Utility model content
The application provides a kind of fluorescence analyser and its liquid phase biological chips detection system, can realize to liquid phase biology core
The automatic detection of piece improves detection efficiency.
It is according to the present utility model in a first aspect, the utility model provides a kind of liquid phase biological chips detection system, including:
It is provided with the imaging chamber of cavity;
Patterning device is sampled, in sampling, being injected into after drawing solution to be detected in the cavity of imaging chamber;It is arranging
During sample, the solution after the completion of being detected in imaging chamber's cavity is discharged;
Magnetic fluorescent microspheres in solution to be detected are attracted and are fixed on imaging by microballoon adsorbent equipment for passing through magnetic field
The bottom of room cavity;
At least one laser, for emitting laser to the indoor solution to be detected of the imaging, so that solution to be detected
In magnetic fluorescent microspheres transmitting stimulated light;
Filtering apparatus is filtered for the stimulated light to different frequency range;
Imaging device, for being imaged to the stimulated light after filtering apparatus filters;
Control module, for sampling patterning device, microballoon adsorbent equipment, laser, filtering apparatus and imaging device into
Row control;
The filtering apparatus and imaging device are successively set on the stimulated light sent after the magnetic fluorescent microspheres are stimulated
Light path on, control module connection sampling patterning device, microballoon adsorbent equipment, laser, filtering apparatus and imaging device.
The liquid phase biological chips detection system, wherein, the filtering apparatus includes being provided with the filter of multiple optical filters
Mating plate turntable, multiple optical filters penetrate wave band difference.
The liquid phase biological chips detection system, wherein, at least four optical filters are set on the filter wheel.
The liquid phase biological chips detection system, wherein, the sampling patterning device includes sampling needle tubing, for controlling
The first solenoid valve, plunger pump and the sampling driving for sampling needle tubing to be driven to be moved in Y-axis and Z-direction of pipeline break-make
Device;For the sampling needle tubing by pipeline and the inlet communication of the cavity, the outlet of the cavity passes through pipeline and plunger pump
Connection, first solenoid valve are arranged on the pipeline between cavity and plunger pump.
The liquid phase biological chips detection system, wherein, the sampling patterning device further includes to place sample tube
Rack for test tube, sample introduction translation stage, the first transport mechanism;For fixing the rack for test tube, described first passes the sample introduction translation stage
Mechanism is sent for sample introduction translation stage to be driven to move in the X-axis direction;The microballoon adsorbent equipment includes magnet and for by described in
Magnet is transmitted to second transport mechanism at imaging chamber rear.
The liquid phase biological chips detection system, wherein, the detecting system further includes waste liquid discharger, described useless
Liquid discharger includes waste liquid pool and waste drains pump, and the waste liquid pool is connected by pipeline with waste drains pump;The sampling patterning device
It further includes cleaning solution and holds storehouse and the second solenoid valve for control pipeline break-make, the cleaning solution holds storehouse and connects with plunger pump
Logical, the second solenoid valve is arranged on the pipeline that cleaning solution is held between storehouse and plunger pump.
The liquid phase biological chips detection system, wherein, the detecting system further includes state-detection subsystem, is used for
The sampling of detection sampling patterning device, stock layout state detect adsorbed state, the rotation shape of filter wheel of microballoon adsorbent equipment
State;The state-detection subsystem is connected with control module.
The liquid phase biological chips detection system, wherein, the state-detection subsystem is detected by optocoupler, bag
It includes:The optocoupler on plunger pump piston stroke top is arranged on, is arranged on light of the sampling needle tubing at the motion track both ends of Y direction
Coupling is arranged on sampling needle tubing in the optocoupler at the motion track both ends of Z-direction, is arranged on sample introduction translation stage motion track both ends
Optocoupler is arranged on the optocoupler at magnet motion track both ends, the optocoupler being arranged on the rotational trajectory of filter wheel.
The liquid phase biological chips detection system, wherein, the control module includes:
Microcontroller, for controlling sampling patterning device, microballoon adsorbent equipment, laser and filtering apparatus;Root
According to the signal of the optocoupler at sample introduction translation stage motion track both ends, judge whether rack for test tube is moved into place;According to sampling needle tubing in Y-axis
The signal of the optocoupler at the motion track both ends in direction, sampling needle tubing are sentenced in the signal of the optocoupler at the motion track both ends of Z-direction
Whether disconnected sampling needle tubing is moved in counter sample pipe;According to the signal of the optocoupler on plunger pump piston stroke top, the first electromagnetism
Whether valve and second solenoid valve are powered, judge whether sampling and stock layout perform in place;According to the optocoupler at magnet motion track both ends
Signal, judge whether magnet is moved into place;According to the signal for the optocoupler being arranged on the rotational trajectory of filter wheel, judge
Whether filter wheel is rotated in place;
Microcontroller connects with laser, filtering apparatus, sampling patterning device, microballoon adsorbent equipment, state-detection subsystem
It connects.
Second aspect according to the present utility model, the utility model provides a kind of fluorescence analyser, including as described above
Liquid phase biological chips detection system.
The beneficial effects of the utility model:By setting an optical filtering for being filtered to the stimulated light of different frequency range
Device is distinguished with the stimulated light sent to different magnetic fluorescent microspheres, so that imaging device obtains different magnetism
The distributed image of fluorescent microsphere realizes detection and differentiation to a variety of fluorescent-labeled magnetic fluorescent microspheres.Even nothing can be reduced
Grade classification need to be carried out to the fluorescence intensity (being excited luminous intensity) of magnetic fluorescent microspheres, reduce the manufacture craft requirement to microballoon.
Specific embodiment
The utility model is described in further detail below by specific embodiment combination attached drawing.
The utility model provides a kind of liquid phase biological chips detection system, in embodiment one, please refers to Fig.1 and Fig. 2, institute
Stating detecting system includes:It is provided with the imaging chamber of cavity, samples patterning device 10, microballoon adsorbent equipment 20, laser 30, optical filtering
Device 40, state-detection subsystem 50, imaging device 60 and control module 70.Sample patterning device 10, microballoon adsorbent equipment 20,
At least one laser 30, filtering apparatus 40, state-detection subsystem 50 and imaging device 60 are all connected with control module 70.
For accommodating solution to be detected (sample solution), the front transparent of imaging chamber certainly, can be set the cavity of imaging chamber
Into all-transparent, convenient for supplying exciting light and stimulated light input and output.The imaging chamber is arranged on base station 150.In the present embodiment, institute
Cavity is stated as flat cavity.
Laser 30, for emitting laser to the indoor solution to be detected of the imaging, so that the magnetic in solution to be detected
Property fluorescent microsphere stimulated emission stimulated light.The quantity of laser 30 is depending on the number of types of magnetic fluorescent microspheres, this implementation
In example, two lasers 30 are set.
Filtering apparatus 40 is filtered for the stimulated light to different frequency range.The filtering apparatus 40 includes setting
There is the filter wheel 410 of multiple optical filters and for driving the transmission device 420 that the filter wheel 410 rotates, it is multiple
Optical filter penetrates wave band difference.At least four optical filters are set on the filter wheel 410, and multiple filter arrays are set
On filter wheel 410, each optical filter can filter the light of other frequency ranges, only allow corresponding frequency band (itself penetrate ripple
Section) stimulated light pass through.
Imaging device 60, for being imaged to the stimulated light after the filtering of filtering apparatus 40.Imaging device 60
CCD the or CMOS industrial cameras of fluoroscopic image can preferably be obtained.Optical filter is sent through wave band and magnetic fluorescent microspheres
The wave band of stimulated light corresponds to, and such imaging device 60 is imaged single stimulated light, and what is obtained only includes a kind of fluorescent marker
Fluorescence picture.Filter wheel 410 rotates one week, and imaging device 60 corresponds to each optical filter into one or many pictures, obtains
To multiple fluorescence pictures, multiple fluorescence pictures progress data analysis and process can be realized the solution to a variety of magnetic fluorescent microspheres
Code.
As it can be seen that by setting a filtering apparatus 40 for being filtered to the stimulated light of different frequency range, with to difference
The stimulated light that sends of magnetic fluorescent microspheres distinguish so that imaging device 60 obtains point of different magnetic fluorescent microspheres
Cloth image realizes detection and differentiation to a variety of fluorescent-labeled magnetic fluorescent microspheres.It can reduce even without to magnetic fluorescence
The fluorescence intensity (being excited luminous intensity) of microballoon carries out grade classification, reduces the manufacture craft requirement to microballoon.
Patterning device 10 is sampled, in sampling, being injected into after drawing solution to be detected in the cavity of imaging chamber;
During stock layout, the solution after the completion of being detected in the cavity of imaging chamber is discharged.
Magnetic fluorescent microspheres in solution to be detected are attracted and are fixed on into for passing through magnetic field by microballoon adsorbent equipment 20
As the bottom of room cavity.The microballoon adsorbent equipment 20 includes magnet 210 and for the magnet 210 to be transmitted under imaging chamber
Second transport mechanism 220 of side.
Control module 70, for sampling patterning device 10, microballoon adsorbent equipment 20, laser 30,40 and of filtering apparatus
Imaging device 60 is controlled;Solution to be detected is sampled specifically, starting sampling patterning device 10, is opened after sampling micro-
Ball adsorbent equipment 20 and laser 30, the solution to be detected containing magnetic fluorescent microspheres shines under the excitation of laser (is excited
Light);Start filtering apparatus 40 and imaging device 60, filtering apparatus 40 are filtered the light of corresponding frequency band, imaging device 60 obtains
The fluorescence picture after stimulated light optical filtering is taken, after imaging device 60 obtains the corresponding fluorescence picture of multiple optical filters, control sampling
Patterning device 10 carries out stock layout.
The filtering apparatus 40 and imaging device 60 be successively set on after the magnetic fluorescent microspheres are stimulated send it is glimmering
In the light path of light (stimulated light), the connection sampling of control module 70 patterning device 10, microballoon adsorbent equipment 20, laser 30, optical filtering
Device 40 and imaging device 60.
As it can be seen that liquid phase biological chips detection system provided by the utility model, without human intervention, from sampling, detect
Stock layout realizes automation, you can liquid phase biochip is automatically detected, it is glimmering to realize high throughput, polymorphic type magnetism
The detection of light microballoon, improves detection efficiency, reduces the division requirement to magnetic fluorescent microspheres fluorescence intensity grade and detection
The requirement of operating personnel.
Further, also referring to Fig. 3, the sampling patterning device includes sampling needle tubing 160, leads to for control pipeline
Disconnected the first solenoid valve 130, the second solenoid valve 140 for control pipeline break-make, for driving sample needle tubing at plunger pump 120
The 160 sampling driving devices 110 moved in Y-axis and Z-direction and cleaning solution hold storehouse 170.The sampling needle tubing 160
By pipeline and the inlet communication of the cavity a, the outlet of the cavity a passes through the first import and export of pipeline and plunger pump 120
Connection, first solenoid valve 130 are arranged on the pipeline between cavity a and plunger pump 120.The cleaning solution holds storehouse 170
It is connected with plunger pump 120, the second solenoid valve 140 is arranged on the second import and export that cleaning solution holds storehouse 170 and plunger pump 120
Between pipeline on.During sampling, control module 70 is moved to sample cell by sampling the driving sampling needle tubing 160 of driving device 110
In, second solenoid valve 140 is closed, the first solenoid valve 130 turns on, the charging stroke of opening plunger pump 120, sampling needle tubing 160
Solution to be detected is drawn from sample cell;Sample solution is flowed into cavity a, completes sampling.During stock layout, sampling needle tubing 160 is motionless,
Second solenoid valve 140 remains off, the first solenoid valve 130 maintains conducting, the discharge stroke of opening plunger pump 120, by Fig. 3 pipelines
In detection after the completion of solution be discharged in sample cell, complete stock layout.
The liquid phase biological chips detection system further includes waste liquid discharger, and the waste liquid discharger includes waste liquid pool
And waste drains pump, the waste liquid pool are connected by pipeline with waste drains pump.The control module 70 is additionally operable to after stock layout, to imaging chamber
It is cleaned, specifically, control module 70 is moved to by sampling the driving sampling needle tubing 160 of driving device 110 in waste liquid pool, it will
Second solenoid valve 140 turns on, the first solenoid valve 130 is closed, and the charging stroke of opening plunger pump 120, cleaning solution enters plunger pump
In;And then second solenoid valve 140 is closed, the first solenoid valve 130 turns on, opening plunger pump 120 discharge stroke, wash liquid stream
It is entered after crossing cavity a in waste liquid pool, this process can be repeated several times, and complete cleaning;Waste drains pump is finally opened, it will be in waste liquid pool
Waste liquid is discharged.
It follows that liquid phase biological chips detection system provided by the utility model, passes through the movement to sampling needle tubing 160
With sampling, the design of stock layout pipeline so that liquid phase biological chips detection system is sustainable ceaselessly to work, sampling, stock layout and clear
Full process automatization is washed, greatly improves the efficiency of detection.
Further, the sampling patterning device further includes to place the rack for test tube 180 of sample tube, sample introduction translation stage
190th, the first transport mechanism 191;The sample introduction translation stage 190 is used to fix the rack for test tube 180, first transport mechanism
191 are used to that sample introduction translation stage 190 to be driven to move in the X-axis direction.It follows that it need to only be injected in several sample tubes different
Sample tube is put into rack for test tube 180 and opens the detecting system by solution to be detected, very convenient quick.
State-detection subsystem 50 for detecting the sampling of sampling patterning device 10, stock layout, cleaning state, detects microballoon
Adsorbed state (specially detecting whether magnet 210 is moved to below imaging chamber), turn of filter wheel of adsorbent equipment magnet
Dynamic state.The state-detection subsystem 50 is connected with control module 70.Specifically, the state-detection subsystem 50 includes:
The optocoupler on 120 piston stroke top of plunger pump is arranged on, is arranged on sampling needle tubing 160 at the motion track both ends of Y direction
Optocoupler is arranged on sampling needle tubing 160 in the optocoupler at the motion track both ends of Z-direction, is arranged on 190 moving rail of sample introduction translation stage
The optocoupler at mark both ends is arranged on the optocoupler at 210 motion track both ends of magnet, the light being arranged on the rotational trajectory of filter wheel
Coupling.The implementation status of each device is detected by optocoupler, it is accurate and efficient.
Further, the control module 70 includes host computer 720 and the microcontroller being connected with the host computer 720
710;The host computer 720 is connected with imaging device 60, and the host computer 720 controls laser 30, filter by microcontroller 710
Electro-optical device 40, sampling patterning device 10 and microballoon adsorbent equipment 20;The microcontroller 710 and laser 30, filtering apparatus 40,
Sampling patterning device 10, microballoon adsorbent equipment 20, state-detection subsystem 50 connect, for by the control instruction of host computer 720
Above-mentioned corresponding device (10,20,30, the 40,50) work of driving instruction driving is converted into, and is examined according to state-detection subsystem 50
The state of survey, judges whether each device (10,20,30,40,50) performs in place, and result is fed back to host computer 720.
The microcontroller 710 is according to the signal of the optocoupler at 190 motion track both ends of sample introduction translation stage, you can judges test tube
Whether frame 180 is moved into place;According to signal of the sampling needle tubing 160 in the optocoupler at the motion track both ends of Y direction, sampling needle tubing
160 the optocoupler at the motion track both ends of Z-direction signal, you can judge sample needle tubing 160 whether be moved to counter sample
Guan Zhong;Whether energization according to the signal, the first solenoid valve and second solenoid valve of the optocoupler on 120 piston stroke top of plunger pump, i.e.,
It can determine whether sampling and stock layout perform in place;According to the signal of the optocoupler at 210 motion track both ends of magnet, you can judge magnet
Whether 210 be moved into place and (be moved to below imaging chamber);According to the optocoupler being arranged on the rotational trajectory of filter wheel
Signal, you can judge whether filter wheel is rotated in place.
The microcontroller 710 is preferably embedded microcontroller, and the microcontroller 710 is specifically used for, and is given birth in liquid phase
After object chip detecting system is opened, by each device initialization, each device resets;The control that host computer 720 is sent is received to refer to
Control instruction is converted into the driving instruction of corresponding intrument by order, corresponding device is driven to perform control instruction, according to corresponding intrument
In the signal that sends of optocoupler, judge whether the device performs correctly, when performing incorrect, corresponding device driven to hold again
Row control instruction when performing correct, will perform status indication to perform completion, feed back to host computer 720, and receive next control
System instruction.
Further, the host computer 720 further includes timing unit and alarm unit, and the timing unit is used for each
The execution time of device carries out timing, judges whether time-out.The alarm unit, for performing time time-out in each device
When, send alarm signal.
The host computer 720 is specifically used for, and receives the instruction of user, sample introduction instruction is sent to microcontroller 710, by micro-
Controller 710 controls the first transport mechanism 191, and the sample introduction translation stage 190 for being mounted with rack for test tube 180 is made to be moved to precalculated position;
Sampling instruction is sent to microcontroller 710, sampling driving device 110 is controlled by microcontroller 710, moves sampling needle tubing 160
It moves in sample cell, plunger pump 120, the first solenoid valve 130 and second solenoid valve 140 is controlled by microcontroller 710, make sampling
Solution to be detected in 160 pipette samples pipe of needle tubing;Timing unit judges whether time-out to this sampling process timing,
When overtime, alarm unit sends alarm signal;After the completion of sampling process execution, absorption instruction is sent to microcontroller 710, is led to
Crossing microcontroller 710 controls the second transport mechanism that magnet is moved to below imaging chamber;After the completion of absorption instruction performs, Xiang Wei
Controller 710 sends laser command, and laser 30 is opened by microcontroller 710;Timing unit is to the second transport mechanism and swashs
The work timing of light device 30, and judge whether time-out, in time-out, alarm unit sends alarm signal;It is completed in laser command
Afterwards, optical filtering instruction is sent to microcontroller 710, by microcontroller 710 filter wheel is controlled to turn to corresponding optical filter
It filters, and opens the fluorescence picture that imaging device 60 gathers solution to be detected;Rotation timing of the timing unit to filter wheel,
And judge whether time-out, in time-out, alarm unit sends alarm signal;After the completion of the instruction that filters performs, to microcontroller
710 send stock layout instruction, control plunger pump 120, the first solenoid valve 130 and second solenoid valve 140 by microcontroller 710, make
The solution after the completion of detection in imaging chamber is discharged from sampling needle tubing 160, after the completion of stock layout instruction performs, to microcontroller
710 send clear instruction, control plunger pump 120, the first solenoid valve 130 and second solenoid valve 140 by microcontroller 710, make
The cleaning of the washed liquid of fluid path;Timing unit judges whether time-out to stock layout and cleaning timing, in time-out, alarm list
Member sends alarm signal.
The host computer 720 receives the instruction of user, and above-mentioned multiple control instructions are exported to microcontroller 710, i.e.
User need to only export an instruction, and the detecting system can carry out automatic detection according to default step.It is of course also possible to
With manual mode, i.e. host computer 720 receives the instruction of user, and correspondence exports a control instruction to microcontroller
710.The host computer 720 can be the intelligent mobile terminals such as computer or mobile phone, tablet computer.
Based on the liquid phase biological chips detection system that above-described embodiment provides, the utility model also provides a kind of fluorescence analysis
Instrument, including liquid phase biological chips detection system as described above.Since the automatically working process of the fluorescence analyser exists
It is elaborated in a upper embodiment, therefore not to repeat here.
Based on the liquid phase biological chips detection system that above-described embodiment provides, the utility model also provides a kind of corresponding liquid
Mutually biological chip detecting method, uses above-mentioned detecting system, refers to Fig. 4 and Fig. 5, and the detection method includes following step
Suddenly:
S10, sampling patterning device sample solution to be detected.The step S10 is specifically included:
S110, host computer send sampling instruction to microcontroller, control sampling driving device by microcontroller, make sampling
Pin is moved in sample cell, controls plunger pump, the first solenoid valve and second solenoid valve by microcontroller, sampling needle is made to draw sample
Solution to be detected in quality control;
S120, microcontroller judge whether sampling instruction performs and (complete) in place according to the signal of corresponding optocoupler;It is not holding
When going in place, timing unit judges whether time-out to this sampling process timing, and in time-out, alarm unit sends alarm
Signal.
After S20, sampling, the magnetic fluorescent microspheres in solution to be detected are attracted and fixed by magnetic field by microballoon adsorbent equipment
In the bottom of imaging chamber's cavity.
S30, laser emit laser to the imaging chamber, and the solution to be detected containing magnetic fluorescent microspheres swashs laser
It gives luminous.
The step S20 and S30 is specifically included:
S210, sampling process execution after the completion of, to microcontroller send absorption instruction, pass through microcontroller control second
Magnet is moved to below imaging chamber by transport mechanism;After the completion of absorption instruction performs, laser command is sent to microcontroller, is led to
It crosses microcontroller and opens laser;
It is (complete in place to judge whether absorption instruction performs with laser command according to the signal of corresponding optocoupler for S220, microcontroller
Into);When being not carried out in place, timing unit judges the second transport mechanism and whether laser works time-out, in time-out, alarm
Unit sends alarm signal.
S40, filtering apparatus are filtered the light of corresponding frequency band, and imaging device obtains the fluorogram after stimulated light filters
Piece.The step S40 is specifically included:
S410, after the completion of laser command, to microcontroller send optical filtering instruction, pass through microcontroller control optical filter turn
Disk turns to corresponding optical filter and filters, and opens the fluorescence picture that imaging device gathers solution to be detected;
Whether according to corresponding optocoupler signal, judging to filter to instruct performs in place for S420, microcontroller;It is being not carried out in place
When, timing unit judges whether the rotation of filter wheel is overtime, and in time-out, alarm unit sends alarm signal.
S50, sampling patterning device carry out stock layout, specifically comprise the following steps:
S510, filter instruction perform after the completion of, to microcontroller send stock layout instruction, plunger is controlled by microcontroller
Pump, the first solenoid valve and second solenoid valve, make the solution after the completion of the detection in imaging chamber be discharged from sampling needle, refer in stock layout
After the completion of order performs, clear instruction is sent to microcontroller, plunger pump, the first solenoid valve and the second electricity are controlled by microcontroller
Magnet valve makes the cleaning of the washed liquid of fluid path;
S520, microcontroller judge whether stock layout instruction and clear instruction perform in place according to corresponding optocoupler signal;
When being not carried out in place, timing unit judges whether stock layout and cleaning are overtime, and in time-out, alarm unit sends alarm signal.
Since the design feature of the detection method and automatic testing principle have elaborated in the above-described embodiments, herein
It does not repeat.
It will be understood by those skilled in the art that all or part of step of various methods can pass through in the above embodiment
Program instructs related hardware to complete, which can be stored in a computer readable storage medium, storage medium can wrap
It includes:Read-only memory, random access memory, disk or CD etc..
Use above specific case is illustrated the utility model, is only intended to help to understand the utility model, and
Not limiting the utility model.For those skilled in the art of the present invention, the think of according to the utility model
Think, several simple deductions, deformation can also be made or replace.