CN110354924A - A kind of integrated bio pattern detection chip and detection method - Google Patents
A kind of integrated bio pattern detection chip and detection method Download PDFInfo
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- CN110354924A CN110354924A CN201910713546.4A CN201910713546A CN110354924A CN 110354924 A CN110354924 A CN 110354924A CN 201910713546 A CN201910713546 A CN 201910713546A CN 110354924 A CN110354924 A CN 110354924A
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Classifications
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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
-
- 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
- B01L3/50273—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 means or forces applied to move the fluids
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- G—PHYSICS
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- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/00584—Control arrangements for automatic analysers
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- B—PERFORMING OPERATIONS; TRANSPORTING
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- B01L2300/00—Additional constructional details
- B01L2300/08—Geometry, shape and general structure
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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
- B01L2400/00—Moving or stopping fluids
- B01L2400/04—Moving fluids with specific forces or mechanical means
- B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
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- B01L2400/00—Moving or stopping fluids
- B01L2400/04—Moving fluids with specific forces or mechanical means
- B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
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Abstract
The invention discloses a kind of integrated bio pattern detection chip and detection method, chip includes at least one well, for sample to be analyzed to be added；At least one reaction tank；At least two reagent reservoirs；Well is connected with reaction tank by flow path, and reagent reservoir is connected with reaction tank by flow path；Device has at least one controllable valve on flow path, controls fluid flow switch of the reagent reservoir reagent to reaction tank；Device has at least one controllable valve on flow path, controls the waste cock of the liquid of reagent reaction tank；In valve cavity, at least device has a kind of magnetic material or has the magnetic control material of interaction force as motor element with magnetic material, opens and closes flow path under the magnetic force；It can be accurately controlled reaction time of the liquid on chip under external magnetic field, ensure that liquid transfers the convenience and accuracy of control, to greatly improve control of the chip for biological detection reaction condition.
Description
Technical field
The present invention relates to detection chip technical fields, and in particular to one kind can accurately carry out the integrated bio sample of reaction controlling
This detection chip and detection method.
Background technique
POCT(point of care testing), refer to the clinical detection carried out beside patient, is commonly called as " inspection by bed
Survey ", the development of technology generally uses the instrument of straightforward procedure and miniaturization, quickly obtains inspection result.Clinical examination POCT is general
Thought is clearly proposed by U.S. AACC in nineteen ninety-five, has obtained within nearly 20 years quick development, global POCT market scale in 2013
Reach 16,000,000,000 dollars, Chinese POCT reaches 8,000,000,000 RMB in market scale in 2015, and Nian Fuhe grows beyond 20%.POCT's
Detection is mainly used for the analysis detection of biological sample, including blood, saliva, urine, sperm, secretion, in body fluid equal samples
Biological components.
Automation equipment and the product development of large-scale producer are at full speed, reliability is quickly promoted, reagent, reaction skill
Art, reliability have reached higher level, Roche, Abbott Laboratories, this western Meikang, Johnson & Johnson, Mai Ruideng enterprise high-end product
Preferable application is obtained on the market, and the product of these enterprises is that the automation of height and systematic product, system pass through
Unified Quality Control and calibration and maintenance, so that entire detection architecture has higher accuracy and precision, but systematic comparison
Valuableness, the complexity of equipment and report result time apply inconvenience in many scenes of clinical detection, to operation and maintenance
It is required that very high.Detection, basic hospital in the preoperative are segmented in the detection scene of department using inconvenience.Current miniaturization and convenient
The subdivision technical research trend of change increasingly becomes hot technology.
Immunochromatography is the technical solution for developing comparative maturity, and Chinese patent 201380015412.6, which discloses, gathers sulfydryl
Aklylene glycol and/or the protection of its derivative, arginine and casein instrument are maintained at dry maintaining part together with marker
Immune chromatography method reduces the interference of non-specific binding bring.United States Patent (USP) 8043866 disclose it is a kind of using silver ion also
Original carries out the detection of signal at silver nano-grain；United States Patent (USP) 8999730, which discloses one kind, can detecte low concentration and high concentration
Immune chromatography method；United States Patent (USP) 7993935 discloses one kind and has immune chromatograph testing strip, but in the side of immunochromatography
In method, temperature, humidity, package amount, the quality of chromatographic film, the factors such as nonspecific high background of combination bring, so that immune
Chromatography method can not obtain accurate quantitative test.
Microfluidic control technology is another hot technology, and United States Patent (USP) US20150087079A1 discloses a kind of miniflow
Chip is controlled, which can be placed in runner by flowing of the pressure control liquid in fluid channel, the detection zone of chip, flow
Liquid can be contacted with runner.United States Patent (USP) 20150087079A1 discloses the valve of a micro-fluidic liquid control, the valve
Shape can be changed by external pressure to open and be closed fluid channel；United States Patent (USP) 20120282625A1 discloses one
Bottom flow passage has the micro-fluidic chip of protrusion；United States Patent (USP) 8834813B2 discloses a dual channel, the directly mutual connection of runner
Chip；Chinese patent 200910007020.0 discloses a kind of microfluidic process centrifugal chip that can carry out liquid distribution,
United States Patent (USP) 9151750B2 discloses a kind of centrifugal chip, and using centrifugal force and geometric jacquard patterning unit surface tension to carry out liquid mixture flow dynamic
Operation.Microflow control technique to avoid the operations such as the complicated liquid feeding mixing of machinery and fluid path, so be concerned, but it is micro-
The processing of runner, sample coating, trace sample transfer and the mixing of fluid channel are so that accurate operation is difficult to realize, miniflow
The liquid resources of road chip are quantitatively and the differences between batches of fluid channel will lead to biggish finesse-loss, while microchannel
The complexity of processing is but also the cost of micro-fluidic chip is difficult to reduce.
Summary of the invention
The object of the present invention is to provide a kind of integrated bio pattern detection chip and detection methods, can be under external magnetic field
It is accurately controlled reaction time of the liquid on chip, ensure that liquid transfers the convenience and accuracy of control, thus greatly
Improve control of the chip for biological detection reaction condition.
A kind of integrated bio pattern detection chip of the present invention includes:
At least one well, for sample to be analyzed to be added；
At least one reaction tank；
At least two reagent reservoirs；
Well is connected with reaction tank by flow path, and reagent reservoir is connected with reaction tank by flow path；
Device has at least one controllable valve on flow path, controls fluid flow switch of the reagent reservoir reagent to reaction tank；
Device has at least one controllable valve on flow path, controls the waste cock of the liquid of reagent reaction tank；
In valve cavity, at least device has a kind of magnetic material or has the magnetic control material of interaction force to make with magnetic material
For motor element, flow path is opened and closed under the magnetic force.
Preferably, also including a waste liquid pool, waste liquid pool is connected with reaction tank by flow path, there is at least device on flow path
One controllable valve, in valve cavity, at least device has a kind of magnetic material or has the magnetism of interaction force with magnetic material
Material is controlled as motor element, opens and closes flow path under the magnetic force.
Further, a Sample Dilution pond, device in sample diluting tank are equipped between the well and reaction tank
There is a mixing component for being used to mix sample.
Further, the Sample Dilution pond and reaction tank separately include with the pre-dilution pond stomata that connect of the external world and
Reaction tank stomata, pre-dilution pond stomata and reaction tank stomata are closed when encapsulating chip, are opened before detection, and connection is used for
With balance atmospheric pressure.
Preferably, a kind of capture for capturing the biological analyte molecules in sample point is contained in the reaction tank
Son.
Further, the capture molecule is coated on solid-phase matrix or is coated in magnetic microsphere surface.
Further, when the capture molecule is coated in magnetic microsphere surface, reaction tank is equipped with mixing component.
A kind of detection method of integrated bio sample of the present invention, specific steps are as follows:
A. chip is placed in and is had in the magnetic instrument for disconnecting and opening multiparty control, the magnetic material of magnetic control point and chip
Position does not invade in the flow path of chip to correspondence, magnetic control point；
B. this addition well is sampled, after sample flows directly into reaction tank or first passes through Sample Dilution pond progress Sample pretreatment
Flow into reaction tank；
C. after reacting the set time, the magnetic force by controlling instrument is controlled, and is opened the valve of reaction tank, is discharged the reaction of reaction tank
Liquid；
D. by the magnetic force control of control instrument, the valve of reagent reservoir is opened, reagent reservoir liquid flows into reaction tank；
E. after reacting the set time, the magnetic force by controlling instrument is controlled, and opens the valve of reaction tank；
F. by temperature control module control chip in system temperature it is constant；
G. the biological respinse of reaction tank is detected using photomultiplier tube, imaging sensor, photoelectric tube, electrode.
It further, is to control instrument into one when on magnetic microsphere containing capture molecule coating in the reaction tank
Step includes magnetic force corresponding with reaction tank position control point, for when cleaning and discharging reaction tank reagent, absorption to retain magnetic
Microballoon.
The beneficial effects of the present invention are: complicated machinery, flow path, sequential operation is integrated on chip, avoid behaviour
The complexity of work and many integrity problems, the reagent on chip ensure that the accurate of liquid quantitative using quantitative prepackage in advance
Property.The liquid flowing and mixing operation of chip are accurately controlled on chip simultaneously, and the design of chip is controlled using valve,
Reaction time of the liquid on chip can be accurately controlled under external magnetic field, ensure that liquid transfer control convenience and
Accuracy, to greatly improve control of the chip for biological detection reaction condition.The design of the flow path of chip uses valve
Control, and the flowing of non-dependent microfluid plays quantitative so the requirement to runner reduces, can using the runner of mm size,
Liquid quantitative is not influenced by runner, reduces the processing request to chip runner, thus be greatly reduced chip cost and
Process complexity.
Detailed description of the invention
The structural schematic diagram of the integrated bio pattern detection chip of Fig. 1.
Fig. 2 is free from the chip schematic diagram in Sample Dilution pond.
Fig. 3 is the example schematic of the valve design of integrated bio pattern detection chip.
Fig. 4 is that control valve shows assembling implementation diagram.
Fig. 5 is the whole result schematic diagram of integrated bio pattern detection chip.
Fig. 6 is the valve mechanism schematic diagram of design chips.
Specific embodiment
In order to which the technical problems, technical solutions and beneficial effects solved by the present invention is more clearly understood, below in conjunction with
Attached drawing and embodiment, the present invention is further illustrated.
As shown in Figs. 1-5, a kind of integrated bio pattern detection integrated chip of the present invention has well 1, and sample can pass through
Chip is added in well 1, and well 1 can be connected directly with reaction tank 16, can be further between well 1 and reaction tank 16
There is a Sample Dilution pond 2 to be used to be diluted sample, or the pre-treatment to sample, can be added in Sample Dilution pond 2
It mixes component 3 to mix the dilution of sample, specific scheme can be used to be added to have with the steel ball of magnetic interaction
It shakes and is mixed under externally-applied magnetic field again.
Integrated chip has reagent reservoir 9,10, and reagent reservoir 9,10 can be preinstalled with reagent, and reagent can pass through examination
Reagent reservoir 9,10 is added in agent adding hole 6,7, and the amount of reagent that reagent reservoir 9,10 stores is not less than 10uL, to guarantee to be added
The accuracy of amount of reagent, reagent reservoir 9,10 are connected with reaction tank 16 by flow path 20,12, reagent reservoir 9,10 other ends
There are a gas flow path, when discharging in reagent reservoir 9,10 reagent to reaction tank 16, gas flow path is in the open state
It is connected with atmospheric pressure, is used for balancing Atmospheric pressure, control valve 14,11 is installed on the gas that reagent reservoir 9,10 communicates with the outside world
Body flow path is installed on the flow path 20,12 that reagent reservoir 9,10 is connected with reaction tank 16, is preferably attached on flow path 20,12 straight
Connect cutting flow path 20,12.
Reaction tank 16 is integrated on chip, reaction tank 16 provides the place of reaction, and sample passes through well 1 or pretreated
Sample Dilution pond 2 is added in reaction tank 16, valve 17 is housed, sample adds in the fluid path 18 that reaction tank 16 is connect with waste liquid pool 19
Fashionable valve 17 is in closed state, can control sample in the stop of reaction tank 16 by the opening time interval of valve 17
Between, sample can exclude sample liquid after reaction tank 16 reaches the predetermined time with Open valve 17, and open reagent reservoir 9
Liquid is added to reaction tank 16, after the liquid of reagent reservoir 9 is docked to the specified time in reaction tank 16, opening valve in valve 14
Door 17 discharges the reaction liquid of reaction tank 16, while reagent reservoir 10 can synchronize unlatching or open later, and reagent enters anti-
It answers pond 16 to open to react in next step, or reaction tank 16 is cleaned, and full reaction tank, to guarantee during detection
The medium of optical path or electric signal is provided.
Reagent reservoir at least two on chip can further include more reagent reservoirs, reagent liquid storage
Pond is connected with reaction tank 16, and the fluid path that is connected is equipped with valve.
Device has a kind of magnetic material or can generate gravitation with magnetic material or the magnetic of repulsion is controlled in the valve of chip
Prepared material, material can the mobile effect to start closing and open flow path under the extraneous field of force, specific valve can be with
Carry out shift design.
As shown in figure 3, having carried out form citing to valve, 1., 2. it is shown in figure using two kinds of materials, utilizes strip
Cavity carries out fluid path control, and black is the material to attract each other, 1. show flow path closed state, 2. show flow path opening
State；3., 4. show oblong cavity carry out flow path control, black is the material to attract each other, 3. show flow path closing
4. state show flow path open state；5., two kinds of materials to attract each other of control valve for 6. showing be in parallel position
It sets, there is bigger attraction between this state material, 5. show the closing shape body of valve, 6. show the opening state of valve
State；7., 8., 9., 10. show and using the surface tension and fluid matasomatism of natural fluid material shown in black be plugged in
Flow path is converted into the state of unlatching under the action of extraneous magnetic field force；The design of valve is so that external magnetic field can control chip
Flow path opening and closing, without invading chip, the structure of valve specifically designed can show a variety of variation shapes
State, a kind of use of material can close flow path, and the material in fixation fluid path that the use of two kinds of materials can be stable is in solid
Determine state, valve body is the state for closing flow path in the state of no external magnetic field, guarantees the closing of storing reagent and is detecting
The sealing liquid of waste liquid pool is completed without outflow.Above-mentioned magnetic material is easy to get commercialization material in the market, such as closes
Gold, ferrite and intermetallic compound etc..
The flowing of the liquid of chip preferably using between gravity and liquid and flow path close and distant waterpower and air pressure control chip
Close and distant waterpower between the flowing of interior liquid, preferably gravity and liquid and flow path, as chip interior liquid flowing driving force,
Driving force is used gravity as, in chip in use, the well 1 of chip is vertically above reaction tank 16, the reagent storage of chip
Liquid pool (9,10) is vertically above reaction tank 16, and the waste liquid pool 19 of chip is vertically below the reaction tank 16 of chip.
The reaction tank 16 of chip is the place of reaction, and the reagent of sample liquid and reagent reservoir 9,10 can flow into reaction tank
16 carry out reaction and cleaning operation.It can wrap captured molecule in Sample Dilution pond 2 or assembling be coated with the core of capture molecule
Piece, for capturing the biomolecule in sample, the labelled reagent which can further be equipped with reagent reservoir 9 is anti-
It answers, is marked, such as fluorescence is micro- or the antibody of quantum penalty kick label, is then cleaned with the reagent of reagent reservoir 10,
And rush and be full of reaction tank, excited using laser irradiation, utilize PMT (photomultiplier tube) or CCD(imaging sensor) carry out fluorescence
Detection.Magnetic microsphere can also be preinstalled in Sample Dilution pond 2, magnetic microsphere is marked with capture antibody, the additional magnetic of reaction tank 16
, so that microballoon is maintained in reaction tank 16, while reaction tank 16 and magnetic microsphere mark capturing molecule knot can be added in sample
It closes, the reagent of reagent reservoir can be controlled by valve enters reaction tank 16.Reagent in reagent reservoir can be fluorescence
Labelled reagent, the quantum dot-labeled reagent of person, enzyme labelled antibody, the labelled reagents such as acridinium ester, if it is enzyme marking reagent or acridine category
Remember that reagent, liquid storage tank need further exist for increasing substrate reactions reagent.
The bead of mm size diameter can be preinstalled in reaction tank 16, reagent reservoir can be equipped with latex reagent, sample
This addition Sample Dilution pond 2, travels further into reaction tank 16, and bead is by movement mixing system under magnetic fields, further
Latex reagent is added, the control reaction time carries out pattern detection.
It can be on chip basis using the detection of biological samples with various principles, chip for the operation reaction of control reagent
Also can Integrated electrode sample is detected using the method for electrochemistry.
A kind of detection method of integrated bio sample of the present invention, specific steps are as follows:
A. chip is placed in and is had in the magnetic instrument for disconnecting and opening multiparty control, the magnetic material of magnetic control point and chip
21,22,23,24 positions do not invade in the flow path 18,15,20,12 of chip to correspondence, magnetic control point；
B. this addition well 1 is sampled, before sample flows directly into reaction tank 16 or first passes through the progress of Sample Dilution pond 2 sample
Reaction tank 16 is flowed into after reason；
C. after reacting the set time, the magnetic force by controlling instrument is controlled, and is opened the valve 17 of reaction tank 16, is discharged reaction tank 16
Reaction liquid；
D. by the magnetic force control of control instrument, the valve 14 and/or 11 of reagent reservoir 9 and/or reagent reservoir 10 is opened,
Reagent reservoir 9 and/or 10 liquid of reagent reservoir flow into reaction tank 16；
E. after reacting the set time, the magnetic force by controlling instrument is controlled, and opens the valve 17 of reaction tank 16；
F. by temperature control module control chip in system temperature it is constant；
G. the biological respinse of reaction tank 16 is detected using photomultiplier tube, imaging sensor, photoelectric tube, electrode.
Further, in the reaction tank 16 containing capture molecule coating for when on magnetic microsphere, control instrument into
One step includes magnetic force corresponding with 16 position of reaction tank control point, for when cleaning and discharging reaction tank reagent, absorption to retain
Magnetic microsphere.
In detection process, the liquid that reaction tank 16 can fill reagent reservoir 10 reduces interference, and serves as optical path or electricity
The medium on road.The entire reaction reaction temperature of control in machine in instrument.Machine can install the position in storehouse of preheating, for pre-
The chip of stand-by heat.
Specifically fixed reaction time foundation in reaction process, the difference of specific reaction system and it is different, can be with
It optimizes and combines in the valve control of chip, the temperature in reaction process is set according to specific reaction, is generally adopted
With 37 DEG C, close to the intracorporal temperature of biological sample people, temperature is can be improved in specific reaction, to accelerate the speed and raising of reaction
The signal of reaction.
During the reaction, reagent reservoir 10 can play the role of cleaning reaction tank, while can also have detection
Reactivity, for example, luminous substrate solution.Sample Dilution pond 2 and reaction tank 16 separately include the pre-dilution connecting with the external world
Pond stomata 4 and reaction tank stomata 5, chip can be further containing the gas controls being connected with pre-dilution pond stomata 4 and reaction tank stomata 5
Component processed is placed in instrument the flowing that liquid is driven by air pressure in chip.
Embodiment 1
As shown in figure 4, the magnetic material 21,22,23,24 of assembling magnetic attraction is assembled in chip, covered on substrate shown in Fig. 5
Cover board 29,29 thickness 1mm of cover board, cover board 29 and chip form detection zone 31, and magnetic material selects PP(polypropylene) material, core
The 29 surface-assembled magnet 25,26,27,28 of cover board of piece.The valve mechanism of design chips shown in Fig. 6, A are magnetic material implantation
Before, valve body, B, shown valve body are in close state, and C, shown valve body are in the open state.
Chip assembles magnetic material substantially, further encapsulates closed plate, and Fig. 5 integrated chip overall schematic is whole
Chip forms a closed system, and installation magnetic material 25,26,27,28 attracts on bottom plate 21,22,23,24 and makes on cover board
Internal implantation material movement is to the position for closing fluid path.
Embodiment 2
As shown in Fig. 2, on the basis of embodiment 1, do not contain Sample Dilution pond 2, chip after version is closed in assembling, it is real
Apply the magnet 25,26,27,28 in mode 1 be changed to insertion chip magnetic attraction material alloys magnet be assembled among chip.
The foregoing is merely presently preferred embodiments of the present invention, is not intended to limit the invention, it is all in spirit of the invention and
Made any modifications, equivalent replacements and improvements within principle, should all fall within the scope and spirit of the invention.
Claims (9)
1. a kind of integrated bio pattern detection chip includes:
At least one well (1), for sample to be analyzed to be added；
At least one reaction tank (16)；
At least two reagent reservoirs (9,10)；
Well (1) is connected with reaction tank (16) by flow path (15), and reagent reservoir (9,10) and reaction tank (16) pass through stream
Road (20,12) is connected；
Device has at least one controllable valve (14,11) on flow path (20,12), controls reagent reservoir (9,10) reagent to reaction
The fluid flow switch in pond (16)；
Device has at least one controllable valve (13) on flow path (15), controls the waste cock of the liquid of reagent reaction tank (16)；
In valve (13,14,11) cavity, at least device has a kind of magnetic material (22,23,24) or has phase interaction with magnetic material
Magnetic control material (28,25,26) firmly be used as motor element, under the magnetic force open and close flow path (12,15,
20).
2. integrated bio pattern detection chip according to claim 1, it is characterised in that: also include a waste liquid pool (19),
Waste liquid pool (19) is connected with reaction tank (16) by flow path (18), and device has at least one controllable valve (17) on flow path (18),
In valve (17) cavity, at least device has a kind of magnetic material (21) or has the magnetic control material of interaction force with magnetic material
Expect that (27) are used as motor element, opens and closes flow path (18) under the magnetic force.
3. integrated bio pattern detection chip according to claim 2, it is characterised in that: the well (1) and anti-
A Sample Dilution pond (2) is equipped between Ying Chi (16), device has a mixing group for being used to mix sample in sample diluting tank (2)
Part (3).
4. integrated bio pattern detection chip according to claim 3, it is characterised in that: the Sample Dilution pond (2)
The pre-dilution pond stomata (4) and reaction tank stomata (5) connecting with the external world, pre-dilution pond stomata are separately included with reaction tank (16)
(4) it is closed with reaction tank stomata (5) when encapsulating chip, is opened before detection, for connection and balance atmospheric pressure.
5. integrated bio pattern detection chip according to claim 1, it is characterised in that: the reaction tank (16) includes
Have a kind of for capturing the capture molecule of the biological analyte molecules in sample.
6. integrated bio pattern detection chip according to claim 5, it is characterised in that: the capture molecule is coated in
On solid-phase matrix or it is coated in magnetic microsphere surface.
7. integrated bio pattern detection chip according to claim 6, it is characterised in that: the capture molecule is coated in magnetic
Property microsphere surface when, reaction tank (16) equipped with mix component (3).
8. a kind of detection method of integrated bio sample, using the integrated bio sample as described in claim 1-10 any one
Detection chip, which is characterized in that specific steps are as follows:
A. chip is placed in and is had in the magnetic instrument for disconnecting and opening multiparty control, the magnetic material of magnetic control point and chip
To correspondence, magnetic control point is not invaded in the flow path (18,15,20,12) of chip for (21,22,23,24) position；
B. it samples this addition well (1), sample, which flows directly into reaction tank (16) or first passes through Sample Dilution pond (2), carries out sample
Reaction tank (16) are flowed into after this pre-treatment；
C. after reacting the set time, the magnetic force by controlling instrument is controlled, and opens the valve (17) of reaction tank (16), discharge reaction
The reaction liquid in pond (16)；
D. by the magnetic force control of control instrument, the valve (14) of reagent reservoir (9) and/or reagent reservoir (10) is opened
And/or (11), reagent reservoir (9) and/or reagent reservoir (10) liquid flow into reaction tank (16)；
E. after reacting the set time, the magnetic force by controlling instrument is controlled, and opens the valve (17) of reaction tank (16)；
F. by temperature control module control chip in system temperature it is constant；
G. the biological respinse of reaction tank (16) is detected using photomultiplier tube, imaging sensor, photoelectric tube, electrode.
9. a kind of detection method of integrated bio sample according to claim 8, it is characterised in that: the reaction tank
(16) containing capture molecule coating for when on magnetic microsphere, control instrument further includes corresponding with reaction tank (16) position in
Magnetic force control point, for clean and discharge reaction tank reagent when, absorption retain magnetic microsphere.
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