CN106226254B - A kind of micro-fluidic chip and preparation method thereof for biological detection - Google Patents

A kind of micro-fluidic chip and preparation method thereof for biological detection Download PDF

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Publication number
CN106226254B
CN106226254B CN201610632348.1A CN201610632348A CN106226254B CN 106226254 B CN106226254 B CN 106226254B CN 201610632348 A CN201610632348 A CN 201610632348A CN 106226254 B CN106226254 B CN 106226254B
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chamber
chip
detection
micro
sample
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CN201610632348.1A
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Chinese (zh)
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CN106226254A (en
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唐城
黄炎彬
梁河立
王兴
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天津喜诺生物医药有限公司
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Abstract

The micro-fluidic chip and preparation method thereof that the invention discloses a kind of for biological detection, micro-fluidic chip includes chip hard lower panel, chip flexibility top panel, air pump control device and optical detection apparatus, chip hard lower panel is equipped with multiple chambers for storing, mixing or test sample, there is runner to be connected between each chamber and is equipped with normally closed micro-valve, chip flexibility top panel is equipped with independent semi-spherical bonnet, it is corresponded with the chamber of lower panel, top is equipped with normally closed inflating port;Air pump control system contains multiple pneumatic heads, corresponds with the normally closed inflating port on each chamber semi-spherical bonnet portion top, realizes the charge operation to each inflating port and connected chamber;The quantitative detection of optical detection apparatus progress sample concentration.To specific chamber, packing is handled in advance in preparation process.This invention simplifies the operating procedures of biological detection, improve detection efficiency and precision, reduce production cost.

Description

A kind of micro-fluidic chip and preparation method thereof for biological detection

Technical field

The invention belongs to engineering in medicine and microfluidic art, especially a kind of micro-fluidic chip for biological detection And preparation method thereof.

Background technique

The diagnosis of clinically relevant disease is fast, accurately detected as to the important biomolecule molecule with aetology foundation Provide very important reference and help.Such as to (1-3)-β-D glucan in serum, BAL fluid or cerebrospinal fluid Positive detection is the microorganism aetology foundation of studies of invasive fungal infections, and the detection to lipopolysaccharide in body fluid is leather The important evidence of Lan Shi negative microbial infections medical diagnosis on disease.From the middle of last century, under the leading in the U.S., have developed more The chromogenic detection reagents box of glucan or bacterial endotoxin of the kind based on reagents, but its is complex for operation step, and technical requirements are high, Significantly limit the efficiency and popularization of clinical diagnosis.

Microfluidic chip technology is to develop a very fast field in recent years, by biology, chemistry, medical analysis The unit operations such as sample preparation, reaction, separation, detection in the process are integrated on the chip of one piece of micro-meter scale, automatically Complete analysis overall process.Micro-fluidic chip has that volume is light and handy, test dose is few, and it is excellent that reaction speed is fast, instant can abandon etc. Point has huge potentiality in fields, the especially field of biological detection such as biology, chemistry, medicine.Such as patent CN A kind of micro-fluidic chip for endotoxin detection, a kind of base disclosed in patent CN 105372429A disclosed in 205308353U In the micro-fluidic chip that reagents bacterial endotoxin and (1-3)-β-D glucan detect.It is then possible to it is noted that provide at present The micro-fluidic chip design of biological detection either suffer from very big drawback in processing technology or practical operation, it is difficult to it is real The batch preparation of existing low cost is not easy to the pre- packing of a variety of required reagents in actually detected, the input side of actual mobile source Formula is also more troublesome or uncontrollable.

Summary of the invention

It is an object of the invention to improve the efficiency of biological detection, precision, and optimize the design and preparation of micro-fluidic chip Technique pushes the functionization and low cost of biological detection microfluidic chip, proposes a kind of micro-fluidic chip for biological detection And preparation method thereof.

The present invention solves its technical problem and adopts the following technical solutions to achieve:

A kind of micro-fluidic chip for biological detection is being examined including detection light source and the detection plate for being equipped with detector It surveys between light source and detection plate and is successively mounted with chip hard lower panel, alignment hot pressing is linked to be the core on chip hard lower panel Piece flexibility top panel and air pump control device,

Wherein, the chip hard lower panel is equipped with multiple for storing or mixing the cylindrical chamber of sample, multiple Cylindrical chamber includes: sample-adding chamber, sample storage chamber, treatment fluid chamber, sample treatment chamber, reaction solution chamber, reaction Chamber, rectangular detection cell and redundant sample store chamber, between sample-adding chamber and sample storage chamber, sample storage chamber with Between sample treatment chamber, between treatment fluid chamber and sample treatment chamber, reaction chamber and rectangular detection cell, and react sap cavity Room is connected between sample treatment chamber and between rectangular detection cell and redundant sample storage chamber by runner, and every The whole story both ends of Duan Liudao are equipped with normally closed micro-valve, are equipped with micropore on the runner between sample-adding chamber and sample storage chamber Filter core;

Wherein, the chip flexibility top panel is equipped with multiple cylinder body cavitys on positions and dimensions and chip hard lower panel The one-to-one semi-spherical bonnet in room is equipped with normally closed inflating port on the top of each semi-spherical bonnet.

Wherein, the air pump control system contains multiple pneumatic heads, the position of each pneumatic head and chip flexibility top panel Semi-spherical bonnet on each normally closed inflating port correspond, independently realized by circuit control to each inflating port and connected chamber Charge operation.

Wherein, detection light source issues detection light, and detection light is received after passing through tested sample by the detector in detection plate, The quantitative detection of sample concentration is carried out by the principle of fluorescence or absorption photometric.

Moreover, the normally closed micro-valve is check valve, normally closed micro-valve is made of the flexible membrane that one end is fixed, flexible membrane it is another Hold has a baffle to realize unidirectional cutoff in the opposite direction of flowing.

Moreover, the material of the chip hard lower panel is one of glass, organic glass or rigid polymer.

Moreover, flexibility membrane material used in the normally closed micro-valve is one of PET, PDMS or PMMA.

Moreover, the chip flexibility top panel material is one of flexibility PET, PDMS or PMMA film, and detecting Material used in pool area is noiseless to detection light source and signal.

A kind of preparation method of the above-mentioned micro-fluidic chip for biological detection, comprises the following steps that

(1) required chamber is cut out on hard substrate with miromaching, runner is connected to and makes normally closed micro- Valve obtains chip hard lower panel;Contain the chip flexibility top panel of multiple semi-spherical bonnets with the preparation of reverse mould technique;The two is right Neat hot pressing is linked to be the entirety of a sealing;

(2) vacuumize process, the flexible plate benging above of chip are carried out by the normally closed inflating port that semi-spherical bonnet top is equipped with So that upper and lower panel is bonded completely;

(3) sterilization treatment is carried out to gained vacuum chip, specific chamber is carried out at pre- packing by normally closed inflating port It manages or is detected and handled with reagent, finally obtain the vacuum one chip of pre-packaged reagent.

Moreover, the pre- packing includes the sample treatment liquid for the treatment of fluid chamber, the reaction solution of reaction solution chamber, reaction chamber Reactant or fluorescent material freeze-dried powder.

The advantages and positive effects of the present invention are:

1, the present invention proposes a kind of micro-fluidic chip and preparation method thereof for biological detection, has comprehensively considered chip Preparation process, reagent be pre-packaged, the input mode of driving power etc. is, it can be achieved that the automatic detection of sample, and is suitble to various biologies The micro-fluidic detection of molecule.

2, the micromation of biological detection, fining is greatly facilitated in micro-fluidic chip provided by the invention and preparation method thereof And automation, the operating procedure of biological detection is simplified, detection efficiency and precision are improved, optimizes the preparation process of chip, Reduce production cost, it is ensured that the stability and reliability of chip production make it have generalization.

Detailed description of the invention

Attached drawing 1 is structural schematic diagram of the invention;

Fig. 2 is the position relationship structural diagram of chip hard lower panel and chip flexibility top panel in the present invention;

Fig. 3 is the structural schematic diagram of chip hard lower panel in the present invention;

Fig. 4 is the schematic perspective view of normally closed micro-valve in the present invention;

Fig. 5 is the structural schematic diagram of chip flexibility top panel in the present invention;

Fig. 6 is the structural schematic diagram of air pump control system in the present invention.

Specific embodiment

The implementation of the invention is further described below, and following examples are merely illustrative and not limiting, cannot It is limited the scope of protection of the present invention with this.

A kind of micro-fluidic chip for biological detection, as shown in Figure 1, including detecting light source 6 and being equipped with detector 2 Detection plate 1, is successively mounted with chip hard lower panel 3 between detection light source and detection plate, and alignment hot pressing is linked to be hard in chip Chip flexibility top panel 4 and air pump control device 5 on matter lower panel,

Wherein, as shown in figures 2 and 3, the chip hard lower panel is equipped with multiple cylindrical chambers for storing or mixing Sample is closed, including sample-adding chamber 7, sample storage chamber 8, treatment fluid chamber 9, sample treatment chamber 15, reaction solution chamber 10, reaction chamber 14, rectangular detection cell 12, redundant sample store chamber 11, between sample-adding chamber and sample storage chamber, sample Between product storage chamber and sample treatment chamber, between treatment fluid chamber and sample treatment chamber, reaction chamber and rectangular detection Between pond, with reaction solution chamber, with sample treatment chamber and rectangular detection cell and redundant sample storage chamber between by runner 16 connections, and it is equipped with normally closed micro-valve 13 at the whole story both ends of every section of runner, between sample-adding chamber and sample storage chamber Runner on micropore filter element 17 is installed;

In specific implementation of the invention, as shown in figure 4, the normally closed micro-valve is check valve, normally closed micro-valve is consolidated by one end Fixed flexible membrane is constituted, and the other end of flexible membrane has a baffle to realize unidirectional cutoff in the opposite direction of flowing.

In specific implementation of the invention, the material of the chip hard lower panel is that glass, organic glass or hard are poly- Close one of object.

In specific implementation of the invention, flexibility membrane material used in the normally closed micro-valve is one in PET, PDMS or PMMA Kind.

Wherein, as shown in figure 5, the chip flexibility top panel is equipped with more in positions and dimensions and chip hard lower panel A cylindrical chamber independent semi-spherical bonnet 18 correspondingly, is equipped with normally closed inflating port on the top of each semi-spherical bonnet 19。

In specific implementation of the invention, the chip flexibility top panel material is in flexibility PET, PDMS or PMMA film One kind, and detection pool area used in material to detection light source and signal it is noiseless.

Wherein, as shown in fig. 6, the air pump control system contains multiple pneumatic heads 20, the position of each pneumatic head and core Each normally closed inflating port corresponds on the semi-spherical bonnet of piece flexibility top panel, is independently realized by circuit control to each inflating port And the charge operation of connected chamber.

Wherein, detection light source issues detection light, and detection light is received after passing through tested sample by the detector in detection plate, The quantitative detection of sample concentration is carried out by the principle of fluorescence or absorption photometric.

Detect working principle

It will be added to test sample from the normally closed inflating port of sample-adding chamber top when test, by chip and external gas apparatus for controlling pump It matches, by the independent inflatable of each chamber of circuit control, the liquid one-way movement in chamber is pushed with the pressure of generation, according to Filtering, processing, reaction and the detection of secondary automatic realization sample.

A kind of preparation method of the above-mentioned micro-fluidic chip for biological detection, comprises the following steps that

(1) required chamber is cut out on hard substrate with miromaching, runner is connected to and makes normally closed micro- Valve obtains chip hard lower panel;Contain the chip flexibility top panel of multiple semi-spherical bonnets with the preparation of reverse mould technique;The two is right Neat hot pressing is linked to be the entirety of a sealing;

(2) vacuumize process, the flexible plate benging above of chip are carried out by the normally closed inflating port that semi-spherical bonnet top is equipped with So that upper and lower panel is bonded completely;

(3) sterilization treatment is carried out to gained vacuum chip, specific chamber is carried out at pre- packing by normally closed inflating port It manages or is detected and handled with reagent, finally obtain the vacuum one chip of pre-packaged reagent.

Wherein, the pre- packing includes the sample treatment liquid for the treatment of fluid chamber, the reaction solution of reaction solution chamber, reaction chamber Reactant or fluorescent material freeze-dried powder.

It vacuumizes and dispenses the normally closed inflating port being equipped with by semi-spherical bonnet top in advance and carry out, normally closed inflation after processing Mouth does not destroy, or passes through the function of its normally closed inflating port of post-processing recovery after destroying.

Embodiment

A kind of micro-fluidic chip for biological detection, including chip hard lower panel, chip flexibility top panel, air pump control The light source and detector of device and optical detection apparatus processed.Chip hard lower panel is equipped with cylindrical chamber for storing or mixing Sample, including sample-adding chamber, sample storage chamber, treatment fluid chamber, sample treatment chamber, reaction solution chamber, reaction chamber, side Shape detection cell, redundant sample store chamber, have runner to be connected between each chamber and are equipped with normally closed micro-valve.Normally closed micro-valve is unidirectional Valve, and have setting at the whole story end of runner.Micro-valve structure is made of the flexible membrane that one end is fixed, and the other end of flexible membrane exists The opposite direction of flowing has a baffle to realize unidirectional cutoff.Flexibility membrane material used in micro-valve is PET, PDMS or PMMA.Feeding chamber Runner is equipped with micropore filter element between room and sample storage chamber.Chip flexibility top panel is equipped with independent semi-spherical bonnet portion, under The chamber of panel corresponds, and top is equipped with normally closed inflating port.Lower panel material be glass, organic glass, rigid polymer, Top panel material is flexibility PET, PDMS, PMMA film, and is detecting material used in pool area to detection light source and signal without dry It disturbs.Air pump control system contains multiple pneumatic heads, corresponds, passes through with the normally closed inflating port on each chamber semi-spherical bonnet portion top Circuit control independently realizes the charge operation to each inflating port and connected chamber.Optical detection apparatus includes light source and detection Device carries out the quantitative detection of sample concentration by the principle of fluorescence or absorption photometric.

Micro-fluidic chip preparation carries out as follows.It is cut out on hard substrate with miromaching first Chamber is connected to runner and makes micro-valve, obtains chip lower panel, the preferred organic glass of material, the preferred PMMA of micro-valve flexible membrane;With Reverse mould technique prepares the chip flexibility top panel containing multiple semi-spherical bonnet portions, the preferred PET of material;The two alignment hot pressing is connected The entirety sealed at one carries out vacuumize process, flexible top panel by the normally closed inflating port that semi-spherical bonnet portion top is equipped with Bending is so that upper and lower panel is bonded completely;To gained vacuum chip carry out sterilization treatment, by normally closed inflating port to processing sap cavity The sample treatment liquid of specific quantity is injected in room, to the reaction solution of reaction solution chamber injection specific quantity, injects specific quantity to reaction chamber Reactant freeze-dried powder, obtain the vacuum one chip of pre-packaged reagent.

It will be added to test sample from the normally closed inflating port of sample-adding chamber top when test, by chip and external gas apparatus for controlling pump It matches, by the independent inflatable of each chamber of circuit control, the liquid one-way movement in chamber is pushed with the pressure of generation, according to Filtering, processing, reaction and the detection of secondary automatic realization sample.

Claims (7)

1. a kind of micro-fluidic chip for biological detection, it is characterised in that: including detection light source and the inspection for being equipped with detector Drafting board is successively mounted with chip hard lower panel between detection light source and detection plate, alignment hot pressing is linked to be under chip hard Chip flexibility top panel and air pump control device on panel,
Wherein, the chip hard lower panel is equipped with multiple for storing or mixing the cylindrical chamber of sample, multiple cylinders Fluid chamber includes: sample-adding chamber, sample storage chamber, treatment fluid chamber, sample treatment chamber, reaction solution chamber, reaction chamber, Rectangular detection cell and redundant sample store chamber, between sample-adding chamber and sample storage chamber, sample storage chamber and sample Between processing chamber housing, between treatment fluid chamber and sample treatment chamber, reaction chamber and rectangular detection cell, and reaction solution chamber, It is connected between sample treatment chamber and between rectangular detection cell and redundant sample storage chamber by runner, and is flowed at every section The whole story both ends in road are equipped with normally closed micro-valve, and micropore filter is equipped on the runner between sample-adding chamber and sample storage chamber Core;
Wherein, the chip flexibility top panel is equipped with multiple cylindrical chambers one on positions and dimensions and chip hard lower panel One corresponding semi-spherical bonnet is equipped with normally closed inflating port on the top of each semi-spherical bonnet;
Wherein, the air pump control device contains multiple pneumatic heads, the position of each pneumatic head and the half of chip flexibility top panel Each normally closed inflating port corresponds in spherical caps, and the inflation to each inflating port and connected chamber is independently realized by circuit control Operation;
Wherein, detection light source issues detection light, and detection light is received by the detector in detection plate after passing through tested sample, passed through The quantitative detection of the principle of fluorescence or absorption photometric progress sample concentration.
2. the micro-fluidic chip according to claim 1 for biological detection, it is characterised in that: the normally closed micro-valve is single To valve, normally closed micro-valve is made of the flexible membrane that one end is fixed, and the other end of flexible membrane has a baffle reality in the opposite direction of flowing Existing unidirectional cutoff.
3. the micro-fluidic chip according to claim 1 for biological detection, it is characterised in that: below the chip hard The material of plate is one of glass, organic glass or rigid polymer.
4. the micro-fluidic chip according to claim 1 for biological detection, it is characterised in that: used in the normally closed micro-valve Flexible membrane material is one of PET, PDMS or PMMA.
5. the micro-fluidic chip according to claim 1 for biological detection, it is characterised in that: the chip is flexible above Plate matter is one of flexibility PET, PDMS or PMMA film, and the material used in detection pool area is to detection light source and signal It is noiseless.
6. the preparation method described in a kind of claim 1-5 any one for the micro-fluidic chip of biological detection, feature It is to comprise the following steps that
(1) required chamber is cut out on hard substrate with miromaching, is connected to runner and makes normally closed micro-valve, is obtained Obtain chip hard lower panel;Contain the chip flexibility top panel of multiple semi-spherical bonnets with the preparation of reverse mould technique;The two is aligned heat Pressure is linked to be the entirety of a sealing;
(2) vacuumize process is carried out by the normally closed inflating port that semi-spherical bonnet top is equipped with, the flexible plate benging above of chip makes Upper and lower panel is bonded completely;
(3) sterilization treatment is carried out to gained vacuum chip, by normally closed inflating port to specific chamber carry out pre- packing processing or It is detected and is handled with reagent, finally obtain the vacuum one chip of pre-packaged reagent.
7. the preparation method of the micro-fluidic chip according to claim 6 for biological detection, it is characterised in that: described pre- Packing reagent include the sample treatment liquid for the treatment of fluid chamber, the reaction solution of reaction solution chamber, reaction chamber reactant or fluorescence The freeze-dried powder of substance.
CN201610632348.1A 2016-08-03 2016-08-03 A kind of micro-fluidic chip and preparation method thereof for biological detection CN106226254B (en)

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CN105170206A (en) * 2015-09-24 2015-12-23 基蛋生物科技股份有限公司 Micro-fluidic chip achieving multi-index detection
CN105396633A (en) * 2015-12-22 2016-03-16 苏州汶颢芯片科技有限公司 Soft microfluidic chip reversible clamp
CN205941345U (en) * 2016-08-03 2017-02-08 天津喜诺生物医药有限公司 A micro -fluidic chip for biological detection

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Publication number Priority date Publication date Assignee Title
TWI509066B (en) * 2012-12-28 2015-11-21 中原大學 Testing microfluid system with a multiple-channel disc and utility thereof

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0470438A1 (en) * 1990-08-06 1992-02-12 Bayer Corporation Self-metering fluid analysis device
CN104411406A (en) * 2012-03-16 2015-03-11 统计诊断与创新有限公司 A test cartridge with integrated transfer module
CN102671729A (en) * 2012-05-07 2012-09-19 博奥生物有限公司 Micro flow control chip used for multi-index biochemical detection
CN104226385A (en) * 2013-06-09 2014-12-24 北京百康芯生物科技有限公司 A novel micro-fluidic chip and a using method thereof
CN105170206A (en) * 2015-09-24 2015-12-23 基蛋生物科技股份有限公司 Micro-fluidic chip achieving multi-index detection
CN105396633A (en) * 2015-12-22 2016-03-16 苏州汶颢芯片科技有限公司 Soft microfluidic chip reversible clamp
CN205941345U (en) * 2016-08-03 2017-02-08 天津喜诺生物医药有限公司 A micro -fluidic chip for biological detection

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