CN109225364A - Portable micro-fluidic chip, detection device and micro-fluidic detection method - Google Patents
Portable micro-fluidic chip, detection device and micro-fluidic detection method Download PDFInfo
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- CN109225364A CN109225364A CN201811142376.0A CN201811142376A CN109225364A CN 109225364 A CN109225364 A CN 109225364A CN 201811142376 A CN201811142376 A CN 201811142376A CN 109225364 A CN109225364 A CN 109225364A
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
- B01L3/502707—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the manufacture of the container or its components
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/01—Arrangements or apparatus for facilitating the optical investigation
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/84—Systems specially adapted for particular applications
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/02—Adapting objects or devices to another
- B01L2200/026—Fluid interfacing between devices or objects, e.g. connectors, inlet details
- B01L2200/027—Fluid interfacing between devices or objects, e.g. connectors, inlet details for microfluidic devices
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/10—Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/12—Specific details about materials
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/01—Arrangements or apparatus for facilitating the optical investigation
- G01N2021/0106—General arrangement of respective parts
- G01N2021/0112—Apparatus in one mechanical, optical or electronic block
Abstract
The invention belongs to technical field of medical detection more particularly to portable micro-fluidic chips, detection device and micro-fluidic detection method.The present invention provides a kind of portable micro-fluidic chip, including micro-fluidic chip substrate, determinand sensing chamber and side throwing polishing are fine；Side throwing polishing fibre is fixed at the surface of micro-fluidic chip substrate, and the surface of micro-fluidic chip substrate is arranged in the fine side throwing mill area's opening upwards of side throwing polishing；Determinand sensing chamber is wrapped in the periphery in the fine side throwing mill area of side throwing polishing, so that determinand is placed in the side throwing mill area of determinand sensing chamber.The invention also discloses a kind of portable micro-fluidic detection device and micro-fluidic detection methods.The invention solves the detection sensitivity of traditional micro-fluidic chip and accuracy is low and the excessive technological deficiency of micro-fluidic detection device.
Description
Technical field
The invention belongs to technical field of medical detection more particularly to portable micro-fluidic chips, detection device and micro-fluidic
Detection method.The Chinese patent (number of patent application 201820190178.0) submitted this application claims on February 05th, 2018
Equity, the full content by above-mentioned application is incorporated herein by reference herein.
Background technique
It is frequently necessary to analyze the content of material composition in solution in chemistry, biology and medical domain, is divided light
Degree meter is the common instrument and equipment of material composition content in measurement solution, is had in chemistry, environmental science, biology and medical domain
Be widely applied.Spectrophotometer is mainly by light source, monochromator, sample room, detector, signal processor and display and storage
System composition.
Micro-fluidic chip has more and more in organic synthesis, microreactor, chemical analysis and field of biomedicine at present
Application, microflow control technique refers to using microchannel (having a size of tens of to hundreds of microns) processing or manipulation minute fluid (volume
For nanoliter to microlitre) involved in Science and Technology, have micromation, integrated feature.Micro-fluidic chip is micro-fluidic skill
The main realization platform of art, microfluidic chip technology (Microfluidics) are biology, chemical, medical analysis process sample
The basic operation units such as this preparation, reaction, separation, detection are integrated on the chip of one piece of micro-meter scale, and it is complete to be automatically performed analysis
Process.Micro-fluidic chip have liquid flowing is controllable, reagent need to be consumed and sample size is few, analysis speed is fast, multifunctional unit,
The advantages that small in size and easy to carry.
With scientific and technical video, medical level and improvement of living standard, the demand to portable detection equipment is more next
Bigger, can be carried out field quick detection, bedside detection and the Portable intelligent equipment voluntarily detected in family is future
The trend of equipment research and development.Whole world smart phone user quantity is up to 2,000,000,000 at present, and domestic smart phone user is close to 500,000,000, Er Qiezhi
The performance of energy mobile phone is being continuously improved, and the high-performance exploitation that can use smart phone is matching used portable with smart phone
Intelligent equipment, this is the trend of technology development and the market demand.
Therefore, research and develop it is a kind of can be matched with smart phone detection sensitivity is high, accuracy is high, it is small in size, convenient for taking
Band, it is simple and quick, can be carried out scene, the quick detection device of bedside and family be those skilled in the art's urgent need to resolve skill
Art problem.
Summary of the invention
In view of this, effectively solving current micro-fluidic chip detection the invention discloses a kind of portable micro-fluidic chip
The technological deficiency that technology portable can not still use.
The present invention provides a kind of portable micro-fluidic chips, including micro-fluidic opaque chip substrate, analyte detection to be measured
Room, side throwing polishing fibre, transparent area and detection zone；
The side throwing polishing fibre is fixed at the surface of the micro-fluidic opaque chip substrate, and the side throwing polishing is fine
Side throwing mill area's opening upwards the surface of the micro-fluidic opaque chip substrate is set；
Micro-fluidic opaque chip corresponding with the fine position of input terminal of side throwing polishing is arranged in the transparent area
On substrate, wherein the transparent area makes light source be transmitted to the fine input terminal of the side throwing polishing；
Micro-fluidic opaque chip corresponding with the fine position of output end of side throwing polishing is arranged in the detection zone
On substrate, wherein the detection zone makes light source be transmitted to the fine output end of the side throwing polishing；
The determinand sensing chamber is wrapped in the periphery in the fine side throwing mill area of the side throwing polishing, so that determinand is placed in institute
It is indoor to state determinand detection.
It should be noted that the side throwing mill area of side throwing polishing fibre is wrapped up by determinand sensing chamber, determinand is stablized
Area is ground by side throwing, and avoids outside contamination.
It should be noted that the transparent area and detection zone of micro-fluidic opaque chip substrate are transparent area, other regions are
Opaque area, the influence that opaque area is used to that other light sources to be avoided to reflect.
Preferably, the inner surface embedded antibody or antigen in side throwing mill area, the antibody and determinand specificity knot
It closes；
Alternatively, the antigen and determinand are specifically bound.
Preferably, the inner surface in side throwing mill area covers liquid crystal layer, the liquid crystal layer is methacrylated conjunction
Object.
It should be noted that the liquid crystal layer material of the inner surface coating in side throwing mill area is methacrylate compound.Institute
Height-oriented, tilted alignment, twist alignment can be provided by stating liquid crystal layer, and the liquid crystal layer compound of coating can be to a certain range wavelength
Light wave carries out selective reflecting, to reach the calibration orientation being oriented to light beam, moreover it is possible to the light wave of a certain range wavelength
Selective deviation is carried out, calibration orientation is oriented to light beam to reach, so that detection is sensitiveer.
Preferably, the micro-fluidic opaque chip substrate is monocrystalline silicon piece, dimethyl silicone polymer, glass, quartz
Or one of polymethyl methacrylate.
Preferably, portable micro-fluidic chip further includes plural sample transfer passage, the plural number bar sample conveying
Channel is connect with the determinand sensing chamber respectively.
Preferably, the determinand sensing chamber further includes valve, the plural number sample transfer passage passes through described
Valve is connect with the determinand sensing chamber.
Preferably, it is described plural number a sample transfer passage include: determinand transfer passage, negative sample transfer passage and
Positive sample transfer passage；The determinand transfer passage, the negative sample transfer passage and positive sample conveying are logical
Road is connect with the determinand sensing chamber respectively.
Preferably, the sample transfer passage controller is connect with the valve of the determinand sensing chamber, so that described
Sample transfer passage controller controls opening or closing for the valve of the determinand sensing chamber.
It should be noted that the side throwing that determinand transfer passage is used to for determinand being transported to determinand sensing chamber grinds area
It is interior；Negative sample transfer passage is used to for negative sample being transported in the side throwing mill area of determinand sensing chamber；Positive sample conveying
Channel is used to for positive sample being transported in the side throwing mill area of determinand sensing chamber.
Preferably, portable micro-fluidic chip further includes sample transfer passage controller, the sample transfer passage control
Device processed is connect with the sample transfer passage, so that the sample channel controller controls the determinand transfer passage, described
The flowing of the determinand, negative sample and positive sample of negative sample transfer passage and the positive sample transfer passage.
More preferably, the sample transfer passage controller is connect with the valve of the determinand sensing chamber, so that institute
It states sample transfer passage controller and controls the valve of the determinand sensing chamber and open or close.
It should be noted that the sample transfer passage controller control the valve of the determinand sensing chamber opening or
It closes, when the opening of the valve of the determinand sensing chamber, the sample transfer passage controller control determinand is described
The flowing of determinand sensing chamber, detects information when determinand dynamic；It is described when the closing of the valve of the determinand sensing chamber
Sample transfer passage controller controls determinand and detects indoor standing in the determinand, detects information when determinand static state,
Therefore, micro-fluidic chip of the invention can detect determinand dynamic or it is static when information.
Preferably, portable micro-fluidic chip further includes waste liquid reservoir part, the waste liquid reservoir part with it is described multiple
Several sample delivery channels connection, so that the waste liquid reservoir part stores the determinand of the determinand sensing chamber, negative sample
Sheet and positive sample.
The invention also discloses a kind of portable micro-fluidic detection devices, including the portable micro-fluidic chip, number
According to processor, luminous component and signal detecting part；
The luminous component input terminal fine with the polishing of the side throwing of the portable micro-fluidic chip is connect, the illumination region
Part is used for the fine input terminal of the side throwing polishing to the portable micro-fluidic chip and issues light source；
The signal detecting part output end fine with the polishing of the side throwing of the portable micro-fluidic chip is connect, the letter
Number detection part is used to obtain the optical signal of the fine output end of side throwing polishing of the portable micro-fluidic chip；
The data processor is connect with the luminous component and the signal detecting part respectively, for obtaining the hair
The optical signal of light component and the signal detecting part and to the optical signal of the luminous component and the signal detecting part into
Row analytical calculation.
Preferably, the luminous component is specially the screen of mobile device.
Preferably, the signal detecting part is specially the camera of mobile device.
Preferably, the data processor is specially the control system that mobile device is arranged in；
The data processor is used to control the parameter of the light source of the screen of the mobile device, and is set by the movement
Standby camera obtains the optical signal of the output end of the side throwing polishing fibre of the portable micro-fluidic chip, is obtained by analytical calculation
To the testing result of determinand.
It should be noted that mobile device is the electronic equipment with screen, camera and processor such as mobile phone or iPad.
It should be noted that data processor is obtained the optical signal of the luminous component and the signal detecting part
The ratio of optical signal.
It should be noted that optical signal is light intensity, spectrum or optical density.
The present invention provides micro-fluidic detection methods, comprising the following steps:
S101: the optical signal of the input terminal of the side throwing polishing fibre of the micro-fluidic chip is obtained；
S102: determinand is ground in area by the side throwing that determinand sensing chamber is placed in the micro-fluidic chip；
S103: the optical signal of the output end of the side throwing polishing fibre of the micro-fluidic chip is obtained, the input terminal is passed through
The optical signal of optical signal and the output end carries out analytical calculation, obtains the analysis result of the determinand.
More preferably, the fine side throwing mill area of the side throwing polishing is full rubbing down area or Fei Quan rubbing down area.
It should be noted that full rubbing down area, i.e. optical fiber fibre core at rubbing down are truncated by rubbing down area completely, optical fiber leans on coat
It is connected with covering, the light that the input terminal fine from side throwing polishing transmits all leaks in full rubbing down area, the light warp leaked
Enter the fine output end of side throwing polishing after the determinand in Guo Quan rubbing down area, the efficiency of transmission of light depends entirely on the property of determinand
And concentration；Fei Quan rubbing down area, i.e. rubbing down area be not completely cut off by fibre core, and the optical fiber at Fei Quan rubbing down area both ends is connected by fibre core
Come, light a part that the input terminal fine from side throwing polishing passes over is leaked from the rubbing down face in Fei Quan rubbing down area, this portion
Point light enter in the fibre core of the rubbing down area other side by the determinand solution in rubbing down area, the light of another part is from rubbing down area bottom
Fibre core propagated, using non-full rubbing down optical fiber can detect simultaneously by determinand solution propagate light and pass through rubbing down area bottom
The light that portion's fibre core is propagated, can compare this two parts light, obtain the property and concentration data of determinand solution.
It is a discovery of the invention that side throwing mill fiber optic applications can effectively solve microflow control technique, due to side in microflow control technique
Rubbing down optical fiber is that ordinary optic fibre covering rubbing down is fallen optical fiber made of a part using optics micro-processing technology, when the coating of optical fiber
When thickness is reduced to region existing for evanscent field as rubbing down processing, it will form the window of a fibre core light field, can use suddenly
Die field excite, control, the propagation light in detection optical fiber fibre core, ordinary optic fibre have low in cost, soft easy processing characteristic,
And the region that evanscent field utilizes can artificially be controlled, back-reflection is small, is easy to and fibre system welding.Therefore, the invention
Property use the fine core element as micro-fluidic detection device of side throwing polishing.Side throwing polishing is fine, and there is soft, optical path easily to adjust
Characteristic, the micro-fluidic detection device made of side throwing polishing fibre has that detection sensitivity is high, accuracy is high, small in size excellent
Point can be incorporated on micro-fluidic chip.The present invention uses the fine core component as micro-fluidic detection device of side throwing polishing, by side
The rubbing down face of rubbing down optical fiber is used as " window " of detection determinand, and determinand is allowed to grind area, light source hair through the fine side throwing of side throwing polishing
Light out leaks when being transmitted to side throwing mill area through side throwing polishing fibre, and the light of leakage is after the determinand in rubbing down face is propagated through side
The output end of rubbing down optical fiber is propagated, and can be detected by signal detecting part and be received optical signal.By the way that side throwing polishing will be passed through
The optical signal of the fine output end of optical signal and the side throwing polishing of fine input terminal is compared, it can be deduced that the property of measured object and
Concentration.
The purpose of the present invention portable can not still be used for micro-fluidic chip detection technique traditional in the prior art, because
This, the present invention discloses a kind of micro-fluidic chip, including micro-fluidic opaque chip substrate, determinand sensing chamber, side throwing polishing it is fine,
Transparent area and detection zone；The side throwing polishing fibre is fixed at the surface of the micro-fluidic opaque chip substrate, the side
The surface of the micro-fluidic opaque chip substrate is arranged in side throwing mill area's opening upwards of rubbing down optical fiber；The transparent area setting
On micro-fluidic chip substrate corresponding with the fine position of input terminal of side throwing polishing, wherein the transparent area makes light
Source is transmitted to the fine input terminal of the side throwing polishing；The position of the output end fine with side throwing polishing is arranged in the detection zone
On corresponding micro-fluidic chip substrate, wherein the detection zone makes light source be transmitted to the fine output end of the side throwing polishing；Institute
The periphery that determinand sensing chamber is wrapped in the fine side throwing mill area of the side throwing polishing is stated, so that determinand is placed in the quality testing to be measured
It surveys indoor.Portable micro-fluidic detection device, including the portable micro-fluidic chip, data processor, luminous component and
Signal detecting part；The luminous component input terminal fine with the polishing of the side throwing of the portable micro-fluidic chip is connect, described
Luminous component is used for the fine input terminal of the side throwing polishing to the portable micro-fluidic chip and issues light source；The signal detecting part
The part output end fine with the polishing of the side throwing of the portable micro-fluidic chip is connect, and the signal detecting part is described for obtaining
The optical signal of the fine output end of the side throwing polishing of portable micro-fluidic chip；The data processor respectively with the luminous component
It is connected with the signal detecting part, for obtaining the optical signal of the luminous component and the signal detecting part and to described
The optical signal of luminous component and the signal detecting part carries out analytical calculation.
When in use, the side throwing that determinand, negative sample and positive sample are individually placed in determinand sensing chamber is ground
In area, the input terminal of luminous component opposite side rubbing down optical fiber issues light source, and signal detecting part detects the side throwing mill of micro-fluidic chip
The optical signal of the output end of optical fiber, the input terminal of opposite side rubbing down optical fiber and the optical signal of output end compare, and polish from side throwing
Fine input terminal is propagated through the light come and spreads into the fine output end of side throwing polishing after the determinand in rubbing down area, and then is believed
Number detection part detects.Portable micro-fluidic chip of the invention can be directly used in mobile device, portable micro-fluidic
Chip is placed on the surface of mobile device, and transparent area is placed on the screen of mobile device, and detection zone is placed on taking the photograph for mobile device
As head, by the data processor of mobile device, the screen for controlling mobile device projects specific light source, and data processor passes through
After the camera acquisition of mobile device spreads into the light source of the fine output end of side throwing polishing after the determinand in rubbing down area, number
The qualitative and/or quantitative information of determinand is obtained after the two light sources are carried out analytical calculation according to processor.
In some embodiments, for the quantitative analysis of determinand, the concentration of the determinand in rubbing down area is higher, side throwing mill
The ratio for the optical signal that the fine input terminal of optical signal and side throwing that the output end of optical fiber detects polishing detects is smaller, by with
The optical signal ratio of master sample compares, the concentration of available determinand solution.Utilize calculation formula: testing concentration=side
The output end optical signal of the rubbing down optical fiber/fine input terminal optical signal × concentration factor of side throwing polishing.Wherein, optical signal be light intensity,
Spectrum or optical density.By formulating the standard curve of determinand, the positive control and negative control sample of determinand
Standard curve preparation method: pass through the input of the positive control of the negative control sample and determinand of determinand
The relationship of output intensity ratio and concentration establishes standard curve, then detects the side throwing polishing of determinand fine input terminal and output
The light intensity ratio at end calculates the concentration of determinand by standard curve, wherein the negative control sample of determinand be without containing
The solvent of determinand, the positive control of determinand are the solvent containing normal concentration determinand.The concentration of different determinands
Coefficient determination is the gradient concentration dilution by preparing determinand, measures various concentration determinand dilution in miniflow of the present invention
The input terminal of detection device and the light intensity of output end are controlled, is that x value, the determinand are dense with the light intensity ratio of the input terminal and output end
Degree is that y value draws standard curve, and testing concentration coefficient is slope of standard curve.
In some embodiments, the qualitative analysis of the determinand low for content, the present invention carry out the concentration of determinand
Amplification, to improve the limit and sensitivity of detection.By side throwing grind area inner surface antibody or antigen, determinand be coated on
Side throwing grinds the antigen of the inner surface in area or antibody combines, and after unbonded Impurity elution, addition can grind area with side throwing is coated on
Inner surface antigen or antibody combine and have fluorophor secondary antibody.Fluorophor in secondary antibody is sent out through light source
Fluorescence is issued after the light excitation of specific wavelength out, is detected by signal detecting part, and the concentration of determinand is analyzed.It is glimmering
The brightness of light and the concentration of test substance are directly proportional, and fluorescence can amplify the concentration information of determinand, therefore can be according to inspection
The brightness of the fluorescence of survey calculates the concentration of determinand, and therefore, the present invention can carry out specificity fluorescent to the concentration of determinand and put
Big reaction.
In some embodiments, the qualitative analysis of the determinand low for content, the present invention carry out the concentration of determinand
Amplification, to improve the limit and sensitivity of detection.It is detected after being amplified to determinand by the characteristic of layer of liquid crystal molecule.By liquid
Brilliant molecular layer is coated on the fine side throwing mill area of side throwing polishing, and before determinand addition, layer of liquid crystal molecule is in tiled state, light source hair
Luminous energy out successfully passes through side throwing mill area and reaches the fine output end of side throwing polishing, is detected by the detector.After determinand is added,
Orderly change occurs for the arrangement mode of liquid crystal molecule, will affect the passability of light, front and back can be added by detection test substance
The variation of light is to be measured the concentration of test substance.Amount of the variation of Liquid Crystal Molecules Alignment mode to the test substance of addition
Very sensitive, micro substance all can make the arrangement mode of liquid crystal molecule that orderly change occur, and influence the passability of light, therefore should
Method can play the role of amplifying the concentration information of test substance.
It should be noted that plural sample transfer passage is equipped with determinand injection port, negative sample pipeline is equipped with feminine gender
Sample injection port, positive sample pipeline are equipped with positive sample injection port, and determinand, negative sample and positive sample are respectively from correspondence
Injection port injection, first carry out the detection of negative sample, followed by the detection of positive sample is finally the detection of determinand.Hair
The fine input terminal of side throwing polishing of the light component to micro-fluidic chip emits light source, and the transmitting through side throwing mill area reaches side throwing polishing
Fine output end, signal detecting part detect the optical signal of the fine output end of side throwing polishing, can obtain the information for beating determinand.
It should be noted that the present invention can detect uric acid, nucleic acid (including DNA and RNA), organic or inorganic object.
A kind of portable micro-fluidic chip disclosed by the invention has the advantages that of the invention portable micro-fluidic
The optical path of chip is simple, detection speed is fast, and setting side throwing grinds area and makes strong antijamming capability, testing result accurate；Due to its knot
Structure is simple, small in size, therefore, manufacturing cost of the present invention is low, it is easy to carry, easy to operate, can at the scene or family uses.From this
The embodiment of invention is it is found that portable micro-fluidic detection device can actually carry out the detection of determinand by mobile phone, either directly
It connects and determinand is detected, or the amplified detection of chromogenic reaction is carried out to determinand, all obtain accurate detection effect,
The accuracy and spectrophotometer of testing result illustrate that detection sensitivity of the invention is high, accurate without significant difference (P > 0.05)
It spends high, small in size and easy to carry.
Detailed description of the invention
In order to more clearly explain the embodiment of the invention or the technical proposal in the existing technology, to embodiment or will show below
There is attached drawing needed in technical description to be briefly described.
Fig. 1 shows a kind of usage scenario figure of portable micro-fluidic chip provided by the invention；
Fig. 2 shows a kind of schematic diagram figure of portable micro-fluidic chip provided by the invention；
Fig. 3 shows a kind of structure sectional view of portable micro-fluidic chip provided by the invention；
Fig. 4 shows a kind of internal structure chart of portable micro-fluidic detection device provided by the invention；
Fig. 5 shows a kind of plane structure chart of portable micro-fluidic detection device provided by the invention
Fig. 6 shows that the present invention provides the concentration of the NaCl solution of portable micro-fluidic chip and the mark of input and output light intensity ratio
Directrix curve；
Fig. 7 shows that the present invention provides the pure water of portable micro-fluidic chip and the continuous spectrum stacking chart of serum, wherein Fig. 7
Negative control continuous spectrum curve be pure water continuous spectrum, sample to be tested continuous spectrum curve be serum continuous spectrum；
Fig. 8 shows that the present invention provides the continuous spectrum figure of the pure water of portable micro-fluidic chip；
Fig. 9 shows that the present invention provides the continuous spectrum figure of the serum of portable micro-fluidic chip；
Figure 10 shows that the present invention provides the cell genomic dna extracted in the HBE cell of the source of people of portable micro-fluidic chip
Characteristic absorption peak stacking chart；
Wherein, appended drawing reference, micro-fluidic chip substrate 1, side throwing mill area 2, side throwing polishing fibre 3, determinand sensing chamber 4, hair
Light component 5, signal detecting part 6, processor 7, display 8, sample transfer passage 9, waste liquid reservoir part 10, transparent area 11,
The fine output end B of the fine input terminal A of camera 12, screen 13, mobile phone 14, detection zone 15, side throwing polishing, side throwing polishing.
Specific embodiment
It is traditional for solving the present invention provides portable micro-fluidic chip, detection device and micro-fluidic detection method
The detection sensitivity of micro-fluidic chip and accuracy is low and the excessive technological deficiency of micro-fluidic detection device.
The technical scheme in the embodiments of the invention will be clearly and completely described below, it is clear that described implementation
Example is only a part of the embodiment of the present invention, instead of all the embodiments.Based on the embodiments of the present invention, this field is common
Technical staff's every other embodiment obtained without making creative work belongs to the model that the present invention protects
It encloses.
Embodiment 1
Please refer to Fig. 1 to Fig. 5, the micro-fluidic chip of the present embodiment, including micro-fluidic opaque chip substrate 1, determinand
Sensing chamber 4, side throwing polishing fibre 3, transparent area 11 and detection zone 15；Side throwing polishing fibre 3 is fixed at micro-fluidic opaque chip
The surface of micro-fluidic opaque chip substrate 1 is arranged in the surface of substrate 1, fine side throwing mill 2 opening upwards of area of side throwing polishing；Thoroughly
Light area 11 is arranged on micro-fluidic opaque chip substrate 1 corresponding with the fine position of input terminal A of side throwing polishing, wherein thoroughly
Light area 11 makes light source be transmitted to the fine input terminal A of side throwing polishing；The position of the output end B fine with side throwing polishing is arranged in detection zone
It sets on corresponding micro-fluidic opaque chip substrate 1, wherein detection zone 15 makes light source be transmitted to the fine output end of side throwing polishing
B；Determinand sensing chamber 4 is wrapped in the periphery in the fine side throwing mill area 2 of side throwing polishing, so that determinand is placed in determinand sensing chamber 4
It is interior.
Further, the inner surface embedded antibody or antigen in side throwing mill area 2, antibody and determinand are specifically bound；Alternatively,
Antigen and determinand are specifically bound.
Further, the inner surface in side throwing mill area 2 covers liquid crystal layer, and liquid crystal layer by side throwing for that will grind the light source in area 2
Focus on the center of side throwing polishing fibre 3.
Further, micro-fluidic opaque chip substrate 1 is monocrystalline silicon piece, dimethyl silicone polymer, glass, quartz or poly-
One of methyl methacrylate.
Further, further include plural sample transfer passage 9, plural sample transfer passage 9 respectively with quality testing to be measured
Room 4 is surveyed to connect.
Further, determinand sensing chamber 4 further includes valve, plural sample transfer passage 9 by valve with it is to be measured
Analyte detection room 4 connects.
Further, a plural sample transfer passage 9 includes: determinand transfer passage, negative sample transfer passage and sun
Property sample transfer passage；Determinand transfer passage, negative sample transfer passage and positive sample transfer passage respectively with determinand
Sensing chamber 4 connects.
It further, further include sample transfer passage controller, sample transfer passage controller and sample transfer passage 9 connect
It connects, so that sample channel controller controls determinand transfer passage, negative sample transfer passage and positive sample transfer passage
The flowing of determinand, negative sample and positive sample.
Further, sample transfer passage controller is connect with the valve of determinand sensing chamber 4, so that sample transfer passage
The valve of controller control determinand sensing chamber 4 opens or closes.
It further, further include waste liquid reservoir part, waste liquid reservoir part 10 is connect with plural sample delivery channel 9,
So that waste liquid reservoir part 10 stores determinand, negative sample and the positive sample of determinand sensing chamber 4.
The present embodiment also discloses a kind of portable micro-fluidic detection device, including at portable micro-fluidic chip, data
Manage device, luminous component 5 and signal detecting part 6；The fine input terminal of the side throwing of luminous component 5 and portable micro-fluidic chip polishing
A connection, luminous component 5 are used for the fine input terminal A of the side throwing polishing to portable micro-fluidic chip and issue light source；Signal detecting part
The output end B fine with the polishing of the side throwing of portable micro-fluidic chip of part 6 is connect, and signal detecting part 6 is for obtaining portable decline
The optical signal of the fine output end B of the side throwing polishing of fluidic chip；Data processor respectively with luminous component 5 and signal detecting part
6 connections, for obtaining the optical signal of luminous component 5 and signal detecting part 6 and to luminous component 5 and the signal detecting part
6 optical signal carries out analytical calculation.
Further, luminous component 5 is specially the screen 13 of mobile device.
Further, signal detecting part 6 is specially the camera 12 of mobile device.
Further, data processor is specially the control system that mobile device is arranged in；Data processor is for controlling
The parameter of the light source of the screen 13 of mobile device, and the camera 12 for passing through mobile device obtains the side of portable micro-fluidic chip
The optical signal of the output end B of rubbing down optical fiber obtains the testing result of determinand by analytical calculation.
Micro-fluidic detection method provided in this embodiment, comprising the following steps:
S101: the optical signal of the input terminal A of the side throwing polishing fibre of micro-fluidic chip is obtained；
S102: determinand is ground in area 2 by the side throwing that determinand sensing chamber 4 is placed in micro-fluidic chip；
S103: obtaining the optical signal of the fine output end B of side throwing polishing of micro-fluidic chip, by the optical signal of input terminal with
The optical signal of output end carries out analytical calculation, obtains the analysis result of determinand.
Embodiment 2
In the present embodiment, determinand is the NaCl solution prepared at random, and negative control sample is pure water, positive control sample
This is the NaCl solution of known concentration.
Table 1 makes standard curve using the NaCl solution of various concentration
Fine input terminal and side throwing, which are polished, using the side throwing of micro-fluidic chip disclosed by the invention respectively polishes fine output
The ratio of the light intensity at end is converted into concentration value according to standard curve, is that the concentration of the determinand of spectrophotometric determination compares,
Experiment is repeated 3 times, and testing result is as shown in table 1- table 2 and Fig. 5.
The testing result for the NaCl solution prepared at random that 2 micro-fluidic chip of table and spectrophotometric measure
Conclusion: the measurement result of micro-fluidic chip of the present invention and the measurement result of spectrophotometer are similar, P > 0.05.
Embodiment 3
The present embodiment uses Quality Control genome sample (0.01g/L) as positive control, and negative control sample is pure
Water, determinand are the cell genomic dna that extracts in the HBE cell of 5million source of people.
Referring to Fig. 9, by negative sample, positive sample and each 1 μ l of determinand by sample transfer passage 9 be separately added into
It surveys in the side throwing mill area 2 of analyte detection room 4, luminous component emits light source in the fine input terminal of the side throwing polishing of micro-fluidic chip,
Light source is the light source of 260nm absorbing wavelength, passes through the fine output end of the light intensity of the fine input terminal of side throwing polishing and side throwing polishing
Light intensity draws standard curve.The detection of negative control sample is first carried out, the concentration value of negative control sample is shown in liquid crystal display
On screen；Then the detection of positive control is carried out, the concentration value of positive control is shown on liquid crystal display.The present invention
The average detected time from bringing into operation display density value is 3.2s.Positive control is Quality Control genome sample
(0.01g/L), negative control sample are pure water, and determinand (cell genomic dna extracted in the HBE cell of source of people) is equally logical
It crosses spectrophotometer to be detected, the use of spectrophotometer is according to manufacturer's operating instruction, when the average detected of spectrophotometer
Between be 4.1s.Negative control sample, positive control and determinand carry out 3 detections, then average statistical and standard deviation,
And the measured value that side throwing polishes fine micro-fluidic chip is compared with the measured value of spectrophotometer.
The testing result for the pure water that 3 micro-fluidic chip of table and spectrophotometric measure
The testing result for the Quality Control genome sample that 4 micro-fluidic chip of table and spectrophotometric measure
The detection of the cell genomic dna extracted in the HBE cell for the source of people that 5 micro-fluidic chip of table and spectrophotometric measure
As a result
Conclusion: micro-fluidic chip and spectrophotometer of the present invention are in the detection to sample of nucleic acid, two kinds of testing result
It is close, no significant difference (P > 0.05).
Embodiment 4
The present embodiment uses uric acid titer (0.05g/L) as positive control, and negative control sample is pure water, to
Survey object is serum.Negative control sample, positive control and determinand carry out 3 detections, then average statistical and standard
Difference, and the measured value that side throwing polishes fine micro-fluidic chip is compared with the measured value of spectrophotometer.
Determinand is before detection and after the first detection reagent hybrid reaction of 5 μ l, and determinand is being placed in this after being handled
The micro-fluidic chip of invention is detected, the first detection reagent be iron (III) solution and Phen solution, iron (III) it is dense
Degree is 20mg/L, and the concentration of Phen is that 1g/L, iron (III) solution and Phen solution are mixed with the ratio of 1:1.
Detection wavelength selects 510nm to default wavelength, first carries out the detection of negative control sample, the concentration of negative control sample
Value display is over the display；Then the detection of positive control is carried out, the concentration value of positive control is shown in display
On.Average detected time of the present invention from bringing into operation display density value is 3.2s, spectrophotometer (upper Nereid section 721G)
The average detected time be 4.2s.
6 micro-fluidic chip of table and the testing result for the pure water that spectrophotometric measures are as follows
The continuous spectrum figure for the pure water that micro-fluidic chip measures is as shown in Figure 7.
7 micro-fluidic chip of table and the testing result for the uric acid titer (0.05g/L) that spectrophotometric measures are as follows
8 micro-fluidic chip of table and the serum testing result that spectrophotometric measures are as follows
The continuous spectrum figure for the serum that micro-fluidic chip measures is as shown in Figure 8.
Conclusion: the measurement result of micro-fluidic chip of the present invention and the measurement result of spectrophotometer, no significant difference (P >
0.05)。
Embodiment 5
The present embodiment uses uric acid titer (0.05g/L) as positive control.Negative control sample is pure water, to
Survey object is serum.Positive control and determinand carry out 3 detections, then average statistical and standard deviation, and side throwing is ground
The measured value of optical fibre micro-fluidic chip is compared with the measured value of spectrophotometer.
Determinand is before detection and after the second detection reagent hybrid reaction of 5 μ l, and determinand is being placed in this after being handled
The micro-fluidic chip of invention is detected, and the second detection reagent is urate oxidase, peroxidase (POD), 4- amino peace are replaced
Than woods (4-AAP) and the bromo- 3- hydroxybenzoic acid (TBHBA) of 2,4,6- tri-.Uric acid can be oxidized to hydrogen peroxide and urine by uricase
Bursin, in the presence of peroxidase (POD), hydrogen peroxide oxidation 4-AA (4-AAP) and 2,4,6- tri- is bromo-
3- hydroxybenzoic acid (TBHBA), reaction generate product red quinone imines, can cause the rising of absorbance at 520nm wavelength,
In, the second detection reagent is configured using existing method.
Detection wavelength selects 510nm to default wavelength, first carries out the detection of negative control sample, the concentration of negative control sample
Value is shown on liquid crystal display；Then the detection of positive control is carried out, the concentration value of positive control is shown in liquid
On crystal display screen.
The testing result for the pure water that 9 micro-fluidic chip of table and spectrophotometric measure
The testing result for the uric acid titer (0.05g/L) that 10 micro-fluidic chip of table and spectrophotometric measure
The testing result for the serum that 11 micro-fluidic chip of table and spectrophotometric measure
The continuous spectrum stacking chart of pure water and serum that micro-fluidic chip measures is as shown in Figure 6.
Conclusion: the measurement result of micro-fluidic chip of the present invention and the measurement result of spectrophotometer are close, no significant difference
(P>0.05)
The above is only a preferred embodiment of the present invention, it is noted that for the ordinary skill people of the art
For member, various improvements and modifications may be made without departing from the principle of the present invention, these improvements and modifications are also answered
It is considered as protection scope of the present invention.
Claims (15)
1. a kind of portable micro-fluidic chip, which is characterized in that including micro-fluidic opaque chip substrate, determinand sensing chamber,
Side throwing polishing fibre, transparent area and detection zone；
The side throwing polishing fibre is fixed at the surface of the micro-fluidic opaque chip substrate, the fine side of the side throwing polishing
The surface of the micro-fluidic opaque chip substrate is arranged in rubbing down area opening upwards；
Micro-fluidic opaque chip substrate corresponding with the fine position of input terminal of side throwing polishing is arranged in the transparent area
On, wherein the transparent area makes light source be transmitted to the fine input terminal of the side throwing polishing；
Micro-fluidic opaque chip substrate corresponding with the fine position of output end of side throwing polishing is arranged in the detection zone
On, wherein the detection zone makes light source be transmitted to the fine output end of the side throwing polishing；
The determinand sensing chamber is wrapped in the periphery in the fine side throwing mill area of side throwing polishing so that determinand be placed in it is described to
It surveys in analyte detection room.
2. portable micro-fluidic chip according to claim 1, which is characterized in that the inner surface embedding in side throwing mill area
Antibody or antigen, the antibody and determinand are specifically bound；
Alternatively, the antigen and determinand are specifically bound.
3. portable micro-fluidic chip according to claim 1, which is characterized in that the inner surface covering in side throwing mill area
Liquid crystal layer, the liquid crystal layer are methacrylate compound.
4. portable micro-fluidic chip according to claim 1, which is characterized in that the micro-fluidic chip substrate is monocrystalline
One of silicon wafer, dimethyl silicone polymer, glass, quartz or polymethyl methacrylate.
5. portable micro-fluidic chip according to claim 1, which is characterized in that further include that plural number sample conveying is logical
Road, the plural number sample transfer passage are connect with the determinand sensing chamber respectively.
6. portable micro-fluidic chip according to claim 5, which is characterized in that the determinand sensing chamber further includes valve
Door, the plural number sample transfer passage pass through the valve and connect with the determinand sensing chamber.
7. portable micro-fluidic chip according to claim 6, which is characterized in that the plural number sample transfer passage packet
It includes: determinand transfer passage, negative sample transfer passage and positive sample transfer passage；It is the determinand transfer passage, described
Negative sample transfer passage and the positive sample transfer passage are connect with the determinand sensing chamber respectively.
8. portable micro-fluidic chip according to claim 7, which is characterized in that further include the control of sample transfer passage
Device, the sample transfer passage controller are connect with the sample transfer passage, so that the sample channel controller controls institute
State determinand transfer passage, the determinand of the negative sample transfer passage and the positive sample transfer passage, negative sample
With the flowing of positive sample.
9. portable micro-fluidic chip according to claim 8, which is characterized in that the sample transfer passage controller with
The valve of the determinand sensing chamber connects, so that the sample transfer passage controller controls the valve of the determinand sensing chamber
Door opens or closes.
10. portable micro-fluidic chip according to claim 8, which is characterized in that it further include waste liquid reservoir part, it is described
Waste liquid reservoir part is connect with the plural sample delivery channel, so that the waste liquid reservoir part stores the quality testing to be measured
Survey determinand, negative sample and the positive sample of room.
11. a kind of portable micro-fluidic detection device, which is characterized in that including as described in claims 1 to 10 any one
Portable micro-fluidic chip, data processor, luminous component and signal detecting part；
The luminous component input terminal fine with the polishing of the side throwing of the portable micro-fluidic chip is connect, and the luminous component is used
Light source is issued in the fine input terminal of the side throwing polishing to the portable micro-fluidic chip；
The signal detecting part output end fine with the polishing of the side throwing of the portable micro-fluidic chip is connect, the signal inspection
Survey the optical signal of the fine output end of side throwing polishing of the component for obtaining the portable micro-fluidic chip；
The data processor is connect with the luminous component and the signal detecting part respectively, for obtaining the illumination region
The optical signal of part and the signal detecting part simultaneously divides the optical signal of the luminous component and the signal detecting part
Analysis calculates.
12. portable micro-fluidic detection device according to claim 11, which is characterized in that the luminous component is specially
The screen of mobile device.
13. portable micro-fluidic detection device according to claim 12, which is characterized in that the signal detecting part tool
Body is the camera of mobile device.
14. portable micro-fluidic detection device according to claim 13, which is characterized in that the data processing implement body
For the control system that mobile device is arranged in；
The data processor is used to control the parameter of the light source of the screen of the mobile device, and passes through the mobile device
Camera obtains the optical signal of the fine output end of side throwing polishing of the portable micro-fluidic chip, by analytical calculation obtain to
Survey the testing result of object.
15. micro-fluidic detection method, which comprises the following steps:
S101: the optical signal of the input terminal of the side throwing polishing fibre of the micro-fluidic chip is obtained；
S102: determinand is ground in area by the side throwing that determinand sensing chamber is placed in the micro-fluidic chip；
S103: obtaining the optical signal of the output end of the side throwing polishing fibre of the micro-fluidic chip, and the light for passing through the input terminal is believed
Number analytical calculation is carried out with the optical signal of the output end, obtains the analysis result of the determinand.
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