CN101923045A - Micro-fluidic chip observing platform and dual-visual field micro-fluidic chip observing system - Google Patents
Micro-fluidic chip observing platform and dual-visual field micro-fluidic chip observing system Download PDFInfo
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- CN101923045A CN101923045A CN 201010166212 CN201010166212A CN101923045A CN 101923045 A CN101923045 A CN 101923045A CN 201010166212 CN201010166212 CN 201010166212 CN 201010166212 A CN201010166212 A CN 201010166212A CN 101923045 A CN101923045 A CN 101923045A
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Abstract
The invention discloses a micro-fluidic chip observing platform and a dual-visual field micro-fluidic chip observing system using the same. The micro-fluidic chip observing platform comprises a first chamber body and a second chamber body which are separated from each other through a light-shielding wall; the first chamber body is parallel with the second chamber body; the upper end faces of the first chamber body and the second chamber body are formed into a chip observing end face; and the upper ends of the first chamber and the second chamber are respectively provided with an observation hole. A high-magnification microscope and a low-magnification microscope are respectively arranged above and under the place where the observing end face of the micro-fluidic chip observing platform is taken as a boundary; and the imaging light paths of the high-magnification microscope and the low-magnification microscope are not interfered with each other. During observing the micro-fluidic chip, the system can observe the multi-parameter and the multi-visual field simultaneously with the high-magnification microscope and the low-magnification microscope, leads the macroscopic data and the microcosmic data of the millimeter level micro-fluidic chip to be capable of being observed at the same time, and can be applied to observing the multi-parameter of experiments such as the hybrid reaction, the separation, the cell operation and the like of the micro-fluidic chip.
Description
Technical field
The present invention relates to micro-fluidic chip observation field, be specifically related to the wild micro-fluidic chip recording geometry of a kind of micro-fluidic chip measuring platform and double vision.
Background technology
Micro-fluidic chip has the generation of saving sample size, minimizing reaction time, reducing disaster accidents such as combustion explosion, design cycle and the development time that shortens the production consersion unit, saves advantages such as development cost.
In the reaction observation of micro-fluidic chip, often run into and exist two little typical structures need carry out visual observation simultaneously in the micro-fluidic chip, or key area need be through the observation of high power visualization system, and another subsidiary surveyed area also needs the comparatively situation of the low power visualization system observation of macroscopic view simultaneously.
Because the apparent size of microchip is less than the size of a microslide, the micro-fluidic chip size is tens millimeters ranks, the stock size of microscope stage is all tens millimeters ranks, therefore prior art is to adopt in the chip primary first-order equation for the reaction observation of a micro-fluidic device, can only use the microscope of a multiple to detect the parameter that can observe under the corresponding multiple; The measurement of other parameter then needs chip is carried out repeatedly identical reflection test, disposes the microscopic examination of different multiples simultaneously.
Repeated detection has increased experiment number, take time and effort, and since macroscopical quantity and microcosmic quantity be not acquisition simultaneously in primary first-order equation, the reliability of experimental result is lowered.
Summary of the invention
In view of this, in order to address the above problem, the invention discloses the wild micro-fluidic chip recording geometry of a kind of micro-fluidic chip measuring platform and double vision, the micro-fluidic chip measuring platform adopts the dual chamber structure to be arranged on the high-power microscope objective table, make high and low power microscope to gather and be one, simultaneously micro-fluidic chip is carried out the mensuration of microcosmic and bulk parameter, reduced unnecessary test loss, improved the reliability of test efficiency and test findings.
The object of the present invention is achieved like this: a kind of micro-fluidic chip measuring platform, comprise first cavity and second cavity that separate by the shading wall, first cavity and second cavity side by side, first cavity and the second cavity upper surface constitute the observation end face of micro-fluidic chip measuring platform; The observation end face of the first cavity correspondence has the first chip observation port, and the observation end face of the second cavity correspondence has the second chip observation port; Airtight shading around second cavity, lower ending opening; At least three airtight shadings of first cavity.
Further, the observation end face of second cavity correspondence top is provided with secondary light source;
Further, first cavity and the second cavity lower surface are stepped, and the second cavity lower surface is lower than the first cavity lower surface.
Use the wild micro-fluidic chip recording geometry of double vision of micro-fluidic chip measuring platform, comprise high-power microscope, low-power microscope, synchronous images acquisition processing system and micro-fluidic chip measuring platform; The micro-fluidic chip measuring platform is fixed on the objective table of high-power microscope; The high-power microscope camera lens is provided with towards the first chip observation port, the low-power microscope camera lens is provided with towards the second chip observation port, the observation end face that high and low power microscope lays respectively at the micro-fluidic chip measuring platform is the upper and lower on boundary, and the imaging optical path of high and low power microscope is opposite; The synchronous images acquisition processing system obtains image and processing by the image acquisition port of high-power microscope and low-power microscope.
Further, the first cavity lower surface is fixed on the objective table of high-power microscope, second cavity is upright to hang on by the objective table of high-power microscope, and high-power microscope is arranged at first cavity top of micro-fluidic chip measuring platform, and the high-power microscope camera lens is towards the first chip observation port; Low-power microscope is arranged in second cavity of micro-fluidic chip measuring platform, and the low-power microscope camera lens is towards the second chip observation port;
Further, be provided with secondary light source in first cavity;
Further, high-power microscope is an inverted microscope; The observation end face of the first cavity correspondence is fixed on the objective table of high-power microscope, and second cavity stands upside down and hangs on by the objective table of high-power microscope, and the high-power microscope camera lens is towards the first chip observation port; Low-power microscope is arranged in second cavity of micro-fluidic chip measuring platform, and the low-power microscope camera lens is towards the second chip observation port;
Further, be provided with secondary light source in first cavity;
Further, high-power microscope is metaloscope or fluorescent microscope or stereomicroscope or detects microscope or biological microscope; Low-power microscope is a portable microscope.
The invention has the beneficial effects as follows: the micro-fluidic chip measuring platform adopt the dual chamber structure on first cavity and second cavity microscope towards each cavity chip observation port is set respectively, make that tens millimeters level fluidic chips can be simultaneously by two microscopic examination; The observation end face that high and low power microscope lays respectively at the micro-fluidic chip measuring platform is the upper and lower on boundary, the imaging optical path of high and low power microscope is opposite, guaranteed that high and low power microscope does not disturb mutually in parallel, vertical moving, made things convenient for little, macro-data observation; In the observation, first, second cavity has adopted peripheral closed structure, has prevented that the mutual pass of light path from disturbing; Microcosmic and macro-data are observed simultaneously, have reduced experiment number, have improved the detected parameters reliability.
Description of drawings
In order to make the purpose, technical solutions and advantages of the present invention clearer, the present invention is described in further detail below in conjunction with accompanying drawing:
Fig. 1 shows the wild micro-fluidic chip recording geometry of double vision structure;
Fig. 2 shows the wild micro-fluidic chip recording geometry of inversion type double vision structure;
Fig. 3 shows the structure of micro-fluidic chip measuring platform;
Fig. 4 shows the another kind of structure of micro-fluidic chip measuring platform;
Fig. 5 shows the wild micro-fluidic chip recording geometry of the double vision structure that adopts Fig. 4 micro-fluidic chip measuring platform;
Fig. 6 shows microfluidic chip structure.
Embodiment
Below will describe in detail the preferred embodiments of the present invention.
In red cell deformability is measured, need on the microcosmic emphatically single erythrocytic mechanical property to be studied, also need glutinousness, light transmission, electric conductivity harmony conduction etc. to measure on the macroscopic view to red blood cell suspension.
The description value of red cell deformability comprises shearing force, flow speed value, force value or the like.Block the change value of pressure that produces when in the present research red blood cell being crossed the microchannel and adopt external pressure mode such as measurement indirectly mostly.The wild micro-fluidic chip recording geometry of double vision is introduced image measurement technology, can at the ultramicroscopic observation red blood cell in microchannel internal strain situation, use the low-power microscope extract real-time red blood cell velocity amplitude of this moment in observation area, flat bed chamber.React getting in touch between red cell deformability and its velocity amplitude intuitively.
Be used for micro-fluidic chip synoptic diagram that this red cell deformability measures as shown in Figure 6, comprise chip lower surface 17, chip upper surface 18, injection port 19, flat bed raceway groove observation area 20, observation area, microchannel 21 and liquid outlet 22.
Experiment can adopt the wild micro-fluidic chip recording geometry of double vision respectively the image acquisition analyzing and processing to be carried out in two typical microstructure flat bed raceway groove observation areas 20 on the chip and the fluid in the observation area, microchannel 21.The fluid acquisition of 20 sections of flat bed raceway groove observation areas is used for the flow velocity of analytical calculation cell in the flat bed chamber in the chip.Under the condition of constant pressure, the red blood cell flow velocity that 21 place's blockage phenomenon will make flat bed see raceway groove observation area 20 in the observation area, microchannel reduces.The stream velocity amplitude of measuring flat bed raceway groove observation area 20 can reflect that red blood cell is in colony's anamorphic effect of crossing 21 sections of observation areas, microchannel.
Image acquisition to observation area, microchannel 21, can obtain single red blood cell and cross the deformation effect of microchannel, the process high speed video system is to monitor herein, can also obtain more the red blood cell of details and cross the microchannel image, work was to the more depth analysis of red blood cell deformation after this view data will help to carry out.
Embodiment one,
As shown in Figure 6, micro-fluidic chip 5 sizes are: long 50mm, wide 28mm, high 5mm;
As shown in Figure 3, the micro-fluidic chip measuring platform comprises by the shading wall every 7 first cavity of opening 1 and second cavitys 2, first cavity 1 and second cavity 2 are side by side, observation end face 11 sizes that the upper surface of first cavity 1 and second cavity 2 constitutes observation end face 11, the first cavity correspondences of micro-fluidic chip measuring platform are: 35 * 35mm
2, first cavity height is 55mm; The observation end face 11 of the first cavity correspondence has size: 20 * 20mm
2The first chip observation port 14; 1 at least three airtight shading of first cavity.
As shown in Figure 1, the wild micro-fluidic chip recording geometry of double vision is made up of the portable low-power microscope 6 of the high power digital display micro mirror 9 of a 50-500 x magnification, 100 times of enlargement factors, micro-fluidic chip measuring platform and synchronous images acquisition processing system 12;
Objective table 8 sizes of high-power microscope 9 are: long 76mm, wide 52mm.
During observation, the lower surface 10 of first cavity is positioned on the objective table 8 of high-power microscope 9 of 200 x magnifications, makes the upright objective table 8 that hangs on of second cavity other;
The high-power microscope 9 of 200 x magnifications is arranged at the first chip observation port, 14 tops, and high-power microscope 9 camera lenses regulate making observation area, microchannel E blur-free imaging towards the first chip observation port 14; According to the imaging needs, can in first cavity 1, secondary light source be set.
100 times of low-power microscope 6 are arranged in second cavity 2, and low-power microscope 6 camera lenses are towards the second chip observation port 13, make raceway groove observation area, the flat bed chamber D blur-free imaging of micro-fluidic chip 5; According to the needs of imaging, can in the secondary light source cavity 3 above the second chip observation port 13 of second cavity 2, secondary light source 4 be set.
Because the imaging light path of first cavity 1 is opposite with the imaging light path of second cavity 2, each microscopical spatial movement is independent of each other, and double microscope can be gathered in the macroscopic view and the micro-data of one observation micro-fluidic chip 5.
In micro-fluidic chip 5 observations, high and low power microscope is conveyed into synchronous images with detected realtime image data and gathers display system 12, and calculates group property and the single red blood cell deformation characteristic that red blood cell is crossed the microchannel in synchronous images collection display system 12.
The present invention adopts two microscopes document image simultaneously on the wild micro-fluidic chip recording geometry of a double vision, image is transferred to synchronous images and gathers display system, can calculate group property and single red blood cell deformation characteristic that red blood cell is crossed the microchannel.
Embodiment two,
Under the situation with embodiment one, the high-power microscope 9 that the wild micro-fluidic chip recording geometry of double vision of the present invention adopts can also be inverted microscope; As shown in Figure 2, the observation end face 11 of first cavity, 1 correspondence is fixed on the objective table 8 of high-power microscope 9, objective table 8 sides that second cavity 2 stands upside down and hangs on high-power microscope 9, and high-power microscope 9 camera lenses are towards the first chip observation port 14; Low-power microscope 6 is arranged in second cavity 5 of micro-fluidic chip measuring platform, and low-power microscope 6 camera lenses are towards the second chip observation port 13.
Embodiment three,
Micro-fluidic chip measuring platform disclosed by the invention such as Fig. 4, shown in Figure 5, more small in low-power microscope 5 physical dimension, can be positioned under the situation on high-power microscope 9 objective tables 8, the micro-fluidic chip measuring platform is on the basis of embodiment one and embodiment two employed micro-fluidic chip measuring platforms as shown in Figure 3, can change the size of second cavity 2 according to the size of low-power microscope 5, and the lower surface 16 of second cavity and the first cavity lower surface 10 are at grade.During observation, as shown in Figure 5, the micro-fluidic chip measuring platform is positioned on high-power microscope 9 objective tables 8, observes with the mode of embodiment one.Also can be by the mode of embodiment two, if adopt the micro-fluidic chip measuring platform shown in 4 to observe, here no longer.
Different with Lens according to micro-fluidic chip 5 sizes that are observed and high-power microscope objective table 8, objective table 8, the height of first, second cavity of micro-fluidic chip measuring platform of the present invention, the size of observation end face 11 and the openings of sizes of first, second chip observation port also will be done adaptive change.
High-power microscope 9 can also be metaloscope or fluorescent microscope or stereomicroscope or detect microscope or biological microscope.
This micro-fluidic chip measuring platform and use the wild micro-fluidic chip recording geometry of double vision of this measuring platform also to can be applicable to the multiparameter observation of the tests such as hybrid reaction, separation, cell manipulation of micro-fluidic chip.
The above only preferably is not limited to the present invention for of the present invention, and obviously, those skilled in the art can carry out various changes and modification and not break away from the spirit and scope of the present invention the present invention.Like this, if of the present invention these are revised and modification belongs within the scope of claim of the present invention and equivalent technologies thereof, then the present invention also is intended to comprise these changes and modification interior.
Claims (9)
1. micro-fluidic chip measuring platform is characterized in that: comprise first cavity and second cavity that separate by the shading wall, first cavity and second cavity side by side, first cavity and the second cavity upper surface constitute the observation end face of micro-fluidic chip measuring platform; The observation end face of the first cavity correspondence has the first chip observation port, and the observation end face of the second cavity correspondence has the second chip observation port; Airtight shading around second cavity, lower ending opening; At least three airtight shadings of first cavity.
2. a kind of micro-fluidic chip measuring platform as claimed in claim 1 is characterized in that: the observation end face top of the second cavity correspondence is provided with secondary light source.
3. a kind of micro-fluidic chip measuring platform as claimed in claim 2 is characterized in that: first cavity and the second cavity lower surface are stepped, and the second cavity lower surface is lower than the first cavity lower surface.
4. use the wild micro-fluidic chip recording geometry of double vision of the described micro-fluidic chip measuring platform of claim 1, it is characterized in that: comprise high-power microscope, low-power microscope, synchronous images acquisition processing system and micro-fluidic chip measuring platform; The micro-fluidic chip measuring platform is fixed on the objective table of high-power microscope; The high-power microscope camera lens is provided with towards the first chip observation port, the low-power microscope camera lens is provided with towards the second chip observation port, the observation end face that high and low power microscope lays respectively at the micro-fluidic chip measuring platform is the upper and lower on boundary, and the imaging optical path of high and low power microscope is opposite; The synchronous images acquisition processing system obtains image and processing by the image acquisition port of high-power microscope and low-power microscope.
5. the wild micro-fluidic chip recording geometry of double vision as claimed in claim 3, it is characterized in that: the first cavity lower surface is fixed on the objective table of high-power microscope, second cavity is upright to hang on by the objective table of high-power microscope, high-power microscope is arranged at first cavity top of micro-fluidic chip measuring platform, and the high-power microscope camera lens is towards the first chip observation port; Low-power microscope is arranged in second cavity of micro-fluidic chip measuring platform, and the low-power microscope camera lens is towards the second chip observation port.
6. the wild micro-fluidic chip recording geometry of double vision as claimed in claim 4 is characterized in that: be provided with secondary light source in first cavity.
7. the wild micro-fluidic chip recording geometry of double vision as claimed in claim 3, it is characterized in that: high-power microscope is an inverted microscope; The observation end face of the first cavity correspondence is fixed on the objective table of high-power microscope, and second cavity stands upside down and hangs on by the objective table of high-power microscope, and the high-power microscope camera lens is towards the first chip observation port; Low-power microscope is arranged in second cavity of micro-fluidic chip measuring platform, and the low-power microscope camera lens is towards the second chip observation port.
8. the wild micro-fluidic chip recording geometry of double vision as claimed in claim 6 is characterized in that: be provided with secondary light source in first cavity.
9. as the wild micro-fluidic chip recording geometry of the described any double vision of claim 3 to 7, it is characterized in that: high-power microscope is metaloscope or fluorescent microscope or stereomicroscope or detects microscope or biological microscope; Low-power microscope is a portable microscope.
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Cited By (12)
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| CN102289063A (en) * | 2011-08-30 | 2011-12-21 | 上海华碧检测技术有限公司 | Method for improving appearance inspection effect of continuous zoom stereomicroscope |
| CN102864078A (en) * | 2012-10-10 | 2013-01-09 | 重庆大学 | Microfluidic cell culture chip and real-time observation system thereof |
| CN105300943A (en) * | 2015-11-03 | 2016-02-03 | 中国科学院天津工业生物技术研究所 | Microscope integrated light path system used for fluorescence detection of liquid drops |
| CN107377021A (en) * | 2017-08-22 | 2017-11-24 | 大连纳普特恩智能科技有限公司 | A kind of human urine detection micro-fluidic chip of integrated globe lens microscopic observation |
| CN107478629A (en) * | 2017-09-04 | 2017-12-15 | 中国科学院苏州生物医学工程技术研究所 | A kind of large area digital pcr droplet fluorescence high pass amount detecting device and method |
| CN108415149A (en) * | 2018-01-29 | 2018-08-17 | 南开大学 | A kind of macro micro- double-view field synchronous imaging microscope |
| CN108732103A (en) * | 2018-06-01 | 2018-11-02 | 大连晓辉医药科技有限公司 | A kind of cell detection and sorter based on optofluidic imaging spectral |
| CN109550528A (en) * | 2018-12-14 | 2019-04-02 | 北京工业大学 | A kind of lossless observation method of multi-angle and device of micro-fluidic chip inner passage |
| CN110542687A (en) * | 2019-07-02 | 2019-12-06 | 中国工程物理研究院激光聚变研究中心 | Detection device and detection method for appearance defects of microscopic elements |
| CN112346231A (en) * | 2019-08-06 | 2021-02-09 | 山东远大朗威教育科技股份有限公司 | Reaction observation system |
| CN114740611A (en) * | 2021-01-07 | 2022-07-12 | 东北大学秦皇岛分校 | Microscopic imaging device for visualization of microfluidic chip channel |
| WO2022156052A1 (en) * | 2021-01-22 | 2022-07-28 | 中国石油大学(华东) | Microfluidic chip experimental platform having visualization and infrared thermal imaging functions |
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| US20040245102A1 (en) * | 2002-09-09 | 2004-12-09 | Gilbert John R. | Implementation of microfluidic components, including molecular fractionation devices, in a microfluidic system |
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| CN102289063A (en) * | 2011-08-30 | 2011-12-21 | 上海华碧检测技术有限公司 | Method for improving appearance inspection effect of continuous zoom stereomicroscope |
| CN102864078A (en) * | 2012-10-10 | 2013-01-09 | 重庆大学 | Microfluidic cell culture chip and real-time observation system thereof |
| CN102864078B (en) * | 2012-10-10 | 2014-03-19 | 重庆大学 | Microfluidic cell culture chip and real-time observation system thereof |
| CN105300943A (en) * | 2015-11-03 | 2016-02-03 | 中国科学院天津工业生物技术研究所 | Microscope integrated light path system used for fluorescence detection of liquid drops |
| CN107377021A (en) * | 2017-08-22 | 2017-11-24 | 大连纳普特恩智能科技有限公司 | A kind of human urine detection micro-fluidic chip of integrated globe lens microscopic observation |
| CN107478629A (en) * | 2017-09-04 | 2017-12-15 | 中国科学院苏州生物医学工程技术研究所 | A kind of large area digital pcr droplet fluorescence high pass amount detecting device and method |
| CN108415149A (en) * | 2018-01-29 | 2018-08-17 | 南开大学 | A kind of macro micro- double-view field synchronous imaging microscope |
| CN108732103A (en) * | 2018-06-01 | 2018-11-02 | 大连晓辉医药科技有限公司 | A kind of cell detection and sorter based on optofluidic imaging spectral |
| CN108732103B (en) * | 2018-06-01 | 2020-10-30 | 大连晓辉医药科技有限公司 | Cell detection and classification device based on optical flow control imaging spectrum |
| CN109550528A (en) * | 2018-12-14 | 2019-04-02 | 北京工业大学 | A kind of lossless observation method of multi-angle and device of micro-fluidic chip inner passage |
| CN109550528B (en) * | 2018-12-14 | 2020-11-27 | 北京工业大学 | Multi-angle nondestructive observation method and device for internal channel of micro-fluidic chip |
| CN110542687A (en) * | 2019-07-02 | 2019-12-06 | 中国工程物理研究院激光聚变研究中心 | Detection device and detection method for appearance defects of microscopic elements |
| CN112346231A (en) * | 2019-08-06 | 2021-02-09 | 山东远大朗威教育科技股份有限公司 | Reaction observation system |
| CN114740611A (en) * | 2021-01-07 | 2022-07-12 | 东北大学秦皇岛分校 | Microscopic imaging device for visualization of microfluidic chip channel |
| WO2022156052A1 (en) * | 2021-01-22 | 2022-07-28 | 中国石油大学(华东) | Microfluidic chip experimental platform having visualization and infrared thermal imaging functions |
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