CN109234157A - A kind of biological reaction container - Google Patents

A kind of biological reaction container Download PDF

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Publication number
CN109234157A
CN109234157A CN201811142520.0A CN201811142520A CN109234157A CN 109234157 A CN109234157 A CN 109234157A CN 201811142520 A CN201811142520 A CN 201811142520A CN 109234157 A CN109234157 A CN 109234157A
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China
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micropore
base band
band
carrier band
fluid channel
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Granted
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CN201811142520.0A
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Chinese (zh)
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CN109234157B (en
Inventor
相欣雨
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Hangzhou Laiyue Technology Co ltd
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Individual
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    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L7/00Heating or cooling apparatus; Heat insulating devices
    • B01L7/52Heating or cooling apparatus; Heat insulating devices with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/5302Apparatus specially adapted for immunological test procedures
    • G01N33/5304Reaction vessels, e.g. agglutination plates
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/5308Immunoassay; Biospecific binding assay; Materials therefor for analytes not provided for elsewhere, e.g. nucleic acids, uric acid, worms, mites
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/02Adapting objects or devices to another
    • B01L2200/026Fluid interfacing between devices or objects, e.g. connectors, inlet details
    • B01L2200/027Fluid interfacing between devices or objects, e.g. connectors, inlet details for microfluidic devices
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/14Process control and prevention of errors
    • B01L2200/143Quality control, feedback systems
    • B01L2200/147Employing temperature sensors

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Immunology (AREA)
  • Molecular Biology (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Urology & Nephrology (AREA)
  • Hematology (AREA)
  • General Health & Medical Sciences (AREA)
  • Biochemistry (AREA)
  • Physics & Mathematics (AREA)
  • Food Science & Technology (AREA)
  • Medicinal Chemistry (AREA)
  • Biotechnology (AREA)
  • Analytical Chemistry (AREA)
  • Microbiology (AREA)
  • Cell Biology (AREA)
  • General Physics & Mathematics (AREA)
  • Pathology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Clinical Laboratory Science (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)

Abstract

The invention discloses a kind of biological reaction containers, comprising: carries, has several micropores on the carrier band, the micropore is through-hole or blind hole;Base band, when micropore is through-hole, a base band covers the side surface that carrier band has micropore, and another base band covers another side surface that carrier band has micropore, wherein a base band uses transparent material;When for blind hole, a base band covers the side surface that carrier band has micropore, this base band uses transparent material;Base band makes micropore form confined reaction room in conjunction with carrier band micropore.The container continuous quantity carries reaction system, and reaction volume can set variable, and the micropore variable amounts of reaction vessel, noise is relatively high, and possibility of pollution is smaller, is a kind of ideal biological reaction container.

Description

A kind of biological reaction container
Technical field
The present invention relates to biological detection analytical equipment field, especially a kind of biological reaction container.
Background technique
It is lower using spectrophotometer accuracy when the biological samples Concentration Testing such as small molecule, nucleic acid, albumen, bacterium, at This is lower, higher using liquid phase digital pcr accuracy, but applied sample amount is smaller, and dynamic range is smaller, and chamber volume is not fixed, Higher cost, higher using solid phase digital pcr accuracy, applied sample amount is smaller, and dynamic range is smaller, although reaction chamber is fixed, It is unable to successive reaction, it can not preparatory default label object.
Summary of the invention
The invention mainly solves the technical problem of providing a kind of biological reaction container, which can continuously be filled Reaction system solves the problems, such as that the fixed applied sample amount of previous reaction vessel is lower compared with atom sample utilization rate.
In order to solve the above technical problems, The technical solution adopted by the invention is as follows: a kind of biological reaction container, comprising:
It carries, there are several micropores on the carrier band, the micropore is through-hole or blind hole;
Base band, when micropore is through-hole, a base band covers the side surface that carrier band has micropore, and another base band covers Another side surface with micropore is carried, wherein a base band uses transparent material;When for blind hole, a base band covers carrier band A side surface with micropore, this base band use transparent material;
Base band makes micropore form confined reaction room in conjunction with carrier band micropore.
Further, the carrier band is carried excellent by hot pressing, injection molding, 3D printing or laser boring mode machine-shaping Select black material.
Further, the Zhou Changwei 4um to 40mm of the micropore.
Further, there is gap, preset fluid channel in gap, the side of carrier band has between the micropore and micropore The other side of fluid channel entrance, carrier band is exported with fluid channel, and liquid enters from fluid channel entrance, is reached by fluid channel each Micropore flows out after passing through micropore from fluid channel outlet;Liquid passes through one of surface tension, gravity, pressure power or many kinds of force Into fluid channel entrance.
Further, the order of magnitude of the volume of the micropore is pL grades, nL grades or uL grades.
Further, the micropore internal surface of hole is hydrophilic, and contact angle is less than 120 degree, preferably 90 degree;The base band Using hydrophobic closed strip material and not compatible with reaction solution, contact angle is greater than 60 degree, preferably 100 degree.
Further, when micropore be through-hole when, another base band is transparent or black material, can also be used metal material, Thermoplastic or thermosetting material.
Further, needed for preset in the micropore or coating biological respinse probe, antibody or aptamer reaction Marker.
Further, reaction vessel is continuous or continuously forms flexible tape or sectional making passes through knot by being connected Structure connection becomes band.
It is a further object of the present invention to provide a kind of application method of biological reaction container, this method is first by reaction system It fills out in the micropore of carrier band, then base band is covered into the micropore on carrier band, carrier band micropore is made to be closed to form confined reaction room, reaction knot Pass through baseband-detection to the result of reaction after beam.
Compared with the existing technology, beneficial effects of the present invention are as follows: chamber volume from 0.1pL, 1pL, 1nL, 1uL, 10uL can be pre-configured with, and applied sample amount is from 5uL, 10uL, 100uL, 200uL dynamic loading, parallel 20,000,100,000,1,000,000,200 The biological respinse of ten thousand even higher quantity, Dynamic Recognition, until biology extract sample load completions completely, avoid Sample Dilution with Sample is discarded, and body of the present invention is smaller, and thinner thickness, heat exchanger effectiveness is higher, is conducive to quick bio reaction, this reaction vessel is adopted With similar sandwich structure, production is simple, and cost is relatively low.Biological respinse system or biological sample are connected according to Poisson distribution principle Continuous to be distributed to multiple reaction chambers, because loading quantity is larger, parallel reaction is more, reachable according to Poisson distribution principle accuracy 0.01%, dynamic range is greatly up to 108, precious biological sample is made full use of, the biologies such as concentration, the intensity of reaction system are disclosed Feature.
Detailed description of the invention
Fig. 1 is the reaction vessel sectional view schematic diagram that micropore is through-hole;
Fig. 2 is the reaction vessel sectional view schematic diagram that micropore is blind hole;
Fig. 3 is micropore layout diagram;
Fig. 4 is the schematic diagram of preset fluid channel in micropore gap;
Fig. 5 a- Fig. 5 g is the combination schematic diagram of base band and carrier band;
Fig. 6 a and Fig. 6 b are the connection schematic diagram between two biological reaction containers;
The components in the drawings are labeled as follows: base band 1, carrier band 2, micropore 3, fluid channel 4, fluid channel entrance 5, miniflow are said Mouth 6.
Specific embodiment
Example embodiments are described in detail here, and the example is illustrated in the accompanying drawings.Following description and attached When figure, unless otherwise indicated, the same numbers in different drawings indicate the same or similar elements.In following exemplary embodiment Described embodiment does not represent all embodiments consistented with the present invention.On the contrary, they be only with it is such as appended It is described in detail in middle claims, the example of the consistent device of some aspects of the invention.Each implementation of this specification Example is described in a progressive manner.
It is to be appreciated that the directional instruction (such as up, down, left, right, before and after ...) of institute is only used in the embodiment of the present invention In explaining in relative positional relationship, the motion conditions etc. under a certain particular pose (as shown in the picture) between each component, if should When particular pose changes, then directionality instruction also correspondingly changes correspondingly.
It in addition, the technical solution between each embodiment can be combined with each other, but must be with ordinary skill Based on personnel can be realized, this technical side will be understood that when the combination of technical solution appearance is conflicting or cannot achieve The combination of case is not present, also not the present invention claims protection scope within.
As depicted in figs. 1 and 2, the embodiment of the present invention provides a kind of biological reaction container, comprising: base band 1 and carrier band 2, institute There are several micropores 3 on the carrier band 2 stated;Base band 1 can be incorporated in by the modes such as bonding, hook, light auxiliary bonding and base band 1 Together, in addition to reacting micropore 3, base band 1 and 2 junctions of carrier band mutually bond or fix, and the micropore 3 on carrier band 2 is made to become closed Reaction chamber;Must wherein there be a base band 1 using transparent material, remaining base band 1 is transparent or dark 1 (preferably fast black base of base band Band), metal base band (aluminium film, copper film etc.) or the higher thermoplastic of heating conduction or thermosetting material can also be used in remaining base band 1 (PC, PVA, COC, COP etc.);The carrier band 2 uses transparent or dark material, preferably black material.
The micropore 3 is through-hole or blind hole, and the perimeter of micropore 3 is generally 4um to 40mm, and the depth in hole is generally 1um To 10mm, hole density is generally 1-50000/cm2, the both ends size in hole can be different, allow hole wall gradient;It is preferred that hole is all Long 200um, hole depth 200um, 5000/cm of hole density.When for through-hole, a base band 1 covers one of carrier band 2 with micropore 3 Side surface, another base band 1 cover another side surface of the carrier band 2 with micropore 3;When for blind hole, a base band 1 covers carrier band 2 side surfaces with micropore 3.Micropore 3 is processed by modes such as hot pressing, injection molding, 3D printing, laser boring, ionizing radiations Type, when being processed as through-hole using ionizing radiation or laser boring mode, through-hole is become blind hole by 2 palpus additional layer tail band of carrier band, Tail band and the surface characteristic of 2 faying faces of carrier band and contact angle are identical as base band 1, and tail band can be metal, polymerization species film, bottom The thickness of band is generally 1um to 2mm, preferably 200um, is conducive to temperature conduction.
3 internal surface of hole of micropore be it is hydrophilic, contact angle is less than 120 degree, preferably 90 degree;The base band 1 is using thin Watertight strip material and not compatible with reaction solution, contact angle are greater than 60 degree, preferably 100 degree.
Base band 1 is typically chosen the preferable film of PC, PVA, COC, COP thermoplasticity translucency, film thickness be generally 50um~ 1000um, preferably 100um, the preferred lyophoby viscose in 1 lower surface of base band are bonded after introduction of the sample with carrier band 2.Base band 1 and carrier band 2 In conjunction with rear, carrying 2 micropore 3, just closing becomes sealed reaction vessel.
As shown in figure 3, the order of magnitude of the volume of the micropore 3 is pL grades, nL grades or uL grades;2 processing micropore 3 of carrier band When, uniform type is distributed in the adjustable section of micropore 3 and preset, micropore 3, laterally non-homogeneous type, Axinlly nonuniform type, and random point Cloth type, preferably first two.The shape of micropore 3 is according to the processing technology and purposes of micropore 3, the orifice shapes of the micropore 3 Default arbitrary shape, can be rule or/symmetric figure, generally circular in cross section, rectangular, rectangle, triangle, hexagon, diamond shape, Parallelogram, irregular figure, preferably hexagon.
As shown in figure 4, having gap between the micropore 3 and micropore 3, preset fluid channel 4 in gap carries the one of 2 Side has fluid channel entrance 5, carries 2 other side and has fluid channel outlet 6, liquid enters from fluid channel entrance 5, passes through miniflow Road 4 reaches each micropore 3, flows out after passing through micropore 3 from fluid channel outlet 6;Liquid passes through in surface tension, gravity, pressure A kind of power or many kinds of force enter fluid channel entrance 5.
As shown in figure 4, can be multiple micropores 3 shares a fluid channel entrance 5 or fluid channel outlet 6, fluid channel entrance 5 Exporting 6 at the both ends of carrier band 2 with fluid channel is in arranged for interval, i.e., the fluid channel 4 between two neighboring fluid channel entrance 5 is carrying It is closing at 2 one end, and is fluid channel outlet 6 at the other end of carrier band 2, it is micro- between two neighboring fluid channel outlet 6 Runner 4 is closing at one end of carrier band 2, and at the other end of carrier band 2 is fluid channel entrance 5;Also can increase fluid channel 4 makes Each or multiple 3 independences of micropore or common microchannel 4, allow drop to reach each micropore 3.The knot of micropore 3 and fluid channel 4 There are many conjunctions, preferably the first.
Fig. 3 is the micropore of closed reaction vessel, and Fig. 4 is the micropore of the reaction vessel of interaction, the closed reaction of preferably Fig. 3 The micropore of container.
As shown in figs 5 a-g, base band 1 and carrier band 2 fixed form have a~g kind be respectively Fig. 5 a be run-in index, Fig. 5 b For under upper packet, Fig. 5 c is under upper half packet, and Fig. 5 d is wrapped under being, Fig. 5 e wraps for lower half, Fig. 5 f is temperature control clamping type, and Fig. 5 g is outer Packet mode, the preferably run-in index of Fig. 5 a.
As shown in figures 6 a and 6b, reaction vessel carrier band 2 can set random length, can be by two when length is fixed A or more than two carrier bands 2 are docked by interface, and when docking can be parallel surface docking, also can be with bumps docking point Mistake proofing docking is carried out, then has and is docked using asymmetric mutually matched male and female tongue and groove, enables to carry 2 continued accesses.
Marker needed for preset or coating biological respinse probe, antibody etc. react in the micropore 3.
Tag slot is also provided on reaction vessel, tag slot and 3rd area of micropore are mutually indepedent, know for reaction vessel reaction chamber Shi Yong not provide may.
The application method of biological reaction container provided by the invention, this method are that reaction system is first filled out the micro- of carrier band 2 In hole 3, then base band 1 combined or be fixed on carrier band 2, so that the closure of micropore 3 of carrier band 2 is formed confined reaction room, after reaction The result of reaction is detected by base band 1.
Embodiment:
Using hot-pressing technique, on the PC film of thickness 0.1mm, hot-pressing transfer printing goes out deep 50 μm, and wide 50 μm square anti- 50 μm of interval between Ying Kong, Kong Yukong, the volume 0.125pL of each reaction, 10000 reactions of distribution every square centimeter, instead Answer container using 10mm effective width (except tag slot), continuous sample introduction 1mm, reaction quantity is 1000, and applied sample amount is 125pL, continuous sample introduction 100mm, reaction quantity are 100000, applied sample amount 12.5uL, continuous sample introduction 1000mm, and reaction quantity is 1000000, applied sample amount 125uL;Its sensitivity reaches 1/1000000, and dynamic range reaches 107, when reaction system determines, Reaction vessel can continuous sample introduction, will extract or the reaction system handled well be continuously loaded into reaction chamber, abundant benefit With precious biological sample.Accuracy is wanted when number of chambers mostly calculates primitive reaction system concentration using Poisson distribution principle When asking certain, dynamic range is wider.
The above description is only a preferred embodiment of the present invention, is not intended to limit the scope of the invention, all utilizations Equivalent structure or equivalent flow shift made by description of the invention and accompanying drawing content is applied directly or indirectly in other correlations Technical field, be included within the scope of the present invention.

Claims (10)

1. a kind of biological reaction container characterized by comprising
It carries, there are several micropores on the carrier band, the micropore is through-hole or blind hole;
Base band, when micropore is through-hole, a base band covers the side surface that carrier band has micropore, and another base band covers carrier band Another side surface with micropore a, wherein base band uses transparent material;When for blind hole, a base band, which covers carrier band, to be had One side surface of micropore, this base band use transparent material;
Base band makes micropore form confined reaction room in conjunction with carrier band micropore.
2. a kind of biological reaction container according to claim 1, which is characterized in that the carrier band by hot pressing, injection molding, 3D printing or laser boring mode machine-shaping, carry preferred black material.
3. a kind of biological reaction container according to claim 1, which is characterized in that the Zhou Changwei 4um of the micropore is extremely 40mm。
4. a kind of biological reaction container according to claim 1, which is characterized in that have between the micropore and micropore Gap, preset fluid channel in gap, the side of carrier band have fluid channel entrance, and the other side of carrier band has fluid channel outlet, liquid Body enters from fluid channel entrance, reaches each micropore by fluid channel, flows out after passing through micropore from fluid channel outlet;Liquid passes through One of surface tension, gravity, pressure power or many kinds of force enter fluid channel entrance.
5. a kind of biological reaction container according to claim 1, which is characterized in that the order of magnitude of the volume of the micropore It is pL grades, nL grades or uL grades.
6. a kind of biological reaction container according to claim 1, which is characterized in that the micropore internal surface of hole is parent Water, contact angle is less than 120 degree, and preferably 90 degree;The base band using hydrophobic closed strip material and not compatible with reaction solution, Contact angle is greater than 60 degree, preferably 100 degree.
7. a kind of biological reaction container according to claim 1, which is characterized in that when micropore is through-hole, another base Band is transparent or black material, and metal material, thermoplastic or thermosetting material can also be used.
8. a kind of biological reaction container according to claim 1, which is characterized in that preset in the micropore or painting overgrowth Object reacts marker needed for probe, antibody or aptamer react.
9. a kind of biological reaction container according to claim 1, which is characterized in that reaction vessel is continuous or passes through linking Flexible tape or sectional making is continuously formed to become band by structure connection.
10. a kind of application method of biological reaction container, which is characterized in that this method is that reaction system is first filled out the micro- of carrier band Kong Zhong, then base band is covered into the micropore on carrier band, make carrier band micropore be closed to form confined reaction room, passes through base band after reaction Detect the result of reaction.
CN201811142520.0A 2018-09-28 2018-09-28 Biological reaction container Active CN109234157B (en)

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Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7282329B2 (en) * 2002-08-22 2007-10-16 Massachusetts Institute Of Technology Suspended microchannel detectors
CN101688861A (en) * 2007-05-18 2010-03-31 爱克瑟拉有限公司 Reaction vessel with integrated optical and fluid control elements
CN102199529A (en) * 2011-03-22 2011-09-28 博奥生物有限公司 Biochip hybridization system
CN103087905A (en) * 2012-09-14 2013-05-08 盛司潼 Sequencing reaction platform and nucleic acid sequence detection device
CN105842324A (en) * 2016-04-27 2016-08-10 河海大学常州校区 Integrated micro-fluidic chip and working method thereof
CN107737615A (en) * 2017-09-20 2018-02-27 南京肯辛顿诊断科技有限公司 A kind of microfluidic device for biochemistry detection
CN108070525A (en) * 2015-11-19 2018-05-25 赛纳生物科技(北京)有限公司 Gene sequencing chip

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7282329B2 (en) * 2002-08-22 2007-10-16 Massachusetts Institute Of Technology Suspended microchannel detectors
CN101688861A (en) * 2007-05-18 2010-03-31 爱克瑟拉有限公司 Reaction vessel with integrated optical and fluid control elements
CN102199529A (en) * 2011-03-22 2011-09-28 博奥生物有限公司 Biochip hybridization system
CN103087905A (en) * 2012-09-14 2013-05-08 盛司潼 Sequencing reaction platform and nucleic acid sequence detection device
CN108070525A (en) * 2015-11-19 2018-05-25 赛纳生物科技(北京)有限公司 Gene sequencing chip
CN105842324A (en) * 2016-04-27 2016-08-10 河海大学常州校区 Integrated micro-fluidic chip and working method thereof
CN107737615A (en) * 2017-09-20 2018-02-27 南京肯辛顿诊断科技有限公司 A kind of microfluidic device for biochemistry detection

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