CN204116189U - The imaging of intelligent optical miniflow and detection system - Google Patents
The imaging of intelligent optical miniflow and detection system Download PDFInfo
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- CN204116189U CN204116189U CN201420114285.7U CN201420114285U CN204116189U CN 204116189 U CN204116189 U CN 204116189U CN 201420114285 U CN201420114285 U CN 201420114285U CN 204116189 U CN204116189 U CN 204116189U
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Abstract
The utility model provides the imaging of a kind of intelligent optical miniflow and detection system, comprise: light source subsystem, liquid stream subsystem, micro-fluidic image collection chip subsystem, intelligent image analyzing subsystem, wherein light source subsystem provides light source, and its light sent is radiated on micro-fluidic image collection chip subsystem; Liquid stream subsystem is made up of sample input port, Micro-flow pipe, sample delivery outlet; Micro-fluidic image collection chip subsystem is made up of the image sensor chip being bonded to micro-fluidic chip, wherein micro-fluidic chip and image sensor chip direct neighbor, and without the need to object lens, and Micro-flow pipe is arranged on micro-fluidic chip; The image that image collection chip subsystem collects is imported into the sub-analytic system of intelligent image and analyzes.Intelligent optical miniflow of the present utility model imaging and detection system eliminate optical lens, inhibit tailing problem.
Description
Technical field
The utility model is a kind of intelligent optical miniflow detection system based on the multi-field cross-development of integrated circuit (IC) chip, MEMS (micro electro mechanical system), optical imagery and bio-science, is mainly applicable to the detection of liquid small (micron dimension) object (such as cell).
Background technology
Cell count all has very important significance in Basic of Biology research and clinical detection application.Such as, in drug development, often need investigate the action effect of medicine to target cell, need quantitatively to count cell; For confirming whether cancer patient exists cancer cell diffusion, also needs to count cancer cell in its blood in hospital.Therefore, to various types of cells, especially the quantitative counting fast and accurately of some specific rare cells seems abnormal important.The general flow cytometry that adopts is as main testing tool at present.Traditional flow cytometry (is entitled as the Chinese patent application No.200810038044.8 of " portable at vivo flow cytometry ", and be entitled as the Chinese patent application No.201020613651.5 of " a kind of flow cytometer ") mainly pass through spectral discrimination method, utilize the lit transmissive of different cell to specific wavelength and the difference of reflected signal, carry out distinguishing and count.But this system needs integrated optical source and optical detector accurately, therefore bulky and involve great expense, process is complicated, and needs professional to operate, and is not suitable for execute-in-place.
Also can pass through formation method in addition, namely distinguish different cell by the method for cell imaging under the microscope.Cell Measurement Technique conventional at present adopts the microchannel of surface chemistry technology to catch cell, and its counting still realizes under conventional microscope, cannot adapt to high-throughout demand.Such as, be entitled as the Chinese patent application No.200810179322.I of " cellanalyzer and analytical approach ", and be entitled as " a kind of method for cell count based on image recognition " Chinese patent application No.201010282484.5 open file in just describe a kind of cell analysis counting assembly needing to use conventional microscope.
Need to carry out micro-imaging to the cell of flowing fast as flow cytometer, usually need to overcome two subject matters: 1) microscopical depth of focus adjustment.In order to make cell imaging clear, the cell of flowing must be constrained in microscopical focal depth range.Depth of focus depends primarily on the numerical aperture of microcobjective, and for the image-forming objective lens that numerical aperture is very large, depth of focus is very little, is difficult to sample to constrain in focal depth range.When the size of cell to be measured is greater than depth of focus, system can only become sharply defined image to the local of cell, and the part be in outside depth of focus will obtain defocus blur picture.2) to the cell imaging of flowing.Owing to there is relative motion between cell and camera, streaking problem can be caused.Usually can by reducing the time shutter, the distance that cell is moved in exposure time range is less than the spatial resolution of imaging, and cell is approximately static, thus overcomes tailing problem, but the shorter time shutter will reduce the sensitivity of system.If adopt the cell of special time delays integration camera (TDI camera) to flowing to take, the flow direction of cell picture is identical with the direction of line scan of camera and synchronous, relative to camera, in whole process, cell remains static, thus overcomes tailing problem.But TDI camera is expensive, bulky, adopt the detection of TDI camera that the cost of system will be made to increase, and if the slightly different step of the line scanning of the flow velocity of cell and TDI camera, also can cause hangover.
Therefore, these cell counter technology existing are difficult to the demand meeting particularly clinical detection field, each field instantly at present.
Utility model content
In view of the above-mentioned subject matter mentioned, the intelligent optical miniflow imaging of setting forth in the utility model and detection system adopt advanced in lens micro imaging system device, comprise light source subsystem, liquid stream subsystem, micro-fluidic image collection chip subsystem, intelligent image analyzing subsystem.
Light source subsystem provides light source, and its light sent is radiated on micro-fluidic image collection chip subsystem.
Liquid stream subsystem is made up of sample input port, Micro-flow pipe, sample delivery outlet.
Micro-fluidic image collection chip subsystem is made up of the image sensor chip being bonded to micro-fluidic chip, wherein micro-fluidic chip and image sensor chip direct neighbor, and without the need to object lens, and Micro-flow pipe is arranged on micro-fluidic chip.
The image that image collection chip subsystem collects is input to intelligent image analyzing subsystem and analyzes, such as cell detection, identification, differential count etc.
In an embodiment of the present utility model, image sensor chip is cmos image sensor chip.In addition, also ccd image sensor chip can be adopted.
In an embodiment of the present utility model, micro-fluidic chip is transparent PDMS(Polydimethylsiloxane, dimethyl silicone polymer) micro-fluidic chip.
In an embodiment of the present utility model, micro-fluidic chip is directly fitted on image sensor chip.
In an embodiment of the present utility model, light source subsystem adopts LED.Can adopt in addition as Halogen lamp LED, monochromatic source, laser beam etc.
In an embodiment of the present utility model, sample input port is equipped with micro-injection pump.
In an embodiment of the present utility model, sample delivery outlet is equipped with the container collecting waste liquid.
Owing to eliminating optical lens, the limitation that when this pick-up unit can not only overcome micro-imaging effectively, depth of focus is little, and be different from the side direction imaging mode of other imaging flow cytometer, the imaging direction of system is parallel with the flow direction of cell, thus can tailing problem be suppressed, image quality is more clear.Relative to traditional flow cytometry, intelligent optical miniflow of the present utility model imaging and detection system have larger advantage, can carry out micro-imaging to cell, obtain form and the internal structural information of cell.Rely on integrated intelligent image analytic system, can different cell be distinguished, be detected simultaneously, improve detection speed, realize high-throughout feature.
The intelligent optical miniflow imaging of setting forth in the utility model and detection system also have low cost, carrying portable, analysis fast, high flux and easy-operating feature.
Accompanying drawing explanation
Fig. 1 is the general frame of intelligent optical miniflow imaging according to the utility model one embodiment and detection system, illustrated therein is the sectional view of micro-fluidic image collection chip subsystem.
Fig. 2 is the vertical view of the micro-fluidic image collection chip subsystem according to the utility model one embodiment.
Fig. 3 is the schematic three dimensional views of the micro-fluidic image collection chip subsystem according to the utility model one embodiment.
Fig. 4 is the concrete block diagram of the image analysis system according to the utility model one embodiment.
Embodiment
In order to understand the utility model better, below in conjunction with accompanying drawing, embodiment of the present utility model is elaborated.But protection domain of the present utility model is not only confined to the following examples.Those skilled in the art can make various changes or modifications the utility model, and these equivalent form of values are equally within the scope of appended claims restriction.
Fig. 1 is the general frame of intelligent optical miniflow imaging according to the utility model one embodiment and detection system 100, illustrated therein is the sectional view of micro-fluidic image collection chip subsystem.
Comprise according to the intelligent optical miniflow imaging of the utility model one embodiment and detection system 100: light source subsystem, liquid stream subsystem, micro-fluidic image collection chip subsystem and intelligent image analyzing subsystem.
Liquid stream subsystem comprises: form the sample input port 101 in sample fluid path, Micro-flow pipe 102 and sample delivery outlet 103; Be contained in the sample input apparatus being used for driving sample reagent loading Micro-flow pipe 102 and Quality control flow velocity of sample input port 101, such as micro-injection pump 104; And be contained in the container 105 of collection waste liquid of sample delivery outlet 103.
Micro-fluidic image collection chip subsystem is integrated with the PDMS micro-fluidic chip 106 and cmos image sensor chip 201 that carry sample in liquid stream subsystem.
The material of micro-fluidic chip can adopt the other materials except PDMS, such as but not limited to PC(polycarbonate, polycarbonate), PMMA(poly-methylmethacrylate, poly-sour methyl esters), PS(polystyrene, polystyrene), PET(polyethylene terephthalate, polyethylene terephthalate), PVC(polyvinyl chloride, Polyvinylchloride), PFA(perfluoroalkoxy, perfluoroalkoxy resin), FEP(fluorinated ethylenepropylene, perfluoroethylene-propylene), COC(Cyclic Olefin Copolymer, cyclic olefine copolymer), TPE(Thermoset Polyester, thermosetting polyester), PUMA(Polyurethane Methacrylate, urethane methacrylate) etc.
Except cmos image sensor chip, image sensor chip can also adopt ccd image sensor chip etc.
Micro-flow pipe is carved with in the bottom surface of micro-fluidic chip 106, its entrance and exit is arranged on the surface of PDMS micro-fluidic chip 106 and is distributed in its two ends, be connected with the Micro-flow pipe 102 outside micro-fluidic chip 106, the size of this Micro-flow pipe 102 depends on the size of sample.Such as when being applied to the Concentration Testing of red blood cell and HepG2 cell in sample, the size of this pipeline 102 can be such as 100 μm (width), 30 μm (highly).
In sample fluid path, Micro-flow pipe 102 is connected with sample delivery outlet 103 with sample input port 101 respectively.Sample input port 101 and sample delivery outlet 103 can be sample I/O flexible pipes.
Present composition graphs 2 is described the image collection chip subsystem in intelligent optical miniflow of the present utility model imaging and detection system 100.Image collection chip subsystem in intelligent optical miniflow of the present utility model imaging and detection system 100 removes object lens, make the micro-fluidic chip with the making of PDMS material and cmos image sensor chip (hereinafter referred to as " CMOS chip ") direct neighbor, thus can directly projection imaging.Traditional biological sample recording geometry adopts microscope or digital camera shooting, needs to arrange object lens, can play the effect of amplifying object under test details, but the method involves great expense between camera and object microslide, and system bulk is comparatively large, should not carry.Light-sensitive surface (the i.e. pel array 202) distance of general Micro-flow pipe and CMOS chip is more near better; if CMOS chip and Micro-flow pipe are at a distance of too large; diffraction effect can reduce image contrast; so in an embodiment of intelligent optical miniflow of the present utility model imaging and detection system; first remove the glassy layer being usually present in and playing insulation blocking effect above cmos sensor encapsulation 203; to expose cmos sensor nude film 204, then the bottom surface of the light-sensitive surface of sensor die 204 and PDMS micro-fluidic chip is directly fit together.
In this embodiment of intelligent optical miniflow of the present utility model imaging and detection system, for ensureing fitting tightly of CMOS chip and PDMS micro-fluidic chip, first cover the very thin PDMS film 205 of one deck on the surface of sensor die 204 by spinning.Afterwards the bottom surface of ready-made micro-fluidic chip is starched with the CMOS chip light-sensitive surface oxygen electricity covering PDMS film 205 and process, then the two is directly compressed laminating.Outside the encapsulation closing line 206 of connecting sensor encapsulation 203 and sensor die 204 is directly exposed to after removing cover glass; therefore after having fitted; also needing to get the PDMS prepared is coated on around micro-fluidic chip 106; to fill up closed by the groove between the sensor package 203 of its surrounding and sensor die 204, thus form complete PDMS sealing 207.
In order to utilize photosensitive regions of pixels completely, Micro-flow pipe Design of length is the catercorner length of the pel array of approximate cmos image sensor, and the width design of passage is 100 μm, and such sample can flow in relatively straight and stable mode in this passage.In addition, the height of passage is 30 μm, slightly higher than normal sample size, thus ensures that sensor surface flowing pressed close to by sample, ensures better projects images contrast.
Usually be arranged on above above-mentioned CMOS chip according to the light source subsystem in the intelligent optical miniflow imaging of the utility model one embodiment and detection system 100.The light sent when light source is incident in Micro-flow pipe, the sample flowed in passage by be projected in bottom CMOS chip pixel array on and photosensitive imaging.In order to avoid the harmful effect that the refraction in passage brings, it will be understood by those skilled in the art that the light that light source sends can be adjusted to vertical or near vertical be incident in Micro-flow pipe.
Light source subsystem can adopt LED.Can adopt in addition as Halogen lamp LED, monochromatic source, laser beam etc.
Micro-injection pump in liquid stream subsystem is by the Micro-flow pipe UNICOM in input flexible pipe and chip, when the biological microfluidic sample injected by syringe pump flows through passage, fluid sport video is recorded by imageing sensor, then through data line, this transmission of video is carried out process and the preservation of image to the situation of intelligent image analyzing subsystem Real Time Observation microfluidic flow, the sample after measurement collected by delivery hose UNICOM waste liquid pool.
Schematic three dimensional views referring now to an embodiment of image collection chip subsystem in Fig. 3 is specifically described it.Different types of flow cell 301 width be W, highly for H Micro-flow pipe 302 in flow, under the irradiation of white light source 303, these flow cells project to the pel array 304 of cmos image sensor, and imageing sensor collects projected low pixel cytological map 305.
Intelligent image analyzing subsystem, based on real-time graphical analysis, obtains the image informations such as the form of sample, size, and then reaches and to identify sample and count.Referring to Fig. 4, intelligent image analyzing subsystem is described.
Fig. 4 is the concrete block diagram of the image analysis system 400 according to the utility model one embodiment.This image analysis system 400 comprises cell image motion detection unit 401, cell classification recognition unit 402 and image structure similarity counting unit 403.
The cell outline of cell image motion detection unit 401 to flowing is analyzed, and detects the original image of cell.
The sample stored under the cell original image detected and line compares by cell classification recognition unit 402.
The cell of structural similarity in threshold value is divided in respective classes by image structure similarity counting unit 403, and the cell count to respective classes.
The utility model provides the imaging of a kind of lensless intelligent optical miniflow and detection system.Compare with the recording geometry of conventional optical microscope, device of the present invention does not need lens can count a large amount of plasmic DNA of Large visual angle.In addition, based on intelligent image analyzing subsystem, the error caused owing to artificially judging can be reduced, save labour simultaneously.Owing to being integrated with microfluid sample passage on image sensor chip, sample passes through the mode of flowing continuously across tested region, therefore can the object of Real-Time Monitoring thousands of variable concentrations, considerably improve flux rate when not affecting quality (precision) of imaging measurement data thus substantially reduce Measuring Time.
The imaging of this intelligent optical miniflow and detection system combine the advantage of digital imagery chip and micro-fluidic chip, show many attracting characteristics, such as: cost is low, miniaturization, robotization, be easy to operation and be easy to the system integration.These character and advantage make the imaging of high-precision intelligent optical miniflow and detection system very be suitable as field detecting device.
Claims (10)
1. the imaging of intelligent optical miniflow and a detection system, comprising:
Light source subsystem, liquid stream subsystem, micro-fluidic image collection chip subsystem, intelligent image analyzing subsystem,
Wherein said light source subsystem provides light source, and its light sent is radiated on described micro-fluidic image collection chip subsystem;
Described liquid stream subsystem is made up of sample input port, Micro-flow pipe, sample delivery outlet;
Described micro-fluidic image collection chip subsystem is made up of the image sensor chip being bonded to micro-fluidic chip, wherein said micro-fluidic chip and described image sensor chip direct neighbor, without the need to object lens, and described Micro-flow pipe is arranged on described micro-fluidic chip;
The image that described image collection chip subsystem collects is imported into described intelligent image analyzing subsystem and analyzes.
2. intelligent optical miniflow imaging as claimed in claim 1 and detection system, it is characterized in that, described image sensor chip is cmos image sensor chip.
3. intelligent optical miniflow imaging as claimed in claim 1 and detection system, it is characterized in that, described micro-fluidic chip is transparent PDMS micro-fluidic chip.
4. intelligent optical miniflow imaging as claimed in claim 3 and detection system, it is characterized in that, described PDMS micro-fluidic chip is directly fitted on described image sensor chip.
5. intelligent optical miniflow imaging as claimed in claim 1 and detection system, is characterized in that, described light source subsystem adopts LED as light source.
6. intelligent optical miniflow imaging as claimed in claim 1 and detection system, it is characterized in that, described Micro-flow pipe is arranged on the bottom surface of described micro-fluidic chip.
7. intelligent optical miniflow imaging as claimed in claim 1 and detection system, it is characterized in that, described sample input port is equipped with micro-injection pump.
8. intelligent optical miniflow imaging as claimed in claim 1 and detection system, is characterized in that, described sample delivery outlet is equipped with the container collecting waste liquid.
9. intelligent optical miniflow imaging as claimed in claim 1 and detection system, it is characterized in that, described image analysis system comprises cell image motion detection unit, cell classification recognition unit and image structure similarity counting unit.
10. intelligent optical miniflow imaging as claimed in claim 2 and detection system, it is characterized in that, the Design of length of described Micro-flow pipe is the catercorner length of the pel array of approximate cmos image sensor.
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| CN106483276A (en) * | 2016-09-29 | 2017-03-08 | 大连理工大学 | A kind of optofluidic blood cell micro imaging system based on smart mobile phone |
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| CN107102058A (en) * | 2017-05-05 | 2017-08-29 | 杭州电子科技大学 | It is a kind of to be imaged based on what surface acoustic wave drove without lens miniflow and its detecting system |
| CN109655383A (en) * | 2017-10-11 | 2019-04-19 | 南京大学 | A kind of detection device and its method based on blood platelet projection imaging |
| CN107907471A (en) * | 2017-10-26 | 2018-04-13 | 刘峰 | A kind of cellular assay counting device |
| CN108680503A (en) * | 2018-05-18 | 2018-10-19 | 王闯 | Liquid controls chip and system |
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