WO2021098583A1 - 用于测量微纳颗粒的装置及方法 - Google Patents

用于测量微纳颗粒的装置及方法 Download PDF

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WO2021098583A1
WO2021098583A1 PCT/CN2020/128400 CN2020128400W WO2021098583A1 WO 2021098583 A1 WO2021098583 A1 WO 2021098583A1 CN 2020128400 W CN2020128400 W CN 2020128400W WO 2021098583 A1 WO2021098583 A1 WO 2021098583A1
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micro
nano particles
micropores
electrical signal
signal data
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PCT/CN2020/128400
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English (en)
French (fr)
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柳可
熊贵
王哲
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瑞芯智造(深圳)科技有限公司
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Priority to EP20890268.4A priority Critical patent/EP4063824A4/en
Priority to US17/757,888 priority patent/US20230236104A1/en
Publication of WO2021098583A1 publication Critical patent/WO2021098583A1/zh

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    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
    • G01N15/02Investigating particle size or size distribution
    • G01N15/0266Investigating particle size or size distribution with electrical classification
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
    • G01N15/10Investigating individual particles
    • G01N15/1031Investigating individual particles by measuring electrical or magnetic effects
    • G01N15/12Investigating individual particles by measuring electrical or magnetic effects by observing changes in resistance or impedance across apertures when traversed by individual particles, e.g. by using the Coulter principle
    • G01N15/134Devices using two or more apertures
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/483Physical analysis of biological material
    • G01N33/487Physical analysis of biological material of liquid biological material
    • G01N33/48707Physical analysis of biological material of liquid biological material by electrical means
    • G01N33/48721Investigating individual macromolecules, e.g. by translocation through nanopores
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
    • G01N2015/0003Determining electric mobility, velocity profile, average speed or velocity of a plurality of particles
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
    • G01N2015/0038Investigating nanoparticles
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
    • G01N15/02Investigating particle size or size distribution
    • G01N2015/0294Particle shape
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
    • G01N15/10Investigating individual particles
    • G01N2015/1029Particle size
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
    • G01N15/10Investigating individual particles
    • G01N2015/103Particle shape
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
    • G01N15/10Investigating individual particles
    • G01N15/1031Investigating individual particles by measuring electrical or magnetic effects
    • G01N15/12Investigating individual particles by measuring electrical or magnetic effects by observing changes in resistance or impedance across apertures when traversed by individual particles, e.g. by using the Coulter principle
    • G01N2015/135Electrodes
    • G01N2015/136Scanning electrodes

Definitions

  • This application relates to the technical field of micro/nano particle measurement, and in particular to a device and method for measuring micro/nano particles.
  • particulate matter Based on the special properties of particulate matter, particulate matter is widely used in the fields of medicine, chemical industry, and materials. In the application of particulate matter, the measurement of the three-dimensional morphology and other properties of particulate matter (hereinafter referred to as particles) is very important.
  • Nanoparticle measurement Scanning electron microscopes and transmission electron microscopes can obtain the three-dimensional morphology of particles by tilting the particle samples at different angles under vacuum conditions.
  • no real morphological information can be obtained. Therefore, there is still a problem in the prior art that the three-dimensional morphology of micro-nano particles in the solution cannot be measured.
  • the embodiments of the present application provide a device for measuring micro-nano particles, and also provide a method for measuring micro-nano particles, which is used to determine the three-dimensional morphological properties of micro-nano particles in a liquid state. Perform testing.
  • a device for measuring micro-nano particles includes: a cavity and at least two microporous membranes, wherein the microporous membranes are arranged in series in the cavity to divide the cavity into a plurality of And the microporous membrane is provided with micropores, two adjacent chambers are connected through the micropores, and each of the chambers has an electrode.
  • the electrode at one end of the cavity is grounded, and the other electrodes are loaded with voltages of different magnitudes.
  • the magnitude of the voltages corresponds to the voltage between the electrodes and the ground electrode. distance.
  • each of the chambers is filled with electrolyte, and the micro-nano particles to be measured continuously pass through the micropores along with the electrolyte.
  • the shape of the micropores on each microporous membrane is the same, and the centers of the micropores are on the same straight line.
  • the inner diameter of the micropore is 1 nanometer to 10 micrometers.
  • the thickness of the microporous membrane is 1 nanometer to 10 micrometers.
  • the microporous membrane is integrally formed with the cavity, or the microporous membrane is arranged in the cavity in the form of a film stack, and each microporous membrane has Separation distance.
  • the microporous film is an inorganic film
  • the material of the inorganic film includes any one of low-stress silicon nitride, silicon oxide, and silicon wafers.
  • the device further includes a liquid driver which is adjacent to a chamber at one end of the cavity and is used to drive the flow of liquid in the device.
  • the driving mode of the liquid driver includes any one of electric field force driving, hydraulic driving, and magnetic field force driving.
  • the distance between adjacent microporous membranes is 1 nanometer to 100 micrometers.
  • a method for measuring micro-nano particles includes: allowing the micro-nano particles to be measured to continuously pass through the micropores of the device as described above along with the electrolyte; and obtaining the micro-nano particles to pass through each of the micro-nano particles.
  • electrical signal data between two electrodes adjacent to each of the micro holes; and determining the attribute data of the micro/nano particles according to the electrical signal data.
  • the determining the attribute data of the micro-nano particles according to the electrical signal data includes: determining, according to the electrical signal data, that the micro-nano particles continuously pass through the two adjacent micro-nano particles. The velocity of the pores and the potential difference between the two adjacent micropores; according to the velocity of the micro-nano particles continuously passing through the two adjacent micro-pores and the potential difference, it is determined that the micro-nano particles continuously pass the The electrical mobility of two adjacent micropores.
  • the determining the attribute data of the micro-nano particles according to the electrical signal data includes: dividing the electrical signal data into a plurality of signal units; and dividing the signal units with standard The signal unit corresponding to the signal is compared to obtain the contrast coefficient between the electrical signal data and the standard signal; the sphericity value corresponding to the standard signal with the highest contrast coefficient is obtained as the sphericity value of the micro-nano particles.
  • the determining the attribute data of the micro/nano particles according to the electrical signal data includes: inputting the electrical signal data into a machine learning model, and the machine learning model is based on A symmetrical micro-nano object is obtained by training the electrical signal data between two adjacent electrodes when passing through the micro-hole; obtaining the three-dimensional prediction of the micro-nano particle from the electrical signal data by the machine learning model form.
  • the method further includes: calculating the initial particle size of the micro-nano particles based on the conductivity of the electrolyte, the approximate sphere radius of the micro-nano particles, and the radius of the micro-holes If the ratio of the approximate sphere radius of the micro-nano particles to the radius of the micropores is greater than a preset threshold, a 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 particles.
  • the cavity of the device for measuring micro-nano particles is divided into a plurality of chambers by a series of microporous membranes, and the adjacent two chambers are connected through the micropores on the microporous membrane, and each Each chamber has electrodes.
  • each chamber is filled with electrolyte, and the electrolyte contains micro-nano particles to be measured.
  • the micro-nano particles pass through each micropore in turn with the flow of the electrolyte.
  • the electrical signal data between two adjacent electrodes of the hole can be analyzed to obtain the three-dimensional morphological properties of the micro-nano particles to be measured in the electrolyte, thereby realizing the measurement of the three-dimensional morphological properties of the micro-nano particles in the solution state.
  • Fig. 1 is a cross-sectional view of a device for measuring micro/nano particles according to an exemplary embodiment
  • Fig. 2 is a schematic diagram of the device for measuring micro-nano particles shown in Fig. 1 in a measuring state;
  • Figure 3 is a set of continuous electrical signal data obtained by collecting electrical signal data between two electrodes adjacent to each micropore in the process of a standard spherical particle continuously passing through each micropore of the device shown in Figure 1 Schematic diagram;
  • Figure 4 is a set of continuous electrical signal data obtained by collecting electrical signal data between two electrodes adjacent to each micropore in the process of a standard cube particle continuously passing through each micropore of the device shown in Figure 1 Schematic diagram;
  • Fig. 5 is a schematic diagram showing signal unit division for electrical signal data according to an exemplary embodiment
  • FIG. 6 is a schematic diagram of electrical signal data collected during the continuous passage of a styrene microsphere with a diameter of 200 nanometers through a plurality of micropores.
  • the micro-nano particles described in this embodiment refer to particle physics with sizes in the micrometer and nanometer levels, which usually include 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, polymer particles, nucleic acids and their chemical variants, deoxyribonucleic acid And its chemical variants, nucleic acid and its chemical variants, protein and its chemical variants.
  • the inorganic particles usually include particulate materials such as silica, titanium dioxide, aluminum oxide, calcium
  • Micro-nano particles have unique electrical, optical and magnetic properties.
  • the physical properties of micro-nano particles such as particle size and potential have a great influence on their performance. Therefore, it is very necessary to measure the physical properties of micro-nano particles.
  • biological macromolecules include nucleic acids, proteins, carbohydrates, and lipids. These biological macromolecules exist in the form of micro-nano particles in the living body. By measuring the physical properties of these biological macromolecules, the study of life behavior Will be of great significance.
  • FIG. 1 is a cross-sectional view of a device 100 for measuring micro-nano particles according to an exemplary embodiment.
  • the device can be used to measure the electrical mobility, sphericity, and particle size of micro-nano particles. And other three-dimensional morphological properties.
  • the device 100 for measuring micro-nano particles includes a cavity 101 and at least two microporous membranes 102 (three are shown in FIG. 1), wherein each microporous The membrane 102 is arranged in series in the cavity 101 to divide the cavity 101 into a plurality of chambers 1011.
  • the microporous membrane 102 is provided with micropores 103, so that two adjacent chambers 1011 are connected through the micropores 103, and each There are electrodes 1012 in each chamber 1011.
  • each chamber 1011 of the device 100 is filled with an electrolyte 105, and the electrolyte 105 contains the micro-nano particles 106 to be measured, so as to provide a solution for the measurement of the micro-nano particles 106. surroundings.
  • the micro-nano particles 106 pass through each micro-hole 103 in turn along with the flow of the electrolyte 105, and the electrode 1012 at one end of the cavity 101 is grounded, and the remaining electrodes 1012 are respectively loaded with voltages of different magnitudes.
  • the conductivity of the electrolyte in the electrolyte 105 may be in the range of 10 -6 to 10 -3 S/cm (Siemens per meter).
  • the electrolyte 105 flows from the cavity 1011 at one end of the cavity 101 to the cavity 1011 at the other end of the cavity 101, and its flow direction is determined by the driving direction of the liquid driver 104 at one end of the cavity 101.
  • the liquid driver 104 is located at the bottom end of the cavity 101 and is adjacent to the cavity 1011 at the bottom end.
  • the driving direction of the liquid driver 104 for the electrolyte 105 can be as shown in FIG. 2 from the top chamber 1011 to the bottom chamber 1011, or from the bottom chamber 1011 to the top chamber 1011. This is not done here. limit.
  • the liquid driver 104 may also be located at the top of the cavity 101 and adjacent to the cavity 1011 at the top.
  • the driving mode of the liquid driver 104 can be electric field force driving, hydraulic driving, magnetic field force driving, fluid driving, air pressure driving, osmotic pressure driving, Brownian motion driving, capillary force driving, temperature diffusion driving and other methods.
  • the liquid driver 104 can It is a device that can provide driving force for the flow of the electrolyte 105, such as a liquid pump, a pneumatic device, and a syringe.
  • the driving method of the liquid driver 104 adopts any one of electric field force driving, hydraulic driving, and magnetic field force driving to provide a fixed driving force for the flow of the electrolyte 105 so as to drive the electrolyte 105 to flow stably.
  • the electrode 1012 at one end of the cavity 101 is grounded, and voltages of different magnitudes are applied to the remaining electrodes 1012.
  • the magnitude of the applied voltages corresponds to the distance between the electrode 1012 and the grounded electrode 1012.
  • the magnitude of the voltage applied to the other three electrodes 1012 is V3 ⁇ V2 ⁇ V1
  • the electrode 1012 can be made of platinum or silver silver chloride and other materials.
  • the electrical signal data between the two electrodes 1012 adjacent to the micro-hole 103 when the micro-nano particle 106 passes through the micro-hole 103 are measured respectively Analyzing the obtained electrical signal data can obtain the electrical mobility, sphericity value, particle size and other three-dimensional morphological properties of the micro-nano particles 106, thereby solving the problem that the properties of the micro-nano particles in a solution state cannot be measured in the prior art.
  • the microporous membrane 102 may be an organic membrane or an inorganic membrane.
  • the microporous membrane 102 is an inorganic membrane, that is, the microporous membrane 102 is made of an inorganic material. Compared with an organic membrane, the inorganic membrane has better stretchability, which is beneficial for the micro-nano particles 106 to follow the electrolyte.
  • the flow of 105 moves through the pores 103.
  • the microporous film 102 may be made of inorganic materials such as low-stress silicon nitride, silicon nitride, or silicon wafers. The microporous film 102 made of these inorganic materials has a better film-forming effect, and the manufacturing technology Also more mature.
  • the thickness of the microporous membrane 102 can be 1 nanometer to 10 micrometers, and the inner diameter of the micropore 103 can be 1 nanometer to 10 micrometers.
  • the inner diameter of the micropore 103 is the pore diameter of the micropore 103, which refers to the measurement with the micronano particles 106. During the process, the direction of movement through the device 100 is perpendicular to the distance.
  • the microhole 103 may be cylindrical, cuboid, conical cone, trapezoidal cone and other geometric shapes. For example, when the microhole 103 is cylindrical, the inner diameter of the microhole 103 is the diameter of the bottom circle of the cylinder.
  • separation distance between two adjacent microporous membranes 102 there is a separation distance between two adjacent microporous membranes 102, and the separation distance between two adjacent microporous membranes 102 may be the same or different. Exemplarily, the separation distance between two adjacent microporous membranes 102 may be 1 nanometer to 100 micrometers.
  • the microporous membrane 102 and the cavity 101 can be integrally formed, so that the shape of the device 100 has high stability.
  • the microporous membrane 102 can also be arranged in the cavity 101 in a film stacking manner, and each microporous membrane 102 has a certain separation distance.
  • a plurality of fluid grooves can be arranged on the inner surface of the cavity 101 , The adjacent fluid grooves are separated by a certain distance, and the microporous membrane 102 is fixed in the fluid groove, so as to realize the laminated arrangement of the microporous membrane 102.
  • the position, inner diameter, and thickness of the micropores 103 on each microporous membrane 102 can be completely consistent, so that the centers of the micropores 103 are on the same straight line, and the movement path of the micro-nano particles in the device 100 is maintained as a straight line.
  • the spacing between each microporous membrane 102 can be the same or different.
  • Another exemplary embodiment of the present invention also provides a method for measuring micro/nano particles.
  • the method is implemented based on the device for measuring micro/nano particles described in the above embodiments to determine the micro/nano particles to be measured. Attribute data.
  • the device for measuring micro/nano particles described in the above embodiment is also equipped with computer components such as a processor and a memory.
  • the computer component executes the method for measuring micro/nano particles provided in this embodiment to determine the Measured attribute data of micro-nano particles.
  • the device for measuring micro/nano particles described in the above embodiment is connected to an external computer device, so that the external computer device performs measurement data obtained by measuring the device for measuring micro/nano particles described in the above embodiment, To execute the method for measuring micro/nano particles provided in this embodiment, this is not limited here.
  • the micro-nano particles to be measured are first allowed to continuously pass through the plurality of micro-pores in the device described in the above-mentioned embodiment along with the electrolyte, and then the micro-nano particles are obtained to pass through each
  • the electrical signal data between the two electrodes adjacent to each micro-hole during the process of micro-holes is used to determine the attribute data of the micro-nano particles according to the acquired electrical signal data.
  • a set of continuous electrical signal data can be obtained. Based on the analysis of the continuous electrical signal data, the attribute information related to the three-dimensional shape of the micro-nano particles can be determined.
  • microporous membranes 102 are provided in the cavity 101.
  • the microporous membrane 102 divides the cavity 101 into four chambers 1011.
  • the micro-nano particles 106 to be measured follow the electrolysis
  • the flow of the liquid 105 continuously passes through the three micropores 103.
  • the micro-nano particles 106 flow with the electrolyte 105, conditions such as overturning and tilting are likely to occur, so that the micro-nano particles 106 pass through each micro-hole 103 in different postures.
  • the electrical signal data between the two electrodes 1012 adjacent to the micro-hole 103 may be different from each other.
  • Figure 3 is obtained by collecting electrical signal data between two electrodes 1012 adjacent to each micropore 103 in the process of a standard spherical particle continuously passing through each micropore 103
  • Figure 4 shows the electrical signal data between two electrodes 1012 adjacent to each micropore 103 during the process of collecting a standard cube particle continuously passing through each micropore 103.
  • micro-nano particles 106 with uniform three-dimensional morphology such as the spherical particles shown in FIG. 3, during the process of passing through each micro-hole 103, the electricity on the two electrodes 1012 adjacent to each micro-hole 103 The signal changes are not much different.
  • micro-nano particles 106 with uneven three-dimensional morphology such as the rectangular parallelepiped particles shown in FIG. 4, the electrical signals on the two electrodes 1012 adjacent to each micro-hole 103 change during the process of passing through each micro-hole 103 big different.
  • the attribute data of the micro/nano particle 106 includes the electric mobility of the micro/nano particle 106.
  • the speed at which the micro-nano particles 106 continuously pass through two adjacent micro-holes 103 and the potential difference between two adjacent micro-pores 103 can be determined, so as to determine that the micro-nano particles 106 continuously pass through two adjacent micro-holes 103 according to the obtained speed and potential difference The electrical mobility of each micropore 103.
  • the time for the micro-nano particles 106 to continuously pass through two adjacent micro-holes 103 can be obtained according to the electrical signal data, and then the ratio of the distance between the two adjacent micro-holes 103 to the time can be calculated to determine that the micro-nano particles 106 continuously pass The speed of two adjacent microholes 103.
  • the potential difference between two adjacent micro holes 103 can be determined according to the electric field strength and distance between two adjacent micro holes 103.
  • the distance between two adjacent micro-holes 103 is 1000 nanometers
  • the time interval for the micro-nano particles 106 to pass through the two micro-holes 103 is 1 millisecond, and the resulting electric potential difference is 100 millivolts, then the micro-nano particle 106 is calculated.
  • the electrical mobility of the particles 106 when they continuously pass through two adjacent micropores 103 is 10 -8 m 2 V -1 s -1 .
  • the surface potential of the micro/nano particle 106 can be further determined according to the determined electrical mobility when the micro/nano particle 106 continuously passes through two adjacent micropores 103.
  • the surface potential of the micro/nano particle 106 corresponds to the micro/nano particle 106 passing through the micropore 103.
  • the posture change of the micro/nano particle 106 in the process of continuously passing through the micropore 103 can be determined, and the micro/nano particle 106 can be analyzed and obtained.
  • the three-dimensional shape of the particles 106 is a three-dimensional shape of the particles 106.
  • the attribute data of the micro/nano particle 106 includes the sphericity value of the micro/nano particle 106.
  • the contrast coefficient between the electrical signal data and the standard signal is obtained, so as to obtain the standard signal with the highest contrast coefficient.
  • the sphericity value is the sphericity value of the micro-nano particles 106.
  • FIG. 5 is a schematic diagram of a set of electrical signal data collected during the process of a micro-nano particle 106 continuously passing through three micropores 103, which contains three independent electrical signal data, each independent electrical signal data.
  • the signal data respectively correspond to the process of the micro-nano particles 106 passing through different micropores 103, and the three independent electrical signal data are continuous in time.
  • the electrical signal data can be divided with the peak value of the electrical signal as the dividing point, thereby obtaining 2 signal units.
  • the electrical signal data can be divided according to the set time interval, or the electrical signal data can be divided according to the slope change trend of the electrical signal, which is not limited here.
  • the slope function f( ⁇ ,r) of each signal unit needs to be calculated.
  • the calculation formula of the slope function f( ⁇ ,r) is as follows:
  • r represents the slope length of a single signal unit
  • represents the slope angle of a single signal unit
  • the standard signal is the known information obtained in advance, and is the electrical signal data collected during the movement of the micro-nano particle 106 determined for the sphericity value through the micro-hole 103. Therefore, the standard signal reflects the sphericity value of the micro-nano particle 106.
  • the standard signal needs to be divided into several signal units in advance according to the above method.
  • the contrast coefficient between each signal unit of the electrical signal data and each signal unit of the standard signal can be obtained.
  • the contrast coefficient reflects The degree of similarity between each signal unit. Therefore, the higher the contrast coefficient between the signal units, the closer the sphericity values between the micro-nano particles 106 are.
  • the contrast coefficient between the electrical signal data and the standard signal is obtained.
  • FIG. 6 is a schematic diagram of a set of electrical signal data collected during the process of a styrene microsphere with a diameter of 200 nanometers continuously passing through three micropores 103 in an actual measurement environment. Based on the above sphericity value acquisition process, the electrical signal data shown in FIG. 6 is analyzed, and the sphericity value of the styrene microspheres can be obtained as 0.95.
  • the sphericity value obtained by the method provided in this embodiment is above 0.8, while for the rod-shaped micro-nano particles 106, the sphericity value obtained is above 0.2 or less.
  • the aspect ratio of the micro/nano particle 106 is relative to the sphericity value of the micro/nano particle 106. Measurements also have an impact.
  • the electrical signal data obtained in the measurement process can also be input to the machine learning model, so that the machine learning model predicts the three-dimensional shape of the micro-nano particles 106 based on the input electrical signal data, thereby directly obtaining the micro-nano particle 106 The three-dimensional shape of the particles 106.
  • the machine learning model used in this embodiment is trained in advance based on the electrical signal data between the two electrodes adjacent to the micro-hole 103 when the micro-nano particles 106 with an asymmetric shape pass through the micro-hole 103. owned.
  • the attribute data of the micro/nano particles 106 further includes the particle size of the micro/nano particles 106.
  • d represents the approximate spherical radius of the micro-nano particles 106
  • D represents the radius of the micropore 103
  • represents the conductivity of the electrolyte 105. If the particle size of the micro-nano particles 106 is much smaller than the radius of the micro-hole 103, for example, the ratio d/D of the approximate spherical radius of the micro-nano particle 106 to the radius of the micro-hole 103 is less than the set threshold, the initial particle size is the micro-nano particle 106 of the particle size.
  • the initial particle size needs to be corrected with a correction coefficient to obtain the particle size of the micro-nano particles 106 Calculated as follows:
  • the correction coefficient S is determined according to the ratio of the approximate spherical radius of the micro-nano particles 106 to the radius of the micropore 103.
  • the correction coefficient S can be determined according to Table 1.
  • the device and method provided by the present application can measure the electrical mobility, sphericity, particle size and other three-dimensional morphological properties of micro-nano particles, thereby solving the problem that the prior art cannot measure micro-nano particles in a solution state.

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Abstract

一种用于测量微纳颗粒(106)的装置(100)和方法。其中,该装置(100)包括腔体(101)和至少两张微孔膜(102),微孔膜(102)串设在腔体(101)内,将腔体(101)分隔为多个腔室(1011),并且微孔膜(102)上具有微孔(103),相邻两个腔室(1101)通过微孔(103)相连通,每个腔室(1011)具有电极(1012)。该方法包括:使待测量的微纳颗粒(106)随电解液连续通过装置(100)的微孔(103);获取微纳颗粒(106)通过每个微孔(103)的过程中,与每个微孔(103)相邻的两个电极(1012)之间的电信号数据;根据电信号数据确定微纳颗粒(106)的属性数据。该方法能够实现对溶液状态下的微纳颗粒(106)的三维形态属性的测量。

Description

用于测量微纳颗粒的装置及方法
本申请要求2019年11月22日递交、申请名称为“用于测量微纳颗粒的装置及方法”的中国专利申请201911158297.3的优先权,在此通过引用将其全部内容合并于此。
技术领域
本申请涉及微纳颗粒测量技术领域,尤其涉及一种用于测量微纳颗粒的装置及方法。
背景技术
基于颗粒物质的特殊属性,颗粒物质被广泛地应用于医药、化工、材料等领域,在颗粒物质的应用中,对于颗粒物质(以下简称为颗粒)的三维形态等属性的测量十分重要。
发明人意识到,目前常用的颗粒测量设备包括光学显微镜、扫描电子显微镜和透射电子显微镜,但由于光学显微镜分辨率较低,使用光学显微镜很难观测到尺寸小于300纳米的颗粒,不适用于微纳颗粒的测量。扫描电子显微镜和透射电子显微镜可以在真空条件下通过不同角度倾斜颗粒样品的方法获取到颗粒的三维形态,但是对于生物颗粒样品或者需要在溶液状态下测量的颗粒样品并不能获得真实的形态信息。因此,现有技术中仍存在无法测量溶液中微纳颗粒的三维形态的问题。
发明内容
为了解决上述技术问题,本申请的实施例提供一种用于测量微纳颗粒的装置,还提供一种用于测量微纳颗粒的方法,用以对微纳颗粒在液态状态下的三维形态属性进行检测。
其中,本申请所采用的技术方案为:
一方面,一种用于测量微纳颗粒的装置,包括:腔体和至少两张微孔膜,其中,所述微孔膜串设在所述腔体内,将所述腔体分隔为多个腔室,并且所述微孔膜上具有微孔,相邻两个腔室通过所述微孔相连通,每个所述腔室具有电极。
在另一示例性实施例中,在测量状态下,位于所述腔体一端的电极接地,其余电极上加载不同大小的电压,所述电压的大小排序对应于所述电极与接地电极之间的距离。
在另一示例性实施例中,在测量状态下,每个所述腔室中填充有电解液,待测量的微纳颗粒随着所述电解液连续通过所述微孔。
在另一示例性实施例中,每张所述微孔膜上微孔的形状相同,所述微孔的中心位于同一直线上。
在另一示例性实施例中,所述微孔的内径为1纳米至10微米。
在另一示例性实施例中,所述微孔膜的厚度为1纳米至10微米。
在另一示例性实施例中,所述微孔膜与所述腔体一体成型,或者所述微孔膜以膜层叠 的形式设置在所述腔体内,每张所述微孔膜之间具有间隔距离。
在另一示例性实施例中,所述微孔膜为无机膜,所述无机膜的材料包括低应力氮化硅、氧化硅、硅晶片中的任意一种。
在另一示例性实施例中,所述装置还包括液体驱动器,所述液体驱动器与位于所述腔体一端的腔室相邻,用于驱动所述装置内的液体流动。
在另一示例性实施例中,所述液体驱动器的驱动方式包括电场力驱动、液压驱动、磁场力驱动中的任意一种。
在另一示例性实施例中,相邻的所述微孔膜之间的间隔距离为1纳米至100微米。
另一方面,一种用于测量微纳颗粒的方法,包括:使待测量的微纳颗粒随电解液连续通过如前所述装置的微孔;获取所述微纳颗粒通过每个所述微孔的过程中,与每个所述微孔相邻的两个电极之间的电信号数据;根据所述电信号数据确定所述微纳颗粒的属性数据。
在另一示例性实施例中,所述根据所述电信号数据确定所述微纳颗粒的属性数据,包括:根据所述电信号数据确定所述微纳颗粒连续通过所述相邻两个微孔的速度和所述相邻两个微孔之间的电势差;根据所述微纳颗粒连续通过所述相邻两个微孔的速度和所述电势差,确定所述微纳颗粒连续通过所述相邻两个微孔时的电迁移率。
在另一示例性实施例中,所述根据所述电信号数据确定所述微纳颗粒的属性数据,包括:将所述电信号数据划分为若干个信号单元;将所述信号单元分别与标准信号对应的信号单元进行对比,得到所述电信号数据与所述标准信号之间的对比系数;获取对比系数最高的标准信号所对应球度值为所述微纳颗粒的球度值。
在另一示例性实施例中,所述根据所述电信号数据确定所述微纳颗粒的属性数据,包括:将所述电信号数据输入至机器学习模型,所述机器学习模型是根据具有非对称形态的微纳物体通过所述微孔时相邻两个电极之间的电信号数据进行训练得到的;获取所述机器学习模型针对所述电信号数据预测得到的所述微纳颗粒的三维形态。
在另一示例性实施例中,所述方法还包括:根据所述电解液的导电率、所述微纳颗粒的近似球半径和所述微孔的半径计算所述微纳颗粒的初始粒径;如果所述微纳颗粒的近似球半径与所述微孔的半径的比值大于预设阈值,则根据所述比值确定修正系数,并通过所述修正系数对所述初始粒径进行修正,获得所述微纳颗粒的粒径。
在上述技术方案中,用于测量微纳颗粒的装置的腔体被串设的微孔膜分隔为多个腔室,相邻两个腔室通过微孔膜上的微孔相连通,并且每个腔室具有电极。在测量状态下,每个腔室中均填充有电解液,电解液中含有待测量的微纳颗粒,微纳颗粒随着电解液的流动依 次通过每个微孔,通过对此过程中与微孔相邻的两个电极之间的电信号数据进行分析,能够得到电解液中待测量的微纳颗粒的三维形态属性,由此实现对溶液状态下的微纳颗粒的三维形态属性的测量。
应当理解的是,以上的一般描述和后文的细节描述仅是示例性和解释性的,并不能限制本申请。
附图说明
此处的附图被并入说明书中并构成本说明书的一部分,示出了符合本申请的实施例,并于说明书一起用于解释本申请的原理。
图1是根据一示例性实施例示出的一种用于测量微纳颗粒的装置的剖视图;
图2是图1所示的用于测量微纳颗粒的装置在测量状态下的示意图;
图3是通过收集一标准球形颗粒连续通过图1所示装置的每个微孔的过程中与每个微孔相邻的两个电极之间的电信号数据,所得到的一组连续的电信号数据的示意图;
图4是通过收集一标准正方体颗粒连续通过图1所示装置的每个微孔的过程中与每个微孔相邻的两个电极之间的电信号数据,所得到的一组连续的电信号数据的示意图;
图5是根据一示例性实施例示出的针对电信号数据进行信号单元划分的示意图;
图6是针对一直径为200纳米的苯乙烯微球连续通过多个微孔的过程中所收集的电信号数据的示意图。
标号说明:100、用于测量微纳颗粒的装置;101、腔体;1011、腔室;1012、电极;102、微孔膜;103、微孔;104、液体驱动装置;105、电解液;106、微纳颗粒。
通过上述附图,已示出本申请明确的实施例,后文中将有更详细的描述,这些附图和文字描述并不是为了通过任何方式限制本申请构思的范围,而是通过参考特定实施例为本领域技术人员说明本申请的概念。
具体实施方式
这里将详细地对示例性实施例执行说明,其示例表示在附图中。下面的描述涉及附图时,除非另有表示,不同附图中的相同数字表示相同或相似的要素。以下示例性实施例中所描述的实施方式并不代表与本申请相一致的所有实施方式。相反,它们仅是与如所附权利要求书中所详述的、本申请的一些方面相一致的装置和方法的例子。
首先需要说明的是,本实施例描述的微纳颗粒是指尺寸在微米和纳米级别的颗粒物理,通常包括有机颗粒、无机颗粒、磁性颗粒、硅石颗粒、琼脂糖凝胶颗粒、苯乙烯颗粒、金属颗粒、胶质颗粒、与分子共扼的颗粒、与生物分子共扼的颗粒、与免疫球蛋白共扼的颗粒、与核酸共扼的颗粒、生物颗粒、生物细胞、血细胞、精子、卵细胞、微生物细胞、细菌细胞、真菌细胞、病毒、亚细胞器、线粒体、细胞核、叶绿体、溶酶体、核糖体、原子颗粒、离子颗粒、分子颗粒、聚合体颗粒、核酸和其化学变体、脱氧核糖核酸和其化学变 体、核酸和其化学变体,蛋白及其化学变体。其中,无机颗粒通常包括二氧化硅、二氧化钛、三氧化二铝、碳酸钙、氮化铝等颗粒物质。
微纳颗粒具有独特的电学、光学以及磁学等性能,微纳颗粒的粒径、电位等物理性质对其性能具有较大影响,因此十分有必要对微纳颗粒的物理性质进行测量。例如,生物大分子包括核酸、蛋白质、糖类和脂质等4类物质,这些生物大分子在生命体内以微纳颗粒的形式存在,通过测量这些生物大分子的物理性质,对于生命行为的研究将具有重要意义。
请参阅图1,图1是根据一示例性实施例示出的一种用于测量微纳颗粒的装置100的剖面图,该装置可用于测量微纳颗粒的电迁移率、球度值、粒径等三维形态属性。
如图1所示,在一示例性实施例中,用于测量微纳颗粒的装置100包括腔体101和至少两张微孔膜102(图1中示出3张),其中每张微孔膜102串设在腔体101内,将腔体101分隔为多个腔室1011,微孔膜102上设有微孔103,使得相邻两个腔室1011通过微孔103相连通,并且每个腔室1011内具有电极1012。
在测量状态下,如图2所示,该装置100的每个腔室1011中均填充有电解液105,电解液105中含有待测量的微纳颗粒106,以为微纳颗粒106的测量提供溶液环境。微纳颗粒106随着电解液105的流动依次通过每一个微孔103,并且位于腔体101一端的电极1012接地,其余的电极1012上分别加载有大小不同的电压。示例性的,电解液105中电解质的电导率可以在10 -6~10 -3S/cm(西门子每米)范围内。
电解液105从位于腔体101一端的腔室1011流向位于腔体101另一端的腔室1011,其流动方向由位于腔体101一端的液体驱动器104的驱动方向决定。如图1和图2所示,在一个实施例中,液体驱动器104位于腔体101的底端,并与底端的腔室1011相邻。液体驱动器104针对电解液105的驱动方向可以是图2所示的由顶端的腔室1011驱动至底端的腔室1011,或者是由底端的腔室1011驱动至顶端的腔室1011,本处不作限制。液体驱动器104还可以位于腔体101的顶端,并与顶端的腔室1011相邻。
液体驱动器104的驱动方式可以采用电场力驱动、液压驱动、磁场力驱动、流体驱动、气压驱动、渗透压驱动、布朗运动驱动、毛细管力驱动、温差扩散驱动等方式,相应的,液体驱动器104可以是液泵、气压装置、注射器等能够为电解液105的流动提供驱动力的装置。示例性的,液体驱动器104的驱动方式采用电场力驱动、液压驱动、磁场力驱动中的任意一种,以为电解液105的流动提供固定的驱动力,从而驱使电解液105稳定流动。
此外,位于腔体101一端的电极1012接地,并在其余电极1012上加载不同大小的电压,所加载电压的大小排序对应于该电极1012与接地的电极1012之间的距离。如图1所示,如果将位于顶端的腔室1011内的电极1012接地,即V0=0V,其它三个电极1012上所加载电压的大小为V3≥V2≥V1,使得相邻两个电极1012之间所形成电场的强度依次增大,保证微纳颗粒106随着电解液105的流动连续地通过每个微孔103。其中,电极1012可以采用铂或者银氯化银等材料。
微纳颗粒106随着电解液105的流动依次通过每个微孔103的过程中,分别测量微纳 颗粒106通过微孔103时与微孔103相邻的两个电极1012之间的电信号数据,针对所得电信号数据进行分析可以得到微纳颗粒106的电迁移率、球度值、粒径等三维形态属性,由此解决现有技术中无法测量溶液状态下微纳颗粒的属性的问题。
微孔膜102可以是有机膜,也可以是无机膜。
在一个实施例中,微孔膜102为无机膜,即微孔膜102由无机材料制成,相较于有机膜,无机膜具备更好的伸展性,有利于微纳颗粒106随着电解液105的流动而运动通过微孔103。示例性的,微孔膜102可以是由低应力氮化硅、氮化硅或者硅晶片等无机材料制成,使用这些无机材料制成的微孔膜102的成膜效果较好,并且制造技术也更加成熟。
微孔膜102的厚度可以为1纳米至10微米,微孔103的内径可以为1纳米至10微米,其中微孔103的内径即为微孔103的孔径,是指与微纳颗粒106在测量过程中运动通过该装置100的方向相垂直方向上的距离。微孔103可以是圆柱形、长方体、锥形台、梯形台等几何形状,示例性的,当微孔103为圆柱形时,微孔103的内径为圆柱的底面圆的直径。
相邻的两张微孔膜102之间具有间隔距离,并且相邻的两张微孔膜102之间的间隔距离可以相同,也可以不同。示例性的,相邻两张微孔膜102之间的间隔距离可以为1纳米至100微米。
微孔膜102和腔体101可以是一体成型的,使得装置100的形态具有很高的稳定性。微孔膜102也可以是以膜层叠的方式的设置在腔体101内,并且每张微孔膜102之间具有一定的间隔距离,例如,可以在腔体101的内表面设置多个流体槽,相邻流体槽之间相距一定距离,将微孔膜102固定在流体槽中,从而实现微孔膜102的膜层叠设置。
每张微孔膜102上微孔103的位置、内径和厚度可以完全一致,使得微孔103的中心位于同一直线上,并使得微纳颗粒在装置100中的运动路径保持为直线。每张微孔膜102之间的间距可以相同,也可以不同。
本发明的另一示例性实施例还提供了一种用于测量微纳颗粒的方法,该方法基于以上实施例所描述的用于测量微纳颗粒的装置实现,以确定待测量的微纳颗粒的属性数据。示例性的,以上实施例所描述的用于测量微纳颗粒的装置还配置有处理器、存储器等计算机组件,通过计算机组件执行本实施例提供的用于测量微纳颗粒的方法,以确定待测量的微纳颗粒的属性数据。或者,以上实施例所描述的用于测量微纳颗粒的装置与外部计算机设备相连接,以使外部计算机设备根据以上实施例所描述的用于测量微纳颗粒的装置进行测量获得的测量数据,来执行本实施例提供的用于测量微纳颗粒的方法,本处不对此进行限制。
在本实施例提供的用于测量微纳颗粒的方法中,先使待测量的微纳颗粒随电解液连续通过上述实施例所描述装置中的多个微孔,然后获取微纳颗粒通过每个微孔的过程中与每个微孔相邻的两个电极之间的电信号数据,以根据所获取的电信号数据确定微纳颗粒的属性数据。
应当说明的是,通过收集微纳颗粒连续通过多个微孔过程中对应的电信号数据,可以 得到一组连续的电信号数据。基于对该连续的电信号数据的分析,即可以确定与微纳颗粒的三维形态相关的属性信息。
下面以图1和图2所示的用于测量微纳颗粒的装置100为示例对本实施例所提供的方法进行详细描述。
在图1和图2所示装置100中,腔体101内设有三张微孔膜102,微孔膜102将腔体101分隔为四个腔室1011,待测量的微纳颗粒106随着电解液105的流动连续通过三个微孔103。微纳颗粒106在随电解液105流动的过程中,容易发生翻转、倾斜等状况,使得微纳颗粒106分别以不同的姿势通过每个微孔103。微纳颗粒106在以不同的姿势通过每个微孔103的过程中,与微孔103相邻的两个电极1012之间的电信号数据可能各不相同。
请参阅图3和图4,其中图3是通过收集一标准球形颗粒连续通过每个微孔103的过程中与每个微孔103相邻的两个电极1012之间的电信号数据所得到的一组连续的电信号数据的示意图,图4是通过收集一标准正方体颗粒连续通过每个微孔103的过程中,与每个微孔103相邻的两个电极1012之间的电信号数据所得到的一组连续的电信号数据的示意图。
可以看出,对于三维形态均匀的微纳颗粒106,例如图3所示意的球体颗粒,其通过每个微孔103的过程中,与每个微孔103相邻的两个电极1012上的电信号变化相差不大。但是对于三维形态不均匀的微纳颗粒106,例如图4所示的长方体颗粒,其通过每个微孔103的过程中,与每个微孔103相邻的两个电极1012上的电信号变化差异较大。
在一个示例性实施例中,微纳颗粒106的属性数据包括微纳颗粒106的电迁移率。根据电信号数据可以确定微纳颗粒106连续通过相邻两个微孔103的速度以及相邻两个微孔103之间的电势差,以根据所得速度和电势差确定微纳颗粒106连续通过相邻两个微孔103时的电迁移率。
其中,可以根据电信号数据获取微纳颗粒106连续通过相邻两个微孔103的时间,然后计算相邻两个微孔103之间的距离与时间的比值即可确定微纳颗粒106连续通过相邻两个微孔103的速度。相邻两个微孔103之间的电势差则可以根据相邻两个微孔103之间的电场强度和距离确定。
示例性的,如果相邻两个微孔103之间距离为1000纳米,微纳颗粒106通过两个微孔103的时间间隔为1毫秒,所引起的电势差为100毫伏,则计算得到微纳颗粒106连续通过相邻两个微孔103时的电迁移率为10 -8m 2V -1s -1
根据所确定的微纳颗粒106连续通过相邻两个微孔103时的电迁移率可以进一步确定微纳颗粒106的表面电位,微纳颗粒106的表面电位对应于微纳颗粒106通过微孔103时的姿势。
由此,根据微纳颗粒106连续通过相邻两个微孔103的过程中表面电位的变化,即可以确定微纳颗粒106在连续通过微孔103过程中的姿势变化情况,从而分析得到微纳颗粒106的三维形态。
在另一示例性实施例中,微纳颗粒106的属性数据包括微纳颗粒106的球度值。通过将电信号数据划分为若干个信号单元,然后将信号单元分别与标准信号对应的信号单元进行对比,得到电信号数据与标准信号之间的对比系数,从而获取对比系数最高的标准信号所对应球度值为微纳颗粒106的球度值。
首先需要说明的是,图5是针对一微纳颗粒106连续通过3个微孔103的过程中收集的一组电信号数据的示意图,其中含有3个独立的电信号数据,每个独立的电信号数据分别对应于微纳颗粒106通过不同微孔103的过程,并且这3个独立的电信号数据在时间上相连续。
如图5所示,针对呈正弦分布的电信号数据,可以以电信号峰值为划分点对电信号数据进行划分,由此得到2个信号单元。而针对其它形态分布的电信号数据,可以按照设定时间间隔对电信号数据进行划分,也可以根据电信号的坡度变化趋势对电信号数据进行划分,本处不进行限制。
将电信号数据划分为若干个信号单元,需计算每个信号单元的坡度函数f(θ,r),坡度函数f(θ,r)的计算公式如下:
f(θ,r)=arctan(θ)
其中r表示单个信号单元的坡长,θ表示单个信号单元的坡度角。
标准信号是预先获得的已知信息,是对球度值确定的微纳颗粒106运动通过微孔103的过程中采集的电信号数据,因此标准信号反映了微纳颗粒106的球度值。标准信号需根据上述方法预先划分为若干信号单元。
通过将每个信号单元的坡度函数与标准信号所对应信号单元的坡度函数进行对比,可以得到电信号数据的每个信号单元与标准信号的每个信号单元之间的对比系数,对比系数反映了每个信号单元之间的相似程度。因此,信号单元之间的对比系数越高,微纳颗粒106之间的球度值也越相近。
针对每个电信号数据,通过计算电信号数据所划分的全部信号单元的对比系数的平均值,即得到电信号数据与标准信号之间的对比系数。
为确保本实施例的可实施性,需预先提供多种球度值确定的微纳颗粒106的标准信号,并计算测量过程中获取的电信号数据分别与不同标准信号之间的对比系数,以确定对比系数最高的标准信号对应的球度值为所测量的微纳颗粒106的球度值。
图6是在实际的测量环境下,针对一直径为200纳米的苯乙烯微球连续通过3个微孔103的过程所收集的一组电信号数据的示意图。基于以上球度值获取过程对图6所示电信号数据进行分析,可以得到该苯乙烯微球的球度值为0.95。
需要说明的是,一般来说,对于近球形的微纳颗粒106,采用本实施例提供的方法获得的球度值在0.8以上,而对于棒状的微纳颗粒106,所获得的球度值在0.2以下。
还需要说明的是,微纳颗粒106的长径比与微纳颗粒106的球度值之间也具有一定的对应关系,因此微纳颗粒106的长径比对于微纳颗粒106的球度值测量也具有一定影响。
在另一示例性实施例中,还可以将测量过程中获取的电信号数据输入至机器学习模型,使机器学习模型针对输入的电信号数据预测微纳颗粒106的三维形态,从而直接得到微纳颗粒106的三维形态。
需要说明的是,本实施例所采用的机器学习模型是预先根据具有非对称形态的微纳颗粒106通过微孔103时,与微孔103相邻的两个电极之间的电信号数据进行训练得到的。
在另一示例性实施例中,微纳颗粒106的属性数据还包括微纳颗粒106的粒径。根据电解液105的导电率、微纳颗粒106的近似球半径和微孔103的半径计算微纳颗粒106的初始粒径,如果微纳颗粒106的近似球半径与微孔103的半径的比值大于预设阈值,则根据比值确定修正系数,并通过修正系数对初始粒径进行修正,获得微纳颗粒106的粒径。
微纳颗粒106的初始粒径
Figure PCTCN2020128400-appb-000001
的计算公式如下:
Figure PCTCN2020128400-appb-000002
其中d表示微纳颗粒106的近似球半径,D表示微孔103的半径,ρ表示电解液105的电导率。如果微纳颗粒106的粒径远小于微孔103的半径,例如微纳颗粒106的近似球半径与微孔103的半径的比值d/D小于设定阈值,该初始粒径即为微纳颗粒106的粒径。
如果微纳颗粒106的近似球半径与微孔103的半径的比值大于预设阈值,需使用修正系数对初始粒径进行修正,以得到微纳颗粒106的粒径
Figure PCTCN2020128400-appb-000003
计算公式如下:
Figure PCTCN2020128400-appb-000004
其中修正系数S是根据微纳颗粒106的近似球半径与微孔103的半径的比值确定的,例如可以根据表1确定修正系数S。
d/D S d/D S
0.1 1.00 0.6 1.21
0.2 1.00 0.7 1.38
0.3 1.02 0.8 1.71
0.4 1.05 0.9 2.56
0.5 1.11 0.95 3.86
表1
综上所述,根据本申请提供的装置和方法可以测量得到微纳颗粒的电迁移率、球度值、粒径等三维形态属性,从而能够解决现有技术中无法测量溶液状态下微纳颗粒的属性的问题。
上述内容,仅为本申请的较佳示例性实施例,并非用于限制本申请的实施方案,本领域普通技术人员根据本申请的主要构思和精神,可以十分方便地进行相应的变通或修改,故本申请的保护范围应以权利要求书所要求的保护范围为准。

Claims (16)

  1. 一种用于测量微纳颗粒的装置,包括腔体和至少两张微孔膜,所述微孔膜串设在所述腔体内,将所述腔体分隔为多个腔室,并且所述微孔膜上具有微孔,相邻两个腔室通过所述微孔相连通,每个所述腔室具有电极。
  2. 如权利要求1所述的装置,其中,所述装置还包括液体驱动器,所述液体驱动器位于所述腔体一端的腔室相邻,用于驱动所述装置内的液体流动。
  3. 如权利要求2所述的装置,其中,所述液体驱动器的驱动方式包括电场力驱动、液压驱动、磁场力驱动中的任意一种。
  4. 如权利要求1所述的装置,其中,在测量状态下,位于所述腔体一端的电极接地,其余电极上加载不同大小的电压,所述电压的大小排序对应于所述电极与接地电极之间的距离。
  5. 如权利要求1所述的装置,其中,在测量状态下,每个所述腔室中填充有电解液,待测量的微纳颗粒随着所述电解液连续通过所述微孔。
  6. 如权利要求1所述的装置,其中,每张所述微孔膜上微孔的形状相同,所述微孔的中心位于同一直线上。
  7. 如权利要求1所述的装置,其中,所述微孔的内径为1纳米至10微米。
  8. 如权利要求1所述的装置,其中,所述微孔膜的厚度为1纳米至10微米。
  9. 如权利要求1所述的装置,其中,所述微孔膜与所述腔体一体成型;或者所述微孔膜以膜层叠的形式设置在所述腔体内,每张所述微孔膜之间具有间隔距离。
  10. 如权利要求1所述的装置,其中,所述微孔膜为无机膜,所述无机膜的材料包括低应力氮化硅、氧化硅、硅晶片中的任意一种。
  11. 如权利要求1所述的装置,其中,相邻的所述微孔膜之间的间隔距离为1纳米至100微米。
  12. 一种用于测量微纳颗粒的方法,所述方法应用于权利要求1-11中任一项所述的装置,并使待测量的微纳颗粒随电解液连续通过所述装置的微孔,所述方法包括:
    获取所述微纳颗粒通过每个所述微孔的过程中,与每个所述微孔相邻的两个电极之间的电信号数据;
    根据所述电信号数据确定所述微纳颗粒的属性数据。
  13. 如权利要求12所述的方法,其中,所述根据所述电信号数据确定所述微纳颗粒的属性数据,包括:
    根据所述电信号数据确定所述微纳颗粒连续通过所述相邻两个微孔的速度和所述相邻两个微孔之间的电势差;
    根据所述微纳颗粒连续通过所述相邻两个微孔的速度和所述电势差,确定所述微纳颗粒连续通过所述相邻两个微孔时的电迁移率。
  14. 如权利要求12所述的方法,其中,所述根据所述电信号数据确定所述微纳颗粒 的属性数据,包括:
    将所述电信号数据划分为若干个信号单元;
    将所述信号单元分别与标准信号对应的信号单元进行对比,得到所述电信号数据与所述标准信号之间的对比系数;
    获取对比系数最高的标准信号所对应球度值为所述微纳颗粒的球度值。
  15. 如权利要求12所述的方法,其中,所述根据所述电信号数据确定所述微纳颗粒的属性数据,包括:
    将所述电信号数据输入至机器学习模型,所述机器学习模型是根据具有非对称形态的微纳物体通过所述微孔时相邻两个电极之间的电信号数据进行训练得到的;
    获取所述机器学习模型针对所述电信号数据预测得到的所述微纳颗粒的三维形态。
  16. 如权利要求12所述的方法,其中,所述方法还包括:
    根据所述电解液的导电率、所述微纳颗粒的近似球半径和所述微孔的半径计算所述微纳颗粒的初始粒径;
    如果所述微纳颗粒的近似球半径与所述微孔的半径的比值大于预设阈值,则根据所述比值确定修正系数,并通过所述修正系数对所述初始粒径进行修正,获得所述微纳颗粒的粒径。
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Publication number Priority date Publication date Assignee Title
CN110823773A (zh) * 2019-11-22 2020-02-21 瑞芯智造(深圳)科技有限公司 用于测量微纳颗粒的装置及方法

Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2006258540A (ja) * 2005-03-16 2006-09-28 Seiko Epson Corp 粒子判別装置、粒子判別方法、およびプログラム
CN101548338A (zh) * 2006-10-13 2009-09-30 阿海珐核能公司 用于检测球形粒子、特别是用于高温或特高温反应堆的核燃料粒子中的结构异常的方法和装置
JP2012230080A (ja) * 2011-04-27 2012-11-22 Nissin Electric Co Ltd マクロパーティクルの計測方法と装置、表面処理方法と装置、および前記表面処理方法を用いて製造された製品
CN104568684A (zh) * 2015-01-30 2015-04-29 中国科学院重庆绿色智能技术研究院 一种纳米颗粒检测系统及筛选分析方法
CN106796169A (zh) * 2014-10-01 2017-05-31 水光科技私人有限公司 探测流体中颗粒的传感器
CN109580718A (zh) * 2018-12-28 2019-04-05 瑞芯智造(深圳)科技有限公司 一种纳米厚度薄膜的制备方法
CN109612890A (zh) * 2018-12-28 2019-04-12 瑞芯智造(深圳)科技有限公司 一种微粒计数系统及应用、检测金属离子和微粒的方法
CN110823773A (zh) * 2019-11-22 2020-02-21 瑞芯智造(深圳)科技有限公司 用于测量微纳颗粒的装置及方法
CN211122430U (zh) * 2019-11-22 2020-07-28 瑞芯智造(深圳)科技有限公司 用于测量微纳颗粒的装置

Family Cites Families (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060073489A1 (en) * 2004-10-05 2006-04-06 Gangqiang Li Nanopore separation devices and methods of using same
KR100624460B1 (ko) * 2005-02-12 2006-09-19 삼성전자주식회사 나노 내지 마이크로 크기의 포어가 형성되어 있는 막을 포함하는 미세유동장치 및 그를 이용하여 분극성 물질을 분리하는 방법
WO2007147167A2 (en) * 2006-06-16 2007-12-21 Porous Power Technologies, Llc Optimized microporous structure of electrochemical cells
GB0808856D0 (en) * 2008-05-15 2008-06-25 Univ Warwick Fabricated nanopores and micropores for chemical and biochemical analysis
CN101382482B (zh) * 2008-10-24 2010-12-01 西北工业大学 一种细胞计数的方法
US20100188457A1 (en) * 2009-01-05 2010-07-29 Madigan Connor F Method and apparatus for controlling the temperature of an electrically-heated discharge nozzle
GB201113309D0 (en) * 2011-08-02 2011-09-14 Izon Science Ltd Characterisation of particles
CN202522535U (zh) * 2012-01-13 2012-11-07 武汉介观生物科技有限责任公司 一种细胞迁移高分辨率阻抗实时跟踪测控装置
US20140099726A1 (en) * 2012-10-10 2014-04-10 Two Pore Guys, Inc. Device for characterizing polymers
GB201306913D0 (en) * 2013-04-16 2013-05-29 Univ Southampton A method of electrically measuring the size of individual particles flowing in a liquid
CN106468648B (zh) * 2015-08-19 2019-09-10 财团法人工业技术研究院 微粒子侦测器及筛选元件的制造方法
CA3067993C (en) * 2017-06-21 2024-02-27 Ontera Inc. Dual pore-control and sensor device
CN111999490B (zh) * 2019-12-19 2021-07-30 瑞芯智造(深圳)科技有限公司 一种检测样品体系中微量蛋白的方法

Patent Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2006258540A (ja) * 2005-03-16 2006-09-28 Seiko Epson Corp 粒子判別装置、粒子判別方法、およびプログラム
CN101548338A (zh) * 2006-10-13 2009-09-30 阿海珐核能公司 用于检测球形粒子、特别是用于高温或特高温反应堆的核燃料粒子中的结构异常的方法和装置
JP2012230080A (ja) * 2011-04-27 2012-11-22 Nissin Electric Co Ltd マクロパーティクルの計測方法と装置、表面処理方法と装置、および前記表面処理方法を用いて製造された製品
CN106796169A (zh) * 2014-10-01 2017-05-31 水光科技私人有限公司 探测流体中颗粒的传感器
CN104568684A (zh) * 2015-01-30 2015-04-29 中国科学院重庆绿色智能技术研究院 一种纳米颗粒检测系统及筛选分析方法
CN109580718A (zh) * 2018-12-28 2019-04-05 瑞芯智造(深圳)科技有限公司 一种纳米厚度薄膜的制备方法
CN109612890A (zh) * 2018-12-28 2019-04-12 瑞芯智造(深圳)科技有限公司 一种微粒计数系统及应用、检测金属离子和微粒的方法
CN110823773A (zh) * 2019-11-22 2020-02-21 瑞芯智造(深圳)科技有限公司 用于测量微纳颗粒的装置及方法
CN211122430U (zh) * 2019-11-22 2020-07-28 瑞芯智造(深圳)科技有限公司 用于测量微纳颗粒的装置

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See also references of EP4063824A4

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