CN105388131A - Fluorescence detection instrument and system based on micro-fluidic chip - Google Patents

Fluorescence detection instrument and system based on micro-fluidic chip Download PDF

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Publication number
CN105388131A
CN105388131A CN201410455944.8A CN201410455944A CN105388131A CN 105388131 A CN105388131 A CN 105388131A CN 201410455944 A CN201410455944 A CN 201410455944A CN 105388131 A CN105388131 A CN 105388131A
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China
Prior art keywords
micro
fluidic chip
instrument
module
fluorescence
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Pending
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CN201410455944.8A
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Chinese (zh)
Inventor
蒋兴宇
沈海滢
张伟
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National Center for Nanosccience and Technology China
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National Center for Nanosccience and Technology China
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Priority to CN201410455944.8A priority Critical patent/CN105388131A/en
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Pending legal-status Critical Current

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Abstract

The invention provides a fluorescence detection instrument and system based on a micro-fluidic chip. The instrument comprises an instrument frame, a light source, a micro-fluidic chip supporting structure, a fluorescence collection module, a light path fixing module and a fluorescence detection module, wherein the light source, the micro-fluidic chip supporting structure, the fluorescence collection module, the light path fixing module and the fluorescence detection module are installed on the instrument frame, the light source is used for stimulating a fluorescent substance on the chip to emit fluorescent light, the micro-fluidic chip supporting structure is used for supporting and moving the chip, and the fluorescence collection module is used for filtering, collecting and focusing a fluorescence signal on the micro-fluidic chip onto the fluorescence detection module; the light path fixing module is used for fixing the position of the fluorescence collection module and for light path adjustment, and the fluorescence detection module is used for converting a received optical signal into an analog electrical signal and then converting the analog electrical signal into a digital electrical signal. The instrument is connected with a computer to form a system. The instrument can meet the requirement for fluorescence detection on the micro-fluidic chip. The instrument is high in resolution ratio and sensitivity, simple and compact in structure, small in size, and convenient to carry and use.

Description

Based on fluorescence detection equipment and the system of micro-fluidic chip
Technical field
The present invention relates to microfluidic chip analysis technical field, particularly relate to a kind of fluorescence detection equipment based on micro-fluidic chip and system.
Background technology
Microfluidic analysis method is the technology that new development is in recent years got up, the method is based on analytical chemistry, in conjunction with biological chemistry, molecular biology, physical chemistry, the achievement of the related disciplines such as immunology, in micron scale construction, manipulation is received and is risen to skin and rise volume fluid, treat side material and carry out analysis detection, there is volume little, specific surface area is large, reaction time is short, analysis speed is fast, reagent and amount of samples few, the advantages such as Multi-example multi objective detects simultaneously, to the discovery of diseases related mark and disease early diagnosis in clinical disease research, there is important practical to be worth.
Conventional diagnostic analysis method needs long analysis time, Liquid-treatment processes is also cumbersome, flux smaller (at every turn can only detect one or several samples), and need many antibody reagents, microfluidic analysis chip then can overcome these shortcomings effectively.Such as, when the sample that analyzing samples amount is considerably less, microflow control technique shows extremely strong advantage, usually need sample size be several milliliters experiment employing microflow control technique after, only need the sample size of a few microlitre, greatly save the consumption of sample and reagent.At clinical immunization detection field, the combination of microfluidic analysis technology and immunoassay, can also overcome other shortcoming that traditional immunization is analyzed to a certain extent, therefore, cause the extensive concern of clinical laboratory medicine in recent years.Microflow control technique is applied to immune detection can the raising of greatly Promote immunity detection technique, is with a wide range of applications and important using value.
In current Microfluidic Immunoassay method, although micro-fluidic chip volume is very little, but the detecting instrument volume supporting with micro-fluidic chip is general very large, is not easy to widespread use and the popularization of micro-fluidic detection method, and can not embody the micro-fluidic advantage in this one side of easy quick detection completely.Therefore, be necessary to develop a kind of small-sized micro-fluidic chip analyzer device, realize the organic combination of sampling and analysis of signal process, make microflow control technique microminiaturized, easy.As CN103674934A discloses a kind of micro-fluidic chip Image-forming instrument for chemiluminescence detection and system, this instrument can carry out effective Collection and analysis to the chemiluminescence signal on micro-fluidic chip, this instrument volume is little, is a kind of novel portable micro-fluidic chip analyzer.
Fluorescence analysis is a kind of conventional analytical approach, fluorescence analysis equipment used is simpler, have the advantage that specificity is good, the range of linearity is wide, oneself is widely used in the every field such as life science, clinical medicine, environment measuring in recent years, plays huge effect in clinical diagnosis work.Effectively can reduce the requirement of micro-fluidic chip to pick-up unit after microfluidic chip technology being combined with fluorescence detection method, reduce the volume of pick-up unit, be convenient to applying of microfluidic chip technology.Such as CN100557419C discloses a kind of fluorescence detection optical device with microflow control chip, applied widely, and flexibly, data processing is completed by computing machine, and the fast precision of speed is high in adjustment; CN1865932A discloses a kind of fluorescence detection device for micro-fluidic chip system, the parasitic light covering fluorescence area in laser can filter by this device, effectively improve the detection sensitivity of instrument, reduce the distance between light source and microchannel as far as possible, reduce the volume of instrument further, reduce cost; CN103529006A discloses a kind of Portable fluorescence pick-up unit based on micro-fluidic chip and detection method thereof, the device invented have volume little, lightweight, be easy to carry and low-cost advantage, can be hand-held, be specially adapted to Site Detection, and detection sensitivity is high, in very faint fluorescence signal context of detection, there is unique advantage.
But the micro-fluidic chip fluorescence detection device of current immune detection aspect can't take into account volume, resolution and sensitivity, the requirement of fast development to its corresponding instrument of present microfluidic chip technology therefore can not be met.
Summary of the invention
The object of the invention is to propose a kind of fluorescence detection equipment based on micro-fluidic chip and system, the needs carrying out fluorescent method detection on micro-fluidic chip can be met, described instrument has higher resolution and sensitivity, and instrument is simple and compact for structure.
For reaching this object, the present invention by the following technical solutions:
On the one hand, the invention provides a kind of fluorescence detection equipment based on micro-fluidic chip, comprising: apparatus frame and the light source, micro-fluidic chip supporting structure, phosphor collection module, light path stuck-module and the fluoroscopic examination module that are installed on described apparatus frame.
Described light source, between phosphor collection module and micro-fluidic chip supporting structure, produces fluorescence for exciting the fluorescent material on micro-fluidic chip; Described micro-fluidic chip supporting structure is used for mobile micro-fluidic chip, and adjustment micro-fluidic chip position, makes the fluorescence signal region of micro-fluidic chip be positioned at immediately below phosphor collection module collection region; Described phosphor collection module is made up of reflective mirror, optical lens group and the optical filter be arranged in optical lens group, for being filtered, collecting and focus on fluoroscopic examination module by the fluorescence signal on micro-fluidic chip; Described light path stuck-module is used for the position of fixed optics lens combination and the adjustment of light path and fixes; Described fluoroscopic examination module is used for changing the optical signalling of reception into analog electrical signal, then changes analog electrical signal into digital electric signal.
As the preferred technical scheme of the present invention, instrument of the present invention also comprises power switch.
Micro-fluidic chip of the present invention, preferably comprises basalis and functional layer from bottom to top successively.Basalis is fixed with catches protein band.Functional layer is made up of two essential parts, and first essential part is linear pattern Micro-flow pipe, and immune response occurs in the substrate in pipeline; Second essential part is the injection port of linear pattern Micro-flow pipe both sides.
Described apparatus frame is light closed structure.
Described light source is LED, bromine tungsten filament lamp or laser instrument.The advantage such as LED has energy-efficient, environmental protection, optical efficiency is high, safety coefficient is large, its wavelength sending light is 488nm; Bromine tungsten filament lamp is also called Halogen lamp LED, bromine tungsten filament lamp adopts hydrogen bromide technique, light efficiency is high, the life-span is long, photochromic good, a kind of objectively novel, and use a kind of lamp widely, its wavelength coverage sending light is 320-2500nm, is the perfect light source of Visible-to-Near InfaRed wave band, can carry out Absorption and fluorescence spectrum analysis to material; Laser instrument utilizes stimulated radiation principle that light is amplified in some material be stimulated or the device launched that vibrates, and it can directional lighting, and the laser brightness sent is high, color is extremely pure and energy density large, and its wavelength coverage sending light is wider.
The wavelength of transmitted light of described light source is less than or equal to the feature excitation wavelength of described fluorescent material.
The center of the reflective mirror of described phosphor collection module, optical lens group and optical filter three is on same level line.
The utilizing emitted light that fluorescent material produces by exciting light elimination, can pass through by described optical filter, so the fluorescence that the fluorescent material on micro-fluidic chip produces arrives optical lens group by described optical filter, is finally detected by fluoroscopic examination module.
Described micro-fluidic chip supporting structure is chip tray, preferred plug-type chip tray.
Described fluoroscopic examination module is CCD camera, described CCD camera horizontal positioned.
Described fluoroscopic examination module is connected with computing machine, and described computing machine receives and processes the digital electric signal from described detection module.
Described instrument entirety is in cuboid; Preferably, the length of described cuboid three adjacent edges is 40cm, 15cm, 15cm respectively.
On the other hand, present invention also offers a kind of fluorescence detecting system based on micro-fluidic chip, comprise the described fluorescence detection equipment based on micro-fluidic chip and connected computing machine.
Fluorescence detection equipment of the present invention and system adopt surface imaging, that the fluorescence signal in a plane is carried out reading and analyzing, photoelectric conversion device is CCD (charge coupled device), can realize the input of multiple passage, and testing result is picture; Adopt LED light source, bromine tungsten filament lamp or laser instrument as light source, effective and reduce cost; Chip tray adopts push-and-pull design, and photophobism is good, and chip is put into convenient to remove, accurately can determine the locus of chip simultaneously, is convenient to detect; Use reflective mirror, light path generation right angle is changed, CCD horizontal positioned can be made, utilize space to the full extent.
Compared with prior art, beneficial effect of the present invention is:
1, instrument has higher resolution and sensitivity, can meet the needs carrying out fluorescent method detection on micro-fluidic chip;
2, instrument is simple and compact for structure, and volume is little, easy to carry and use, achieves the integrated of detection system, is convenient to carry out Site Detection;
3, system is simple, and processing and manufacturing is with low cost.
Accompanying drawing explanation
Fig. 1 is the structural representation of the fluorescence detecting system that the present invention is based on micro-fluidic chip.
Fig. 2 is the light path schematic diagram of the fluorescence detecting system that the present invention is based on micro-fluidic chip.
Fig. 3 is the micro-fluidic immune detection result photo that the present invention passes through to read based on the fluorescence detecting system of micro-fluidic chip.
Wherein: 1, light source; 2, reflective mirror; 3, optical filter; 4, optical lens group; 5, light path stuck-module; 6, fluoroscopic examination module; 7, micro-fluidic chip supporting structure; 8, apparatus frame; 9, power switch; 10, computing machine; 11, micro-fluidic chip.
Embodiment
Technical scheme of the present invention is further illustrated by embodiment below in conjunction with accompanying drawing.
Be illustrated in figure 1 the structural representation of the fluorescence detecting system based on micro-fluidic chip.System combines primarily of apparatus frame 8, light source 1, reflective mirror 2 and optical lens group 4, optical filter 3, light path stuck-module 5, fluoroscopic examination module 6, micro-fluidic chip supporting structure 7, power switch 9 and computing machine 10.Wherein, apparatus frame 8 fixing for each module position of instrument; Light source 1 is for exciting the fluorescent material on micro-fluidic chip 11; Reflective mirror 2 and optical lens group 4 are for by the fluorescence signal collection on micro-fluidic chip 11, the surface focusing on fluoroscopic examination module 6; Optical filter 3 is for producing the veiling glare beyond fluorescence in Filter Examination; Light path stuck-module 5 is for the position of fixed optics lens combination 4 and the adjustment of light path and fix; Fluoroscopic examination module 6 changes the optical signalling obtained into analog electrical signal, then analog electrical signal is changed into digital electric signal and be transferred to computing machine 10; Micro-fluidic chip supporting structure 7 is for supporting and mobile micro-fluidic chip 11, and adjustment micro-fluidic chip 11 position, and the fluorescence signal region of micro-fluidic chip 11 is in immediately below the observation area of detection system.
Fig. 2 is the light path schematic diagram of the fluorescence detecting system based on micro-fluidic chip.Micro-fluidic chip supporting structure 7 pulled out, micro-fluidic chip 11 is placed on micro-fluidic chip supporting structure chip tray 7, pushes micro-fluidic chip supporting structure 7, avoids external light influence; The fluorescent material of micro-fluidic chip 11, under the exciting of light source 1, is produced fluorescence signal, is collected after signal is reflected by reflective mirror 2 by optical filter 3 and optical lens group 4; Fluoroscopic examination module 6 changes the optical signalling being irradiated to its surface into electrical signal, and then is transferred to computing machine 10 and carries out data processing and analysis.
Embodiment 1
Its functional layer of micro-fluidic chip 11 that the present embodiment is selected is formed primarily of rectangular parallelepiped passage and conical injection port, and channel width is 500 microns, is highly 500 microns.The optical filter 3 that the present embodiment is selected is the FF-05 optical filter at Daheng's optical thin film center; Fluorescent material on micro-fluidic chip 11 is FITC, and its molecular weight is 389.4, and absorption maximum optical wavelength is 490 ~ 495nm, and emission maximum optical wavelength is 525 ~ 530nm; The light source 1 selected is LED light source; The fluoroscopic examination module 6 selected is CCD camera; The micro-fluidic chip supporting structure 7 selected is chip tray.Micro-fluidic chip 11 substrate covers longitudinal Micro-flow pipe, and pass into AFP (first tire antigen) capture antibody in A/B/C/D/E pipeline, sucking-off after 30 minutes, throws off longitudinal Micro-flow pipe; Cover horizontal Micro-flow pipe, in pipeline after bovine serum albumin solution is closed, AFP antigen 0ng/mL is added successively in 1/2/3/4/5 pipeline, 20ng/mL, 40ng/mL, 80ng/mL, 160ng/mL, after hatching 30 minutes, pass into cleaning fluid successively, FITC mark AFP detects antibody, cleaning fluid; Be placed on the chip tray of this instrument by micro-fluidic chip 11, push pallet to assigned address, open instrument and detect analytic function software, read fluorescence signal, test findings as shown in Figure 3.As can be seen from the figure, along with the rising of AFP antigen concentration, fluorescence signal intensity strengthens gradually.
Applicant states; the foregoing is only the specific embodiment of the present invention; but protection scope of the present invention is not limited thereto; person of ordinary skill in the field should understand; anyly belong to those skilled in the art in the technical scope that the present invention discloses; the change that can expect easily or replacement, all drop within protection scope of the present invention and open scope.

Claims (10)

1. the fluorescence detection equipment based on micro-fluidic chip, comprise: apparatus frame and the micro-fluidic chip supporting structure, phosphor collection module, light path stuck-module and the fluoroscopic examination module that are installed on described apparatus frame, it is characterized in that, described apparatus frame is also provided with light source;
Described light source, between phosphor collection module and micro-fluidic chip supporting structure, produces fluorescence for exciting the fluorescent material on chip;
Described phosphor collection module is made up of reflective mirror, optical lens group and the optical filter be arranged in optical lens group, for being filtered, collecting and focus on fluoroscopic examination module by the fluorescence signal on micro-fluidic chip;
Described micro-fluidic chip supporting structure is used for supporting chip, and adjustment chip position, makes the fluorescence signal region of chip be positioned at immediately below phosphor collection module collection region;
Described light path stuck-module is used for the fixing position of phosphor collection module and the adjustment of light path and fixes;
Described fluoroscopic examination module is used for changing the optical signalling of reception into analog electrical signal, then changes analog electrical signal into digital electric signal.
2. instrument according to claim 1, is characterized in that, also comprises power switch.
3. instrument according to claim 1 and 2, is characterized in that, described apparatus frame is light closed structure.
4. according to the instrument one of claim 1-3 Suo Shu, it is characterized in that, described light source is LED, bromine tungsten filament lamp or laser instrument.
Preferably, the wavelength of transmitted light of described light source is less than or equal to the feature excitation wavelength of described fluorescent material.
5. according to the instrument one of claim 1-4 Suo Shu, it is characterized in that, the center of the reflective mirror of described phosphor collection module, optical lens group and optical filter three is on same level line.
6. according to the instrument one of claim 1-5 Suo Shu, it is characterized in that, the utilizing emitted light of fluorescent material by exciting light elimination, can pass through by described optical filter.
7. according to the instrument one of claim 1-6 Suo Shu, it is characterized in that, described fluoroscopic examination module is CCD camera.
Preferably, described CCD camera horizontal positioned.
8. the instrument according to claim 1-7, is characterized in that, described chip supporting structure is chip tray, preferred plug-type chip tray.
9. according to the instrument one of claim 1-8 Suo Shu, it is characterized in that, described fluoroscopic examination module is connected with computing machine, and described computing machine receives and processes the digital electric signal from described detection module.
10., based on a fluorescence detecting system for micro-fluidic chip, comprise the fluorescence detection equipment based on micro-fluidic chip as described in any one of claim 1-9 and connected computing machine.
CN201410455944.8A 2014-09-09 2014-09-09 Fluorescence detection instrument and system based on micro-fluidic chip Pending CN105388131A (en)

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106546743A (en) * 2016-11-04 2017-03-29 中山大学 A kind of real-time monitoring system and monitoring method of amniotic embolism serological index
CN106706590A (en) * 2017-02-16 2017-05-24 韶关市食品药品检验所 Portable fluorescence chip data collector
CN111189814A (en) * 2020-02-21 2020-05-22 厦门大学 Fluorescence detection device based on micro-fluidic chip and micro-fluidic chip detection system
CN114505105A (en) * 2022-01-13 2022-05-17 电子科技大学 Micro-fluidic chip based on memory calculation

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EP1757923A2 (en) * 2005-08-24 2007-02-28 DR. Chip Biotechnology Incorporation Optical detection apparatus and method thereof
EP1797955A2 (en) * 2005-11-28 2007-06-20 Seiko Epson Corporation Microfluidic system, sample analysis device, and target substance measurement method
US20080013092A1 (en) * 2006-05-19 2008-01-17 George Maltezos Fluorescence detector, filter device and related methods
CN102253022A (en) * 2011-05-04 2011-11-23 博奥生物有限公司 Digital signal processing method for detecting microfluidic chip and applied detection device
CN103674934A (en) * 2013-10-23 2014-03-26 国家纳米科学中心 Microfluidic chip imaging instrument and system for chemiluminiscence detection

Patent Citations (6)

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Publication number Priority date Publication date Assignee Title
CN2672649Y (en) * 2003-12-23 2005-01-19 沈阳药科大学 Multipurpose laser induced fluorescent detector for micro flow control chip analysis
EP1757923A2 (en) * 2005-08-24 2007-02-28 DR. Chip Biotechnology Incorporation Optical detection apparatus and method thereof
EP1797955A2 (en) * 2005-11-28 2007-06-20 Seiko Epson Corporation Microfluidic system, sample analysis device, and target substance measurement method
US20080013092A1 (en) * 2006-05-19 2008-01-17 George Maltezos Fluorescence detector, filter device and related methods
CN102253022A (en) * 2011-05-04 2011-11-23 博奥生物有限公司 Digital signal processing method for detecting microfluidic chip and applied detection device
CN103674934A (en) * 2013-10-23 2014-03-26 国家纳米科学中心 Microfluidic chip imaging instrument and system for chemiluminiscence detection

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106546743A (en) * 2016-11-04 2017-03-29 中山大学 A kind of real-time monitoring system and monitoring method of amniotic embolism serological index
CN106706590A (en) * 2017-02-16 2017-05-24 韶关市食品药品检验所 Portable fluorescence chip data collector
CN111189814A (en) * 2020-02-21 2020-05-22 厦门大学 Fluorescence detection device based on micro-fluidic chip and micro-fluidic chip detection system
CN111189814B (en) * 2020-02-21 2020-09-29 厦门大学 Fluorescence detection device based on micro-fluidic chip and micro-fluidic chip detection system
CN114505105A (en) * 2022-01-13 2022-05-17 电子科技大学 Micro-fluidic chip based on memory calculation

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Application publication date: 20160309