WO2009076904A1 - 具有溶液储室兼泵体结构的微流体样品舟 - Google Patents

具有溶液储室兼泵体结构的微流体样品舟 Download PDF

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Publication number
WO2009076904A1
WO2009076904A1 PCT/CN2008/073472 CN2008073472W WO2009076904A1 WO 2009076904 A1 WO2009076904 A1 WO 2009076904A1 CN 2008073472 W CN2008073472 W CN 2008073472W WO 2009076904 A1 WO2009076904 A1 WO 2009076904A1
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Prior art keywords
chamber
solution
diameter
cylindrical
microchannel
Prior art date
Application number
PCT/CN2008/073472
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English (en)
French (fr)
Inventor
Yunhua Gao
Original Assignee
Technical Institute of Physics and Chemistry of the Chinese Academy of Sciences
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Publication date
Application filed by Technical Institute of Physics and Chemistry of the Chinese Academy of Sciences filed Critical Technical Institute of Physics and Chemistry of the Chinese Academy of Sciences
Priority to US12/747,889 priority Critical patent/US8323573B2/en
Priority to JP2010537242A priority patent/JP5156839B2/ja
Publication of WO2009076904A1 publication Critical patent/WO2009076904A1/zh

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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
    • B01L3/502715—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 interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
    • 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
    • B01L2200/16—Reagents, handling or storing thereof
    • 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
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0809—Geometry, shape and general structure rectangular shaped
    • B01L2300/0816—Cards, e.g. flat sample carriers usually with flow in two horizontal directions
    • 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
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/0867—Multiple inlets and one sample wells, e.g. mixing, dilution
    • 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
    • B01L2400/0475—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
    • B01L2400/0478—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure pistons
    • 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
    • B01L2400/06—Valves, specific forms thereof
    • B01L2400/0633—Valves, specific forms thereof with moving parts
    • 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
    • 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
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N2035/1027—General features of the devices
    • G01N2035/1034—Transferring microquantities of liquid
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
    • G01N27/72—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating magnetic variables
    • G01N27/74—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating magnetic variables of fluids
    • G01N27/745—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating magnetic variables of fluids for detecting magnetic beads used in biochemical assays
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T137/00—Fluid handling
    • Y10T137/0753—Control by change of position or inertia of system
    • Y10T137/0801—Position relative body of water [e.g., marine governors]
    • Y10T137/085—Pressure or head controlled
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T137/00—Fluid handling
    • Y10T137/206—Flow affected by fluid contact, energy field or coanda effect [e.g., pure fluid device or system]
    • Y10T137/218—Means to regulate or vary operation of device
    • Y10T137/2202—By movable element
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T137/00—Fluid handling
    • Y10T137/206—Flow affected by fluid contact, energy field or coanda effect [e.g., pure fluid device or system]
    • Y10T137/218—Means to regulate or vary operation of device
    • Y10T137/2202—By movable element
    • Y10T137/2218—Means [e.g., valve] in control input
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T137/00—Fluid handling
    • Y10T137/7722—Line condition change responsive valves
    • Y10T137/7837—Direct response valves [i.e., check valve type]
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T137/00—Fluid handling
    • Y10T137/9029—With coupling

Definitions

  • the present invention relates to a microfluidic biochip for chemical and biological sample detection, in particular, a microfluidic sample loaded with a micromagnetic sensor biochip in a microfluidic channel to perform injection, reaction, separation and detection of biological samples and chemical samples. boat. Background technique
  • microfluidic systems are increasingly used, such as microfluidic transport, trace compound synthesis, sample separation, component analysis, and chemical reactions.
  • the microfluidic chip is mainly composed of an electrophoresis chip, and the injection of the reaction reagent is realized by electrophoresis and electroosmosis.
  • the purpose of microinjection can be achieved, the repeatability is poor.
  • the method of injecting with a syringe is simple, but the amount of the solution used is large, and there is often a waste of reagent.
  • many scholars have conducted extensive research and proposed a variety of different methods to develop various micro-pumps and micro-valves to achieve the exact sequence of solutions. Quantitative injection system. Summary of the invention
  • the object of the present invention is to reduce the production cost of the microfluidic chip, reduce the volume of the microfluidic chip, provide a quantitative liquid supply in combination with a simple microstructure and an external pressure driving, and promote the thorough mixing of the microfluids in the microchannel. Reaction, improve mixing Efficiency, thus providing a microfluidic sample boat loaded with tiny biochips.
  • the microfluidic sample boat has the characteristics of strong practicability, simple structure and low cost.
  • the invention provides a microfluidic sample boat having a solution storage chamber and a pump body structure, comprising: a chamber passage layer, a chamber passage sealing layer, a printed circuit board soldered with a magnetic sensor chip, and a fluid injection port; :
  • a waste liquid pool, a reaction detection chamber, a solution storage chamber and a pump chamber, and a microchannel are disposed in the chamber passage layer;
  • the waste liquid pool is provided with a waste liquid outlet, and the waste liquid pool is connected to the reaction detection chamber through the microchannel.
  • the other port of the reaction detection chamber is connected to the solution storage chamber and the pump inlet through the microchannel;
  • the solution storage chamber and pump chamber comprises a sample storage chamber and a reagent storage chamber, and is composed of a cylindrical chamber and a resilient spherical body acting as a seal and a valve for storing a sample or a reaction reagent;
  • the chamber channel sealing layer and the chamber channel layer are aligned and sealed to form a complete waste liquid pool, a reaction detection chamber, a sealable solution injection port, a solution storage chamber and a pump chamber, and a microchannel;
  • the chamber channel sealing layer has a chip window at a position corresponding to the reaction detecting chamber; after the printed circuit board and the chamber channel sealing layer soldered with the magnetic sensor chip are aligned and sealed, the magnetic sensor chip and the chip The window is aligned to form a reaction detecting surface located at the bottom of the reaction detecting chamber;
  • the surface of the magnetic sensor chip is bio-functionalized to form a biochip that is connected to a tester outside the microfluidic sample by wires on the printed circuit board.
  • the solution chamber and pump chamber is constituted by a chamber having a cylindrical shape and an elastic spherical body or cylinder which acts as a seal.
  • the cylindrical chamber is divided into upper, middle, and lower portions, the upper diameter is larger than the middle diameter and the lower diameter, and the outlet diameter near the microchannel end is the lower diameter, and the lower diameter is equal to or larger than the central diameter of the cylindrical chamber.
  • one elastic sphere has a diameter slightly larger than the upper diameter of the cylindrical chamber; the other sphere has a diameter slightly larger than the central diameter of the cylindrical chamber, and is slightly smaller than the lower outlet diameter near the microchannel end; when the upper elastic sphere is pushed When the direction is toward the lower outlet of the cylindrical chamber, the upper elastic sphere squeezes the solution out of the outlet of the cylindrical solution chamber, and seals the chamber of the cylinder, while the sphere in the middle of the chamber is pushed toward the cylindrical chamber by the pressurized liquid.
  • the sealing action of the elastic sphere disappears, and the solution flows out of the outlet of the chamber and flows into the reaction detection chamber through the microchannel.
  • the diameter of the elastic sphere is slightly larger than the diameter of the upper half of the cylindrical chamber, and when the elastic sphere is pushed toward the outlet direction of the lower portion of the cylindrical chamber, the elastic sphere extrudes the solution out of the cylindrical solution storage chamber. Exit, and seal the chamber of the cylinder.
  • the printed circuit board soldered with the chip comprises a printed circuit board, a magnetic sensor chip and a connecting wire.
  • the surface of the sealable solution injection port is sealed with a sealing material.
  • the microfluidic sample microchip of the micro-magnetic sensor biochip with the solution storage chamber and the pump body structure provided by the invention has the structure of the solution storage chamber and the pump chamber, and has three advantages: 1) the solution storage chamber and the pump body are integrated At the same time, it also has the function of pump and valve.
  • the solution storage chamber can store the solution quantitatively, and the solution is injected into the microchannel by the external pressure to drive the movement of the elastomer, and the micro-quantitative supply reaction is solved in a simple manner.
  • the problem of reagents 2)
  • the external drive can be programmed, and it is very easy to achieve the purpose of sequential injection;
  • Figure 1 is a front plan view of a microfluidic sample boat chamber channel layer of Example 1 of the present invention.
  • Fig. 2A is a schematic view showing the upper surface of the cavity channel sealing layer of the embodiment 1 of the present invention.
  • Fig. 2B is a schematic view showing the lower surface of the cavity channel sealing layer of the embodiment 1 of the present invention.
  • Figure 3 is a schematic view of a printed circuit board with a chip soldered according to Embodiment 1 of the present invention.
  • Fig. 4A is a schematic view showing the solution storage chamber and the pump chamber in the solution state in the first embodiment of the present invention.
  • Fig. 4B is a schematic view showing the solution storage chamber and the pump chamber in the state after the solution has flowed out in the embodiment 1 of the present invention.
  • Figure 4C is a schematic view of a solution storage chamber and a pumping chamber in Embodiment 2 of the present invention.
  • Fig. 5 is a schematic view showing the solution injection port of the embodiment 1 of the present invention.
  • Fig. 6 is a side view showing the assembly of the microfluidic sample boat structure of the embodiment 1 of the present invention.
  • Figure 7 is a schematic view of the lower surface of the microfluidic sample boat structure of the embodiment of the present invention.
  • a chamber channel layer 10 a solution chamber and a pump chamber 11; a cylindrical chamber 12; a cylindrical chamber upper portion 121; a cylindrical chamber central portion 122; a cylindrical chamber lower portion 123;
  • Elastomer 13 elastic sphere 131, 132; elastic cylinder 133, 134; substrate 101; sealable solution injection port 102; 103 solution chamber inlet; microchannel 104; reaction detection chamber 105; waste liquid pool 106; Exit 107.
  • a printed circuit board 30 soldered with a chip; a magnetic sensor chip 301; a printed circuit board 302; a connecting wire 303.
  • the microfluidic sample boat basic structure includes a chamber channel layer 10 and a chamber channel sealing layer
  • a 101 substrate is built in the chamber channel layer 10; Sealing solution injection port; 11 solution storage chamber and pump chamber; 104 microchannel; 105 reaction detection chamber; 106 waste liquid pool; 107 waste liquid outlet.
  • the waste liquid pool 106 is provided with a waste liquid outlet 107, which communicates with the reaction detection chamber 105 through the microchannel 104, and another port of the reaction detection chamber 105 passes through the microchannel 104 and the solution storage chamber and pump chamber 11 And the solution injection port 102 is in communication.
  • the chamber passage sealing layer 20 is divided into an upper surface 21 and a lower surface 22.
  • the chamber passage sealing layer 20 has a chip window 201 at a position corresponding to the reaction detecting chamber 105.
  • the upper surface 21 of the chamber passage sealing layer 20 and the chamber passage layer 10 are aligned and sealed to form a complete waste liquid pool 106, a reaction detection chamber 105, a sealable solution injection port 102, a solution storage chamber and a pump chamber. 11 and microchannel 104.
  • the edge of the chip window 201 of the lower surface 22 of the chamber channel sealing layer 20 has a chip bonding line sealing space 203.
  • the magnetic sensor chip 301 and the chip window 201 are aligned to form a reaction detection located at the bottom of the reaction detecting chamber 105.
  • the printed circuit board 30 with the chip soldered includes a printed circuit board 302, a magnetic sensor chip 301, and a connecting wire 303.
  • the solution chamber and pump chamber 11 can be used to store a sample or reagent, and the sample or reagent is introduced into the chamber through the inlet 103 of the solution chamber and pump chamber.
  • the solution chamber and pump chamber 11 are mainly It consists of a chamber 12 which is cylindrical in shape and an elastic body 13 which acts as a seal.
  • the cylindrical chambers 12 are divided into two types, one is composed of two columns of different diameters, the upper portion 121 is larger in diameter than the lower portion 123; the other is composed of three different diameter cylinders, the upper portion 121 The diameter is larger than the diameter of the middle portion 122 and the bottom portion 123, and the middle diameter is slightly smaller than the bottom diameter.
  • the elastomer 13 acts as a valve for sealing the solution reservoir.
  • the elastomer 13 has a diameter that is slightly larger than the diameter of the cylindrical chamber. As shown in FIG. 4B, when the elastic sphere 131 is pushed under the cylindrical chamber, the elastic sphere squeezes the solution out of the lower outlet of the cylindrical chamber, and the solution flows into the reaction detection chamber through the microchannel 104. When there are two elastic spheres in the solution storage chamber and pump chamber 11, an elastic sphere
  • the diameter of 131 is slightly larger than the diameter of the upper portion 121 of the cylindrical chamber.
  • An elastomeric sphere 132 has a diameter that is slightly larger than the diameter of the central portion 122 of the cylindrical chamber and slightly smaller than the diameter of the lower portion 123 of the cylindrical chamber.
  • the sealable solution injection port 102 is an inlet for injecting a buffer or a reagent.
  • the surface of the inlet is sealed with a sealing material.
  • the solution injection head 40 device other than the sample boat.
  • Figure 6 is a side view of the assembled sample boat.
  • the sample to be tested is dropped into one of the solution reservoirs, sealed with an elastic ball or an elastic column, and then inserted into a specific position of the detector.
  • a programmable drive rod a program-controlled up and down moving part, like a cylindrical piston that pushes the ball or column down and pushes the solution out of the chamber.
  • the sealable solution injection port also corresponds to the position of the corresponding syringe on the instrument.
  • the syringe can move up and down or sequentially up and down.
  • the solution injection head 40 is tied. The solution is injected into the sealed solution injection port, and the injection port is sealed when the solution injection head leaves the injection port.
  • the difference between this embodiment and the first embodiment is that the structure of the solution storage chamber and the pump chamber 11 is different, and the pump chamber is sealed by the elastic cylinders 133, 134.
  • the solution chamber and pump chamber 11 can be used to store a sample or a reaction reagent.
  • the sample or reagent is introduced into the chamber through the inlet 103 of the solution chamber and the pump chamber.
  • the solution chamber and pump chamber 11 is mainly composed of a cylindrical chamber.
  • the chamber 12 is formed with a sealing elastomer 13 .
  • the cylindrical chambers 12 are divided into two types, one is composed of two columns of different diameters, the upper portion 121 is larger in diameter than the lower portion 123; the other is composed of three different diameter cylinders, the upper portion 121 The diameter is larger than the diameter of the central portion 122 and the bottom portion 123, and the central diameter is slightly smaller than the diameter of the bottom portion.
  • the elastomer 13 acts as a valve for sealing the solution reservoir.
  • the elastomer 13 has a diameter that is slightly larger than the diameter of the cylindrical chamber. As shown in FIG. 4C, when the elastic cylinder 133 is pushed under the cylindrical chamber, the elastic cylinder squeezes the solution out of the lower outlet of the cylindrical chamber, and the solution flows into the reaction detecting chamber 105 through the microchannel 104;
  • one of the elastic cylinders 133 has a diameter slightly larger than the diameter of the upper portion 121 of the cylindrical chamber.
  • a resilient cylinder 134 has a diameter that is slightly larger than the diameter of the central portion 122 of the cylindrical chamber and slightly smaller than the diameter of the lower portion 123 of the cylindrical chamber.
  • the microfluidic sample boat basic structure includes a chamber channel layer 10 and a chamber channel sealing layer
  • 101 substrate is established in the chamber channel layer 10; 102 sealable solution injection 11; solution storage chamber and pump chamber; 104 microchannel; 105 reaction detection chamber; 106 waste liquid pool; 107 waste liquid outlet.
  • the waste liquid pool 106 is provided with a waste liquid outlet 107, which communicates with the reaction detection chamber 105 through the microchannel 104, and another port of the reaction detection chamber 105 passes through the microchannel 104 and the solution storage chamber and the pump chamber, respectively. 11 and the solution injection port 102 are connected.
  • the other structure is as in Embodiment 1, and the chamber passage sealing layer 20 is divided into the upper surface 21 and the lower surface 22.
  • the chamber passage sealing layer 20 has a chip window 201 at a position corresponding to the reaction detecting chamber 105.
  • the upper surface 21 of the chamber passage sealing layer 20 and the chamber passage layer 10 are aligned and sealed to form a complete waste liquid pool 106, a reaction detection chamber 105, a sealable solution injection port 102, a solution storage chamber and a pump chamber. 11 and microchannel 104.
  • the edge of the chip window 201 of the lower surface 22 of the chamber channel sealing layer 20 has a chip bonding line sealing space 203.
  • the magnetic sensor chip 301 and the chip window 201 are aligned to form a reaction detection located at the bottom of the reaction detecting chamber 105.
  • the printed circuit board 30 with the chip soldered includes a printed circuit board 302, a magnetic sensor chip 301, and a connecting wire 303.
  • the sealable solution injection port 102 is an inlet for injecting a buffer or a reagent.
  • the surface of the injection inlet is sealed with a sealing material, and when a solution is required to be injected, the solution injection head 40 (a device other than the sample boat) is inserted into the sealable solution injection port 102 to inject the solution.
  • the invention is illustrated by the above examples, but the invention is not limited to the specific examples and embodiments described herein. The specific examples and embodiments are included herein to assist those skilled in the art in practicing the invention. Any further modifications and improvements will be apparent to those skilled in the art without departing from the scope of the invention and the scope of the invention.
  • the invention as defined in the appended claims God and the range of alternatives and equivalents (

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  • Health & Medical Sciences (AREA)
  • Dispersion Chemistry (AREA)
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  • General Health & Medical Sciences (AREA)
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Description

具有溶液储室兼泵体结构的微流体样品舟 技术领域
本发明涉及用于化学和生物样品检测的微流体生物芯片， 特别 是在微流体通道内装载微小磁敏传感器生物芯片， 实现生物样品、 化学样品的进样、 反应、 分离和检测的微流体样品舟。 背景技术
由于使用微量溶液的微流体技术的发展，使得实验室芯片 (LOC) 或微流体芯片的用途得以脱离传统研究实验的束缚， 更进一步迈向 较具实用性价值的商业应用上。 在化学、 生物等领域， 微流体系统 得到越来越多的应用， 如微量流体的传输、 微量化合物合成、 样品 分离、 成分分析及化学反应。
目前微流体芯片以电泳芯片为主， 反应试剂的注入是靠电泳、 电渗来实现， 虽然能实现微量注液的目的， 但是重复性差。 而使用 注射器注入的方法虽然简单， 但是使用的溶液量多， 往往会有试剂 的浪费。 针对准确微量进样问题， 特别是多种溶液顺序进样问题， 近年来， 很多学者进行了广泛的研究， 并提出了多种不同方法， 开 发各种微泵、 微阀来实现溶液的准确顺序定量注入系统。 发明内容
本发明的目的是为了能够降低微流体芯片的生产成本， 减小微 流体芯片体积， 结合结构简单的特殊微结构和外在压力驱动的方式 提供定量供液并且促进微通道内微流体的充分混合反应， 提高混合 效率， 从而提供装载微小生物芯片的微流体样品舟。 该微流体样品 舟具有实用性强、 结构简单、 成本低等特点。
本发明提供了一种具有溶液储室兼泵体结构的微流体样品舟， 包括： 腔室通道层、 腔室通道密封层、 焊接有磁敏传感器芯片的印 刷电路板、 和流体注入口； 其中：
在腔室通道层中设置有废液池、 反应检测室、 溶液储室兼泵室 以及微通道； 所述废液池带有废液出口， 该废液池通过微通道与反 应检测室连通， 反应检测室的另一端口通过微通道与溶液储室兼泵 室以及流体注入口连通；
所述溶液储室兼泵室包括样品储室和试剂储室， 由形状为柱形 的腔室和起密封与阀作用的弹性球体构成， 用于储存样品或反应试 剂；
所述腔室通道密封层和所述腔室通道层对准密封， 以形成完整 的废液池、 反应检测室、 可密封溶液注入口、 溶液储室兼泵室以及 微通道；
所述腔室通道密封层在对应所述反应检测室的位置开有芯片窗 口； 所述焊接有磁敏传感器芯片的印刷电路板和腔室通道密封层对 准密封后， 磁敏传感器芯片和芯片窗口对准形成坐落在反应检测室 底部的反应检测表面；
所述磁敏传感器芯片表面被生物功能化后形成生物芯片， 该生 物芯片通过印刷电路板上的导线与微流体样品舟外的测试仪连接。
根据本发明， 所述溶液储室兼泵室由形状为柱形的腔室和起密 封作用的弹性球体或柱体构成。
根据本发明， 所述柱形腔室分为上中下三部分， 上部直径大于 中部直径和下部直径， 靠近微通道端的出口直径为下部直径， 下部 直径等于或大于柱形腔室的中部直径。
根据本发明， 在一个柱形腔室内有两个起密封与阀作用的弹性 球体。 其中， 一个弹性球体直径略大于所述柱形腔室上部直径； 另 一个球体直径略大于所述柱形腔室中部直径， 并且略小于靠近微通 道端的下部出口直径； 当上面的弹性球体被推向柱形腔室下部出口 方向时， 上面弹性球体把溶液挤压出柱形溶液储室之出口， 并且密 封柱体的腔室， 同时在腔室中部的球体被受压液体推向柱形腔室下 部出口和微通道相连的一端时， 弹性球体密封作用消失， 溶液流出 腔室出口， 经微通道流入反应检测室。
其中， 所述弹性球体的直径略大于所述柱形腔室上半部分的直 径， 当弹性球体被推向柱形腔室下方出口方向时， 弹性球体把溶液 挤压出柱形溶液储室之出口， 并且密封柱体的腔室。
根据本发明，所述焊接有芯片的印刷电路板包括印刷电路底板、 磁敏传感器芯片和连接导线。
根据本发明，所述可密封溶液注入口的表面使用密封材料密封。 本发明所提供的具有溶液储室兼泵体结构的微型磁敏传感器生 物芯片的微流体样品舟内含有溶液储室兼泵室的结构， 具有三个优 点： 1 ) 溶液储室和泵体一体化， 使其同时又兼有了泵和阀的作用， 溶液储室内能定量储存溶液， 通过外在压力驱动弹性体的运动使溶 液定量注入微通道内， 以简便的方法解决了微量定量供给反应试剂 的难题； 2)外在驱动能够程序控制，非常容易达到顺序注射的目的；
3 )结构简单， 易于加工， 特别适用于预先储存反应试剂的一次性生 物芯片样品舟类的产品。 附图说明
图 1本发明实施例 1的微流体样品舟腔室通道层的正面俯视图。 图 2A本发明实施例 1的腔体通道密封层上表面示意图。
图 2B本发明实施例 1的腔体通道密封层下表面示意图。
图 3本发明实施例 1的焊接有芯片的印刷电路板示意图。 图 4A本发明实施例 1中溶液储室兼泵室在有溶液状态下的示意 图。
图 4B本发明实施例 1中溶液储室兼泵室在溶液流出后状态下的 示意图。
图 4C本发明实施例 2中溶液储室兼泵室的示意图。
图 5本发明实施例 1的溶液注入口示意图。
图 6本发明实施例 1的微流体样品舟结构侧面组装示意图。 图 7本发明实施例 3微流体样品舟结构的下表面示意图。 附图标记
腔室通道层 10; 溶液储室兼泵室 11 ; 柱形的腔室 12; 柱形的腔 室上部 121 ; 柱形的腔室中部 122; 柱形的腔室下部 123;
弹性体 13， 弹性球体 131， 132； 弹性柱体 133， 134； 衬底 101 ; 可密封溶液注入口 102; 103 溶液储室入口； 微通道 104； 反应检测室 105; 废液池 106; 废液出口 107。
腔室通道密封层 20; 腔室通道密封层的上表面 21 ; 腔室通道密 封层的下表面 22; 芯片窗口 201 ; 芯片焊接线密封空间 203;
焊接有芯片的印刷电路板 30; 磁敏传感器芯片 301 ; 印刷电路 底板 302; 连接导线 303。
溶液注射头 40; 具体实施方式
实施例 1
请参见图 1、 图 2A、 图 2B、 图 3、 图 4A、 图 4B、 图 5和图 6。 微流体样品舟基本结构包括腔室通道层 10 和腔室通道密封层
20。
如图 1所示， 所述的腔室通道层 10中建立有 101衬底； 102可 密封溶液注入口； 11溶液储室兼泵室； 104微通道； 105反应检测室； 106废液池； 107废液出口。
所述的废液池 106带有废液出口 107，该废液池 106通过微通道 104与反应检测室 105连通，反应检测室 105的另一端口通过微通道 104与溶液储室兼泵室 11以及溶液注入口 102连通。
参见图 2A和图 2B, 所述腔室通道密封层 20分上表面 21和下 表面 22。腔室通道密封层 20在对应所述反应检测室 105的位置开有 芯片窗口 201。所述腔室通道密封层 20的上表面 21和所述腔室通道 层 10对准密封以形成完整的废液池 106、 反应检测室 105、 可密封 溶液注入口 102、 溶液储室兼泵室 11以及微通道 104。
所述腔室通道密封层 20的下表面 22的芯片窗口 201边缘有芯 片焊接线密封空间 203。如图 3所示，焊接有磁敏传感器的印刷电路 板 30和腔室通道密封层 20对准密封后， 磁敏传感器芯片 301和芯 片窗口 201对准形成坐落在反应检测室 105底部的反应检测表面； 所述的焊接有芯片的印刷电路板 30包括印刷电路底板 302、 磁敏传 感器芯片 301和连接导线 303。
参见图 4A和图 4B,所述溶液储室兼泵室 11可以用来储存样品 或反应试剂， 样品或反应试剂通过溶液储室兼泵室的入口 103加入 室内， 溶液储室兼泵室 11主要由形状为柱形的腔室 12和起密封作 用的弹性体 13构成。 所述柱形的腔室 12分为两种， 一种是由两个 不同直径的柱体组成， 上部 121直径大于下部 123直径； 另一种是 由三个不同直径的柱体组成，上部 121直径大于中部 122和底部 123 直径， 中部直径略小于底部直径。所述弹性体 13即对溶液储室起到 密封作用也起到阀的作用。弹性体 13直径略大于所述柱形腔室直径。 如图 4B所示， 当弹性球体 131被推向柱形腔室下方时， 弹性球体把 溶液挤压出柱形腔室下方出口， 溶液经微通道 104流入反应检测室 所述溶液储室兼泵室 11内当有两个弹性球体时，一个弹性球体
131直径略大于所述柱形腔室上部 121直径。一个弹性球体 132直径 略大于所述柱形腔室中部 122直径并略小于柱形腔室下部 123直径。 当溶液储室内存有液体时，弹性球体 132封在柱形腔室中部 122，当 上面的弹性球体 131被推向柱形腔室下方出口方向时， 上面弹性球 体 131 把溶液挤压出柱形溶液储室之出口， 并且密封柱形腔室 121 下部。 下面的球体 132被受压液体推向柱形腔室下方出口和微通道 104相连的一端时，下面的弹性球体 132密封作用消失，溶液流出腔 室出口， 经微通道 104流入反应检测室 105。
如图 5所示，所述可密封溶液注入口 102，是用来注入缓冲液或 反应试剂的入口。 注入口的表面使用密封材料密封， 当需要注入溶 液时， 使用溶液注射头 40 (样品舟之外的器件） 扎入可密封溶液注 入口 102即可注入溶液。
图 6是组装后的样品舟的侧视图。
该样品舟使用时将待测样品滴加到其中一个溶液储池， 用弹性 球或弹性柱封口， 然后插到检测仪的特定位置。 检测仪上对应的溶 液储室上方是可程序驱动的移动杆 （可以程序控制的上下移动的部 件， 像柱状活塞）， 该驱动杆推动弹性球或柱向下移动同时将溶液挤 出腔室。
另外， 样品舟安放在仪器上后， 可密封溶液注入口也对应着仪 器上相应的注射器的位置， 注射器在程序控制下可以同时上下移动 或顺序上下移动， 当向下运动时溶液注射头 40扎入密封的溶液注入 口将溶液注入， 当溶液注射头离开注入口时， 注入口被密封住。
实施例 2
参见图 4C。
本实施例与实施例 1的区别是在于溶液储室兼泵室 11的结构 不同， 该泵室内由弹性柱体 133， 134起密封作用。 所述溶液储室兼泵室 11可以用来储存样品或反应试剂，样品或 反应试剂通过溶液储室兼泵室的入口 103加入室内， 溶液储室兼泵 室 11主要由形状为柱形的腔室 12和起密封作用的弹性体 13构成。 所述柱形的腔室 12分为两种， 一种是由两个不同直径的柱体组成， 上部 121直径大于下部 123直径； 另一种是由三个不同直径的柱体 组成， 上部 121直径大于中部 122和底部 123直径， 中部直径略小 于底部直径。所述弹性体 13即对溶液储室起到密封作用也起到阀的 作用。 弹性体 13直径略大于所述柱形腔室直径。 如图 4C所示， 当 弹性柱体 133被推向柱形腔室下方时， 弹性柱体把溶液挤压出柱形 腔室下方出口， 溶液经微通道 104流入反应检测室 105;
所述溶液储室兼泵室 11 内当有两个弹性柱体时， 一个弹性柱体 133直径略大于所述柱形腔室上部 121直径。一个弹性柱体 134直径 略大于所述柱形腔室中部 122直径并略小于柱形腔室下部 123直径。 当溶液储室内存有液体时，弹性柱体 134封在柱形腔室中部 122， 当 上面的弹性柱体 133被推向柱形腔室下方出口方向时， 上面弹性柱 体 133把溶液挤压出柱形溶液储室之出口， 并且密封柱形腔室 121 下部。 下面的柱体 134被受压液体推向柱形腔室下方出口和微通道 104相连的一端时，下面的弹性柱体 134密封作用消失，溶液流出腔 室出口， 经微通道 104流入反应检测室 105。
实施例 3
参见图 7。
本实施例与实施例 1的区别是在于溶液储室兼泵室 11的位置与 溶液注入口不在同一条微通道上。
微流体样品舟基本结构包括腔室通道层 10 和腔室通道密封层
20。
所述的腔室通道层 10中建立有 101衬底； 102可密封溶液注入 口； 11溶液储室兼泵室； 104微通道； 105反应检测室； 106废液池； 107废液出口。
所述的废液池 106带有废液出口 107，该废液池 106通过微通道 104与反应检测室 105连通，反应检测室 105的另一端口通过微通道 104分别与溶液储室兼泵室 11以及溶液注入口 102连通。
其他结构如实施例 1，所述腔室通道密封层 20分上表面 21和下 表面 22。腔室通道密封层 20在对应所述反应检测室 105的位置开有 芯片窗口 201。所述腔室通道密封层 20的上表面 21和所述腔室通道 层 10对准密封以形成完整的废液池 106、 反应检测室 105、 可密封 溶液注入口 102、 溶液储室兼泵室 11以及微通道 104。
所述腔室通道密封层 20的下表面 22的芯片窗口 201边缘有芯 片焊接线密封空间 203。如图 3所示，焊接有磁敏传感器的印刷电路 板 30和腔室通道密封层 20对准密封后， 磁敏传感器芯片 301和芯 片窗口 201对准形成坐落在反应检测室 105底部的反应检测表面； 所述的焊接有芯片的印刷电路板 30包括印刷电路底板 302、 磁敏传 感器芯片 301和连接导线 303。
所述可密封溶液注入口 102，是用来注入缓冲液或反应试剂的入 口。 注入口的表面使用密封材料密封， 当需要注入溶液时， 使用溶 液注射头 40 (样品舟之外的器件） 扎入可密封溶液注入口 102即可 注入溶液。 本发明通过上面的实施例进行举例说明， 但是， 本发明并不限于这 里所描述的特殊实例和实施方案。 在这里包含这些特殊实例和实施 方案的目的在于帮助本领域中的技术人员实践本发明。 任何本领域 中的技术人员很容易在不脱离分发明精神和范围的情况下进行进一 步的改进和完善， 因此分发明只受到本发明权利要求的内容和范围 的限制， 其意图涵盖所有包括在由附录权利要求所限定的本发明精 神和范围内的备选方案和等同方案(

Claims

权利要求
1、一种具有溶液储室兼泵体结构的微流体样品舟， 包括： 腔室 通道层、 腔室通道密封层、 焊接有磁敏传感器芯片的印刷电路板、 和流体注入口； 其特征在于：
在腔室通道层中设置有废液池、 反应检测室、 溶液储室兼泵室 以及微通道； 所述废液池带有废液出口， 该废液池通过微通道与反 应检测室连通， 反应检测室的另一端口通过微通道与溶液储室兼泵 室以及流体注入口连通；
所述溶液储室兼泵室包括样品储室和试剂储室， 由形状为柱形 的腔室和起密封与阀作用的弹性体构成，用于储存样品或反应试剂； 所述腔室通道密封层和所述腔室通道层对准密封， 以形成完整 的废液池、 反应检测室、 可密封溶液注入口、 溶液储室兼泵室以及 微通道；
所述腔室通道密封层在对应所述反应检测室的位置开有芯片窗 口； 所述焊接有磁敏传感器芯片的印刷电路板和腔室通道密封层对 准密封后， 磁敏传感器芯片和芯片窗口对准形成坐落在反应检测室 底部的反应检测表面；
所述磁敏传感器芯片表面被生物功能化后形成生物芯片， 该生 物芯片通过印刷电路板上的导线与微流体样品舟外的测试仪连接。
2、 根据权利要求 1所述的微流体样品舟， 其特征在于： 所述弹 性体为弹性球体或者弹性柱体。
3、 根据权利要求 2所述的微流体样品舟， 其特征在于： 所述柱 形腔室分为上中下三部分， 上部直径大于中部直径和下部直径， 靠 近微通道端的出口直径为下部直径， 下部直径等于或大于柱形腔室 的中部直径。
4、 根据权利要求 2所述的微流体样品舟， 其特征在于： 在一个 柱形腔室内有两个起密封与阀作用的弹性球体。
5、 根据权利要求 4所述的微流体样品舟， 其特征在于： 一个弹 性球体直径略大于所述柱形腔室的上部直径； 另一个球体直径略大 于所述柱形腔室的中部直径， 并且略小于靠近微通道端的出口直径 或下部直径； 当上面的弹性球体被推向柱形腔室下部出口方向时， 上面弹性球体把溶液挤压出柱形溶液储室之出口， 并且密封柱体的 腔室， 同时在腔室中部的球体被受压液体推向柱形腔室下部出口和 微通道相连的一端时， 弹性球体密封作用消失， 溶液流出腔室出口， 经微通道流入反应检测室。
6、 根据权利要求 2， 所述的微流体样品舟， 其特征在于： 所述 弹性球体的直径略大于所述柱形腔室上半部分的直径， 当弹性球体 被推向柱形腔室下方出口方向时， 弹性球体把溶液挤压出柱形溶液 储室之出口， 并且密封柱体的腔室。
7、 根据权利要求 1所述的微流体样品舟， 其特征在于： 所述焊 接有芯片的印刷电路板包括印刷电路底板、 磁敏传感器芯片和连接 导线
8、 根据权利要求 1所述的微流体样品舟， 其特征在于： 所述可 密封溶液注入口的表面使用密封材料密封。
PCT/CN2008/073472 2007-12-14 2008-12-12 具有溶液储室兼泵体结构的微流体样品舟 WO2009076904A1 (zh)

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