WO2009140796A1 - A particle concentration measuring device and method - Google Patents

A particle concentration measuring device and method Download PDF

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Publication number
WO2009140796A1
WO2009140796A1 PCT/CN2008/001007 CN2008001007W WO2009140796A1 WO 2009140796 A1 WO2009140796 A1 WO 2009140796A1 CN 2008001007 W CN2008001007 W CN 2008001007W WO 2009140796 A1 WO2009140796 A1 WO 2009140796A1
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WO
WIPO (PCT)
Prior art keywords
particle
module
detecting
solution
light
Prior art date
Application number
PCT/CN2008/001007
Other languages
French (fr)
Chinese (zh)
Inventor
郭旻
杨宏伟
蔡浩原
贺伯特·格里布
卓越
库特·贝滕豪森
Original Assignee
西门子公司
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Application filed by 西门子公司 filed Critical 西门子公司
Priority to PCT/CN2008/001007 priority Critical patent/WO2009140796A1/en
Publication of WO2009140796A1 publication Critical patent/WO2009140796A1/en

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Classifications

    • BPERFORMING OPERATIONS; TRANSPORTING
    • B03SEPARATION OF SOLID MATERIALS USING LIQUIDS OR USING PNEUMATIC TABLES OR JIGS; MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03CMAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03C5/00Separating dispersed particles from liquids by electrostatic effect
    • B03C5/02Separators
    • B03C5/022Non-uniform field separators
    • B03C5/026Non-uniform field separators using open-gradient differential dielectric separation, i.e. using electrodes of special shapes for non-uniform field creation, e.g. Fluid Integrated Circuit [FIC]
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B03SEPARATION OF SOLID MATERIALS USING LIQUIDS OR USING PNEUMATIC TABLES OR JIGS; MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03CMAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03C5/00Separating dispersed particles from liquids by electrostatic effect
    • B03C5/005Dielectrophoresis, i.e. dielectric particles migrating towards the region of highest field strength
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • 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
    • G01N15/06Investigating concentration of particle suspensions
    • G01N15/0656Investigating concentration of particle suspensions using electric, e.g. electrostatic methods or magnetic methods

Definitions

  • the present invention relates to the field of particle detection, and more particularly to a device and method for detecting particle concentration. Background technique
  • the fermentation or cultivation processes of particles such as animals, plants, or microorganisms.
  • Control relies to a large extent on the measurement of process parameters, especially the measurement of the state parameters of the particles.
  • the particle state parameter the content of the particles in the particle solution, which can also be called the particle concentration, is the most important parameter among them.
  • the particle content is usually measured by off-line manual method. Taking cells as an example, for example, one method is: Measurement based on a microscope. Since most cells are translucent, the cells need to be chemically or physically colored before detection to enhance the contrast of the cells under the microscope.
  • the cell solution needs to be diluted to make each cell easy to observe.
  • another method is: first, the cells are separated by a centrifuge, and the separated cells are weighed using a balance.
  • specific fine equipment and experienced operators are required to realize complex, and manual measurement is time consuming and cannot meet the requirements of real-time control.
  • the cell content is measured. At that time, only the content of living cells is desired, and in the above method, dead cells and living cells cannot be separated.
  • some online measurement methods have been proposed for the measurement of the particle content.
  • one method is: integrating a light source and a photodetector in a microprobe, and then immersing the sensor with the microprobe in a bioreactor, because the cells reflect and scatter light, Therefore, the cell content can be detected based on the correspondence between the reflected light and the scattered light and the cell content.
  • the detection results of the micro probe are susceptible to the color and turbidity of the cell solution, as well as the dead cells.
  • the method comprises the following steps: measuring the permittivity of the cell solution and the cell-free medium solution filtered through the filter cover in the radio frequency range, comparing the two permittivity rates, and obtaining the change of the permittivity caused by the change of the cell content, thereby determining Cell content.
  • the filter cover is easily blocked by cells, and it is necessary to replace or clean the filter cover from time to time.
  • the present invention provides an apparatus for detecting the concentration of particles, and on the other hand, a method for detecting the concentration of particles, so that the detection of the concentration of particles is completed without interference.
  • the apparatus for detecting the concentration of particles comprises: a dielectrophoresis generating unit for forming an uneven electric field in a predetermined volume of the microparticle solution, so that the particles in the microparticle solution move in a set direction to form particles.
  • a detection unit configured to detect width information of the particle stack in the set direction;
  • a result generating unit receiving the particle pile width information, according to the width information and the stored particle pile width and The corresponding relationship of the particle concentrations gives the concentration of the particles.
  • the dielectrophoresis generating unit comprises: a solution chamber having a predetermined volume for holding the particle solution; and a signal generating sub-module for generating N different phase traveling wave signals, N being greater than or An integer equal to 3; a plurality of parallel electrodes including a plurality of parallel electrodes on one side or opposite sides of the solution chamber; N wires for respectively using the N different phase traveling wave signals The in-phase electrodes of the parallel electrodes are connected to generate a traveling wave electric field.
  • each of the traveling wave signals is a sinusoidal signal having an angular frequency of 100 Hz to 100 MHz, an amplitude of 0 to 100 volts, and a phase difference of 360° / N between the signals.
  • the solution chamber (210) is at least partially made of a transparent material; the electrode is made of indium tin oxide.
  • the detecting unit comprises: a light source for emitting light to a solution chamber of the dielectrophoresis generating unit; and an optical processing module for receiving light transmitted through the solution chamber to generate One-dimensional or two-dimensional graphic light; one detection mode a block, configured to generate width information of the particle stack in the solution chamber in the set direction according to the light processed by the optical processing module.
  • the detection module is a one-dimensional detection module having a linear array of charge coupled devices;
  • the optical processing module includes: a first imaging sub-module having at least one optical lens for receiving The light in the solution chamber, and thereby forming a two-dimensional pattern of light; and, a second imaging sub-module having a cylindrical lens for converting the two-dimensional graphic light into a one-dimensional graphic light.
  • the detecting module is a two-dimensional detecting module having a planar charge coupled device array
  • the optical processing module includes: a first imaging sub-module having at least one optical lens for receiving a transmission The light in the solution chamber is formed, and thereby a two-dimensional pattern of light is formed.
  • the detection module is a photodiode array or a photomultiplier or position sensor detector or a photoresistor.
  • the detecting unit includes: a capacitance measuring module for measuring capacitance between adjacent parallel electrodes; and a position determining module receiving each of the measured adjacent parallel electrodes And a capacitance value, and determining an edge position of the particle stack in the set direction according to the change of the capacitance value, and generating width information of the particle pile according to the data.
  • the result generating unit is a processor having a storage and computing function.
  • the dielectrophoresis generating unit and a particulate solution storage unit are connected by a liquid processing unit having an injection valve.
  • the liquid processing unit further includes: a cleaning liquid reservoir and an infusion pump for introducing the cleaning liquid into the dielectrophoresis generating unit.
  • the invention provides a method for detecting the concentration of particles, comprising: applying a traveling wave electric field generated by a plurality of parallel electrodes in a predetermined volume of the sampled particle solution, so that the particles in the particle solution move in a set direction, forming a particle stack; detecting width information of the particle stack in the set direction; collecting the particle pile width information, and obtaining a concentration of the particles according to the width information and a correspondence relationship between the particle pile width and the particle concentration.
  • the detecting the width information of the particle stack in the set direction comprises: emitting light to the solution chamber; and receiving the optical lens through the optical lens The light of the solution chamber is formed, and a pattern light is formed; and the width of the particle pile in the set direction is determined according to the pattern light.
  • the detecting the width information of the particle stack in the set direction comprises: measuring a capacitance between adjacent electrodes in the parallel electrode; according to a capacitance between adjacent electrodes Varying, determining the edge position of the particle stack in the set direction and thereby determining the width of the particle stack.
  • a non-uniform electric field is added to the sampled particle solution, and the particles in the particle solution are moved in a set direction to obtain a moving particle pile, and the particle pile is detected in the device.
  • the width in the direction is obtained, and the width information of the particle pile is obtained.
  • the concentration of the particles is obtained, thereby realizing the automatic measurement of the particle concentration.
  • living particles such as cells
  • the medium solution can usually enter the dead cells through the cell membrane, the dead cells have a dielectric constant different from that of the living cells, and do not mix into the living cells, so that the measurement of the cell concentration does not occur. Interfered with factors such as dead cells.
  • FIG. 2 is a schematic structural view of a liquid processing unit in the system shown in FIG. 1;
  • FIG. 3 is a schematic structural view of a system-intermediate electrophoresis generating unit shown in FIG. 1;
  • FIG. 4 is a schematic structural view of a traveling wave electric field generating module in the dielectrophoresis generating unit shown in FIG.
  • Figure 5a and Figure 5b are schematic views of the state of the particles in the particle solution before and after the generation of the traveling wave electric field;
  • Figures 6a and 6b are schematic views of a structure of the detecting unit in the system of Figure 1;
  • Figure 7a shows the detection shown in Figures 6a and 6b.
  • Figure 7b is a schematic diagram showing the correspondence relationship between the particle stack width and the particle concentration
  • Figure 7c is a schematic diagram of step signals for different particle concentrations
  • FIG. 8 is a schematic diagram showing still another structure of the detecting unit in the system shown in FIG. 1.
  • FIG. 9 is a schematic diagram showing capacitance measurement of the traveling wave electric field generating module in the dielectrophoresis generating unit shown in FIG.
  • FIG. 10 is a schematic structural view of a specific application example in the present invention.
  • FIG. 11a and 1b are schematic structural views of a microfluidic chip in the application example shown in FIG. 10;
  • FIG. 11c is another schematic structural view of the microfluidic chip in the application example shown in FIG. 10;
  • dielectrophoresis is a kind of electric uniform electric field which can polarize neutral particles under the action of uneven electric field and the polarized particles generate motion under the action of dielectric power. Dielectrophoresis is produced. Further, in the case of living microparticles such as cells, since the medium solution can normally enter the dead cells through the cell membrane of the dead cells, the dead cells have a dielectric constant consistent with the medium solution and are not mixed into the living cells.
  • a detection scheme for particle concentration based on dielectrophoresis is proposed, that is, an uneven electric field is formed in the sampled particle solution, and the particles in the particle solution are moved in a set direction to obtain a moving
  • the particle stack obtains the width information of the particle pile by detecting the width of the particle pile in the set direction, and obtains the concentration of the particles based on the width information of the particle pile and the correspondence between the particle pile width and the particle concentration.
  • Fig. 1 is an explanatory structural view showing a system for detecting a particle concentration in an embodiment of the present invention.
  • the system includes: a liquid processing unit 100, a dielectrophoresis generating unit 200, a detecting unit 300, and a result generating unit 400.
  • a logic control unit may be provided, and the logic control unit may be independent of the above units, or may set the function of the logic control unit to any one or any of the above units.
  • the logic control unit can be through a computer, or an embedded central processing unit (CPU), or a digital Implemented by a signal processor (DSP), or a programmable logic controller (PLC).
  • the liquid processing unit 100 is for injecting the sampled microparticle solution into the dielectrophoresis generating unit 200.
  • the liquid processing unit 100 can include an injection valve 110 between the particle solution storage device and the dielectrophoresis generating unit 200, as shown in FIG. 2, for opening under the control of the logic control unit.
  • the self-valve, the microparticle solution in the microparticle solution storage device is injected into the dielectrophoresis generating unit 200 under the action of external power (such as pressure or pump power); and the microelectrophoresis is filled with the dielectrophoresis generating unit 200 or the injected microparticles.
  • external power such as pressure or pump power
  • the liquid processing unit 100 may further include a cleaning liquid reservoir 120 and an infusion pump 130.
  • the injection pump 130 is configured to pump the cleaning liquid in the cleaning liquid reservoir 120 into the dielectrophoresis generating unit 200 under the control of the logic control unit to clean the dielectrophoresis generating unit. 200. Further, the waste liquid such as the start-up solution or the cleaning liquid processed in the dielectrophoresis generating unit 200 can be discharged into the waste liquid storage.
  • the liquid processing unit 100 may further include a discharge valve 140 between the dielectrophoresis generating unit 200 and the waste liquid storage device, for opening the self valve under the control of the logic control unit, so that the dielectrophoresis The particulate solution in the generating unit 2Q0 is discharged into the waste liquid reservoir; and when the particulate solution is injected into the dielectrophoresis generating unit 200, the valve itself is closed.
  • the discharge valve 140 may not be provided.
  • the dielectrophoresis generating unit 200 shown in FIG. 1 is configured to form a non-uniform electric field in the microparticle solution under the control, and to cause particles in the microparticle solution to move in a set direction to obtain a moving microparticle. stack.
  • the uneven electric field may be a traveling wave electric field or other non-uniform electric field.
  • the structure of the dielectrophoresis generating unit 200 can be as shown in FIG. 3, and includes: a solution chamber 210 and a traveling wave electric field generating module 220.
  • the solution chamber 210 is for holding a particulate solution from the liquid processing unit 100.
  • the fine particle solution enters the solution chamber 210 through the inlet. After the end of the detection, the waste liquid composed of the fine particle solution is discharged from the outlet, and further, the cleaning liquid can be injected into the solution chamber 210 through the inlet to clean the solution chamber 210, and the waste after washing The liquid is discharged from the outlet.
  • the traveling wave electric field generating module 220 is configured to generate in the particle solution of the solution chamber 210 Moving in a fixed direction, the moving particle pile is obtained in the particle solution.
  • a structure of the traveling wave electric field generating module 220 can be as shown in FIG. 4, and specifically includes: a signal generating sub-module 221, a parallel electrode 222, and a wire 223, which may be implemented in a specific implementation. To be integrated, it can also be discrete.
  • the signal generating sub-module 221 is configured to generate N traveling wave signals of different phases. Where N is an integer greater than or equal to 3.
  • the value of a can range from 100 Hz to 100MHz, V can range from 0 to 100 ⁇ ⁇ _ ⁇ .
  • Parallel electrode 222 includes a plurality of parallel electrodes that are located on one side or opposite sides of solution chamber 210. In Fig. 4, taking the case of nine electrodes as an example, in general, the number of electrodes is greater than or equal to ⁇ .
  • the electrode may be made of any electrically conductive material. If the detecting unit 300 is based on optical detection, the conductive material from which the electrode is made should also be light transmissive.
  • the electrode may be made of indium tin oxide (Indium Tin Oxide). . Further, in this embodiment, the distance between the electrodes may range from 0.1 to 500 ⁇ m.
  • the wire 223 is configured to connect the N different phase traveling wave signals to the same phase electrode in the parallel electrode 222.
  • N is 4 in the present embodiment shown in Fig. 4
  • the two electrodes separated by three electrodes are the same phase electrodes, that is, the two electrodes separated by (N-1) electrodes are the same phase electrodes.
  • the first wire connects the signal A and the first, fifth, and ninth electrodes in the parallel electrode, and the second wire will signal B.
  • the third wire connects the signal C to the 3rd and 7th electrodes in the parallel electrode, and the fourth wire will be in the signal D and the parallel electrode
  • the 4th and 8th electrodes are connected together, and the connection mode causes the signal generation sub-module 221 to generate a traveling wave letter When the number is formed, a traveling wave electric field from right to left in the viewing angle shown in FIG. 4 is formed.
  • the particle state of the particle solution in the solution chamber 210 is as shown in Fig. 5b, that is, the particle in the traveling wave electric field from right to left in the viewing angle shown in Fig. 4, under the action of the shaped wave dielectric power , moving from right to left to the left, forming a pile of particles with a small width and located on the left side of the solution chamber.
  • the detecting unit 300 shown in Fig. 1 is for detecting the width of the particle stack in the set direction (in the present embodiment, the direction of the traveling wave electric field), and generating the width information of the particle pile.
  • the detecting unit 300 may perform detection based on optics, or may perform detection based on electrical.
  • the composition of the detecting unit 300 can be as shown in Figs. 6a and 6b, and Figs. 6a and 6b are schematic views of a structure of the detecting unit 300.
  • Figure 6a is a front view and Figure 6b is a right view.
  • the detecting unit 300 may include a light source 3 10, an optical processing module 320, and a detecting module 330.
  • the light source 310 is for emitting light to the solution chamber 210 in the dielectrophoresis generating unit 200.
  • the optical processing module 320 is configured to receive light transmitted through the solution chamber 210 and optically process the light.
  • the detecting module 330 is configured to generate width information of the particle stack in the solution chamber (210) in the set direction according to the processed light of the optical processing module 320.
  • the detection module 330 can be a one-dimensional detection module, such as a linear charge coupled device (CCD) array.
  • the lens unit 320 may include: a first imaging sub-module 321 and a second imaging sub-module 322.
  • the first imaging sub-module 321 is configured to receive light transmitted through the solution chamber 210, and image the light to obtain a two-dimensional graphic light.
  • the first imaging sub-module can be implemented by a lens group, a spherical lens or an aspheric lens.
  • the second imaging sub-module 322 is configured to convert the two-dimensional graphic light obtained by the first imaging sub-module 321 into one-dimensional graphic light.
  • the second imaging sub-module can be implemented by a cylindrical lens or the like.
  • the detection module 330 can be a two-dimensional detection module, such as a planar CCD array.
  • the lens unit 320 may include only the first imaging sub-module 321 and not the second imaging sub-module 322. At this time, the planar CCD array can directly receive the two-dimensional graphic light obtained by the first imaging sub-module 321 .
  • the CCD array generates a corresponding step signal according to the pattern light from the optical processing module 320.
  • the step edge position of the step signal corresponds to the edge position of the particle pile in the solution chamber 210.
  • the width before the step of the jump signal corresponds to the width of the particle stack in the solution chamber 210.
  • the correspondence between the width of the particle pile in the predetermined volume of the particle solution in the solution chamber 210 and the concentration of the particles in the entire particle solution can be obtained in advance by empirical data or experimental means. For example, for a rectangular solution chamber 210 having a rectangular cross section and a main viewing surface, a linear relationship between the width of the particle stack and the concentration of the particles as shown in Fig. 7b can be obtained.
  • Figure 7c shows the step signal corresponding to several different particle stack concentrations based on the linear correspondence shown in Figure 7b.
  • the leftmost step signal corresponds to a lower particle concentration
  • the intermediate step signal corresponds to a medium particle. Concentration, the rightmost step signal corresponds to a higher particle concentration.
  • the detection module 330 may also be a Photo Diode Array or a Photomultiplier Tube or Position Sensing Detector (PSD) or a photoresistor.
  • PSD Position Sensing Detector
  • the composition of the detecting unit 300 can be as shown in Fig. 8, and Fig. 8 is a schematic view showing still another structure of the detecting unit 300.
  • the detecting unit 300 may include: a capacitance measuring module 340 and a position determining module 350.
  • the capacitance measuring module 340 is configured to measure the capacitance between adjacent electrodes in the parallel electrodes, such as Cl, C2 C8 in FIG. 9, to provide the measured capacitance value to the position determining module 350.
  • An edge position of the particle stack in the set direction is determined, and width information of the particle pile is generated according to an edge position of the particle pile.
  • the result generating unit 400 shown in FIG. 1 is configured to calculate the width and the particle width according to the width
  • the relationship between the degree and the particle concentration gives the concentration of the particles.
  • the particle can be determined according to the width before the step signal generated by the detecting module 330, and the corresponding relationship between the particle stack width and the particle concentration shown in FIG. 7b. concentration.
  • the dielectrophoresis generating unit 200, the detecting unit 300, and the result generating unit 400 may constitute a detecting device for the particle concentration in the embodiment of the present invention.
  • FIG. 10 is a schematic structural view of a specific application example in the present invention.
  • the liquid processing unit 100 includes: an injection valve 110, a cleaning liquid reservoir 120, and an injection pump 130.
  • the dielectrophoresis generating unit 200 includes: a signal generating sub-module 221 and a microfluidic chip.
  • the structure of the microfluidic chip is shown in FIG. 11a and FIG. 1 ib, and FIG. 11a is a bottom view, and FIG.
  • the microfluidic chip includes: a rectangular parallelepiped solution chamber 210, parallel electrodes 222 on one side of the solution chamber 210, and a traveling wave signal connecting the signal generating sub-module 221 and an isotropic electrode in the parallel electrode 222 223, and the microfluidic chip further comprises at least one inlet for the inflow of the solution and the cleaning solution, at least one outlet for the outflow of the waste liquid, the substrate and the casing, the microfluidic chip can be penetrated by the light, and the material of the chip It is not electrically conductive, for example, the chip can be made of plastic, glass or silicon.
  • the solution chamber 210 in the fluid chip can also have other shapes. For example, the bottom view can also be a triangle as shown in Fig. 11c.
  • the detecting unit 300 includes: a light source 310, a first imaging sub-module 321, a second imaging sub-module 322, and a detecting module 330, which is a linear CCD array.
  • the valve of the injection valve 110 is first opened, and the microparticle solution in the microparticle solution storage device is injected into the dielectrophoresis generating unit 200 under the action of external power, and when the microparticle solution is filled with the dielectrophoresis generating unit 200, Close your own valve.
  • the signal generation sub-module 221 generates a plurality of traveling wave signals of different phases, and the traveling wave signals are applied to the microfluidic chip, that is, connected to the parallel electrodes 222 through the wires 223 to generate a traveling wave electric field.
  • the movement takes place underneath, and after a while, a heap of particles is formed.
  • the detecting unit 300 composed of the light source 310, the first imaging sub-module 321, the second imaging sub-module 322, and the linear CCD array detects the particle pile and generates width information of the Vis particle pile.
  • the result generation unit 400 reads the width information from the linear CCD array, that is, the step signal, determines the particle based on the width before the step of the step signal, and the correspondence between the particle stack width and the particle concentration similar to that shown in FIG. 7b. concentration.
  • the traveling wave electric field can be stopped, and the cleaning liquid in the cleaning liquid reservoir 120 is pumped into the dielectrophoresis generating unit 200 by the infusion pump 130 to clean the dielectrophoresis generating unit 200 for the next detection of the particle concentration.
  • the dielectrophoresis generating unit 200, the detecting unit 300, and the result generating unit 400 may constitute a detecting device for the particle concentration in the embodiment of the present invention.
  • Figure 12 is an exemplary flow chart of a method of detecting particle concentration in an embodiment of the present invention. As shown in Figure 12, the process includes the following steps:
  • Step 1201 adding a non-uniform electric field to the sampled particle solution to cause the particles in the particle solution to move in a set direction to obtain a moving particle pile.
  • a predetermined volume of the sampled particle solution may be first injected into the solution chamber, and a plurality of parallel electrodes are distributed on one side or opposite sides of the solution chamber to form parallel electrodes. Then, N traveling wave signals of different phases are generated, and the N different phase traveling wave signals are respectively connected to the same phase electrodes in the parallel electrodes through a wire to generate a traveling wave electric field. Thereafter, the living particles in the fine particle solution are moved by the action of the traveling wave electric field, that is, under the action of the electric power of the traveling wave electric field, to form a particle pile.
  • N is an integer greater than or equal to 3.
  • Step 1202 Detect a width of the particle stack in the set direction, and generate width information of the particle pile.
  • the light source can emit light to the solution chamber, then receive the light passing through the solution chamber, optically process the light through the lens group, and determine the particle pile in the solution chamber according to the optically processed light.
  • the width in the set direction and a corresponding width signal is generated.
  • the phase in the parallel electrode can also be measured. a capacitance between adjacent electrodes, and a change in capacitance between adjacent electrodes, determining an edge position of the particle stack in the set direction, determining a width of the particle pile according to an edge position of the particle pile, and Generate corresponding width information.
  • Step 1203 Obtain a concentration of the particles according to the width information and the correspondence between the particle pile width and the particle concentration.
  • the particle pile width information may be collected, and then the concentration of the particles is obtained according to the stored width information and the corresponding relationship between the particle pile width and the particle concentration.

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Abstract

A particle concentration measuring device includes a dielectrophoresis generating unit (200), a measuring unit (300) and a result generating unit (400). The dielectrophoresis generating unit forms an uneven electric field in the particle solution with a preset volume, so that the particles in the particle solution are made to move along a given direction to form a particle mass; the measuring unit measures the width information of the particle mass along the given direction; the result generating unit receives the width information, and then obtains the particle concentration according to the width information and the pre-stored corresponding relation between the width information and the particle concentration.

Description

一种微粒浓度的检测装置和方法 技术领域  Device and method for detecting particle concentration
本发明涉及微粒检测领域, 特别涉及一种微粒浓度的检测装置和 方法。 背景技术  The present invention relates to the field of particle detection, and more particularly to a device and method for detecting particle concentration. Background technique
在工业发酵、 环境监测、 生物分析以及临床诊断等应用领域中, 为了得到理想的结果或便于检测, 需要对微粒, 如动、 植物细胞或微 生物等的发酵或培育等过程进行控制, 而过程的控制很大程度上依靠 过程参数的测量, 尤其是微粒的状态参数测量。 而在微粒状态参数中, 微粒在微粒溶液中的含量, 也可称微粒浓度又是其中最主要的参数之 传统方法中, 通常采用离线手工方式对微粒含量进行测量。 以细 胞为例, 例如, 有一种方法是: 基于显微镜进行测量。 由于多数细胞 是半透明的, 因此在检测之前需要对细胞进行化学或物理的着色, 以 增强细胞在显微镜下的对比度, 此外, 还需要对细胞溶液进行稀释, 以使各个细胞便于观察。 又如, 还有一种方法是: 先将细胞通过离心 机进行分离, 再利用天平对分离出的细胞进行称重。 但这些方法中, 需要特定的精细设备和有经验的操作人员, 实现复杂, 并且人工测量 比较耗时, 不能满足实时控制的需求; 此外由于只有活细胞才具有繁 殖及生长能力, 因此测量细胞含量时, 只希望得到活细胞的含量, 而 上述方法中, 死亡细胞和活细胞是无法分开的。  In industrial fermentation, environmental monitoring, bioanalysis, and clinical diagnostic applications, in order to obtain desired results or to facilitate detection, it is necessary to control the fermentation or cultivation processes of particles, such as animals, plants, or microorganisms. Control relies to a large extent on the measurement of process parameters, especially the measurement of the state parameters of the particles. In the particle state parameter, the content of the particles in the particle solution, which can also be called the particle concentration, is the most important parameter among them. The particle content is usually measured by off-line manual method. Taking cells as an example, for example, one method is: Measurement based on a microscope. Since most cells are translucent, the cells need to be chemically or physically colored before detection to enhance the contrast of the cells under the microscope. In addition, the cell solution needs to be diluted to make each cell easy to observe. As another example, another method is: first, the cells are separated by a centrifuge, and the separated cells are weighed using a balance. However, in these methods, specific fine equipment and experienced operators are required to realize complex, and manual measurement is time consuming and cannot meet the requirements of real-time control. In addition, since only living cells have the ability to reproduce and grow, the cell content is measured. At that time, only the content of living cells is desired, and in the above method, dead cells and living cells cannot be separated.
目前, 针对微粒含量的测量又提出了一些在线测量方法。 仍以细 胞为例, 例如, 有一种方法是: 将光源和光检测器集成在一个微型探 头里, 然后将带有该微型探头的传感器浸入生物反应器中, 由于细胞 对光有反射和散射作用, 因此可根据反射光和散射光与细胞含量之间 的对应关系, 对细胞含量进行检测。 但该方法中, 微型探头的检测结 果易受细胞溶液的颜色和浊度, 以及死亡细胞的影响。 又如, 还有一 种方法是: 分别测量细胞溶液和通过过滤罩过滤出的不含细胞的介质 溶液在无线电频率范围内的电容率, 将二个电容率进行比较, 得到细 胞含量变化引起的电容率变化, 进而确定细胞含量。 但该方法中, 过 滤罩容易被细胞堵塞, 需要不时的更换或清洗过滤罩。 At present, some online measurement methods have been proposed for the measurement of the particle content. Still taking cells as an example, for example, one method is: integrating a light source and a photodetector in a microprobe, and then immersing the sensor with the microprobe in a bioreactor, because the cells reflect and scatter light, Therefore, the cell content can be detected based on the correspondence between the reflected light and the scattered light and the cell content. However, in this method, the detection results of the micro probe are susceptible to the color and turbidity of the cell solution, as well as the dead cells. Another example, there is one The method comprises the following steps: measuring the permittivity of the cell solution and the cell-free medium solution filtered through the filter cover in the radio frequency range, comparing the two permittivity rates, and obtaining the change of the permittivity caused by the change of the cell content, thereby determining Cell content. However, in this method, the filter cover is easily blocked by cells, and it is necessary to replace or clean the filter cover from time to time.
可见, 目前这些在线测量方法容易受各种因素的影响, 如细胞溶 液的颜色、 死亡细胞等的影响。 发明内容  It can be seen that these online measurement methods are currently susceptible to various factors such as the color of the cell solution, dead cells, and the like. Summary of the invention
为了解决以上问题, 本发明一方面提供一种微粒浓度的检测装置, 另一方面提供一种微粒浓度的检测方法, 以便不受干扰地完成微粒浓 度的检测。  In order to solve the above problems, the present invention provides an apparatus for detecting the concentration of particles, and on the other hand, a method for detecting the concentration of particles, so that the detection of the concentration of particles is completed without interference.
本发明提供的微粒浓度的检测装置, 包括: 一个介电电泳产生单 元, 用于在预定体积的微粒溶液中形成不均勾电场, 使得所述微粒溶 液中的微粒沿设定方向移动, 形成微粒堆; 一个检测单元, 用于检测 得到所述微粒堆在所述设定方向上的宽度信息; 一个结果生成单元, 接收所述微粒堆宽度信息, 根据所述宽度信息及存储的微粒堆宽度与 微粒浓度的对应关系, 得到微粒的浓度。  The apparatus for detecting the concentration of particles provided by the present invention comprises: a dielectrophoresis generating unit for forming an uneven electric field in a predetermined volume of the microparticle solution, so that the particles in the microparticle solution move in a set direction to form particles. a detection unit, configured to detect width information of the particle stack in the set direction; a result generating unit, receiving the particle pile width information, according to the width information and the stored particle pile width and The corresponding relationship of the particle concentrations gives the concentration of the particles.
其中, 所述介电电泳产生单元包括: 一个溶液室, 具有一个预定 的容积, 用于盛放微粒溶液; 一个信号产生子模块, 用于产生 N个不 同相位的行波信号, N为大于或等于 3 的整数; 多个平行电极, 包括 位于所述溶液室的一侧或相向的两侧的多个平行的电极; N 个导线, 用于将所述 N个不同相位的行波信号分别与所述平行电极中的同相位 电极相连, 以使其产生行波电场。  Wherein the dielectrophoresis generating unit comprises: a solution chamber having a predetermined volume for holding the particle solution; and a signal generating sub-module for generating N different phase traveling wave signals, N being greater than or An integer equal to 3; a plurality of parallel electrodes including a plurality of parallel electrodes on one side or opposite sides of the solution chamber; N wires for respectively respectively using the N different phase traveling wave signals The in-phase electrodes of the parallel electrodes are connected to generate a traveling wave electric field.
具体地,所述的各行波信号为正弦信号,其角频率为 100Hz 至 100 MHz, 其振幅为 0 至 100 伏, 各信号之间的相位差为 360° / N。  Specifically, each of the traveling wave signals is a sinusoidal signal having an angular frequency of 100 Hz to 100 MHz, an amplitude of 0 to 100 volts, and a phase difference of 360° / N between the signals.
优选地, 所述的溶液室 (210 )至少局部由透明材料制成; 所述电 极是由铟锡氧化物制成。  Preferably, the solution chamber (210) is at least partially made of a transparent material; the electrode is made of indium tin oxide.
作为一种优选实施方式, 所述检测单元包括: 一个光源, 用于向 所述介电电泳产生单元的溶液室发射光线; 一个光学处理模块, 用于 接收透过所述溶液室的光线, 生成一维或二维图形光线; 一个探测模 块, 用于根据所述光学处理模块处理后的光线, 生成所述溶液室中微 粒堆在所述设定方向上的宽度信息。 As a preferred embodiment, the detecting unit comprises: a light source for emitting light to a solution chamber of the dielectrophoresis generating unit; and an optical processing module for receiving light transmitted through the solution chamber to generate One-dimensional or two-dimensional graphic light; one detection mode a block, configured to generate width information of the particle stack in the solution chamber in the set direction according to the light processed by the optical processing module.
在一个实施例中, 所述探测模块为具有线性电荷耦合器件阵列的 一维探测模块; 所述光学处理模块包括: 第一成像子模块, 其具有至 少一个光学透镜, 用于接收透过所述溶液室的光线, 并由此形成二维 图形光线; 和, 第二成像子模块, 其具有一个柱面透镜, 用于将所述 二维图形光线转换为一维图形光线。  In one embodiment, the detection module is a one-dimensional detection module having a linear array of charge coupled devices; the optical processing module includes: a first imaging sub-module having at least one optical lens for receiving The light in the solution chamber, and thereby forming a two-dimensional pattern of light; and, a second imaging sub-module having a cylindrical lens for converting the two-dimensional graphic light into a one-dimensional graphic light.
在另一个实施例中, 所述探测模块为具有平面电荷耦合器件阵列 的二维探测模块; 所述光学处理模块包括: 第一成像子模块, 其具有 至少一个光学透镜, 用于接收透过所述溶液室的光线, 并由此形成二 维图形光线。  In another embodiment, the detecting module is a two-dimensional detecting module having a planar charge coupled device array; the optical processing module includes: a first imaging sub-module having at least one optical lens for receiving a transmission The light in the solution chamber is formed, and thereby a two-dimensional pattern of light is formed.
在其他另选实施例中, 所述探测模块为光电二级管阵列或光电倍 增管或位置传感器探测器或光敏电阻。  In other alternative embodiments, the detection module is a photodiode array or a photomultiplier or position sensor detector or a photoresistor.
作为另一种优选实施方式, 所述检测单元包括: 一个电容测量模 块, 用于测量相邻平行电极之间的电容; 一个位置确定模块, 接收测 得的所述相邻平行电极之间的各个电容值, 并根据所述电容值的变化, 确定微粒堆在所述设定方向上的边缘位置, 并据此生成所述微粒堆的 宽度信息。  As another preferred embodiment, the detecting unit includes: a capacitance measuring module for measuring capacitance between adjacent parallel electrodes; and a position determining module receiving each of the measured adjacent parallel electrodes And a capacitance value, and determining an edge position of the particle stack in the set direction according to the change of the capacitance value, and generating width information of the particle pile according to the data.
具体地, 所述结果生成单元是一个具有存贮和计算功能的处理器。 进一步地, 所述介电电泳产生单元与一个微粒溶液存放器之间通 过一个具有注入阀的液体处理单元连接。 所述液体处理单元进一步包 括: 一个清洗液存放器和一个将清洗液导入所述介电电泳产生单元的 注入泵。  Specifically, the result generating unit is a processor having a storage and computing function. Further, the dielectrophoresis generating unit and a particulate solution storage unit are connected by a liquid processing unit having an injection valve. The liquid processing unit further includes: a cleaning liquid reservoir and an infusion pump for introducing the cleaning liquid into the dielectrophoresis generating unit.
本发明提供的一种微粒浓度的检测方法, 包括: 在预定体积的采 样微粒溶液中施加一个由多个平行电极生成的行波电场, 使得所述微 粒溶液中的微粒沿设定方向移动, 形成微粒堆; 检测得到所述微粒堆 在所述设定方向上的宽度信息; 收集所述微粒堆宽度信息, 根据所述 宽度信息及微粒堆宽度与微粒浓度的对应关系, 得到微粒的浓度。  The invention provides a method for detecting the concentration of particles, comprising: applying a traveling wave electric field generated by a plurality of parallel electrodes in a predetermined volume of the sampled particle solution, so that the particles in the particle solution move in a set direction, forming a particle stack; detecting width information of the particle stack in the set direction; collecting the particle pile width information, and obtaining a concentration of the particles according to the width information and a correspondence relationship between the particle pile width and the particle concentration.
作为一种优选实施方式, 所述检测得到所述微粒堆在所述设定方 向上的宽度信息包括: 向所述溶液室发射光线; 光学透镜接收透过所 述溶液室的光线, 并形成图形光线; 根据所述图形光线, 确定所述微 粒堆在所述设定方向上的宽度。 As a preferred embodiment, the detecting the width information of the particle stack in the set direction comprises: emitting light to the solution chamber; and receiving the optical lens through the optical lens The light of the solution chamber is formed, and a pattern light is formed; and the width of the particle pile in the set direction is determined according to the pattern light.
作为另一种优选实施方式, 所述检测得到所述微粒堆在所述设定 方向上的宽度信息包括: 测量所述平行电极中相邻电极之间的电容; 根据相邻电极之间的电容变化, 确定微粒堆在所述设定方向上的边缘 位置, 并由此确定所述微粒堆的宽度。  As another preferred embodiment, the detecting the width information of the particle stack in the set direction comprises: measuring a capacitance between adjacent electrodes in the parallel electrode; according to a capacitance between adjacent electrodes Varying, determining the edge position of the particle stack in the set direction and thereby determining the width of the particle stack.
从上述方案可以看出, 本发明中, 在采样的微粒溶液中加入不均 匀电场, 促使所述微粒溶液中的微粒沿设定方向移动, 得到移动后的 微粒堆, 通过检测微粒堆在该设定方向上的宽度, 得到微粒堆的宽度 信息, 再根据微粒堆的宽度信息及微粒堆宽度与微粒浓度的对应关系, 得到微粒的浓度, 从而实现了微粒浓度的自动测量。 对于细胞等活体 微粒, 由于介质溶液通常可以透过其细胞膜而进入死亡细胞内, 因此 死亡细胞具有与活体细胞不一样的介电常数, 而不会混入活体细胞中, 使得细胞浓度的测量不会受死亡细胞等因素的.干扰。 此外, 由于无需 使用侵入溶液中的探头以及用于过滤的过滤罩, 因此也不会受这些外 界因素的干扰。 附图说明  It can be seen from the above scheme that in the present invention, a non-uniform electric field is added to the sampled particle solution, and the particles in the particle solution are moved in a set direction to obtain a moving particle pile, and the particle pile is detected in the device. The width in the direction is obtained, and the width information of the particle pile is obtained. Then, according to the width information of the particle pile and the corresponding relationship between the particle pile width and the particle concentration, the concentration of the particles is obtained, thereby realizing the automatic measurement of the particle concentration. For living particles such as cells, since the medium solution can usually enter the dead cells through the cell membrane, the dead cells have a dielectric constant different from that of the living cells, and do not mix into the living cells, so that the measurement of the cell concentration does not occur. Interfered with factors such as dead cells. In addition, there is no need to use the probe in the intrusion solution and the filter cover for filtration, so it is not affected by these external factors. DRAWINGS
下面将通过参照附图详细描述本发明的示例性实施例, 使本领域 的普通技术人员更清楚本发明的上述及其他特征和优点, 附图中: 图 1为本发明实施例中微粒浓度的检测系统的示例性结构图; 图 2为图 1所示系统中液体处理单元的结构示意图;  The above and other features and advantages of the present invention will become more apparent to those skilled in the <RTIgt FIG. 2 is a schematic structural view of a liquid processing unit in the system shown in FIG. 1;
图 3为图 1所示系统中介电电泳产生单元的结构示意图; 图 4为图 3所示介电电泳产生单元中行波电场发生模块的一个结 构示意图;  3 is a schematic structural view of a system-intermediate electrophoresis generating unit shown in FIG. 1; FIG. 4 is a schematic structural view of a traveling wave electric field generating module in the dielectrophoresis generating unit shown in FIG.
图 5a和图 5b为行波电场产生前后微粒溶液中微粒状态的示意图; 图 6a和图 6b为图 1所示系统中检测单元的一个结构的示意图; 图 7a为图 6a和图 6b所示检测单元中探测模块产生的阶跃信号与 微粒堆宽度的对应关系示意图;  Figure 5a and Figure 5b are schematic views of the state of the particles in the particle solution before and after the generation of the traveling wave electric field; Figures 6a and 6b are schematic views of a structure of the detecting unit in the system of Figure 1; Figure 7a shows the detection shown in Figures 6a and 6b. A schematic diagram of the correspondence between the step signal generated by the detecting module and the width of the particle stack in the unit;
图 7b为微粒堆宽度与微粒浓度的对应关系示意图; 图 7c为不同微粒浓度的阶跃信号示意图; Figure 7b is a schematic diagram showing the correspondence relationship between the particle stack width and the particle concentration; Figure 7c is a schematic diagram of step signals for different particle concentrations;
图 8为图 1所示系统中检测单元的又一个结构的示意图; 图 9为图 3所示介电电泳产生单元中行波电场发生模块的电容测 量示意图;  8 is a schematic diagram showing still another structure of the detecting unit in the system shown in FIG. 1. FIG. 9 is a schematic diagram showing capacitance measurement of the traveling wave electric field generating module in the dielectrophoresis generating unit shown in FIG.
图 10为本发明中一个具体应用示例的结构示意图;  10 is a schematic structural view of a specific application example in the present invention;
图 11 a和图 l ib为图 10所示应用示例中微流体芯片的结构示意图; 图 11c为图 10所示应用示例中微流体芯片的另一个结构示意图; 图 12为本发明实施例中微粒浓度的检测方法的示例性流程图。 具体实施方式  11a and 1b are schematic structural views of a microfluidic chip in the application example shown in FIG. 10; FIG. 11c is another schematic structural view of the microfluidic chip in the application example shown in FIG. 10; An exemplary flow chart of a method of detecting concentration. detailed description
本发明中, 考虑到介电电泳是一种能使中性粒子在不均勾电场作 用下被极化, 且极化后的粒子在介电力的作用下产生运动的一种电动 均匀电场中可产生介电电泳现象。 此外, 对于细胞等活体微粒来说, 由于介质溶液通常可以透过死亡细胞的细胞膜而进入死亡细胞内, 因 此死亡细胞具有与介质溶液一致的介电常数, 而不会混入活体细胞中。 因此, 本发明中提出一种基于介电电泳的微粒浓度的检测方案, 即在 采样的微粒溶液中形成不均勾电场, 促使所述微粒溶液中的微粒沿设 定方向移动, 得到移动后的微粒堆, 通过检测微粒堆在该设定方向上 的宽度, 得到微粒堆的宽度信息, 再根据微粒堆的宽度信息及微粒堆 宽度与微粒浓度的对应关系, 得到微粒的浓度。  In the present invention, it is considered that dielectrophoresis is a kind of electric uniform electric field which can polarize neutral particles under the action of uneven electric field and the polarized particles generate motion under the action of dielectric power. Dielectrophoresis is produced. Further, in the case of living microparticles such as cells, since the medium solution can normally enter the dead cells through the cell membrane of the dead cells, the dead cells have a dielectric constant consistent with the medium solution and are not mixed into the living cells. Therefore, in the present invention, a detection scheme for particle concentration based on dielectrophoresis is proposed, that is, an uneven electric field is formed in the sampled particle solution, and the particles in the particle solution are moved in a set direction to obtain a moving The particle stack obtains the width information of the particle pile by detecting the width of the particle pile in the set direction, and obtains the concentration of the particles based on the width information of the particle pile and the correspondence between the particle pile width and the particle concentration.
为使本发明的目的、 技术方案及优点更加清楚明白, 以下参照附 图并举实施例, 对本发明进一步详细说明。  The present invention will be further described in detail below with reference to the accompanying drawings.
图 1 为本发明实施例中微粒浓度的检测系统的示例性结构图。 如 图 1所示, 该系统包括: 液体处理单元 100、 介电电泳产生单元 200、 检测单元 300和结果生成单元 400。  Fig. 1 is an explanatory structural view showing a system for detecting a particle concentration in an embodiment of the present invention. As shown in Fig. 1, the system includes: a liquid processing unit 100, a dielectrophoresis generating unit 200, a detecting unit 300, and a result generating unit 400.
其中, 为了使整个系统能够协同工作, 可设置逻辑控制单元, 该 逻辑控制单元可独立于上述各单元之外, 也可将逻辑控制单元的功能 设置在上述各单元中的任意一个或任意几个之中。 具体实现时, 该逻 辑控制单元可以通过计算机、 或嵌入式中央处理单元(CPU )、 或数字 信号处理器 (DSP )、 或可编程逻辑控制器 (PLC )等实现。 In order to enable the entire system to work together, a logic control unit may be provided, and the logic control unit may be independent of the above units, or may set the function of the logic control unit to any one or any of the above units. Among them. In specific implementation, the logic control unit can be through a computer, or an embedded central processing unit (CPU), or a digital Implemented by a signal processor (DSP), or a programmable logic controller (PLC).
液体处理单元 100用于将取样的微粒溶液注入所述介电电泳产生 单元 200中。  The liquid processing unit 100 is for injecting the sampled microparticle solution into the dielectrophoresis generating unit 200.
具体实现时, 该液体处理单元 100可如图 2所示, 包括介于微粒 溶液存放器与所述介电电泳产生单元 200之间的注入阀 110,用于在逻 辑控制单元的控制下, 开启自身阀门, 使微粒溶液存放器中的微粒溶 液在外部动力(如压力或泵动力)的作用下注入介电电泳产生单元 200 中; 并在微粒溶液注满介电电泳产生单元 200或注入的微粒溶液达到 预定体积时, 关闭自身阀门。 进一步地, 该液体处理单元 100还可包 括清洗液存放器 120和注入泵 130。 其中, 所述注入泵 130用于在逻辑 控制单元的控制下, 将所述清洗液存放器 120 中的清洗液泵入所述介 电电泳产生单元 200中, 以清洗所述介电电泳产生单元 200。 此外, 介 电电泳产生单元 200 中处理完的啟粒溶液或清洗液等废液可排放到废 液存放器中。 具体实现时, 液体处理单元 100还可包括位于介电电泳 产生单元 200与废液存放器之间的排出阀 140,用于在逻辑控制单元的 控制下, 开启自身阀门, 使所述介电电泳产生单元 2Q0 中的微粒溶液 排入废液存放器中; 并在微粒溶液注入所述介电电泳产生单元 200 中 时, 关闭自身阀门。 或者, 也可以没有该排出阀 140。  In a specific implementation, the liquid processing unit 100 can include an injection valve 110 between the particle solution storage device and the dielectrophoresis generating unit 200, as shown in FIG. 2, for opening under the control of the logic control unit. The self-valve, the microparticle solution in the microparticle solution storage device is injected into the dielectrophoresis generating unit 200 under the action of external power (such as pressure or pump power); and the microelectrophoresis is filled with the dielectrophoresis generating unit 200 or the injected microparticles. When the solution reaches a predetermined volume, close its own valve. Further, the liquid processing unit 100 may further include a cleaning liquid reservoir 120 and an infusion pump 130. The injection pump 130 is configured to pump the cleaning liquid in the cleaning liquid reservoir 120 into the dielectrophoresis generating unit 200 under the control of the logic control unit to clean the dielectrophoresis generating unit. 200. Further, the waste liquid such as the start-up solution or the cleaning liquid processed in the dielectrophoresis generating unit 200 can be discharged into the waste liquid storage. In a specific implementation, the liquid processing unit 100 may further include a discharge valve 140 between the dielectrophoresis generating unit 200 and the waste liquid storage device, for opening the self valve under the control of the logic control unit, so that the dielectrophoresis The particulate solution in the generating unit 2Q0 is discharged into the waste liquid reservoir; and when the particulate solution is injected into the dielectrophoresis generating unit 200, the valve itself is closed. Alternatively, the discharge valve 140 may not be provided.
图 1所示介电电泳产生单元 200用于在所述的控制下, 在所述微 粒溶液中形成不均勾电场, 促使所述微粒溶液中的微粒沿设定方向移 动, 得到移动后的微粒堆。 其中, 不均匀电场可以为行波电场或其他 不均匀电场。  The dielectrophoresis generating unit 200 shown in FIG. 1 is configured to form a non-uniform electric field in the microparticle solution under the control, and to cause particles in the microparticle solution to move in a set direction to obtain a moving microparticle. stack. The uneven electric field may be a traveling wave electric field or other non-uniform electric field.
以行波电场为例, 具体实现时, 介电电泳产生单元 200 的结构可 如图 3所示, 包括: 溶液室 210和行波电场发生模块 220。  Taking the traveling wave electric field as an example, the structure of the dielectrophoresis generating unit 200 can be as shown in FIG. 3, and includes: a solution chamber 210 and a traveling wave electric field generating module 220.
其中, 溶液室 210用于盛放来自液体处理单元 100的微粒溶液。 微粒溶液通过入口进入溶液室 210 中, 检测结束之后, 微粒溶液构成 的废液从出口排出, 并进一步地, 可将清洗液通过入口注入溶液室 210 中, 以清洗溶液室 210, 清洗后的废液从出口排出。  The solution chamber 210 is for holding a particulate solution from the liquid processing unit 100. The fine particle solution enters the solution chamber 210 through the inlet. After the end of the detection, the waste liquid composed of the fine particle solution is discharged from the outlet, and further, the cleaning liquid can be injected into the solution chamber 210 through the inlet to clean the solution chamber 210, and the waste after washing The liquid is discharged from the outlet.
行波电场发生模块 220用于在所述溶液室 210的微粒溶液中产生 定方向移动, 在微粒溶液中得到移动后的微粒堆。 具体实现时, 行波 电场发生模块 220的一种结构可如图 4所示, 具体包括: 信号产生子 模块 221、 平行电极 222和导线 223, 它们在具体实现时可。以集成在一 起, 也可以是分立的。 The traveling wave electric field generating module 220 is configured to generate in the particle solution of the solution chamber 210 Moving in a fixed direction, the moving particle pile is obtained in the particle solution. In a specific implementation, a structure of the traveling wave electric field generating module 220 can be as shown in FIG. 4, and specifically includes: a signal generating sub-module 221, a parallel electrode 222, and a wire 223, which may be implemented in a specific implementation. To be integrated, it can also be discrete.
其中, 信号产生子模块 221用于产生 N个不同相位的行波信号。 其中, N为大于或等于 3的整数。 图 4中, N为 4, 所产生的 4个不同 相位的行波信号分别为正弦信号: A = Vsin(a*t)、 B = Vsin(a *t + 90°)、 C = Vsin(a*t + 180°;^nD = Vsin(a*t + 270°)。其中, V为正弦信号的振幅, a为正弦信号的角频率, 本实施例中, a的取值范围可以为 100Hz到 100MHz, V的取值范围可以为 0至 100νρ_ρ。 图 4中, 4个信号中相邻 信号间的相位差为 360°/4 = 90°。 相应地, 若 Ν为 3, 则产生的 3个信 号中相邻信号间的相位差为 360°/3 = 120°; 若 Ν为 5, 则产生的 5个信 号中相邻信号间的相位差为 360°/5 = 72°; 若 Ν为 6, 则产生的 6个信 号中相邻信号间的相位差为 360°/6 = 60°, 依此类推, 即 Ν个信号中相 邻信号间的相位差为 360° I Ν。 The signal generating sub-module 221 is configured to generate N traveling wave signals of different phases. Where N is an integer greater than or equal to 3. In Figure 4, N is 4, and the generated four different phased traveling wave signals are sinusoidal signals: A = Vsin(a*t), B = Vsin(a *t + 90°), C = Vsin(a *t + 180°; ^nD = Vsin(a*t + 270°), where V is the amplitude of the sinusoidal signal and a is the angular frequency of the sinusoidal signal. In this embodiment, the value of a can range from 100 Hz to 100MHz, V can range from 0 to 100ν ρ _ ρ . In Figure 4, the phase difference between adjacent signals in the four signals is 360° / 4 = 90°. Correspondingly, if Ν is 3, then The phase difference between adjacent signals among the three signals is 360°/3 = 120°; if Ν is 5, the phase difference between adjacent signals among the five generated signals is 360°/5 = 72°; When Ν is 6, the phase difference between adjacent signals among the six signals generated is 360°/6 = 60°, and so on, that is, the phase difference between adjacent signals in one signal is 360° I Ν.
平行电极 222包括多个平行的电极, 这些电极位于溶液室 210内 的一侧或相向的两侧。 图 4中, 以 9个电极的情况为例, 通常情况下, 电极的个数大于或等于 Ν。 该电极可由任何导电的材料制成, 若检测 单元 300基于光学进行检测, 则制作该电极的导电材料还应该是透光 的, 例如, 电极可由铟锡氧化物(ΙΤΟ, Indium Tin Oxide)制成。 此外, 本实施例中, 各电极之间的距离的取值范围可以为 0.1到 500微米。  Parallel electrode 222 includes a plurality of parallel electrodes that are located on one side or opposite sides of solution chamber 210. In Fig. 4, taking the case of nine electrodes as an example, in general, the number of electrodes is greater than or equal to Ν. The electrode may be made of any electrically conductive material. If the detecting unit 300 is based on optical detection, the conductive material from which the electrode is made should also be light transmissive. For example, the electrode may be made of indium tin oxide (Indium Tin Oxide). . Further, in this embodiment, the distance between the electrodes may range from 0.1 to 500 μm.
导线 223, 用于将所述 N个不同相位的行波信号分别与所述平行 电极 222中的同相位电极相连。 对于图 4所示的本实施例中 N为 4的 情况, 每相隔 3个电极的两个电极为同相位电极, 即, 每相隔 (N-1 ) 个电极的两个电极为同相位电极。 例如, 对于图 4中电极个数为 9的 情况, 可有: 第一条导线将信号 A和平行电极中的第 1、 第 5和第 9 个电极连接在一起, 第二条导线将信号 B和平行电极中的第 2和第 6 个电极连接在一起, 第三条导线将信号 C和平行电极中的第 3和第 7 个电极连接在一起, 第四条导线将信号 D和平行电极中的第 4和第 8 个电极连接在一起, 该连接方式使得信号产生子模块 221 产生行波信 号时, 形成图 4所示视角中从右向左的行波电场。 The wire 223 is configured to connect the N different phase traveling wave signals to the same phase electrode in the parallel electrode 222. In the case where N is 4 in the present embodiment shown in Fig. 4, the two electrodes separated by three electrodes are the same phase electrodes, that is, the two electrodes separated by (N-1) electrodes are the same phase electrodes. For example, for the case where the number of electrodes in FIG. 4 is 9, there may be: the first wire connects the signal A and the first, fifth, and ninth electrodes in the parallel electrode, and the second wire will signal B. Connected to the 2nd and 6th electrodes in the parallel electrode, the third wire connects the signal C to the 3rd and 7th electrodes in the parallel electrode, and the fourth wire will be in the signal D and the parallel electrode The 4th and 8th electrodes are connected together, and the connection mode causes the signal generation sub-module 221 to generate a traveling wave letter When the number is formed, a traveling wave electric field from right to left in the viewing angle shown in FIG. 4 is formed.
其中, 当信号产生子模块 221没产生行波信号时, 即 A=B=C=D=0 时, 溶液室 210中微粒溶液的微粒状态如图 5a所示, 当信号产生子模 块 221产生上述 4个信号时, 一段时间后, 溶液室 210中微粒溶液的 微粒状态如图 5b所示, 即微粒在图 4所示视角中从右向左的行波电场 中, 在形波介电力的作用下, 按照从右向左的方向移动到左侧, 形成 宽度变小且位于溶液室左侧的微粒堆。  Wherein, when the signal generating sub-module 221 does not generate a traveling wave signal, that is, when A=B=C=D=0, the particle state of the particle solution in the solution chamber 210 is as shown in FIG. 5a, and the signal generating sub-module 221 generates the above. After 4 signals, after a period of time, the particle state of the particle solution in the solution chamber 210 is as shown in Fig. 5b, that is, the particle in the traveling wave electric field from right to left in the viewing angle shown in Fig. 4, under the action of the shaped wave dielectric power , moving from right to left to the left, forming a pile of particles with a small width and located on the left side of the solution chamber.
图 1所示检测单元 300用于检测所述微粒堆在设定方向 (本实施 例中即为上述行波电场的方向)上的宽度, 并生成所述微粒堆的宽度 信息。 其中, 检测单元 300 可基于光学进行检测, 也可基于电学进行 检测。  The detecting unit 300 shown in Fig. 1 is for detecting the width of the particle stack in the set direction (in the present embodiment, the direction of the traveling wave electric field), and generating the width information of the particle pile. The detecting unit 300 may perform detection based on optics, or may perform detection based on electrical.
基于光学进行 4 测时, 该检测单元 300的组成可如图 6a和图 6b 所示, 图 6a和图 6b为检测单元 300的一个结构的示意图。 图 6a为正 视图, 图 6b为右视图。 其中, 检测单元 300可包括光源 3 10、 光学处 理模块 320和探测模块 330。  The composition of the detecting unit 300 can be as shown in Figs. 6a and 6b, and Figs. 6a and 6b are schematic views of a structure of the detecting unit 300. Figure 6a is a front view and Figure 6b is a right view. The detecting unit 300 may include a light source 3 10, an optical processing module 320, and a detecting module 330.
其中,光源 310用于向所述介电电泳产生单元 200中的溶液室 210 发射光线。  The light source 310 is for emitting light to the solution chamber 210 in the dielectrophoresis generating unit 200.
光学处理模块 320用于接收透过所述溶液室 210的光线, 并对所 述光线进行光学处理。  The optical processing module 320 is configured to receive light transmitted through the solution chamber 210 and optically process the light.
探测模块 330用于根据所述光学处理模块 320处理后的光线, 生 成所述溶液室 (210 ) 中微粒堆在所述设定方向上的宽度信息。  The detecting module 330 is configured to generate width information of the particle stack in the solution chamber (210) in the set direction according to the processed light of the optical processing module 320.
具体实现时, 该探测模块 330 可以为一维的探测模块, 如线性电 荷藕合器件 (CCD ) 阵列。 则相应地, 透镜单元 320可包括: 第一成 像子模块 321和第二成像子模块 322。  In a specific implementation, the detection module 330 can be a one-dimensional detection module, such as a linear charge coupled device (CCD) array. Accordingly, the lens unit 320 may include: a first imaging sub-module 321 and a second imaging sub-module 322.
其中, 第一成像子模块 321用于接收透过所述溶液室 210的光线, 并对所述光线进行成像处理, 得到二维图形光线。 具体实现时, 该第 一成像子模块可通过镜头组、 球面透镜或非球面透镜等实现。  The first imaging sub-module 321 is configured to receive light transmitted through the solution chamber 210, and image the light to obtain a two-dimensional graphic light. In specific implementation, the first imaging sub-module can be implemented by a lens group, a spherical lens or an aspheric lens.
第二成像子模块 322用于将第一成像子模块 321得到的二维图形 光线转换为一维图形光线。 具体实现时, 该第二成像子模块可通过柱 面透镜等实现。 或者,该探测模块 330可以为二维的探测模块,如平面 CCD阵列。 则相应地, 透镜单元 320可只包括: 第一成像子模块 321 , 而不包括第 二成像子模块 322。 此时, 平面 CCD阵列可直接接收第一成像子模块 321得到的二维图形光线。 The second imaging sub-module 322 is configured to convert the two-dimensional graphic light obtained by the first imaging sub-module 321 into one-dimensional graphic light. In a specific implementation, the second imaging sub-module can be implemented by a cylindrical lens or the like. Alternatively, the detection module 330 can be a two-dimensional detection module, such as a planar CCD array. Accordingly, the lens unit 320 may include only the first imaging sub-module 321 and not the second imaging sub-module 322. At this time, the planar CCD array can directly receive the two-dimensional graphic light obtained by the first imaging sub-module 321 .
其中, CCD阵列根据来自光学处理模块 320的图形光线, 生成对 应的阶跃信号,如图 7a所示,该阶跃信号的阶跃边缘位置与溶液室 210 中微粒堆的边缘位置相对应, 阶跃信号阶跃之前的宽度与溶液室 210 中微粒堆的宽度相对应。 此外, 可事先通过经验数据或实验的方式得 到溶液室 210 中预定体积的微粒溶液中微粒堆的宽度与整个微粒溶液 中微粒的浓度的对应关系。 例如, 对于横截面和主视面均为矩形的长 方体溶液室 210, 可得到如图 7b所示的微粒堆的宽度与微粒的浓度之 间的线性关系示意图。 相应的, 对于其它形状的溶液室, 如横截面为 矩形、 主视面为三角形等形状的溶液室, 也可以得到其它的对应关系, 如非线性关系的对应关系。 图 7c示出了基于图 7b所示线性对应关系 时, 几种不同微粒堆浓度对应的阶跃信号, 最左侧的阶跃信号对应较 低的微粒浓度, 中间的阶跃信号对应中等的微粒浓度, 最右侧的阶跃 信号对应较高的微粒浓度。  The CCD array generates a corresponding step signal according to the pattern light from the optical processing module 320. As shown in FIG. 7a, the step edge position of the step signal corresponds to the edge position of the particle pile in the solution chamber 210. The width before the step of the jump signal corresponds to the width of the particle stack in the solution chamber 210. Further, the correspondence between the width of the particle pile in the predetermined volume of the particle solution in the solution chamber 210 and the concentration of the particles in the entire particle solution can be obtained in advance by empirical data or experimental means. For example, for a rectangular solution chamber 210 having a rectangular cross section and a main viewing surface, a linear relationship between the width of the particle stack and the concentration of the particles as shown in Fig. 7b can be obtained. Correspondingly, for solution chambers of other shapes, such as a solution chamber having a rectangular cross section and a triangular shape of the main viewing surface, other correspondences, such as a correspondence of nonlinear relationships, can also be obtained. Figure 7c shows the step signal corresponding to several different particle stack concentrations based on the linear correspondence shown in Figure 7b. The leftmost step signal corresponds to a lower particle concentration, and the intermediate step signal corresponds to a medium particle. Concentration, the rightmost step signal corresponds to a higher particle concentration.
具体实现时, 除了 CCD阵列, 探测模块 330也可以是光电二级管 阵列 (Photo Diode Array )或光电倍增管或位置传感探测器 (PSD, Position Sensing Detector )或光敏电阻等。  In specific implementation, in addition to the CCD array, the detection module 330 may also be a Photo Diode Array or a Photomultiplier Tube or Position Sensing Detector (PSD) or a photoresistor.
此外, 基于电学进行检测时, 该检测单元 300的组成可如图 8所 示, 图 8为检测单元 300的又一个结构的示意图。 如图 8所示, 该检 测单元 300可包括: 电容测量模块 340和位置确定模块 350。  Further, when the detection is based on electrical power, the composition of the detecting unit 300 can be as shown in Fig. 8, and Fig. 8 is a schematic view showing still another structure of the detecting unit 300. As shown in FIG. 8, the detecting unit 300 may include: a capacitance measuring module 340 and a position determining module 350.
其中 , 电容测量模块 340用于测量平行电极中相邻电极之间 .的电 容, 如图 9中的 Cl、 C2 C8, 将测得的电容值提供给所述位置 确定模块 350。 确定微粒堆在所述设定方向上的边缘位置, 根据所述微粒堆的边缘位 置, 生成所述微粒堆的宽度信息。  The capacitance measuring module 340 is configured to measure the capacitance between adjacent electrodes in the parallel electrodes, such as Cl, C2 C8 in FIG. 9, to provide the measured capacitance value to the position determining module 350. An edge position of the particle stack in the set direction is determined, and width information of the particle pile is generated according to an edge position of the particle pile.
图 1所示的结果生成单元 400用于根据所述宽度信息及微粒堆宽 度与微粒浓度的对应关系, 得到微粒的浓度。 以图 6a和图 6b所示检 测单元 300为例, 可根据探测模块 330产生的阶跃信号阶跃之前的宽 度, 以及图 7b所示的微粒堆宽度与 〔粒浓度的对应关系, 可确定微粒 的浓度。 The result generating unit 400 shown in FIG. 1 is configured to calculate the width and the particle width according to the width The relationship between the degree and the particle concentration gives the concentration of the particles. Taking the detecting unit 300 shown in FIG. 6a and FIG. 6b as an example, the particle can be determined according to the width before the step signal generated by the detecting module 330, and the corresponding relationship between the particle stack width and the particle concentration shown in FIG. 7b. concentration.
其中, 介电电泳产生单元 200、 检测单元 300和结果生成单元 400 可构成本发明实施例中的微粒浓度的检测装置。  The dielectrophoresis generating unit 200, the detecting unit 300, and the result generating unit 400 may constitute a detecting device for the particle concentration in the embodiment of the present invention.
下面列举一个微粒浓度检测系统的一个具体应用示例:  A specific application example of a particle concentration detection system is listed below:
如图 10所示, 图 10为本发明中一个具体应用示例的结构示意图。 本应用示例中, 液体处理单元 100 包括: 注入阀 110、 清洗液存放器 120和注入泵 130。  As shown in FIG. 10, FIG. 10 is a schematic structural view of a specific application example in the present invention. In the application example, the liquid processing unit 100 includes: an injection valve 110, a cleaning liquid reservoir 120, and an injection pump 130.
介电电泳产生单元 200包括: 信号产生子模块 221和微流体芯片。 其中, 微流体芯片的结构如图 11a和图 l ib所示, 图 Tl a为仰视图, 图 l i b为正视图的剖视图。 该微流体芯片包括; 长方体溶液室 210、 位于 所述溶液室 210的一侧的平行电极 222和连接所述信号产生子模块 221 的行波信号和所述平行电极 222中的等相位电极的导线 223 ,且该微流 体芯片还包括至少一个用于溶液和清洗液流入的进口、 至少一个用于 废液流出的出口、 基底及壳体, 该微流体芯片能够被光线穿透, 并且 芯片的材料是不导电的, 例如, 该芯片可以由塑料、 玻璃或硅等制成。 此外, 该; ί啟流体芯片中的溶液室 210也可以为其它形状, 例如, 仰视 图也可为如图 11c所示的三角形。  The dielectrophoresis generating unit 200 includes: a signal generating sub-module 221 and a microfluidic chip. The structure of the microfluidic chip is shown in FIG. 11a and FIG. 1 ib, and FIG. 11a is a bottom view, and FIG. The microfluidic chip includes: a rectangular parallelepiped solution chamber 210, parallel electrodes 222 on one side of the solution chamber 210, and a traveling wave signal connecting the signal generating sub-module 221 and an isotropic electrode in the parallel electrode 222 223, and the microfluidic chip further comprises at least one inlet for the inflow of the solution and the cleaning solution, at least one outlet for the outflow of the waste liquid, the substrate and the casing, the microfluidic chip can be penetrated by the light, and the material of the chip It is not electrically conductive, for example, the chip can be made of plastic, glass or silicon. In addition, the solution chamber 210 in the fluid chip can also have other shapes. For example, the bottom view can also be a triangle as shown in Fig. 11c.
检测单元 300包括: 光源 310、 第一成像子模块 321、 第二成像子 模块 322和探测模块 330, 该探测模块 330为线性 CCD阵列。  The detecting unit 300 includes: a light source 310, a first imaging sub-module 321, a second imaging sub-module 322, and a detecting module 330, which is a linear CCD array.
具体应用时, 首先开启注入阀 110 的阀门, 使微粒溶液存放器中 的微粒溶液在外部动力的作用下注入介电电泳产生单元 200 中, 并在 微粒溶液注满介电电泳产生单元 200时, 关闭自身阀门。  In a specific application, the valve of the injection valve 110 is first opened, and the microparticle solution in the microparticle solution storage device is injected into the dielectrophoresis generating unit 200 under the action of external power, and when the microparticle solution is filled with the dielectrophoresis generating unit 200, Close your own valve.
信号产生子模块 221 产生多个不同相位的行波信号, 该行波信号 施加到微流体芯片中, 即通过导线 223连接至平行电极 222, 产生行波 电场。 下发生移动, 一段时间后, 形成微粒堆。 由光源 310、 第一成像子模块 321、 第二成像子模块 322 和线性 CCD阵列构成的检测单元 300对微粒堆进行检测, 生 Vis微粒堆的宽度 信息。 The signal generation sub-module 221 generates a plurality of traveling wave signals of different phases, and the traveling wave signals are applied to the microfluidic chip, that is, connected to the parallel electrodes 222 through the wires 223 to generate a traveling wave electric field. The movement takes place underneath, and after a while, a heap of particles is formed. The detecting unit 300 composed of the light source 310, the first imaging sub-module 321, the second imaging sub-module 322, and the linear CCD array detects the particle pile and generates width information of the Vis particle pile.
结果生成单元 400读取来自线性 CCD阵列的宽度信息, 即阶跃信 号, 根据该阶跃信号阶跃之前的宽度, 以及类似图 7b所示的微粒堆宽 度与微粒浓度的对应关系, 确定微粒的浓度。  The result generation unit 400 reads the width information from the linear CCD array, that is, the step signal, determines the particle based on the width before the step of the step signal, and the correspondence between the particle stack width and the particle concentration similar to that shown in FIG. 7b. concentration.
之后, 可停止产生行波电场, 由注入泵 130将清洗液存放器 120 中的清洗液泵入介电电泳产生单元 200 中, 以清洗介电电泳产生单元 200, 便于下次检测微粒浓度使用。  Thereafter, the traveling wave electric field can be stopped, and the cleaning liquid in the cleaning liquid reservoir 120 is pumped into the dielectrophoresis generating unit 200 by the infusion pump 130 to clean the dielectrophoresis generating unit 200 for the next detection of the particle concentration.
其中, 介电电泳产生单元 200、 检测单元 300和结果生成单元 400 可构成本发明实施例中的微粒浓度的检测装置。  The dielectrophoresis generating unit 200, the detecting unit 300, and the result generating unit 400 may constitute a detecting device for the particle concentration in the embodiment of the present invention.
以上对本发明实施例中微粒浓度的检测系统及装置进行了详细描 述, 下面再对本发明实施例中微粒浓度的检测方法进行详细描述。  The system and apparatus for detecting the particle concentration in the embodiments of the present invention have been described in detail above, and the method for detecting the particle concentration in the embodiment of the present invention will be described in detail below.
图 12为本发明实施例中微粒浓度的检测方法的示例性流程图。 如 图 12所示, 该流程包括如下步骤:  Figure 12 is an exemplary flow chart of a method of detecting particle concentration in an embodiment of the present invention. As shown in Figure 12, the process includes the following steps:
步骤 1201 , 在采样的微粒溶液中加入不均匀电场, 促使所述微粒 溶液中的微粒沿设定方向移动, 得到移动后的微粒堆。  Step 1201: adding a non-uniform electric field to the sampled particle solution to cause the particles in the particle solution to move in a set direction to obtain a moving particle pile.
本步骤中, 具体实现时, 可首先将预定体积的采样微粒溶液注入 溶液室中, 该溶液室的一侧或相向的两侧分布有多个平行的电极, 构 成平行电极。 之后, 产生 N个不同相位的行波信号, 通过导线将所述 N个不同相位的行波信号分别连接至所述平行电极中的同相位电极上, 产生行波电场。 之后, 微粒溶液中的活体微粒在行波电场的作用下, 即在行波电场中介电力的作用下, 进行运动, 形成微粒堆。  In this step, in a specific implementation, a predetermined volume of the sampled particle solution may be first injected into the solution chamber, and a plurality of parallel electrodes are distributed on one side or opposite sides of the solution chamber to form parallel electrodes. Then, N traveling wave signals of different phases are generated, and the N different phase traveling wave signals are respectively connected to the same phase electrodes in the parallel electrodes through a wire to generate a traveling wave electric field. Thereafter, the living particles in the fine particle solution are moved by the action of the traveling wave electric field, that is, under the action of the electric power of the traveling wave electric field, to form a particle pile.
其中, N为大于或等于 3的整数。  Where N is an integer greater than or equal to 3.
步骤 1202, 检测所述微粒堆在所述设定方向上的.宽度, 并生成所 述微粒堆的宽度信息。  Step 1202: Detect a width of the particle stack in the set direction, and generate width information of the particle pile.
本步骤中, 具体实现时, 可通过光源向溶液室发射光线, 之后接 收透过该溶液室的光线, 通过透镜组对光线进行光学处理, 根据光学 处理的光线, 确定所述溶液室中微粒堆在所述设定方向上的宽度, 并 生成对应的宽度信号。 或者, 本步骤中, 也可通过测量平行电极中相 邻电极之间的电容, 并 居相邻电极之间的电容变化, 确定微粒堆在 所述设定方向上的边缘位置, 根据所述微粒堆的边缘位置, 确定所述 微粒堆的宽度, 并生成对应的宽度信息。 In this step, in a specific implementation, the light source can emit light to the solution chamber, then receive the light passing through the solution chamber, optically process the light through the lens group, and determine the particle pile in the solution chamber according to the optically processed light. The width in the set direction and a corresponding width signal is generated. Alternatively, in this step, the phase in the parallel electrode can also be measured. a capacitance between adjacent electrodes, and a change in capacitance between adjacent electrodes, determining an edge position of the particle stack in the set direction, determining a width of the particle pile according to an edge position of the particle pile, and Generate corresponding width information.
步骤 1203 , 根据所述宽度信息及微粒堆宽度与微粒浓度的对应关 系, 得到微粒的浓度。  Step 1203: Obtain a concentration of the particles according to the width information and the correspondence between the particle pile width and the particle concentration.
具体实现时, 可收集所述微粒堆宽度信息, 然后根据存储的宽度 信息及微粒堆宽度与微粒浓度的对应关系, 得到微粒的浓度。  In a specific implementation, the particle pile width information may be collected, and then the concentration of the particles is obtained according to the stored width information and the corresponding relationship between the particle pile width and the particle concentration.
以上所述仅为本发明的较佳实施例而已, 并非用于限定本发明的 保护范围。 凡在本发明的精神和原则之内, 所作的任何修改、 等同替 换以及改进等, 均应包含在本发明的保护范围之内。  The above is only the preferred embodiment of the present invention and is not intended to limit the scope of the present invention. Any modifications, equivalents, and improvements made within the spirit and scope of the present invention are intended to be included within the scope of the present invention.

Claims

权 利 要 求 书 Claims
1、 一种微粒浓度的检测装置, 包括: 1. A device for detecting the concentration of particles, comprising:
一个介电电泳产生单元(200 ), 用于在预定体积的微粒溶液中形 成不均匀电场, 使得所述微粒溶液中的微粒沿设定方向移动, 形成微 粒堆;  a dielectrophoresis generating unit (200) for forming an inhomogeneous electric field in a predetermined volume of the microparticle solution, so that the particles in the microparticle solution move in a set direction to form a microparticle stack;
一个检测单元 ( 300 ), 用于检测得到所述微粒堆在所述设定方向 上的宽度信息;  a detecting unit (300) for detecting width information of the particle pile in the set direction;
一个结果生成单元 (400 ), 接收所述微粒堆宽度信息, 根据所述 宽度信息及存储的微粒堆宽度与微粒浓度的对应关系, 得到微粒的浓 度。  A result generating unit (400) receives the particle pile width information, and obtains a concentration of the particles based on the width information and the correspondence relationship between the stored particle pile width and the particle concentration.
2、如权利要求 1所述的装置,其中,所述介电电泳产生单元(200 ) 包括:  2. Apparatus according to claim 1 wherein said dielectrophoresis generating unit (200) comprises:
一个溶液室 (210 ), 具有一个预定的容积, 用于盛放微粒溶液; 一个信号产生子模块(221 ), 用于产生 N个不同相位的行波信号, N为大于或等于 3的整数;  a solution chamber (210) having a predetermined volume for holding a particulate solution; a signal generating sub-module (221) for generating N different phase traveling wave signals, N being an integer greater than or equal to 3;
多个平行电极(222 ), 包括位于所述溶液室 (210 )的一侧或相向 的两侧的多个平行的电极;  a plurality of parallel electrodes (222) including a plurality of parallel electrodes on one side or opposite sides of the solution chamber (210);
N个导线 (223 ), 用于将所述 N个不同相位的行波信号分别与所 述平行电极(222 ) 中的同相位电极相连, 以使其产生行波电场。  N wires (223) are used for respectively connecting the N different phase traveling wave signals to the same phase electrodes in the parallel electrode (222) to generate a traveling wave electric field.
3、 如权利要求 2所述的装置, 其特征在于: 所述的各行波信号为 正弦信号, 其角频率为 100Hz至 100 MHz, 其振幅为 0 至 100 伏, 各信号之间的相位差为 360° / N。  3. The apparatus according to claim 2, wherein: each of said traveling wave signals is a sinusoidal signal having an angular frequency of 100 Hz to 100 MHz, an amplitude of 0 to 100 volts, and a phase difference between each signal of 360 ° / N.
4、 如权利要求 2 所述的装置, 其特征在于: 所述的溶液室(210 ) 至少局部由透明材料制成; 所述电极(222 )是由铟锡氧化物制成。  4. Apparatus according to claim 2, wherein: said solution chamber (210) is at least partially made of a transparent material; said electrode (222) is made of indium tin oxide.
5、如权利要求 2或 4 所述的装置,其特征在于,所述检测单元( 300 ) 包括:  The device according to claim 2 or 4, wherein the detecting unit (300) comprises:
一个光源 (310 ), 用于向所述介电电泳产生单元(200 ) 的溶液室 ( 210 )发射光线;  a light source (310) for emitting light to a solution chamber (210) of the dielectrophoresis generating unit (200);
一个光学处理模块(320 ), 用于接收透过所述溶液室 (210 ) 的光 线, 生成一维或二维图形光线; An optical processing module (320) for receiving light transmitted through the solution chamber (210) Line, generating one-dimensional or two-dimensional graphic light;
一个探测模块(330 ), 用于根据所述光学处理模块(320 )处理后 的光线, 生成所述溶液室(210 ) 中微粒堆在所述设定方向上的宽度信  a detecting module (330), configured to generate, according to the processed light of the optical processing module (320), a width letter of the particle stack in the solution chamber (210) in the set direction
6、 如权利要求 5所述的装置, 其特征在于, 所述探测模块( 330 ) 为具有线性电荷耦合器件阵列的一维探测模块; 所述光学处理模块6. The apparatus according to claim 5, wherein the detecting module (330) is a one-dimensional detecting module having a linear charge coupled device array; the optical processing module
( 320 ) 包括: ( 320 ) Includes:
第一成像子模块 (321 ), 其具有至少一个光学透镜, 用于接收透 过所述溶液室 (210 ) 的光线, 并由此形成二维图形光线; 和,  a first imaging sub-module (321) having at least one optical lens for receiving light that passes through the solution chamber (210) and thereby forming a two-dimensional pattern of light;
第二成像子模块 ( 322 ), 其具有一个柱面透镜, 用于将所述二维 图形光线转换为一维图形光线。  A second imaging sub-module (322) having a cylindrical lens for converting the two-dimensional graphic light into a one-dimensional graphic light.
7、 如权利要求 5所述的装置, 其特征在于, 所述探测模块( 330 ) 为具有平面电荷耦合器件阵列的二维探测模块; 所述光学处理模块 7. The apparatus according to claim 5, wherein the detecting module (330) is a two-dimensional detecting module having a planar charge coupled device array; the optical processing module
( 320 ) 包括: 第一成像子模块(321 ), 其具有至少一个光学透镜, 用 于接收透过所述溶液室 (210 ) 的光线, 并由此形成二维图形光线。 (320) comprising: a first imaging sub-module (321) having at least one optical lens for receiving light transmitted through the solution chamber (210) and thereby forming a two-dimensional pattern of light.
8、 如权利要求 5所述的装置, 其特征在于, 所述探测模块( 330 ) 为光电二级管阵列或光电倍增管或位置传感器探测器或光敏电阻。  8. The apparatus according to claim 5, wherein the detecting module (330) is a photodiode array or a photomultiplier tube or a position sensor detector or a photoresistor.
9、 如权利要求 2 所述的装置, 其特征在于, 所述检测单元(300 ) 包括:  9. The device according to claim 2, wherein the detecting unit (300) comprises:
一个电容测量模块( 340 ), 用于测量相邻平行电极( 222 )之间的 电容;  a capacitance measuring module (340) for measuring a capacitance between adjacent parallel electrodes (222);
一个位置确定模块( 350 ), 接收测得的所述相邻平行电极之间的 各个电容值, 并根据所述电容值的变化, 确定微粒堆在所述设定方向 上的边缘位置, 并据此生成所述微粒堆的宽度信息。  a position determining module (350), receiving the measured respective capacitance values between the adjacent parallel electrodes, and determining an edge position of the particle stack in the set direction according to the change in the capacitance value, and according to This generates width information for the particle stack.
10、 如权利要求 1 所述的装置, 其特征在于, 所述结果生成单元 ( 400 )是一个具有存贮和计算功能的处理器。  10. Apparatus according to claim 1 wherein said result generating unit (400) is a processor having storage and computing functions.
1 1、 如权利要求 1 所述的装置, 其特征在于, 所述介电电泳产生 单元( 200 ) 与一个微粒溶液存放器之间通过一个具有注入阀 ( 1 10 ) 的液体处理单元(100 )连接。  1 1. The device according to claim 1, wherein a liquid processing unit (100) having an injection valve (1 10 ) is passed between the dielectrophoresis generating unit (200) and a particulate solution storage device. connection.
12、 如权利要求 1 1 所述的装置, 其特征在于, 所述液体处理单元 ( 100 )进一步包括: 一个清洗液存放器 (120 )和一个将清洗液导入 所述介电电泳产生单元(200 ) 的注入泵 (130 )。 12. The device according to claim 11, wherein the liquid processing unit (100) further comprising: a cleaning liquid reservoir (120) and an infusion pump (130) for introducing the cleaning liquid into the dielectrophoresis generating unit (200).
13、 一种微粒浓度的检测方法, 包括:  13. A method for detecting the concentration of particles, comprising:
,在预定体积的采样微粒溶液中施加一个由多个平行电极生成的行 波电场, 使得所述微粒溶液中的微粒沿设定方向移动, 形成微粒堆; 检测得到所述微粒堆在所述设定方向上的宽度信息;  Applying a traveling wave electric field generated by a plurality of parallel electrodes in a predetermined volume of the sampled particle solution, so that the particles in the particle solution move in a set direction to form a particle pile; and detecting that the particle pile is in the set Width information in a fixed direction;
收集所述微粒堆宽度信息, 根据所述宽度信息及微粒堆宽度与微 粒浓度的对应关系, 得到微粒的浓度。  The particle pile width information is collected, and the concentration of the particles is obtained based on the width information and the correspondence relationship between the particle pile width and the particle concentration.
14、 如权利要求 13所述的方法, 其特征在于, 所述检测得到所述 微粒堆在所述设定方向上的宽度信息包括:  The method according to claim 13, wherein the detecting the width information of the particle pile in the set direction comprises:
向所述溶液室发射光线;  Emitting light to the solution chamber;
光学透镜接收透过所述溶液室的光线, 并形成图形光线; 根据所述图形光线, 确定所述微粒堆在所述设定方向上的宽度。 The optical lens receives light transmitted through the solution chamber and forms a patterned light; and determines a width of the particle stack in the set direction based on the graphic light.
15、 如权利要求 13所述的方法, 其特征在于, 所述检测得到所述 微粒堆在所述设定方向上的宽度信息包括: The method according to claim 13, wherein the detecting the width information of the particle pile in the set direction comprises:
测量所述平行电极中相邻电极之间的电容;  Measuring a capacitance between adjacent ones of the parallel electrodes;
根据相邻电极之间的电容变化, 确定^:粒堆在所述设定方向上的 边缘位置, 并由此确定所述^:粒堆的宽度。  According to the change in capacitance between adjacent electrodes, the edge position of the grain pile in the set direction is determined, and thereby the width of the grain pile is determined.
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