

SUMMARY

There are provided a device for measuring micro/nano-sized particles, and a method for measuring micro/nano-sized particles according to embodiments of the present disclosure.

The Technical Solution is as Below:

In one aspect, a device for measuring micro/nano-sized particles, comprising a cavity and at least two microporous membranes. The microporous membranes are arranged in series in the cavity and divide the cavity into a plurality of chambers. Each of the microporous membranes is provided with micropores, and two adjacent chambers are in communication via the micropores. Each of the chambers is provided with an electrode.

In another aspect, a method for measuring micro/nano-sized particles, comprising: allowing the micro/nano-sized particles to be measured to continuously pass through the micropores of the aforementioned device along with an electrolyte solution; acquiring electric signal data between two electrodes adjacent to each of the micropores in the process of the micro/nano-sized particles passing through each of the micropores; and determining attribute data of the micro/nano-sized particles according to the electric signal data.

In the above technical solution, the cavity of the device for measuring micro/nano-sized particles is divided into a plurality of chambers by a series of microporous membranes, and two adjacent chambers are communicated through the micropores on the microporous membrane, and each chamber has electrodes. In the measurement state, each chamber is filled with an electrolyte solution, and the electrolyte solution contains the micro/nano-sized particles to be measured. The micro/nano-sized particles pass through each micropore in turn with the flow of the electrolyte solution. By analyzing the electrical signal data between two electrodes adjacent to the micropore, the three-dimensional morphological attributes of the micro/nano-sized particles to be measured in the electrolyte solution can be obtained, thereby realizing the measurement of the three-dimensional morphological attributes of the micro/nano-sized particles in the solution state.

By the above-mentioned drawings, the specific embodiments of the present application have been shown, and a more detailed description will follow. These drawings and written descriptions are not intended to limit the scope of the concepts of the present application in any way, but by reference to specific embodiments, the concepts of the present application are explained to those skilled in the art.

DETAILED DESCRIPTION

The description will now be made in detail of exemplary embodiments, examples of which are illustrated in the accompanying drawings. Where the following description refers to the drawings, the same numerals in different drawings refer to the same or similar elements unless otherwise indicated. The implementations described in the illustrative examples below are not intended to represent all implementations consistent with this application. Rather, they are merely examples of apparatus and methods consistent with some aspects of the present application as recited in the appended claims.

First of all, it should be noted that the micro/nano-sized particles described in this embodiment refer to particle physics with a size in the micro-and nano-scale, usually including organic particles, inorganic particles, magnetic particles, silica particles, agarose gel particles, styrene particles, metal particles, colloidal particles, particles conjugated with molecules, particles conjugated with biomolecules, particles conjugated with immunoglobulins, particles conjugated with nucleic acids, biological particles, biological cells, blood cells, sperm, egg cells, microbial cells, bacterial cells, fungal cells, viruses, subcellular organelles, mitochondria, nuclei, chloroplasts, lysosomes, ribosomes, atomic particles, ionic particles, molecular particles, polymeric particles, nucleic acids and their chemical variants, deoxyribonucleic acid and chemical variants thereof, nucleic acids and chemical variants thereof, proteins and chemical variants thereof. Among them, the inorganic particles usually include particulate matter such as silicon dioxide, titanium dioxide, aluminum oxide, calcium carbonate, and aluminum nitride.

Micro/nano-sized particles have unique electrical, optical and magnetic attributes. Physical attributes such as particle size and potential of micro/nano-sized particles have a great influence on their performance. Therefore, it is necessary to measure the physical attributes of micro/nano-sized particles. For example, a biological macromolecule includes four types of substances such as nucleic acids, proteins, carbohydrates and lipids. These biological macromolecules exist in the form of micro/nano-sized particles in the living body. By measuring the physical attributes of these biological macromolecules, the study of life behavior will be of great significance.

Referring toFIG.1,FIG.1is a cross-sectional view of a device for measuring micro/nano-sized particles according to an exemplary embodiment. The device can be used to measure three-dimensional morphological attributes of micro/nano-sized particles such as the electrical mobility, sphericity value, and particle size and other.

As shown inFIG.1, in an exemplary embodiment, the device100for measuring micro/nano-sized particles includes a cavity101and at least two microporous membranes102(three are shown inFIG.1). Each microporous membrane102is arranged in series in the cavity101, dividing the cavity101into a plurality of chambers1011, and the microporous membrane102is provided with micropores103, so that two adjacent chambers1011are connected through the micropores103, and each chamber1011has electrodes1012therein.

In the measurement state, as shown inFIG.2, each chamber1011of the device100is filled with an electrolyte solution105, and the electrolyte solution105contains the micro/nano-sized particles106to be measured, so as to provide a solution environment for the measurement of the micro/nano-sized particles106. The micro/nano-sized particles106pass through each micropore103in turn with the flow of the electrolyte solution105, and the electrode1012at one end of the cavity101is grounded, and the other electrodes1012are respectively loaded with voltages of different magnitudes. Exemplarily, the conductivity of the electrolyte in the electrolyte solution105may be in the range of 10−6to 10−3S/cm (Siemens per meter).

The electrolyte solution105flows from the chamber1011at one end of the chamber101to the chamber1011at the other end of the chamber101, and its flow direction is determined by the driving direction of the liquid driver104at one end of the chamber101. As shown inFIGS.1and2, in one embodiment, the liquid driver104is located at the bottom end of the cavity101and is adjacent to the cavity1011at the bottom end. The driving direction of the liquid driver104for the electrolyte solution105can be driven from the chamber1011at the top to the chamber1011at the bottom as shown inFIG.2, or from the chamber1011at the bottom to the chamber1011at the top, which is not limited here. The liquid driver104may also be located at the top end of the cavity101and adjacent to the cavity1011at the top end.

The driving mode of the liquid driver104can be electric field force driving, hydraulic driving, magnetic field driving, fluid driving, air pressure driving, osmotic pressure driving, Brownian motion driving, capillary force driving, temperature difference diffusion driving, etc. Correspondingly, the liquid driver104may be a device that can provide a driving force for the flow of the electrolyte solution105, such as a liquid pump, a pneumatic device, a syringe, and the like. Exemplarily, the driving mode of the liquid driver104adopts any one of electric field driving, hydraulic driving, and magnetic field driving, so as to provide a fixed driving force for the flow of the electrolyte solution105, thereby driving the electrolyte solution105to flow stably.

In addition, the electrode1012at one end of the cavity101is grounded, and voltages of different magnitudes are applied to the remaining electrodes1012, and the order of the applied voltages corresponds to the distance between the electrode1012and the grounded electrode1012. As shown inFIG.1, if the electrode1012in the top chamber1011is grounded, that is, V0=0V, the magnitude of the applied voltage on the other three electrodes1012is V3≥V2≥V1, so that the strength of the electric field formed between the two adjacent electrodes1012increases sequentially, ensuring that the micro/nano-sized particles106continuously pass through each micropore103along with the flow of the electrolyte solution105. The electrode1012can be made of platinum or silver chloride and other materials.

During the process that the micro/nano-sized particles106pass through each micropore103in turn with the flow of the electrolyte solution105, the electrical signal data between the two electrodes1012adjacent to the micropore103are obtained by respectively measured when the micro/nano-sized particles106pass through the micropore103. By analyzing the obtained electrical signal data, three-dimensional morphological attributes such as electrical mobility, sphericity value, particle size, of the micro/nano-sized particles106can be obtained, thereby solving the problem that the attributes of the micro/nano-sized particles in solution state cannot be measured in tradition.

The microporous membrane102may be an organic membrane or an inorganic membrane.

In one embodiment, the microporous membrane102is an inorganic membrane, that is, the microporous membrane102is made of an inorganic material. Compared with an organic membrane, the inorganic membrane has better stretchability, which is beneficial for the micro/nano-sized particles106to flow with the electrolyte solution105and move through the micropores103. Exemplarily, the microporous membrane102may be made of inorganic materials such as low-stress silicon nitride, silicon nitride or silicon wafers. The microporous membrane102made of these inorganic materials has better membrane-forming effect, and the manufacturing technology is also more mature.

The thickness of the microporous membrane102may be 1 nanometer to 10 micrometers, and the inner diameter of the micropores103may be 1 nanometer to 10 micrometers. The inner diameter of the micropore103is the diameter of the micropore103, which refers to the distance in the direction perpendicular to the direction in which the micro/nano-sized particles106move through the device100during the measurement process. The micropore103can be cylindrical, rectangular parallelepiped, conical table, trapezoidal table and other geometric shapes. Exemplarily, when the micropore103is cylindrical, the inner diameter of the micropore103is the diameter of the bottom circle of the cylinder.

There is a separation distance between two adjacent microporous membranes102, and the separation distance between two adjacent microporous membranes102may be the same or different. Exemplarily, the separation distance between two adjacent microporous membranes102may be 1 nanometer to 100 micrometers.

The microporous membrane102and the cavity101can be integrally formed, so that the shape of the device100has high stability. The microporous membranes102can also be arranged in the cavity101in a manner of membrane stacking, and there is a certain distance between each microporous membrane102. For example, a plurality of fluid grooves can be arranged on the inner surface of the cavity101, there is a certain distance between adjacent fluid grooves, and the microporous membrane102is fixed in the fluid groove, so as to realize the membrane stacking arrangement of the microporous membrane102.

The positions, inner diameters and thicknesses of the micropores103on each microporous membrane102can be completely consistent, so that the centers of the micropores103are located on the same straight line, and the moving paths of the micro/nano-sized particles in the device100remain straight. The separation distance between two adjacent microporous membranes102may be the same or different.

In the above technical solution, the cavity of the device for measuring micro/nano-sized particles is divided into a plurality of chambers by a series of microporous membranes, and two adjacent chambers are communicated through the micropores on the microporous membrane, and each chamber has electrodes. In the measurement state, each chamber is filled with an electrolyte solution, and the electrolyte solution contains the micro/nano-sized particles to be measured. The micro/nano-sized particles pass through each micropore in turn with the flow of the electrolyte solution. By analyzing the electrical signal data between two electrodes adjacent to the micropore, the three-dimensional morphological attributes of the micro/nano-sized particles to be measured in the electrolyte solution can be obtained, thereby realizing the measurement of the three-dimensional morphological attributes of the micro/nano-sized particles in the solution state.

Another exemplary embodiment of the present invention also provides a method for measuring micro/nano-sized particles, which is implemented based on the device for measuring micro/nano-sized particles described in the above embodiments, so as to determine the micro/nano-sized particles to be measured attribute data. Exemplarily, the device for measuring micro/nano-sized particles described in the above embodiments is further configured with computer components such as a processor and a memory, and the method for measuring micro/nano-sized particles provided in this embodiment is executed by the computer components, so as to determine the attribute data of micro/nano-sized particles. Alternatively, the device for measuring micro/nano-sized particles described in the above embodiments is connected to an external computer equipment, so that the external computer equipment performs measurement according to the device for measuring micro/nano-sized particles described in the above embodiments to obtain measurement data, to execute the method for measuring micro/nano-sized particles provided in this embodiment, which is not limited here.

In the method for measuring micro/nano-sized particles provided in this embodiment, first enabling the micro/nano-sized particles to be measured so as to continuously pass through the plurality of micropores of the aforementioned device along with an electrolyte solution, and then acquiring electric signal data between two electrodes adjacent to each of the micropores in the process of the micro/nano-sized particles passing through each of the micropores, to determine attribute data of the micro/nano-sized particles according to the electric signal data.

It should be noted that a set of continuous electrical signal data can be obtained by collecting the corresponding electrical signal data during the continuous passage of the micro/nano-sized particles through a plurality of micropores. Based on the analysis of the continuous electrical signal data, attribute information related to the three-dimensional morphology of the micro/nano-sized particles can be determined.

The method provided in this embodiment will be described in detail below by taking the device100for measuring micro/nano-sized particles shown inFIG.1andFIG.2as an example.

In the device100shown inFIG.1andFIG.2, three microporous membranes102are arranged in the cavity101, and the microporous membranes102divide the cavity101into four chambers1011. The micro/nano-sized particles106to be measured continuously pass through the three micropores103along with the flow of the electrolyte solution105. In the process of flowing with the electrolyte solution105, the micro/nano-sized particles106are prone to inversion, inclination, etc., so that the micro/nano-sized particles106pass through each micropore103in different postures. When the micro/nano-sized particles106pass through each micropore103in different postures, the electrical signal data between the two electrodes1012adjacent to the micropore103may be different.

Referring toFIG.3andFIG.4,FIG.3is a schematic diagram of a set of continuous electrical signal data obtained by collecting electrical signal data between two electrodes1012adjacent to each micropore103during the continuous passage of a standard spherical particle through each micropore103,FIG.4is a schematic diagram of a set of continuous electrical signal data obtained by collecting electrical signal data between two electrodes1012adjacent to each micropore103during the continuous passage of a standard cube particle through each micropore103.

It can be seen that for the micro/nano-sized particles106with uniform three-dimensional morphology, such as the spherical particles shown inFIG.3, during the process of passing through each micropore103, the electrical signals on the two electrodes1012adjacent to each micropore103have little difference. However, for the micro/nano-sized particles106with non-uniform three-dimensional morphology, such as the cuboid particles shown inFIG.4, during the process of passing through each micropore103, the electrical signals on the two electrodes1012adjacent to each micropore103is quite different.

In an exemplary embodiment, the attribute data of the micro/nano-sized particles106includes an electrical mobility of the micro/nano-sized particles106. The speed of the micro/nano-sized particles106passing through two adjacent micropores103and the potential difference between the two adjacent micropores103can be determined according to the electrical signal data, so as to determine the electric mobility of the micro/nano-sized particles106when the micro/nano-sized106continuously pass through two adjacent micropores103according to the obtained speed and potential difference.

The time for the micro/nano-sized particles106continuously passing through two adjacent micropores103can be obtained according to the electrical signal data, and then the ratio of the distance between the two adjacent micropores103to the time can be calculated to determine the speed of the micro/nano-sized particles106continuously passing through two adjacent micropores103. The potential difference between two adjacent micropores103can be determined according to the electric field strength and distance between two adjacent micropores103.

Exemplarily, if the distance between two adjacent micropores103is 1000 nanometers, the time interval for the micro/nano-sized particles106passing through the two micropores103is 1 millisecond, and the resulting potential difference is 100 millivolts, then the calculated electric mobility of the micro/nano-sized particles106passing through the two adjacent micropores103is 10−8m2v−1s−1.

The surface potential of the micro/nano-sized particles106can be further determined according to the determined electric mobility of the micro/nano-sized particles106when passing through two adjacent micropores103continuously, and the surface potential of the micro/nano-sized particles106corresponds to the posture when the micro/nano-sized particles106passing through the micropores103.

Therefore, according to the change of the surface potential of the micro/nano-sized particles106in the process of continuously passing through the two adjacent micropores103, the posture change of the micro/nano-sized particles106in the process of continuously passing through the micropores103can be determined, so that three-dimensional morphology of the micro/nano-sized particles106can be obtained by analysis.

In another exemplary embodiment, the attribute data of the micro/nano-sized particles106includes a sphericity value of the micro/nano-sized particles106. By dividing the electrical signal data into several signal units, and then comparing the signal units with the corresponding signal units of the standard signal, the contrast coefficient between the electrical signal data and the standard signal is obtained, so as to obtain the sphericity value of the standard signal with the highest contrast coefficient as the sphericity value of the micro/nano-sized particles106.

First of all, it should be noted thatFIG.5is a schematic diagram of a set of electrical signal data collected in the process of a micro/nano-sized particle106passing through three micropores103continuously, which contains three independent electrical signal data, each independent electrical signal data respectively corresponds to the process of the micro/nano-sized particles106passing through different micropores103, and the three independent electrical signal data are continuous in terms of time.

As shown inFIG.5, for the electrical signal data with sinusoidal distribution, the electrical signal data can be divided by taking the electrical signal peak value as a dividing point, thereby obtaining two signal units. For the electrical signal data distributed in other forms, the electrical signal data can be divided according to the set time interval, or the electrical signal data can be divided according to the gradient change trend of the electrical signal, which is not limited here.

The electrical signal data is divided into several signal units, and the gradient function f(θ, r)of each signal unit needs to be calculated. The calculation formula of the gradient function f(θ, r)is as follows:
f(θ,r)=arctan(θ)

Where r represents the slope length of a single signal unit, and θ represents the slope angle of a single signal unit.

The standard signal is known information obtained in advance, and is the electrical signal data collected during the movement of the micro/nano-sized particles106with determined sphericity values through the micropores103. Therefore, the standard signal reflects the sphericity value of the micro/nano-sized particles106. The standard signal needs to be divided into several signal units in advance according to the above method.

By comparing the slope function of each signal unit with the slope function of the corresponding signal unit of the standard signal, the contrast coefficient between each signal unit of the electrical signal data and each signal unit of the standard signal can be obtained, and the contrast coefficient reflects similarity between each signal unit. Therefore, the higher the contrast coefficient between the signal units, the closer the sphericity values between the micro/nano-sized particles106are.

For each electrical signal data, by calculating the average value of the contrast coefficients of all the signal units divided into which the electrical signal data is divided, the contrast coefficient between the electrical signal data and the standard signal is obtained.

In order to ensure the practicability of this embodiment, it is necessary to provide a variety of standard signals of the micro/nano-sized particles106with determined sphericity values in advance, and calculate the contrast coefficients between the electrical signal data obtained during the measurement process and different standard signals, to determine the sphericity value corresponding to the standard signal with the highest contrast coefficient as the sphericity value of the micro/nano-sized particles106to be measured.

FIG.6is a schematic diagram of a set of electrical signal data collected during the process of a 200 nm diameter styrene microsphere continuously passing through three micropores103under an actual measurement environment. By analyzing the electrical signal data shown inFIG.6based on the above acquisition process of sphericity value, it can be obtained that the sphericity value of the styrene microsphere is 0.95.

It should be noted that, in general, for the nearly spherical micro/nano-sized particles106, the sphericity value obtained by the method provided in this embodiment is above 0.8, while for the rod-shaped micro/nano-sized particles106, the obtained sphericity value is 0.2 or less.

It should also be noted that there is also a certain correspondence between the aspect ratio of the micro/nano-sized particles106and the sphericity value of the micro/nano-sized particles106. Therefore, the aspect ratio of the micro/nano-sized particles106also has a certain influence on the measurement of the sphericity value of the micro/nano-sized particles106.

In another exemplary embodiment, the electrical signal data obtained during the measurement process can also be input into a machine learning model, so that the machine learning model can predict the three-dimensional shape of the micro/nano-sized particles106according to the input electrical signal data, so as to directly obtain the three-dimensional morphology of the micro/nano-sized particles.

It should be noted that the machine learning model used in this embodiment is pre-trained according to the electrical signal data between the two electrodes adjacent to the micropore103when the micro/nano-sized particles106with asymmetric morphology pass through the micropore103.

In another exemplary embodiment, the attribute data of the micro/nano-sized particles106further includes a particle size of the micro/nano-sized particles106. The initial particle size of the micro/nano-sized particles106is calculated according to the electrical conductivity of the electrolyte solution105, the approximate spherical radius of the micro/nano-sized particles106and the radius of the micro/nano-sized particles103. If the ratio of the approximate spherical radius of the micro/nano-sized particles106to the radius of the micro/nano-sized particles103is greater than the preset threshold, the correction coefficient is determined according to the ratio, and the initial particle size is corrected by the correction coefficient to obtain the particle size of the micro/nano-sized particles106.

The calculation formula of the initial particle size ∇R of the micro/nano-sized particles106is as follows:
VR=(4pd3)/(πD4)

Wherein d represents the approximate spherical radius of the micro/nano-sized particles106, D represents the radius of the micropore103, and ρ represents the conductivity of the electrolyte solution105. If the particle size of the micro/nano-sized particles106is much smaller than the radius of the micro/nano-sized particles103, for example, the ratio d/D of the approximate spherical radius of the micro/nano-sized particles106to the radius of the micro/nano-sized particles103is smaller than the set threshold, the initial particle size is the particle size of the micro/nano-sized particles106.

If the ratio of the approximate spherical radius of the micro/nano-sized particles106to the radius of the micropores103is greater than the preset threshold, the initial particle size needs to be corrected by a correction coefficient to obtain the particle size of the micro/nano-sized particles106. The calculation formula is as follows:
VR′=(4pd3)S/(πD4)

Wherein, the correction coefficient S is determined according to the ratio of the approximate spherical radius of the micro/nano-sized particles106to the radius of the micropores103. For example, the correction coefficient S can be determined according to Table 1.

To sum up, according to the device and method provided in this application, three-dimensional morphological attributes such as electric mobility, sphericity value, particle size, of micro/nano-sized particles can be measured, thereby solving the problem that the micro/nano-sized particles in solution state cannot be measured in the existing technology.

The above contents are only preferred exemplary embodiments of the present application, and are not intended to limit the embodiments of the present application. Those of ordinary skill in the art can easily make corresponding changes or modifications according to the main concept and spirit of the present application, therefore, the protection scope of this application shall be subject to the protection scope required by the claims.