CN107976402A - It is a kind of based on the modularization bio-analysis system of droplet array chip and its application - Google Patents
It is a kind of based on the modularization bio-analysis system of droplet array chip and its application Download PDFInfo
- Publication number
- CN107976402A CN107976402A CN201710978928.0A CN201710978928A CN107976402A CN 107976402 A CN107976402 A CN 107976402A CN 201710978928 A CN201710978928 A CN 201710978928A CN 107976402 A CN107976402 A CN 107976402A
- Authority
- CN
- China
- Prior art keywords
- chip
- module
- permanent magnet
- control module
- modularization
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/01—Arrangements or apparatus for facilitating the optical investigation
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
Landscapes
- Physics & Mathematics (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Automatic Analysis And Handling Materials Therefor (AREA)
- Investigating, Analyzing Materials By Fluorescence Or Luminescence (AREA)
- Apparatus Associated With Microorganisms And Enzymes (AREA)
Abstract
The invention discloses a kind of based on the modularization bio-analysis system of droplet array chip and its application.The system includes at least one set of functional module group and more than one battery and electronic circuit module；Functional module group includes optical detecting module, chip motion control module, magnetic field control module and temperature control modules；Optical detecting module, chip motion control module, magnetic field control module and temperature control modules are connected with battery and electronic circuit module respectively, optical detecting module is connected with chip motion control module, and magnetic field control module and temperature control modules are located at the lower section of chip motion control module.The application of modularization bio-analysis system based on droplet array chip, applied to biological detection.The system have the advantages that it is easy to operate, using flexible, information flux is high, the degree of automation is high, be very suitable for the development of basic unit clinic, diagnosis by bed, Site Detection and the limited regional biological detection of medical resource.
Description
Technical field
The invention belongs to bioanalysis and technical field of medical examination, more particularly to a kind of mould based on droplet array chip
Block bio-analysis system and its application.
Background technology
Bioanalysis and medical test generally comprise multiclass detection content, as biochemistry detection, detection of nucleic acids, immune detection,
Microorganism detection etc..At present, these detection contents use mutually independent analysis system mostly, and analytic process is related to multistep
Operation.Therefore, traditional bioanalysis and medical test are more demanding not only for place, operator quality, and face
Cumbersome, analysis time is long and the problem of testing cost is high.
There is the Microfluidic droplet technology (droplet microfluidics) developed in the recent period analysis throughput height, sample to disappear
Low advantage is consumed, is the powerful for realizing quick bio medical analysis.Although Microfluidic droplet analytical technology achieves important
Progress, but the technology still has some aspects to be left to be desired, such as：(1) integrate and test the balance between flux in function：Mesh
Before, most fully integrated flow control apparatus that decline can only analyze a sample every time, and high throughput analysis device then fails to integrate
The whole process of foranalysis of nucleic acids, therefore integrated differential analysis apparatus of the development with higher flux then can more preferably meet clinical practice
Demand；(2) easy flexible liquid transfer scheme is needed：The quantitative and positioning transfer of reagent, sample is that micro-fluidic chip faces
A significant challenge；Although having reported a series of chip Micropump micro-valve technologies before, due to high processing costs, control system
The problems such as system is complicated and be difficult to promote；(3) chip-test tube docking is solved the problems, such as：It is stored in how reagent and sample in test tube draw
It is that micro-fluidic chip moves towards practical medical using another problem for needing to solve in the chip for entering closing；In analysis often
Batch sample operates, and realizes that chip-test tube docking is the required of automatic fluid transfer operation；(4) chip manufacture cost is reduced：
Since micro-fluidic chip needs the micro-processing technology of specialty mostly, thus manufacture cost and remain high, seriously affect the technology
Popularization.The solution of the above problem, it will help promote Microfluidic droplet analytical technology to move towards practical application.
The content of the invention
The shortcomings that primary and foremost purpose of the present invention is to overcome the prior art and deficiency, there is provided one kind is based on droplet array chip
Modularization bio-analysis system.
Another object of the present invention is to provide answering for the modularization bio-analysis system based on droplet array chip
With.
The purpose of the present invention is achieved through the following technical solutions：A kind of modularization bioanalysis based on droplet array chip
System, including at least one set of functional module group and at least one battery and electronic circuit module；Functional module group is examined including optics
Survey module, chip motion control module, magnetic field control module and temperature control modules；Optical detecting module, chip motion control
Module, magnetic field control module and temperature control modules are connected with battery and electronic circuit module respectively, optical detecting module and core
The connection of piece motion-control module, magnetic field control module and temperature control modules are located at the lower section of chip motion control module；
Chip motion control module includes motor and the chip carrier being connected with motor；
Optical detecting module includes photoelectric detector, Optical Dark Solitary Pulse storehouse and optical electrical excitation control and signal acquisition processing circuit；
Optical Dark Solitary Pulse storehouse is body structure, and chip carrier entrance is set in the bottom in Optical Dark Solitary Pulse storehouse, and photoelectric detector is controlled with optical electrical excitation
It is connected with signal acquisition processing circuit；Photoelectric detector is located at the top of chip carrier entrance；
Magnetic field control module includes magnet and the circuit that is connected with magnet, magnet be vertically installed in chip carrier top or
Lower section；
If temperature controller and be connected with temperature controller some separate that temperature control modules include dry passage
Heating module, heating module is arranged at the lower section of chip carrier.
Specifically, the effect of the chip motion control module is driving chip entry/exit Optical Dark Solitary Pulse storehouse, chip with respect to magnetic
Control module and temperature control modules do relative motion, chip relative to the relative motion of fluorescence detector and drop with
The relative motion of chip.Specifically：Driving chip does the action of entry/exit Optical Dark Solitary Pulse storehouse to facilitate placement/replacement, the sample of chip
The loading of product/reagent：Driving chip relative magnetic field control module performs relative motion movement, fusion, division to realize drop etc.
Operation：Driving chip relative temperature control module is performed relative motion to be followed with the heating, temperature switching or heat for realizing chip/drop
Ring, the heat of drop trigger fusion etc.；The relative motion of driving chip and fluorescence detector is to realize that chip detection zone and optics are examined
Survey the scan operation of the alignment or fluorescence detector of device to chip detection zone；Driving chip is with respect to liquid drop movement to realize drop
Vibration mixes operation.
The structure of the chip carrier is preferably as follows：Trailing arm, side trailing arm are respectively arranged with the both sides of chip carrier
Be provided with the half opening sliding slot for cutting ferrule optical axis, opposite side trailing arm be provided with position limit arm, sliding block bolt, sliding block and parallel to
The through hole of optical axis direction, chip carrier are installed in place the top that state lower limit arm is placed exactly in screw, and sliding block is inserted by sliding block
Pin is fixed on chip carrier；Side of the sliding block away from chip carrier is provided with the convex tooth of the sliding block contacted with screw, the convex tooth of sliding block
Move towards parallel to wire rod thread groove precession direction, so that, under motor effect, screw rotation, band movable slider, and then drive core
Piece bracket is run.
The chip motion control module further includes the motion base for being used to support chip carrier；The one of motion base
Side sets screw, screw and motor coaxle；The optical axis parallel with screw is set respectively in the both sides of motion base；
The motion base further includes magnetic field control module interface and temperature control modules interface, and magnetic field control module connects
Mouth and temperature control modules interface are arranged at the lower section of chip carrier space.
The motor is preferably stepper motor or servomotor.
Specifically, the optical detecting module is used for the optical signalling in detection chip drop.When described based on liquid
The modularization bio-analysis system of drop array chip enables or during using fluoroscopic examination, the mould based on droplet array chip
Block bio-analysis system also includes photoelectricity exciter, photoelectricity exciter and optical electrical excitation control and signal acquisition processing circuit
Connection, positioned at the top of chip carrier entrance；Photoelectricity exciter is fluorescence excitation module, and it includes fluorescent light source, excitation to filter
Piece and transmitting optical filter, along light direction of advance, fluorescent light source, exciter filter, transmitting optical filter and photoelectric detector according to
Secondary arrangement, light path are 45 ° of oblique fire light path designs or coaxial optical path design, and fluorescent light source is LED bulb or LED bulb array；Institute
The optional collector lens of transmitting optical filter stated, dichroic filter disc etc..When the modularization biology based on droplet array chip
Analysis system enables or during using chemiluminescence detection, and photoelectricity exciter does not enable or default.
Ccd image sensor, cmos image sensor, photomultiplier, photoelectricity two can be selected in the photoelectric detector
Pole pipe array or other electro-optic detector parts.
Specifically, the magnetic field control module is used for the movement for driving magnetic particle.The magnet for permanent magnet or
Electromagnet.When the magnet is permanent magnet, the circuit is drive circuit；Permanent magnet moveable vertical is arranged at chip carrier
Above or below, it is preferably lower section, so as to be pasted by permanent magnet on the direction perpendicular to chip plane close or remote from dynamic
Make, the size of the presence or absence of magnetic field and intensity suffered by control chip respective regions, and then in control chip drop magnetic particle turn
Move, aggregation or scattered.When the magnet is electromagnet, circuit circuit in order to control；Electromagnet fixed vertical is arranged at
Be preferably lower section above or below chip carrier, thus by control the current direction of electromagnet or electromagnetic array, size or
Whether there is the transfer for carrying out magnetic particle in control chip drop, aggregation or scattered.
The number of the permanent magnet is more than one；For more than 2 when, formed permanent magnet array.
The number of the electromagnet is more than one；For more than 2 when, formed electromagnet array.
When the magnet is permanent magnet, the magnetic field control module further includes permanent magnet bracket, optical axis, base, silk
Thick stick, motor, slide bar, sliding block, convex tooth；Permanent magnet is arranged on permanent magnet bracket；Leading screw leads to the motor coaxle in circuit, motor
Electric machine support is crossed to be fixed on base；One end of slide bar is fixed on base, and sliding block passes through slide bar, is relatively fixed on slide bar,
Sliding block is connected with screw；The through hole passed through for optical axis is provided with the both sides of permanent magnet bracket, the lower end of optical axis is fixed
In on base, permanent magnet bracket is relatively fixed on base by optical axis；Convex tooth is arranged on a side of permanent magnet bracket,
Convex tooth is connected with sliding block；Under motor effect, screw rotary motion, drives slide block movement, and then drives permanent magnet movement of bracket.
The motor is preferably stepper motor.
Specifically, the temperature control modules are to the temperature in control chip reaction tank.The heating module bag
Heat-conducting block, temperature sensor, heater and heat-proof device are included, the flat heated of heat-conducting block is parallel to be attached at chip baseplane, temperature
Degree sensor is arranged on the middle section of the flat heated of heat-conducting block, and heater is embedded in heat-conducting block or with sandwich in heat-conducting block
Between heat-proof device；When heater is embedded in heat-conducting block, the bottom surface on heat-conducting block parallel to flat heated be attached at every
Thermal；Heat-proof device is adiabatic base；Or it is arranged on heat dissipation base comprising heat dissipation base and radiator fan, radiator fan
Near.When the modularization bio-analysis system based on droplet array chip uses heated at constant temperature mode, temperature control
Module enables or using one group of temperature controller passage and heating module, heat-conducting block bottom surface connects adiabatic bottom in heating module at this time
Seat, the size of current or heater voltage of heater are supplied to by temperature controller according to the control of the signal of temperature sensor feedback
The length and frequency of make-and-break time, to reach or maintain design temperature；When system, using alternating temperature mode of heating, (such as polymerase chain is anti-
Should) when, temperature control modules enable or using one group of temperature controller passage and heating modules, at this time heat-conducting block in heating module
Bottom surface connects heat dissipation base, is supplied to the electric current side of heater according to the control of the signal of temperature sensor feedback by temperature controller
To and size, to reach or maintain predetermined temperature；When system, using constant temperature heating circulating-heating mode, (fluid motion crosses over multiple perseverances
Warm area) when, temperature control modules enable or using multigroup temperature controller passage and heating module, at this time heat conduction in heating module
The adiabatic base of block bottom surface connection, is controlled according to the signal of temperature sensor feedback in each heating module by temperature controller and provided
To the size of current of corresponding heater or the length and frequency of heater voltage make-and-break time, to reach or maintain predetermined temperature.
When the heat-proof device is heat dissipation base and radiator fan, the heater is preferably semiconductor chilling plate.
The modularization bio-analysis system based on droplet array chip further includes intelligent terminal, intelligent terminal
Equipment is connected with optical detecting module.
The mode of the connection includes wired connection and radio connection.
The intelligent terminal includes computer and mobile phone.
The application based on the modularization bio-analysis system of droplet array chip in biological detection, including it is as follows
Step：
(1) after droplet array chip adds reaction reagent and sample, droplet array chip is positioned on chip carrier,
Chip carrier enters Optical Dark Solitary Pulse storehouse；
(2) droplet array chip motion to temperature control modules or magnetic field are driven to control by chip motion control module
Above module, according to actual demand, the reaction temperature of set temperature control module, and temperature control modules and magnetic field control mould
The priority method of operation of block；
(3) optical detecting module starts, and is detected；
(4) reaction terminates, and chip export, removes droplet array chip.
The droplet array chip includes some micro- pool structures of parallel series connection；Pass through slit phase between micro- pond of series connection
Unicom；Micro- pond completely or partially has Open architecture, i.e. top surface opening is led directly to the external world.
The drop bioanalysis chip further includes hydrophobic coating, and hydrophobic coating is arranged on micro- pond and the surface of slit.
The hydrophobic coating is preferably Teflon AF1600 hydrophobic coatings.
The material of the droplet array chip is preferably glass, plastics, polytetrafluoroethylene (PTFE), polypropylene or silica gel.
The area of the droplet array chip is preferably 10~100 square centimeters.
The present invention technical principle be：In micro- pond with hydrophobic surface, order loads oil phase and aqueous phase solution, due to
Surface tension effect forms water-in-oil type drop.Connected between micro- pond by slit, under surface tension effects, oil phase can fill
Slit and water phase then cannot.When containing magnetic grain in the drop of micro- pond carrying, external magnetic field driving magnetic grain movement can be utilized；When
When magnetic force suffered by magnetic grain is more than oil water interfacial tension, magnetic grain can break through oil-water interfaces and split off from stoste drop；Point
The magnetic grain drop separated out can enter another drop under field drives or be included by slit into another micro- pond
Drop.Therefore, manipulated with reference to drop and magnetic, can complete detection object capture involved by bioanalysis, the washing of magnetic grain (and
Sample elution) and reaction；The reaction signal in drop is finally detected, detection object and content are determined with this.In this way, it can utilize
Open drop chip is basic operation platform, realizes different analytic functions in disparate modules with similar operating process.
Using wired or wireless communication modes, multiple modules can be manipulated with a terminal, neatly tackle different detection demands.
The present invention is had the following advantages relative to the prior art and effect：
(1) modularization bio-analysis system provided by the invention, can be by different types of detection content in same system
Interior completion, meets the parallel parsing of single sample multi-target analysis and batch sample.This system has leads to using flexible, information
Measure the advantages of high.
(2) modularization bio-analysis system provided by the invention uses open droplet array chip, this chip manufacture
Cost is extremely low.
(3) reagent/specimen whole process exists with water in oil form on the open droplet array chip, and evaporation loss is small, anti-
Conditional stability is answered, and allows sample analysis volume flexibility and changeability, reagent consumption small.
(4) modularization bio-analysis system chips analysis uses fully integrated mode, easy to operate, and analysis is quick.
(5) the modularization bio-analysis system have it is compact it is portable, energy consumption is small, the degree of automation is high, be very suitable for
Diagnosed by basic unit clinic, bed, the development for the regional biological detection that Site Detection and medical resource are limited.
Brief description of the drawings
Fig. 1 is the structure diagram of the modularization bio-analysis system based on droplet array chip.
Fig. 2 is the structure diagram of optical detecting module.
Fig. 3 A-3D display chip motion-control modules；Wherein, Fig. 3 A are the top views of chip motion module, and Fig. 3 B are fortune
The structure diagram of dynamic base, Fig. 3 C are the structure diagrams of chip carrier, and Fig. 3 D are the structure diagrams of sliding block.
Fig. 4 A-4B show magnetic field control module；Wherein, Fig. 4 A are the front view of magnetic field control module, and Fig. 4 B are controlled for magnetic field
Molding block broken away view.
Fig. 5 A are the broken away views of temperature control modules, are not temperature control modules containing heat dissipation base and radiator fan, Fig. 5 B
Another visual angle broken away view.
Fig. 6 is the fundamental diagram of the modularization bio-analysis system based on droplet array chip.
Fig. 7 is suitable for the structure diagram of the droplet array chip of the modularization bio-analysis system；Wherein, dotted line frame
Shown A-E regions respectively are the micro- pond of sample, the micro- pond 1 of washing, the micro- pond 2 of washing, the micro- pond of elution, the micro- pond of reaction.
Fig. 8 is the structure diagram of combined modularization bio-analysis system.
Fig. 9 is the structure diagram of network distribution type modularization bio-analysis system.
1 it is optical detecting module, 2 be chip motion control module, 3 be magnetic field control module, 4 is temperature control modules, 5
It is droplet array chip for battery and electronic circuit module, 6,7 be smart mobile phone, 8 is laptop；1-1 is Photoelectric Detection
Device, 1-2 are photoelectricity testing part installation interface, 1-3 is transmitting optical filter, 1-4 is excitation source installation cartridge, 1-5 is sharp
Light emitting source, 1-6 are exciter filter, 1-7 is Optical Dark Solitary Pulse storehouse；2-1 is chip carrier, 2-2 is motion base, 2-3 is screw, 2-
4 be motor, 2-5 is optical axis, 2-6 is magnetic field control module interface, 2-7 is temperature control modules interface, 2-8 is magnet installation
Storehouse, 2-9 are motor installation position, 2-10 is half opening sliding slot, 2-11 is through hole, 2-12 is position limit arm, 2-13 is sliding block bolt, 2-
14 be sliding block, 2-15 is sliding block card slot, 2-16 is the convex tooth of sliding block；3-1 is permanent magnet array, 3-2 is permanent magnet array bracket, 3-
3 be optical axis, 3-4 is base, 3-5 is screw, 3-6 is slide bar, 3-7 is stepper motor, 3-8 is stepping motor bracket, 3-9 is sliding
Block, 3-10 are convex tooth；4-1 is heat-conducting block, 4-2 is temperature sensor, 4-3 is heater, 4-4 is adiabatic base, 4-5 is heat dissipation
Base, 4-6 are radiator fan.
Embodiment
With reference to embodiment and attached drawing, the present invention is described in further detail, but embodiments of the present invention are unlimited
In this.
Embodiment 1
As shown in Figure 1, a kind of modularization bio-analysis system based on droplet array chip, including optical detecting module 1,
Chip motion control module 2, magnetic field control module 3, temperature control modules 4 and battery and electronic circuit module 5.Optical detection mould
Block 1, chip motion control module 2, magnetic field control module 3 and temperature control modules 4 be can independent operating control subsystem,
And provide electric power support, Collaborative Control by battery and electronic circuit module 5.Optical detecting module 1, magnetic field control module 3 and temperature
Degree control module 4 is connected with chip motion control module 2 respectively.
As shown in Fig. 2, optical detecting module 1 includes photoelectricity testing part 1-1, photoelectricity testing part installation interface 1-2, hair
Penetrate optical filter 1-3, excitation source installation cartridge 1-4, excitation source 1-5, exciter filter 1-6, Optical Dark Solitary Pulse storehouse 1-7 and optical electrical
Excitation control and signal acquisition processing circuit.Photoelectricity testing part 1-1 and photoelectric converter installation interface 1-2 are located at Optical Dark Solitary Pulse storehouse
The top of 1-7, its act on be connect and fixed photoelectricity testing part 1-1 and excitation source 1-5 respectively with optical electrical excitation control with
Signal acquisition processing circuit connects.Excitation source installation cartridge 1-4 is installed on the inner side of Optical Dark Solitary Pulse storehouse 1-7, excitation source
1-5 is installed in excitation source cartridge 1-4, and exciter filter 1-6 is located at the front of excitation source 1-5, and excitation source 1-5, swash
The mounting surface of hair optical filter 1-6 irradiates downwards with launching the plane of optical filter 1-3 in 45 degree of angles, when being detected, light
It can be irradiated to and be positioned on the droplet array chip 6 of Optical Dark Solitary Pulse storehouse 1-7 bottoms.The photoelectric detector is preferably cmos image
Sensor or ccd image sensor.The excitation source is preferably blue-ray LED array or blue-ray LED area source.
As shown in figs. 3 a-3d, chip motion control module 2 mainly carries out motion in one dimension comprising motor and its driving
Chip carrier；Specifically comprising chip carrier 2-1, motion base 2-2, screw 2-3, motor 2-4, optical axis 2-5, magnetic field control module
Interface 2-6, temperature control modules interface 2-7, magnet installation storehouse 2-8, motor installation position 2-9, half opening sliding slot 2-10, through hole 2-
11st, position limit arm 2-12, sliding block bolt 2-13, sliding block 2-14, sliding block card slot 2-15 and the convex tooth 2-16 of sliding block.Screw 2-3 is arranged on
The side of motion base 2-2, motor 2-4 are fixed on motion base 2-2 by motor installation position 2-9, motor 2-4 and screw 2-
3 is coaxial, and optical axis 2-5 is arranged at the both sides of motion base 2-2, parallel with screw 2-3 respectively.Chip carrier 2-1 is arranged at movement
On base 2-2, chip carrier 2-1 does motion in one dimension along parallel optical axis 2-5 directions, sets and is used in the center of chip carrier 2-1
The card slot of droplet array chip 6 is placed, trailing arm is respectively arranged with the both sides of chip carrier 2-1, side trailing arm, which is provided with, to be used for
The half opening sliding slot 2-10 of cutting ferrule optical axis 2-5, opposite side trailing arm are provided with the through hole 2-11 parallel to optical axis 2-5 directions, and
Position limit arm 2-12, sliding block bolt 2-13 and sliding block 2-14, are installed in place state lower limit arm 2-12 and are placed exactly in the upper of screw 2-3
Side, sliding block 2-14 are fixed on chip carrier 2-1 by sliding block bolt 2-13, and the side that sliding block 2-14 is located at screw 2-3 has two
The section convex tooth 2-16 of sliding block, the convex tooth 2-16 trends of the sliding block are parallel to screw 2-3 thread groove precessions direction, and sliding block 2-14 is away from silk
There is circular socket in the side of bar 2-3, and barrel band is matched with circular socket 2-13, therebetween with spring control room away from.Movement
Magnetic field control module interface 2-6 and temperature control modules interface 2- is set positioned at the underface in chip motion space on base 2-2
7.Motor is stepper motor or servomotor.Magnet installation storehouse 2-8 is arranged at the bottom of motion base 2-2, for magnetic array
Accurate installation is protected with operation.
As illustrated in figures 4 a and 4b, magnetic field control module 3 is installed on the lower section of chip motion control module 2, includes permanent magnet
Array 3-1, permanent magnet array bracket 3-2, optical axis 3-3, base 3-4, screw 3-5, slide bar 3-6, stepper motor 3-7, stepping electricity
Machine support 3-8, sliding block 3-9, convex tooth 3-10.Permanent magnet array 3-1 is set in qually spaced in the round of permanent magnet array bracket 3-2
In, the round both sides of permanent magnet array bracket 3-2 are respectively arranged with through hole.Optical axis 3-3 passes through above-mentioned through hole, its lower end is fixed on
In the mounting hole of base 3-4.The stepping motor bracket 3-8 and guide rail for being used to support stepper motor 3-7 are fixed on base 3-4,
Stepper motor 3-7 and screw 3-5 are coaxial, and the convex tooth 3-10 on permanent magnet array bracket 3-2 is stuck in the card slot of sliding block 3-9, sliding
One end of bar 3-6 is fixed on base 3-4, and sliding block 3-9 is provided with for the through hole through slide bar 3-6, is relatively fixed to slide bar
The sliding block 3-9 of 3-6 can be moved along screw 3-5.Moved up and down by permanent magnet array 3-1 close to or away from droplet array chip,
Control is applied to the presence or absence of magnetic field and size on droplet array chip, and coordinates the motion in one dimension of said chip motion module to realize
The Magnetic driving and magnetic of drop are operated.
Temperature control modules 4 include some temperature control channels or temperature controller and the heated mould being attached thereto accordingly
Group is formed.As shown in Figure 5 A and 5B, heating module includes heat-conducting block 4-1, temperature sensor 4-2, heater 4-3, heat-proof device；
Heat-proof device is adiabatic base 4-4, or includes heat dissipation base 4-5 and the radiator fan 4- being arranged near heat dissipation base 4-5
6.The flat heated of heat-conducting block 4-1 is parallel to be attached at chip baseplane, and temperature sensor 4-2 is arranged on the heating of heat-conducting block 4-1
The middle section of plane, heater 4-3 are embedded in heat-conducting block 4-1 or with sandwich between heat-conducting block 4-1 and heat-proof device；When
When heater 4-3 is embedded in heat-conducting block 4-1, the bottom surface on heat-conducting block 4-1 parallel to flat heated is attached at heat-proof device.Such as
Shown in Fig. 5 A, thermostatic type heating module is connected successively by heat-conducting block 4-1, temperature sensor 4-2, heater 4-3 and thermal insulation base 4-4
Composition is connect, wherein preferable temperature sensor 4-2 is NTC film resistors or thermocouple, preferable heater 4-3 is thin for polyamide
Film heater or aluminium oxide ceramics heating plate.As shown in Figure 5 B, temperature swing type heating module is by heat-conducting block 4-1, temperature sensor 4-
2nd, heater 4-3, heat dissipation base 4-5 and radiator fan 4-6 are formed, wherein heat-conducting block 4-1, temperature sensor 4-2, heater 4-
3 and heat dissipation base 4-5 is sequentially connected, and radiator fan 4-6 is arranged on beside heat dissipation base 4-5；Heat-conducting block 4-1 and heat dissipation base 4-
5 be preferably aluminium material, and temperature sensor 4-2 is preferably thermocouple, and heater 4-3 is preferably TE semiconductor chilling plates.
The operation principle of modularization bio-analysis system based on droplet array chip is as shown in fig. 6, chip motion control
Molding block 2 controls droplet array chip 6 into the Optical Dark Solitary Pulse storehouse 1-7 of optical detecting module 1；When the drop that micro- pond of chip carries
In when containing magnetic grain, external magnetic field control module 3 can be utilized to drive the movement of magnetic grain；When the magnetic force suffered by magnetic grain is more than grease
During interfacial tension, magnetic grain can break through oil-water interfaces and split off from stoste drop；The magnetic grain drop isolated is in field drives
Another drop or the drop included by slit into another micro- pond can be entered down.Therefore, with reference to drop and magnetic
Manipulation, can complete the detection object capture involved by bioanalysis, magnetic grain washing (and sample elution) and react；Finally utilize
Optical detecting module 1 detects the reaction signal in drop, and detection object and content are determined with this.
It is suitable for the droplet array chip of the modularization bio-analysis system as shown in fig. 7, joining micro- pond comprising some string formations；
It is connected per string formation between micro- pond of connection by slit；Micro- pond completely or partially has Open architecture.Preferable structure is as follows：
Join micro- pond containing 15 string formations, micro- pond is joined per string formation and contains 5 micro- pond A-E, respectively the micro- pond of counter sample, the micro- pond 1 of washing, the micro- pond of washing
2nd, micro- pond, the micro- pond of reaction are eluted.
Embodiment 2
A kind of combined modularization bio-analysis system, as shown in figure 8, including it is some set independent operatings functional module groups and
Battery and electronic circuit module 5, functional module group are connected with battery and electronic circuit module 5 respectively；Each functional module group includes such as
Optical detecting module 1, chip motion control module 2, magnetic field control module 3 and temperature control modules 4 shown in Fig. 1；Optics is examined
Survey module 1, chip motion control module 2, magnetic field control module 3 and the difference of temperature control modules 4 as described in Example 1.Optics
The detection signal that detection module 1 is collected wirelessly is transferred to intelligent terminal, such as smart mobile phone 7, notebook
Computer 8 etc., carries out the display output of result.
Embodiment 3
A kind of network distribution type modularization bio-analysis system, as shown in figure 9, the mould described in comprising some set embodiments 1
Block metaplasia thing analyzing subsystem either the combined modularization bioanalysis subsystem described in embodiment 2 or the two any group
Close, each subsystem is connected to the monitoring that system equipment status is carried out on host, detection by cable network (such as LAN, Ethernet)
Task allotment and management, the Macro or mass analysis of testing result and the issue of project.
Embodiment 4
Using embodiment 1 describe based on the modularization bio-analysis system of droplet array chip (in temperature control modules
Heating module select temperature swing type heating module) detected on droplet array chip based on real-time fluorescence nucleic acid constant-temperature amplification
(SAT) NEISSERIA GONORRHOEAE RNA detection and analysis flows.
(1) chip prepares：A certain amount of mineral oil and examination are added to each micro- pond of droplet array chip (as shown in Figure 7)
Agent, forms independent Water-In-Oil drop respectively.Wherein sample cell adds 25 μ L mineral oil, 20 μ L RNA capture magnetic grain suspensions, washes
Wash pond 1 and add 20 μ L mineral oil, 100 μ L cleaning solutions, kitchen sink 2 adds 20 μ L mineral oil, 100 μ L cleaning solutions, and elution pool adds
10 μ L mineral oil, 16 μ L SAT amplification reaction solutions, reaction tank add 10 μ L mineral oil, 4 μ L enzyme liquids；
(2) loading：100 μ L swabs eluents or negative control are separately added into the micro- pond of each sample of droplet array chip
Sample preparation product or positive control sample；
(3) machine on：Chip carrier export (Optical Dark Solitary Pulse storehouse), droplet array chip is compressed and is positioned over chip carrier 2-1's
In card slot, chip carrier warehouse entry；
(4) drive above droplet array chip motion to temperature control modules, make the micro- pond of sample on droplet array chip
Close to thermally conductive sheet, thermally conductive sheet temperature setting is 65 DEG C, and high-frequent reciprocating moves driving chip by a small margin, vibration mix sample and
RNA captures magnetic grain suspension, maintains this process 3-5 minutes；
(5) magnetic field control module starts, and permanent magnet array is risen close to the bottom surface of droplet array chip, drives droplet array
Chip 6 the micro- pond of chip sample is slow transitted through above permanent magnet array until wash micro- center of pond 1 positioned at permanent magnet array just on
Side, then permanent magnet array is lowered back to initial position；
(6) driving droplet array chip, high-frequent reciprocating moves by a small margin, and vibration mixes magnetic grain suspension, cleaning solution, maintains
This process 1-3 minutes；
(7) magnetic field control module starts, and permanent magnet array, which is risen close to droplet array die bottom surface, driving chip, makes chip
The micro- pond 1 of washing slow transit through above permanent magnet array until wash micro- center of pond 2 directly over permanent magnet array, Ran Houyong
Magnet array is lowered back to initial position；
(8) repeat step (6)；
(9) magnetic field control module starts, and permanent magnet array, which is risen close to 6 bottom surface of droplet array chip, driving chip, makes core
The micro- pond 2 of washing of piece is slow transitted through above permanent magnet array until eluting micro- pond center directly over permanent magnet array, then
Permanent magnet array is lowered back to initial position；
(10) repeat step (6)；
(11) droplet array chip motion is driven the micro- pond of elution is close to thermally conductive sheet to the top of temperature control modules 4, maintain
65 DEG C of thermally conductive sheet temperature, while high-frequent reciprocating moves driving chip by a small margin, maintains this process 1-3 minutes；
(12) magnetic field control module starts, and permanent magnet array, which is risen close to droplet array die bottom surface, driving chip, makes core
The micro- pond of elution, the micro- pond of reaction of piece slow transit through above permanent magnet array until reacting micro- pond center away from permanent magnet battle array successively
Row, then permanent magnet array is lowered back to initial position；
(13) driving chip is moved to above temperature control modules, the micro- pond of reaction is close to thermally conductive sheet, maintains heating plate temperature
42 DEG C of degree, while high-frequent reciprocating moves certain time interval driving chip by a small margin, maintains this process 20-40 minutes；
(14) optical detecting module starts during the execution of step (14), with certain frequency excitation fluorescence and gathers core
Piece reacts the fluorescence signal in micro- pond, and extraction fluorescence intensity information draws amplification curve；
(15) reaction terminates, and chip export, removes droplet array chip.
Embodiment 5
Device (heating module in temperature control modules selects thermostatic type heating module) is described in drop using embodiment 1
Bacillus coli gene detection and analysis flow based on ring mediated isothermal amplification (LAMP) on array chip.
(1) chip prepares：A certain amount of mineral oil and examination are added to each micro- pond of droplet array chip (as shown in Figure 7)
Agent, forms independent Water-In-Oil drop respectively.Wherein sample cell add 25 μ L mineral oil, 20 μ L cracking buffering, 50 μ L combinations liquid,
2 μ L magnetic grain suspensions, with reference to liquid, kitchen sink 1 adds 20 μ L mineral oil, 100 μ L cleaning solutions, kitchen sink 2 add 20 μ L mineral oil,
100 μ L cleaning solutions, elution pool add 15 μ L mineral oil, 10 μ L eluents, and reaction tank adds 10 μ L mineral oil, 10 2 × LAMP of μ L
Reaction premixed liquid (includes normal constituent, 81 fluorescent dye of enzyme, primer and SYTO)；
(2) loading：Cracking drop into the micro- pond of each sample of droplet array chip is separately added into 20 μ L samples or the moon
Property control or positive control；
(3) machine on：Droplet array chip, is compressed the card slot for being positioned over chip carrier by chip carrier export (Optical Dark Solitary Pulse storehouse)
In, chip carrier warehouse entry；
(4) drive above droplet array chip motion to temperature control modules, make the micro- pond of the sample on chip close to heat conduction
Piece, thermally conductive sheet temperature setting are 56 DEG C；
(5) magnetic field control module starts, and permanent magnet array is risen close to droplet array die bottom surface.Driving chip makes chip
Magnetic grain suspension drop in the micro- pond of sample, slow transit through above permanent magnet array with reference to liquid drop, cracking drop, Ran Houhuan successively
Slowly the initial position of the step is returned to.Action 1-3 times is repeated, the micro- pond central part of the sample of chip is finally stayed in into permanent magnetism
Directly over volume array, then permanent magnet array is lowered back to initial position；
(6) high-frequent reciprocating movement is mixed driving chip with vibrating by a small margin, maintains this process 3-5 minutes；
(7) magnetic field control module starts, and permanent magnet array, which is risen close to droplet array die bottom surface, driving chip, makes chip
The micro- pond of sample slow transit through above permanent magnet array and rested on until washing micro- 1 central part of pond directly over permanent magnet array,
Then permanent magnet array is lowered back to initial position；
(8) high-frequent reciprocating movement is mixed driving chip with vibrating by a small margin, maintains this process 1-3 minutes；
(9) magnetic field control module starts, and permanent magnet array, which is risen close to droplet array die bottom surface, driving chip, makes chip
The micro- pond 1 of washing slow transit through above permanent magnet array and rested on until washing micro- 2 central part of pond directly over permanent magnet array,
Then permanent magnet array is lowered back to initial position；
(10) repeat step (8)；
(11) driving chip is moved to above temperature control modules, the micro- pond of elution is close to thermally conductive sheet, maintains thermally conductive sheet temperature
65 DEG C of degree, while high-frequent reciprocating moves driving chip by a small margin, maintains this process 1-3 minutes；
(12) magnetic field control module starts, and permanent magnet array, which is risen close to droplet array die bottom surface, driving chip, makes core
The micro- pond of elution, the micro- pond of reaction of piece slow transit through above permanent magnet array until reacting micro- pond center away from permanent magnet battle array successively
Row, then permanent magnet array is lowered back to initial position；
(13) driving chip is moved to above temperature control modules, the micro- pond of reaction is close to thermally conductive sheet, maintains heating plate temperature
65 DEG C of degree, while high-frequent reciprocating moves certain time interval driving chip by a small margin, maintains this process 10-40 minutes；
(14) optical detecting module starts during the execution of step (14), with certain frequency excitation fluorescence and gathers core
Piece reacts the fluorescence signal in micro- pond, and extraction fluorescence intensity information draws amplification curve；
(15) reaction terminates, and chip export, removes droplet array chip.
Embodiment 6
Device (heating module in temperature control modules selects temperature swing type heating module) is described in drop using embodiment 1
Realize that the hepatitis B virus DNA analyzed based on time-domain fluorescent quantitative PCR and melt curve analysis tests and analyzes flow on array chip
(1) chip prepares：A certain amount of mineral oil and reagent are added to each micro- pond of droplet array chip, is formed respectively only
Vertical Water-In-Oil drop.Wherein sample cell adds 25 μ L mineral oil, 20 μ L cracking buffering, 50 μ L combinations liquid, 2 μ L magnetic grain suspensions,
With reference to liquid, kitchen sink 1 adds 20 μ L mineral oil, 100 μ L cleaning solutions, and kitchen sink 2 adds 20 μ L mineral oil, 100 μ L cleaning solutions, washes
De- pond adds 15 μ L mineral oil, 10 μ L eluents, and reaction tank adds 10 μ L mineral oil, 10 μ L 2 × PCR reaction premixed liquids (include
Normal constituent, enzyme, primer and fluorescent dye or fluorescence probe)；
(2) loading：Cracking drop into the micro- pond of each sample of droplet array chip is separately added into 20 μ L samples or the moon
Property control or positive control；
(3) machine on：Chip carrier export, droplet array chip is compressed and is positioned in the card slot of chip carrier, chip support
Frame warehouse entry；
(4) driving chip is moved to above temperature control modules, makes the micro- pond of the sample on chip close to thermally conductive sheet, thermally conductive sheet
Temperature setting is 56 DEG C；
(5) magnetic field control module starts, and permanent magnet array is risen close to droplet array die bottom surface.Driving chip makes chip
Magnetic grain suspension drop in the micro- pond of sample, slow transit through above permanent magnet array with reference to liquid drop, cracking drop, Ran Houhuan successively
Slowly the initial position of the step is returned to.Action 1-3 times is repeated, the micro- pond central part of the sample of chip is finally stayed in into permanent magnetism
Directly over volume array, then permanent magnet array is lowered back to initial position；
(6) high-frequent reciprocating movement is mixed driving chip with vibrating by a small margin, maintains this process 3-5 minutes；
(7) magnetic field control module starts, and permanent magnet array, which is risen close to droplet array die bottom surface, driving chip, makes chip
The micro- pond of sample slow transit through above permanent magnet array and rested on until washing micro- 1 central part of pond directly over permanent magnet array,
Then permanent magnet array is lowered back to initial position；
(8) high-frequent reciprocating movement is mixed driving chip with vibrating by a small margin, maintains this process 1-3 minutes；
(9) magnetic field control module starts, and permanent magnet array, which is risen close to droplet array die bottom surface, driving chip, makes chip
The micro- pond 1 of washing slow transit through above permanent magnet array and rested on until washing micro- 2 central part of pond directly over permanent magnet array,
Then permanent magnet array is lowered back to initial position；
(10) repeat step (8)；
(11) driving chip is moved to above temperature control modules, the micro- pond of elution is close to thermally conductive sheet, maintains thermally conductive sheet temperature
65 DEG C of degree, while high-frequent reciprocating moves driving chip by a small margin, maintains this process 1-3 minutes；
(12) magnetic field control module starts, and permanent magnet array, which is risen close to droplet array die bottom surface, driving chip, makes core
The micro- pond of elution, the micro- pond of reaction of piece slow transit through above permanent magnet array until reacting micro- pond center away from permanent magnet battle array successively
Row, then permanent magnet array is lowered back to initial position；
(13) driving chip is moved to above temperature control modules, the micro- pond of reaction is close to thermally conductive sheet, at the same it is certain when
Between be spaced driving chip by a small margin high-frequent reciprocating move, during this heater perform Standard PCR thermocycling program；
(14) optical detecting module starts during the execution of step (13), when thermally conductive sheet temperature reaches in each circulation
Fluorescence is excited during elongating temperature and acquisition chip reacts the fluorescence signal in micro- pond, to draw amplification curve；
(15) after last thermal cycle of PCR, heter temperature is first risen into denaturation temperature and maintains the several seconds,
Then annealing temperature is cooled to rapidly, then is progressively warming up to annealing temperature by certain liter temperature rate.During this period, phosphor persistence
Excite and gather, to draw fluorescence melt curve analysis；
(16) reaction terminates, and chip export, removes droplet array chip.
Embodiment 7
Using embodiment 1 describe device (temperature control modules are multichannel temperature control+multigroup thermostatic type heating module,
Heat-conducting block is respectively thermally conductive sheet A, thermally conductive sheet B, thermally conductive sheet C or more) realize on droplet array chip and determined based on spatial domain fluorescence
Measure the hepatitis B virus DNA detection and analysis flow of PCR
(1) chip prepares：A certain amount of mineral oil and reagent are added to each micro- pond of droplet array chip, is formed respectively only
Vertical Water-In-Oil drop.Wherein sample cell adds 25 μ L mineral oil, 20 μ L cracking buffering, 50 μ L combinations liquid, 2 μ L magnetic grain suspensions,
With reference to liquid, kitchen sink 1 adds 20 μ L mineral oil, 100 μ L cleaning solutions, and kitchen sink 2 adds 20 μ L mineral oil, 100 μ L cleaning solutions, washes
De- pond adds 15 μ L mineral oil, 10 μ L eluents, and reaction tank adds 10 μ L mineral oil, 10 μ L 2 × PCR reaction premixed liquids (include
Normal constituent, enzyme, primer and fluorescent dye or fluorescence probe)；
(2) loading：Cracking drop into the micro- pond of each sample of droplet array chip is separately added into 20 μ L samples or the moon
Property control or positive control；
(3) machine on：Chip carrier export, droplet array chip is compressed and is positioned in the card slot of chip carrier, chip support
Frame warehouse entry；
(4) driving chip is moved to above temperature control modules, makes the micro- pond of the sample on chip close to thermally conductive sheet A, heat conduction
Piece A temperature settings are 56 DEG C；
(5) magnetic field control module starts, and permanent magnet array is risen close to droplet array die bottom surface.Driving chip makes chip
Magnetic grain suspension drop in the micro- pond of sample, slow transit through above permanent magnet array with reference to liquid drop, cracking drop, Ran Houhuan successively
Slowly the initial position of the step is returned to.Action 1-3 times is repeated, the micro- pond central part of the sample of chip is finally stayed in into permanent magnetism
Directly over volume array, then permanent magnet array is lowered back to initial position；
(6) high-frequent reciprocating movement is mixed driving chip with vibrating by a small margin, maintains this process 3-5 minutes；
(7) magnetic field control module starts, and permanent magnet array, which is risen close to droplet array die bottom surface, driving chip, makes chip
The micro- pond of sample slow transit through above permanent magnet array and rested on until washing micro- 1 central part of pond directly over permanent magnet array,
Then permanent magnet array is lowered back to initial position；
(8) high-frequent reciprocating movement is mixed driving chip with vibrating by a small margin, maintains this process 1-3 minutes；
(9) magnetic field control module starts, and permanent magnet array, which is risen close to droplet array die bottom surface, driving chip, makes chip
The micro- pond 1 of washing slow transit through above permanent magnet array and rested on until washing micro- 2 central part of pond directly over permanent magnet array,
Then permanent magnet array is lowered back to initial position；
(10) repeat step (8)；
(11) driving chip is moved to above temperature control modules, the micro- pond of elution is close to thermally conductive sheet, maintains to add thermally conductive sheet
65 DEG C of temperature, while high-frequent reciprocating moves driving chip by a small margin, maintains this process 1-3 minutes；
(12) magnetic field control module starts, and permanent magnet array, which is risen close to droplet array die bottom surface, driving chip, makes core
The micro- pond of elution, the micro- pond of reaction of piece slow transit through above permanent magnet array until reacting micro- pond center away from permanent magnet battle array successively
Row, then permanent magnet array is lowered back to initial position；
(13) driving chip is moved to above temperature control modules, maintain thermally conductive sheet A, B, C temperature be respectively annealing temperature,
Elongating temperature and denaturation temperature, and start optical detecting module.Driving chip makes the micro- bottom of pond portion of chip reaction be adjacent to heat conduction successively
Piece C, thermally conductive sheet A, thermally conductive sheet B are simultaneously stopped certain time on each thermally conductive sheet, are often repeated the action and are once completed one
PCR thermal cycles, when chip reacts excitation fluorescence and the fluorescence in acquisition chip reaction micro- pond when micro- bottom of pond portion is rested on thermally conductive sheet B
Signal, to draw amplification curve；
(14) reaction terminates, and chip export, removes droplet array chip.
Embodiment 8
Describing device using embodiment 1, (heating module is thermostatic type heating module in temperature control modules, optical detection mould
Optical electrical exciter is default in block or does not enable) realized on droplet array chip and C- reaction eggs are quantitatively detected based on chemiluminescence
The analysis process of (CRP) in vain.
(1) chip prepares：A certain amount of mineral oil and reagent are added to each micro- pond of droplet array chip, is formed respectively only
Vertical Water-In-Oil drop.Wherein sample cell adds 25 μ L mineral oil, 50 μ L dilutions, 2 μ L Bead Anti-CRP, 2 μ L biologies
Plain Anti-CRP, 2 μ L Streptavidin Anti-HRP, kitchen sink 1 add 20 μ L mineral oil, 100 μ L cleaning solutions, and kitchen sink 2 adds
Enter 20 μ L mineral oil, 100 μ L cleaning solutions, elution pool adds 10 μ L mineral oil, 15 μ L substrate reactions liquids, and reaction tank adds 20 μ L ore deposits
Thing oil；
(2) loading：2-5 μ L samples or negative control or sun are separately added into the micro- pond of each sample of droplet array chip
Property control；
(3) machine on：Chip carrier export, droplet array chip is compressed and is positioned in the card slot of chip carrier, chip support
Frame warehouse entry；
(4) driving chip is moved to above temperature control modules, makes the micro- pond of the sample on chip close to thermally conductive sheet, thermally conductive sheet
Temperature setting is 37 DEG C；
(5) magnetic field control module starts, and permanent magnet array is risen close to droplet array die bottom surface.Driving chip makes chip
Bead Anti-CRP drops, biotin Anti-CRP drops, Streptavidin Anti-HRP drops, sample in the micro- pond of sample
Drop slow transits through above permanent magnet array successively, then slowly returns to the initial position of the step.Action 1-3 times is repeated,
Finally the micro- pond central part of the sample of chip is stayed in directly over permanent magnet array, then permanent magnet array is lowered back to initial bit
Put；
(6) high-frequent reciprocating movement is mixed driving chip with vibrating by a small margin, maintains this process 3-7 minutes；
(7) magnetic field control module starts, and permanent magnet array, which is risen close to droplet array die bottom surface, driving chip, makes chip
The micro- pond of sample is slow transitted through above permanent magnet array to be located at directly over permanent magnet array until washing micro- center of pond 1, then permanent magnetism
Volume array is lowered back to initial position；
(8) high-frequent reciprocating movement is mixed driving chip with vibrating by a small margin, maintains this process 0.5-1 minutes；
(9) magnetic field control module starts, and permanent magnet array, which is risen close to droplet array die bottom surface, driving chip, makes chip
The micro- pond 1 of washing slow transit through above permanent magnet array until wash micro- center of pond 2 directly over permanent magnet array, Ran Houyong
Magnet array is lowered back to initial position；
(10) high-frequent reciprocating movement is mixed driving chip with vibrating by a small margin, maintains this process 3-5 minutes；
(11) driving chip is moved to above temperature control modules, the micro- pond of elution is close to thermally conductive sheet, maintains thermally conductive sheet temperature
37 DEG C of degree, while high-frequent reciprocating moves driving chip by a small margin, maintains this process 1-3 minutes；
(12) optical detecting module starts during the execution of step (11), and acquisition chip reacts the chemiluminescence letter in micro- pond
Number and extract intensity level；
(13) reaction terminates, and chip export, removes droplet array chip.
Embodiment 9
Utilize modular drop chip biological analysis system joint investigating hepatitis B virus described by embodiment 2 (Fig. 8)
Nucleic acid in blood serum and surface antigen, the analysis process of antibody (HBsAg, HBsAb, HBeAg, HBeAb, HBcAb) of infection.
(1) chip prepares：A certain amount of mineral oil and reagent are added to each micro- pond of modules A, B chips, is formed mutual
Independent Water-In-Oil drop.Wherein 25 μ L mineral oil, 20 μ L cracking buffering, 50 μ L are added to the sample cell of modules A chip to combine
Liquid, 2 μ L magnetic grain suspensions, with reference to liquid, kitchen sink 1 adds 20 μ L mineral oil, 100 μ L cleaning solutions, and kitchen sink 2 adds 20 μ L mineral
Oil, 100 μ L cleaning solutions, elution pool add 15 μ L mineral oil, 10 μ L eluents, reaction tank add 10 μ L mineral oil, 10 μ L 2 ×
PCR reaction premixed liquids (include normal constituent, enzyme, hbv nucleic acid sequence specific primers and fluorescent dye or fluorescence
Probe)；To 5 sample cells of module B chips add 25 μ L mineral oil, 50 μ L dilutions, (mark is anti-for 2 μ L antibody mark magnetic bead
Body is Anti-HBsAg, Anti-HBsAb, Anti-HBeAg, Anti-HBeAb and Anti-HBcAb respectively), 2 μ L biotinylations
Anti-HBs ((or biotin-HBs or biotin Anti-HBe or biotin HBe or biotin Anti-HBc), 2 μ L strepto-s parents
With plain Anti-HRP, kitchen sink 1 adds 20 μ L mineral oil, 100 μ L cleaning solutions, and kitchen sink 2 adds 20 μ L mineral oil, 100 μ L are washed
Liquid is washed, elution pool adds 10 μ L mineral oil, 15 μ L substrate reactions liquids, and reaction tank adds 20 μ L mineral oil；
(2) loading：Cracking drop into the micro- pond of each sample of A chips be separately added into 20 μ L samples or negative control or
Positive control；2-5 μ L samples or negative control or positive control are separately added into the micro- pond of each sample of B chips.
(3) machine on：Chip carrier export, A chips are compressed and are positioned in the card slot of A module chip brackets, by B chip pressures
Tightly it is positioned in the card slot of B module chip brackets, the respective warehouse entry of chip carrier.
(4) run：In process of the operation such as the step of embodiment 7 shown in (4)-(16) on A modules；Run on B modules
Process such as the step of embodiment 8 shown in (4)-(13)
(5) result transmission and display：The signal that A, B module are collected is handled by battery and electronic circuit module 5
After conversion, wirelessly (such as WIFI, bluetooth) be transmitted on intelligent terminal carry out result display output and
Interpretation.
Embodiment 10
Using described by embodiment 3 (Fig. 9) on network distribution type modularization pathogen detection system carry out different time sequence
The analysis process of the disparity items index " with to inspection " of sample.
(1) chip prepares：A certain amount of mineral oil is added to each micro- pond of a collection of droplet array chip and is applicable in different inspections
Survey the reagent of index, and the Water-In-Oil drop of each self-forming independence wherein；Prepare the chip of preloaded reagent before use
Deposit in 4 DEG C of sterile closed environment.
(2) task is distributed：Detection project/index according to required by submitted sample at different moments, selects corresponding prepackage
Chip, while resources idle is distributed by the principle of " arrive first and first examine " and " anxious inspection is preferential " by host task adjustmenting management system
Subsystem or subfunction module, ensure upper machine in time perform needed for detection project/index.
(3) interpretation of result and issue：Match the ID of submitted sample, detection project/index ID, tasks carrying subsystem ID and
Its testing result, forms the examining report of " sample-result ".
Above-described embodiment is the preferable embodiment of the present invention, but embodiments of the present invention and from above-described embodiment
Limitation, other any Spirit Essences without departing from the present invention with made under principle change, modification, replacement, combine, simplification,
Equivalent substitute mode is should be, is included within protection scope of the present invention.
Claims (10)
- A kind of 1. modularization bio-analysis system based on droplet array chip, it is characterised in that：Including at least one set of function Module and more than one battery and electronic circuit module；Functional module group include optical detecting module, chip motion control module, Magnetic field control module and temperature control modules；Optical detecting module, chip motion control module, magnetic field control module and temperature control Molding block is connected with battery and electronic circuit module respectively, and optical detecting module is connected with chip motion control module, magnetic field control Molding block and temperature control modules are located at the lower section of chip motion control module；Chip motion control module includes motor and the chip carrier being connected with motor；Optical detecting module includes photoelectric detector, Optical Dark Solitary Pulse storehouse and optical electrical excitation control and signal acquisition processing circuit；Optics Dark storehouse is body structure, and chip carrier entrance, photoelectric detector and optical electrical excitation control and letter are set in the bottom in Optical Dark Solitary Pulse storehouse The connection of number acquisition process circuit；Photoelectric detector is located at the top of chip carrier entrance；Magnetic field control module includes magnet and the circuit that is connected with magnet, magnet be vertically installed in chip carrier top or under Side；If temperature control modules include dry passage temperature controller and be connected with temperature controller it is some it is mutually independent add Thermal module, heating module are arranged at the lower section of chip carrier.
- 2. the modularization bio-analysis system based on droplet array chip according to claim 1, it is characterised in that：The structure of the chip carrier is as follows：Trailing arm is respectively arranged with the both sides of chip carrier, side trailing arm is provided with use In the half opening sliding slot of cutting ferrule optical axis, opposite side trailing arm is provided with position limit arm, sliding block bolt, sliding block and parallel to optical axis direction Through hole, chip carrier is installed in place the top that state lower limit arm is placed exactly in screw, and sliding block is fixed on by sliding block bolt On chip carrier；Side of the sliding block away from chip carrier is provided with the convex tooth of the sliding block contacted with screw, and the convex tooth of sliding block moves towards parallel In wire rod thread groove precession direction；The chip motion control module further includes the motion base for being used to support chip carrier；Set in the side of motion base Put screw, screw and motor coaxle；The optical axis parallel with screw is set respectively in the both sides of motion base.
- 3. the modularization bio-analysis system based on droplet array chip according to claim 2, it is characterised in that：The motion base further includes magnetic field control module interface and temperature control modules interface, magnetic field control module interface and Temperature control modules interface is arranged at the lower section of chip carrier space.
- 4. the modularization bio-analysis system based on droplet array chip according to claim 1, it is characterised in that：The modularization bio-analysis system based on droplet array chip also includes photoelectricity exciter, photoelectricity exciter with Optical electrical excitation control is connected with signal acquisition processing circuit, positioned at the top of chip carrier entrance.
- 5. the modularization bio-analysis system based on droplet array chip according to claim 4, it is characterised in that：The photoelectricity exciter is fluorescence excitation module, it includes fluorescent light source, exciter filter and launches optical filter, along Light direction of advance, fluorescent light source, exciter filter, transmitting optical filter and photoelectric detector are arranged in order, and light path is 45 ° of oblique fires Light path design or coaxial optical path design, fluorescent light source is LED bulb or LED bulb array.
- 6. the modularization bio-analysis system based on droplet array chip according to claim 1, it is characterised in that：The magnet is permanent magnet or electromagnet；When the magnet is permanent magnet, the circuit is drive circuit；Permanent magnet moveable vertical is arranged at chip carrier Above or below；When the magnet is electromagnet, circuit circuit in order to control；Electromagnet fixed vertical is arranged at chip carrier Above or below.
- 7. the modularization bio-analysis system based on droplet array chip according to claim 1, it is characterised in that：When the magnet is permanent magnet, the magnetic field control module further includes permanent magnet bracket, optical axis, base, leading screw, electricity Machine, slide bar, sliding block, convex tooth；Permanent magnet is arranged on permanent magnet bracket；Leading screw passes through electricity with the motor coaxle in circuit, motor Machine support is fixed on base；One end of slide bar is fixed on base, and sliding block passes through slide bar, is relatively fixed on slide bar, sliding block Connected with screw；The through hole passed through for optical axis is provided with the both sides of permanent magnet bracket, bottom is fixed in the lower end of optical axis On seat, permanent magnet bracket is relatively fixed on base by optical axis；Convex tooth is arranged on a side of permanent magnet bracket, convex tooth It is connected with sliding block.
- 8. the modularization bio-analysis system based on droplet array chip according to claim 1, it is characterised in that：The heating module includes heat-conducting block, temperature sensor, heater and heat-proof device, and the flat heated of heat-conducting block is parallel Chip baseplane is attached at, temperature sensor is arranged on the middle section of the flat heated of heat-conducting block, and heater is embedded in heat conduction In block or with sandwich between heat-conducting block and heat-proof device；When heater is embedded in heat-conducting block, parallel to adding on heat-conducting block The bottom surface of hot plane is attached at heat-proof device；Heat-proof device is adiabatic base；Or include heat dissipation base and radiator fan, heat dissipation Fan is arranged near heat dissipation base.
- 9. the modularization bio-analysis system based on droplet array chip according to claim 1, it is characterised in that：Intelligent terminal is further included, intelligent terminal is connected with optical detecting module.
- 10. the modularization bio-analysis system based on droplet array chip should according to any one of claim 1 to 9 With, it is characterised in that：Applied to biological detection.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710978928.0A CN107976402B (en) | 2017-10-19 | 2017-10-19 | Modular biological analysis system based on liquid drop array chip and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710978928.0A CN107976402B (en) | 2017-10-19 | 2017-10-19 | Modular biological analysis system based on liquid drop array chip and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN107976402A true CN107976402A (en) | 2018-05-01 |
| CN107976402B CN107976402B (en) | 2021-06-04 |
Family
ID=62012522
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710978928.0A Active CN107976402B (en) | 2017-10-19 | 2017-10-19 | Modular biological analysis system based on liquid drop array chip and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107976402B (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109289949A (en) * | 2018-10-15 | 2019-02-01 | 苏州锐讯生物科技有限公司 | A kind of full-automatic microlayer model emulsion generating means and its generation method |
| CN111808744A (en) * | 2020-08-03 | 2020-10-23 | 齐鲁工业大学 | Portable full-automatic nucleic acid constant temperature amplification detector |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2102758C1 (en) * | 1989-11-17 | 1998-01-20 | Лаборатуар Мерк-Клевено | Devices, method and reagent for performing automated immune analysis in several sequential stages of at least one biological substance from a set of biological samples |
| JP2007185101A (en) * | 2006-01-11 | 2007-07-26 | Hitachi High-Technologies Corp | Biological sample-analyzing apparatus |
| CN102980996A (en) * | 2012-12-31 | 2013-03-20 | 广州市第一人民医院 | Chemiluminescence immunoassay system, as well as method and application thereof |
| CN103409317A (en) * | 2013-07-23 | 2013-11-27 | 广州市第一人民医院 | Capillary bioanalysis system, and analytical method and applications thereof |
| WO2014107698A1 (en) * | 2013-01-07 | 2014-07-10 | The General Hospital Corporation | System and method for picoliter volume microfluidic diagnotics |
| JP2015053893A (en) * | 2013-09-11 | 2015-03-23 | 公益財団法人神奈川科学技術アカデミー | High-speed gene amplification detection device |
| CN105203746A (en) * | 2015-10-26 | 2015-12-30 | 深圳华迈兴微医疗科技有限公司 | POCT (Point of Care Testing) chemiluminescence immunoassay system and method |
-
2017
- 2017-10-19 CN CN201710978928.0A patent/CN107976402B/en active Active
Patent Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2102758C1 (en) * | 1989-11-17 | 1998-01-20 | Лаборатуар Мерк-Клевено | Devices, method and reagent for performing automated immune analysis in several sequential stages of at least one biological substance from a set of biological samples |
| JP2007185101A (en) * | 2006-01-11 | 2007-07-26 | Hitachi High-Technologies Corp | Biological sample-analyzing apparatus |
| CN102980996A (en) * | 2012-12-31 | 2013-03-20 | 广州市第一人民医院 | Chemiluminescence immunoassay system, as well as method and application thereof |
| CN102980996B (en) * | 2012-12-31 | 2014-09-10 | 广州市第一人民医院 | Chemiluminescence immunoassay system, as well as method and application thereof |
| WO2014107698A1 (en) * | 2013-01-07 | 2014-07-10 | The General Hospital Corporation | System and method for picoliter volume microfluidic diagnotics |
| CN103409317A (en) * | 2013-07-23 | 2013-11-27 | 广州市第一人民医院 | Capillary bioanalysis system, and analytical method and applications thereof |
| JP2015053893A (en) * | 2013-09-11 | 2015-03-23 | 公益財団法人神奈川科学技術アカデミー | High-speed gene amplification detection device |
| CN105203746A (en) * | 2015-10-26 | 2015-12-30 | 深圳华迈兴微医疗科技有限公司 | POCT (Point of Care Testing) chemiluminescence immunoassay system and method |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109289949A (en) * | 2018-10-15 | 2019-02-01 | 苏州锐讯生物科技有限公司 | A kind of full-automatic microlayer model emulsion generating means and its generation method |
| CN109289949B (en) * | 2018-10-15 | 2024-03-08 | 苏州锐讯生物科技有限公司 | Full-automatic micro-droplet emulsion generation device and generation method thereof |
| CN111808744A (en) * | 2020-08-03 | 2020-10-23 | 齐鲁工业大学 | Portable full-automatic nucleic acid constant temperature amplification detector |
Also Published As
| Publication number | Publication date |
|---|---|
| CN107976402B (en) | 2021-06-04 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Sista et al. | Development of a digital microfluidic platform for point of care testing | |
| CA2536221C (en) | Apparatus for processing a fluid sample | |
| JP5759411B2 (en) | Device for transferring samples | |
| JP5054096B2 (en) | Biochemistry based on droplets | |
| JP5266208B2 (en) | Droplet treatment system | |
| CN103820316B (en) | Based on the real-time PCR detection system of rotary micro-fluidic chip | |
| CN101932927B (en) | Integrated apparatus for conducting and monitoring chemical reactions | |
| JP2003522322A (en) | Structures and methods for automatic analysis of samples | |
| CN102618439B (en) | Deoxyribonucleic acid (DNA) fragment amplification and quantitative detection system based on closed reactors | |
| JP2015070840A (en) | Method of processing sample including at least one kind of biological element | |
| CN108760686A (en) | Scattered light urbidmetry detects micro-fluidic chip and the biochemical immunity machine using the chip | |
| CN107976402A (en) | It is a kind of based on the modularization bio-analysis system of droplet array chip and its application | |
| CN106405131A (en) | Cell and protein combined analysis device and combined analysis method | |
| CN109946460A (en) | Chemiluminescence immunoassay detection device and application method based on micro-fluidic chip | |
| CN113528326A (en) | Microfluidic nucleic acid detection device and application | |
| CN111378573A (en) | Micro-pipeline nucleic acid amplification system | |
| CN207210433U (en) | A kind of gene assaying device based on the control of liquid section | |
| CN221720822U (en) | Microfluidic chip for simultaneously performing molecular diagnosis, immunodiagnosis and biochemical detection | |
| RU229059U1 (en) | PROGRAMMABLE LABORATORY STATION FOR AUTOMATION OF LABORATORY PROCEDURES | |
| Wang et al. | Design of automatic fluorescence in situ hybridization system | |
| CN117778174A (en) | Microfluidic chip for simultaneously performing molecular diagnosis, immunodiagnosis and biochemical detection and testing method thereof | |
| Yin et al. | Slipchip Device Development in Molecular Diagnostics | |
| CN117126729A (en) | Efficient moving integrated machine for sample detection and control method thereof | |
| CN114574347A (en) | Multi-index detection device, multi-index detection chip and using method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |