CN115121303B - Microfluidic device for nanopore sensor and method of assembling the same - Google Patents
Microfluidic device for nanopore sensor and method of assembling the same Download PDFInfo
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- CN115121303B CN115121303B CN202210774477.XA CN202210774477A CN115121303B CN 115121303 B CN115121303 B CN 115121303B CN 202210774477 A CN202210774477 A CN 202210774477A CN 115121303 B CN115121303 B CN 115121303B
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- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 8
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- 229910052697 platinum Inorganic materials 0.000 claims description 5
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- 238000007738 vacuum evaporation Methods 0.000 claims description 4
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 claims description 3
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 claims description 3
- 230000000712 assembly Effects 0.000 claims description 3
- 238000000429 assembly Methods 0.000 claims description 3
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
- B01L3/502707—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the manufacture of the container or its components
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/483—Physical analysis of biological material
- G01N33/487—Physical analysis of biological material of liquid biological material
- G01N33/48707—Physical analysis of biological material of liquid biological material by electrical means
- G01N33/48721—Investigating individual macromolecules, e.g. by translocation through nanopores
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/10—Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
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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
- B01L2300/00—Additional constructional details
- B01L2300/06—Auxiliary integrated devices, integrated components
- B01L2300/0627—Sensor or part of a sensor is integrated
- B01L2300/0645—Electrodes
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- Chemical & Material Sciences (AREA)
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- Hematology (AREA)
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Abstract
The embodiment of the invention discloses a microfluidic device for a nanopore sensor and an assembly method thereof, wherein the microfluidic device comprises a bearing plate, a cover plate and a nanopore sensing assembly positioned on a fluid path, wherein a microfluidic cavity which is provided with a fluid inlet and a fluid outlet and is used for flowing sequencing liquid is arranged on the upper side of the bearing plate; the cover plate is connected with the bearing plate; the nanopore sensing assembly comprises a printed circuit board, a nanopore chip and a conductive element; the nanopore chip is arranged on the upper side of the printed circuit board, and is provided with a sensing chamber which is provided with a plurality of nanopores and is communicated with the microfluidic cavity; the conductive member is connected with the printed circuit board and extends into the sensing chamber. The micro-fluidic device provided by the embodiment of the invention has the advantages of simple structure realization, convenience in assembly and disassembly, better practicability, and capability of completing membrane laying/hole embedding operation with a minimum amount of sequencing liquid through the infusion device, and no waste of the sequencing liquid.
Description
Technical Field
The present invention relates to the field of sequencing, disease analysis and medical condition analysis by biological nanopore sensors, and more particularly to a microfluidic device for nanopore sensors and a method of assembling the same.
Background
At present, the biological nanopore technology is generally based on natural pore-forming proteins, channels formed by the pore-forming proteins can be penetrated by DNA long-chain or polypeptide-chain molecules, corresponding current changes can be generated due to different bases or amino acids, and the instrument can infer the sequence of the bases or amino acids passing through the nanopore by recognizing the changes of electric signals.
Various microfluidic devices and sensors are known. A microfluidic device for preparing a test liquid for sensing an analyte present therein, such as disclosed by patent WO2018/007819, which microfluidic device, after assembly, the nanopore sensor inside the microfluidic device must be soaked in the liquid, has strict specifications on the time of manufacture and use, i.e. has a certain shelf life, if it cannot be used during shelf life, the liquid is easily dried out or the nanopore falls off, etc., resulting in failure of the nanopore chip sensor.
Meanwhile, in the prior art, the operation is complex and the waste of the sequencing solution is caused in the process of membrane laying/pore embedding of the sequencing solution, that is, the cost of the sequencing solution is very high based on the DNA sequencing field, and if the sequencing solution cannot finish membrane laying/pore embedding operation in a small amount, the cost of the prior art microfluidic system is high.
Disclosure of Invention
The invention aims to provide a microfluidic device for a nanopore sensor and an assembly method thereof, and aims to solve the problem that the conventional microfluidic system can cause waste of sequencing liquid when sampling the sequencing liquid.
In order to solve the technical problems, the aim of the invention is realized by the following technical scheme: there is provided a microfluidic device for a nanopore sensor, comprising:
the upper side of the bearing plate is provided with a microfluidic cavity which is provided with a fluid inlet and a fluid outlet and is used for flowing sequencing liquid;
the cover plate is connected with the bearing plate and is used for sealing the micro-fluid cavity between the fluid inlet and the fluid outlet;
a nanopore sensing assembly located in a fluid path, the nanopore sensing assembly comprising:
the printed circuit board is connected with the lower side of the bearing plate through the fixing plate;
the nanopore chip is arranged on the upper side of the printed circuit board, penetrates through the fixing plate and is in airtight contact with the lower side of the bearing plate, and the nanopore chip is provided with a sensing chamber which is provided with a plurality of nanopores and is communicated with the microfluidic cavity and is used for receiving at least one part of sequencing liquid;
and the conductive piece is connected with the printed circuit board and extends into the sensing chamber.
Further, the method further comprises the following steps:
a first seal coupled to the carrier plate for sealing the fluid inlet;
and the second sealing piece is connected with the bearing plate and is used for sealing the fluid outlet.
Further, the conductive member is a conductive electrode comprising a contact part, a connection part and a connection part which are sequentially connected;
wherein, a part of the connecting part is embedded on the upper side of the bearing plate and is exposed from the upper side of the bearing plate;
the contact part penetrates through the bearing plate and stretches into the sensing chamber;
the connecting part penetrates through the bearing plate and is connected with the printed circuit board.
Further, all the nanopores are surrounded to be annular, the geometric center line of the contact part coincides with the geometric center line formed by all the nanopores, and the tail end of the contact part and the bottom of the sensing chamber have a preset gap.
Further, the conductive member is manufactured by vacuum evaporation, printing, electroplating or ink-jet.
Further, the conductive member is made of one or more noble metals such as ruthenium, rhodium, palladium, platinum, gold or silver, or a compound thereof.
Further, a third sealing piece for sealing the sensing chamber is arranged between the sensing chamber and the bearing plate.
Further, a waterproof and breathable film is arranged at the fluid outlet.
Further, the cover plate is provided with a drip hole communicated with the fluid inlet, and the first sealing piece is tightly matched with the drip hole so as to be used for sealing the drip hole;
the dropping hole comprises a guiding part and a communicating part which are communicated, the bottom surface of the guiding part is inclined and extends downwards, 2 side surfaces of the guiding part are contracted towards the communicating part, the upper end of the communicating part is positioned at the lowest end of the guiding part, and the lower end of the communicating part is communicated with the fluid inlet.
Further, the device further comprises a fourth sealing piece, a liquid inlet column is arranged on the lower side of the bearing plate, a liquid inlet hole communicated with the fluid inlet is formed in the liquid inlet column, and the fourth sealing piece is used for sealing the liquid inlet hole.
Further, the conductive member comprises a plurality of groups of negative electrodes and positive electrodes arranged on the nanopore chip, wherein the negative electrodes are positioned in the sensing chamber and used for providing negative voltage, and the positive electrodes are used for providing positive voltage.
Further, an identifier for identifying the position of the pin on the nanopore chip is arranged on the nanopore chip.
The embodiment of the invention also provides an assembling method of the micro-fluid device for the nano-pore sensor, which comprises the following steps:
s101, fixing the pre-installed nanopore sensing assemblies on the lower side of the fixing plate in a bolting mode;
s102, fixing the fixing plate on the lower side of the bearing plate in a bolting way;
s103, embedding the conductive electrode from the upper side of the bearing plate, and enabling one end of the conductive electrode to extend into the sensing chamber and the other end of the conductive electrode to be connected with the printed circuit board;
and S104, fixing the cover plate on the upper side of the bearing plate in an adhesive manner so as to form a micro-fluid cavity with a fluid inlet and a fluid outlet.
The embodiment of the invention provides a micro-fluidic device for a nanopore sensor and an assembly method thereof, wherein: the microfluidic device for the nanopore sensor comprises a bearing plate, a cover plate and a nanopore sensing assembly positioned on a fluid path, wherein a microfluidic cavity which is provided with a fluid inlet and a fluid outlet and is used for flowing a sequencing liquid is arranged on the upper side of the bearing plate; the cover plate is connected with the bearing plate and is used for sealing the micro-fluid cavity between the fluid inlet and the fluid outlet; the nanopore sensing assembly comprises a printed circuit board, a nanopore chip and a conductive piece, wherein the printed circuit board is connected with the lower side of the bearing plate through a fixed plate; the nanopore chip is arranged on the upper side of the printed circuit board, penetrates through the fixing plate and is in airtight contact with the lower side of the bearing plate, and the nanopore chip is provided with a sensing chamber which is provided with a plurality of nanopores and is communicated with the microfluidic cavity and is used for receiving at least one part of sequencing liquid; and the conductive piece is connected with the printed circuit board and extends into the sensing chamber.
The micro-fluidic device provided by the embodiment of the invention has the advantages of simple structure realization, convenience in assembly and disassembly and better practicability.
Drawings
In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings required for the description of the embodiments will be briefly described below, and it is obvious that the drawings in the following description are some embodiments of the present invention, and other drawings may be obtained according to these drawings without inventive effort for a person skilled in the art.
Fig. 1 is a schematic structural diagram of a micro-fluidic device for a nanopore sensor according to a first embodiment of the present invention;
FIG. 2 is an exploded view of a microfluidic device for a nanopore sensor according to an embodiment of the present invention;
FIG. 3 is a top view of a microfluidic device for a nanopore sensor according to a first embodiment of the present invention;
FIG. 4 is a schematic diagram of a nanopore chip in a microfluidic device for a nanopore sensor according to an embodiment of the present invention;
FIG. 5 is a partial cross-sectional view of a microfluidic device for a nanopore sensor according to an embodiment of the present invention;
FIG. 6 is a bottom view of a microfluidic device for a nanopore sensor according to an embodiment of the present invention;
fig. 7 is a schematic structural diagram of a nanopore chip in a microfluidic device for a nanopore sensor according to a second embodiment of the present invention;
fig. 8 is a flowchart of a method for assembling a microfluidic device for a nanopore sensor according to a third embodiment of the present invention.
The figure identifies the description:
1. a carrying plate; 11. a fluid inlet; 12. a fluid outlet; 13. a microfluidic cavity; 14. a liquid inlet flow channel; 15. a waste liquid collecting flow channel; 2. a cover plate; 3. a fixing plate; 31. a printed circuit board; 311. a contact; 32. a nanopore chip; 321. a nanopore; 322. a sensing chamber; 323. pins; 33. a conductive electrode; 331. a contact portion; 332. a joint portion; 333. a connection part; 34. a fixing bolt; 35. a locking bolt; 36. a negative electrode; 37. a positive electrode; 38. a marking piece; 4. a first seal; 41. a second seal; 42. a bonding part; 43. a sealing part; 5. a third seal; 6. a drip hole; 7. a fourth seal; 71. a liquid inlet column; 72. a liquid inlet hole; 73. a waterproof breathable film; 8. a lower liquid column; 81. a liquid discharging hole; 9. positioning a sinking platform; 10. a relief hole; 101. a non-slip bump.
Detailed Description
The following description of the embodiments of the present invention will be made clearly and fully with reference to the accompanying drawings, in which it is evident that the embodiments described are some, but not all embodiments of the invention. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
It should be understood that the terms "comprises" and "comprising," when used in this specification and the appended claims, specify the presence of stated features, integers, steps, operations, elements, and/or components, but do not preclude the presence or addition of one or more other features, integers, steps, operations, elements, components, and/or groups thereof.
It is also to be understood that the terminology used in the description of the invention herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. As used in this specification and the appended claims, the singular forms "a," "an," and "the" are intended to include the plural forms as well, unless the context clearly indicates otherwise.
It should be further understood that the term "and/or" as used in the present specification and the appended claims refers to any and all possible combinations of one or more of the associated listed items, and includes such combinations.
Embodiment one:
referring to fig. 1 to 6, an embodiment of the present invention provides a microfluidic device for a nanopore sensor, comprising:
a carrying plate 1, wherein a micro-fluid cavity 13 provided with a fluid inlet 11 and a fluid outlet 12 and used for flowing a sequencing liquid is arranged on the upper side of the carrying plate 1;
a cover plate 2, wherein the cover plate 2 is connected with the bearing plate 1 and is used for sealing a micro-fluid cavity 13 between the fluid inlet 11 and the fluid outlet 12;
a nanopore sensing assembly located in a fluid path, the nanopore sensing assembly comprising:
a printed circuit board 31, wherein the printed circuit board 31 is connected with the lower side of the bearing plate 1 through a fixed plate 3;
a nanopore chip 32, wherein the nanopore chip 32 is arranged on the upper side of the printed circuit board 31, passes through the fixing plate 3 and is in airtight contact with the lower side of the bearing plate 1, and the nanopore chip 32 is provided with a sensing chamber 322 which is provided with a plurality of nanopores 321 and is communicated with the microfluidic cavity 13 and is used for receiving at least a part of sequencing liquid;
and a conductive member connected to the printed circuit board 31 and extending into the sensing chamber 322.
In this embodiment, based on the characteristics that PMMA materials have high transparency, the carrier plate 1, the cover plate 2 and the fixing plate 3 of the present application are made by preferentially selecting PMMA materials, so that a user can observe the microfluidic cavity 13 and the sequencing liquid flowing on the microfluidic cavity 13, but in the actual application scenario, the materials of the carrier plate 1, the cover plate 2 and the fixing plate 3 can be other types, so long as the materials do not react with the sequencing liquid, and the present application will not be described.
In this embodiment, referring to fig. 2 and 3, the micro-fluidic cavity 13 is of a groove structure, that is, the micro-fluidic cavity 13 is recessed downwards from the carrier plate 1 to form a groove, so that the thickness and the material consumption of the whole carrier plate 1 can be reduced while the structural strength of the carrier plate 1 is ensured, the contact area between the cover plate 2 and the carrier plate 1 can be increased, and more preferably, the cover plate 2 is embedded on the upper side of the carrier plate 1, that is, the upper surface of the cover plate 2 is flush with the upper surface of the carrier plate 1; however, in another embodiment, 2 protruding strips may be formed upward from the upper side of the carrier plate 1, and the space between the 2 protruding strips forms the microfluidic cavity 13 of the present application, so this application will not be described.
It should be noted that the cover plate 2 may be hollow and, since the microfluidic cavity 13 is defined to be closed except for the fluid opening and the fluid outlet 12, it is ensured that the sequencing solution entering from the fluid inlet 11 may smoothly enter the sensing chamber 322 along the fluid path until the sensing chamber 322 is filled with the sequencing solution, during which the gas (typically air) in the microfluidic cavity 13 is displaced by the sequencing solution and is discharged through the fluid outlet 12.
At the time of manufacture, the fluid inlet 11 and the fluid outlet 12 may be arranged at opposite ends of the carrier plate 1, but the present application is: the fluid inlet 11 and the fluid outlet 12 are arranged at the same end of the carrier plate 1 to increase the length of the fluid path, which may or may not be configured in a straight line manner, in other words, the fluid path may have a portion of at least one of various special shapes such as a curved shape, etc., it should be understood that the micro-fluidic cavity 13 of the present application has a reason to change its area on each vertical section based on the required flow rate of the sequencing liquid.
In connection with fig. 4, it should be noted that the type of the nanopore chip 32 is not particularly limited, and the nanopore chip 32 may be used for sequencing nucleic acids (e.g., DNA) according to actual detection requirements, and the nanopore chip 32 includes a large number of sensors (not shown) arranged in an array, so that a polynucleotide or a polymer of nucleic acids, such as a polypeptide of proteins, a polysaccharide or a fusion other polymer passing through the nanopore 321 may contact the sensors, so that the sensors may sense a sequencing solution, and transmit detected information to an external device analyzer, in other words, the number and pore size of the nanopore 321 may be formulated according to the type of the nanopore chip 32.
Referring back to fig. 2 and 3, the sensing chamber 322 of the present embodiment is located in the middle of the fluid path near the fluid inlet 11, and for convenience, the present embodiment uses the sensing chamber 322 as a dividing point, the micro-fluid cavity 13 between the sensing chamber 322 and the fluid inlet 11 is named as a liquid inlet channel 14, and the micro-fluid cavity 13 between the sensing chamber 322 and the fluid outlet 12 is named as a waste liquid collecting channel 15, since the nanopore chip 32 is located at the lower side of the carrier plate 1, the liquid inlet channel 14 extends from the fluid inlet 11 to the position right above the sensing chamber 322, then extends downward and is communicated with the sensor, while the waste liquid collecting channel 15 extends upward from the port communicated with the sensing chamber 322 and extends horizontally to the fluid outlet 12, in general, under the actual sequencing use situation, the user introduces sequencing liquid from the fluid inlet 11 (can use a pump or other equipment) into the sensing chamber 322 along the liquid inlet channel 14, fills the sensing chamber 322, then enters the collecting channel 15 through the port of the waste liquid collecting channel 15, in this process, and the sensing liquid is simply operated by the cooperation of the nanopore chip 32 and the nanopore chip.
More specifically, the cover plate 2 is fixed with the carrier plate 1 by means of bonding (using a chemical adhesive such as a shadowless glue) so as to seal the micro-fluidic cavity 13, the fixing plate 3 is fixedly connected with the carrier plate 1 by means of bolting (using a fixing bolt 34, for example), the printed circuit board 31 is fixedly connected with the carrier plate 1 by means of bolting (using a locking bolt 35, for example), wherein the fixing bolt 34 and the locking bolt 35 are uniformly arranged in a plurality of numbers, for example, 6 numbers, respectively, so as to ensure the structural strength of the fixing plate 3 and the carrier plate 1, and the structural strength of the printed circuit board 31 and the carrier plate 1, and the specific assembly steps of the micro-fluidic device of the application can be as follows:
firstly, fixing the nanopore chip 32 on a corresponding position of the printed circuit board 31, wherein a plurality of contacts 311 are arranged on the lower side of the printed circuit board 31 away from the nanopore chip 32 in advance and are used for being connected with pins 323 of the nanopore chip 32, and then the printed circuit board 31 is fixedly arranged on the lower side of the carrier plate 1 by using a locking bolt 35, wherein a yielding hole 10 for the chip to pass through is arranged on the fixed plate 3; and then the fixing plate 3 is fixedly connected with the bearing plate 1 by the fixing bolts 34, and finally the cover plate 2 is fixedly connected with the bearing plate 1 by using shadowless glue, so that the micro-fluid device is assembled.
Referring back to fig. 2 and 3, in a specific embodiment, the microfluidic device for a nanopore sensor of the present application further comprises:
a first seal 4, said first seal 4 being connected to said carrier plate 1 for sealing said fluid inlet 11;
a second sealing member 41, the second sealing member 41 is connected with the carrier plate 1, and is used for sealing the fluid outlet 12.
In this embodiment, after the assembly of the microfluidic device is completed, the fluid inlet 11 is further sealed by the first sealing member 4 and the fluid outlet 12 is further sealed by the second sealing member 41 to prevent foreign matters from entering the microfluidic cavity 13 during transportation, and at the same time, in an actual detection scenario, after the entire microfluidic cavity 13 is filled with the sequencing solution, the entire microfluidic cavity 13 is required to be sealed by the first sealing member 4 and the second sealing member 41, and it is further required to be noted that the first sealing member 4 and the second sealing member 41 are detachably attached.
In a specific embodiment, a waterproof and breathable membrane 73 is disposed at the fluid outlet 12.
In this embodiment, the lower liquid column 8 is integrally formed at the lower side of the fixing plate 3, the lower liquid column 8 is integrally formed with a lower liquid hole 81 communicated with the flow outlet, the lower liquid hole 81 can be connected with a filling device (such as a pump) in a pipeline manner, sequencing liquid is pumped out of the micro-fluidic cavity 13 through the pump to drain the sequencing liquid in the micro-fluidic cavity 13, wherein the second sealing member 41 is arranged at the lower side of the lower liquid hole 81 to seal the lower liquid hole 81, namely to seal the fluid outlet 12, the waterproof breathable film 73 is embedded on the fixing plate 3 and is positioned right below the fluid outlet 12 and right above the lower liquid hole 81, the waste liquid can be prevented from flowing out of the micro-fluidic device through the waterproof breathable film 73, so that potential safety hazards caused by corrosiveness of the sequencing liquid on the basis of the self can be avoided, and the waterproof breathable film 73 is based on the breathable property, so that the smoothness of vacuum negative pressure drainage can be ensured.
In one embodiment, the conductive member is a conductive electrode 33 including a contact portion 331, a connection portion 332, and a connection portion 333 connected in sequence;
wherein, a part of the engagement portion 332 is embedded on the upper side of the bearing plate 1 and is exposed from the upper side of the bearing plate 1;
the contact part 331 passes through the carrier plate 1 and protrudes into the sensing chamber 322;
the connection part 333 passes through the carrier plate 1 and is connected with the printed circuit board 31.
In this embodiment, the contact portion 331, the engagement portion 332, and the connection portion 333 that are sequentially connected form a U-shaped structure, so that the conductive electrode 33 can be inserted into the carrier plate 1 in a U-shaped manner, and the operation is simple and convenient.
Referring to fig. 4 and fig. 5, in a specific embodiment, all the nanopores 321 are enclosed into a ring shape, the geometric center line of the contact portion 331 coincides with the geometric center line formed by all the nanopores 321, and a preset gap is formed between the end of the contact portion 331 and the bottom of the sensing chamber 322.
In the present embodiment, the nanopores 321 are disposed on the bottom wall of the sensing chamber 322, and all the nanopores 321 are enclosed in a square shape, but alternatively, all the nanopores 321 may be enclosed in a round shape, or other abnormal shapes, which is not specifically limited in this application.
In a specific embodiment, a third sealing member 5 for sealing the sensing chamber 322 is disposed between the sensing chamber 322 and the carrier plate 1.
In this embodiment, the space of the sensing chamber 322 is in a circular truncated cone shape, so the third sealing member 5 is in a circular ring shape, the outer side of the third sealing member 5 can be connected with the sensing chamber 322 in an adhesive manner, so that the surface of the third sealing member 5 is conveniently deformed due to extrusion of the lower side of the bearing plate 1 when the fixing plate 3 and the bearing plate 1 are fixedly installed, the sensing chamber 322 is sealed, the overflow of sequencing liquid is avoided, and the sequencing liquid flows only at the position of the nano hole 321.
In a specific embodiment, a plurality of positioning and sinking tables 9 are disposed on the upper side of the fixing plate 3, and positioning slots (not shown) for embedding the positioning and sinking tables 9 are disposed on the lower side of the carrying plate 1.
Referring back to fig. 2, in this embodiment, 3 groups of positioning and sinking tables 9 are uniformly arranged, each group of positioning and sinking tables 9 comprises 2 positioning and sinking tables 9 which are symmetrically arranged, correspondingly, 6 positioning grooves are formed in the lower side of the bearing plate 1, in the assembly process, the positioning and sinking tables 9 are directly embedded in the positioning grooves, so that the relative positions of the fixing plate 3 and the bearing plate 1 can be rapidly positioned, and the communication between the sensing chamber 322 and the waste liquid collecting flow channel 15 and the liquid inlet flow channel 14 is ensured.
More preferably, the positioning sinking platform 9 of the present application is provided with a threaded hole along its length direction for being cooperatively connected with the fixing bolt 34 passing through the carrier plate 1, so as to improve the structural compactness of the microfluidic device of the present application.
In a specific embodiment, referring to fig. 1 and 2, the cover plate 2 is provided with a drip hole 6 communicating with the fluid inlet 11, and the first sealing member 4 is tightly matched with the drip hole 6 for sealing the drip hole 6.
In this embodiment, the position of the drip hole 6 is higher than the fluid inlet 11, so that the user can conveniently drip the sequencing liquid from the drip hole 6 through a drip tool (such as a drip tube), and the sequencing liquid falls into the fluid inlet 11 and the micro-fluid cavity 13 from the drip hole 6 under the action of gravity.
When the micro-fluid cavity 13 needs to be sealed, the first sealing piece 4 is directly embedded into the drip hole 6, and the first sealing piece 4 is deformed after being extruded by the hole wall of the drip hole 6, so that the drip hole 6 is sealed, and the assembly and the disassembly are convenient.
In a specific embodiment, the dropping hole 6 includes a guiding portion and a communicating portion that are connected, the bottom surface of the guiding portion is inclined and extends downward, 2 side surfaces of the guiding portion are contracted towards the communicating portion, the side surfaces and the bottom surface of the guiding portion are arc structures, the upper end of the communicating portion is located at the lowest end of the guiding portion, and the lower end of the communicating portion is communicated with the fluid inlet 11.
In this embodiment, the first sealing member 4 includes a fitting portion 42 with a shape matching with the guiding portion and a sealing portion 43 integrally formed at a lower side of the fitting portion 42, the sealing portion 43 is tightly connected with the connecting portion 333, the fitting portion 42 is fitted to the guiding portion, in other words, the first sealing member 4 is embedded in the drip hole 6 and forms a clamping relationship with the cover plate 2, so as to seal the drip hole 6. The guide portion of the present application is triangular, and is used for receiving the sequencing solution falling on the surface of the guide portion, guiding the sequencing solution to the connection portion 333, and flowing from the connection portion 333 to the fluid inlet 11, so that the connection portion 333 is integrally formed at the lower side of the tip of the guide portion.
More preferably, the microfluidic device for a nanopore sensor of the present application further comprises a fourth sealing member 7, a liquid inlet column 71 is disposed on the lower side of the carrier plate 1, and a liquid inlet hole 72 communicating with the fluid inlet 11 is disposed on the liquid inlet column 71, wherein the fourth sealing member 7 is used for sealing the liquid inlet hole 72.
In this embodiment, the fixing plate 3 is provided with a through hole through which the liquid inlet column 71 passes, and in a practical application scenario, the liquid inlet hole 72 can be connected with a filling device (for example, a pump) through a pipeline, and the sequencing liquid is injected into the micro-fluidic cavity 13 through the pump, so that compared with a mode of dripping the sequencing liquid from the liquid dripping hole 6 by using a liquid dripping pipe, the method has the advantages of reducing manual operation and improving detection efficiency.
It should be noted that in the actual design process of the microfluidic device, only the microfluidic device with the drip hole 6 may be designed, only the microfluidic device with the liquid inlet column 71 may be designed, and even the microfluidic device with both the drip hole 6 and the liquid inlet column 71 may be designed, so as to improve the choice diversity and practicality of the microfluidic device.
It should be noted that, the first sealing member 4, the second sealing member 41, the third sealing member 5 and the fourth sealing member 7 of the present application may be made of silica gel, but it should be understood that all sealing members may be made of other materials with better sealing performance, and the liquid inlet column 71 and the liquid outlet column 8 of the present application are connected to corresponding pumps, so the second sealing member 41 and the fourth sealing member 7 are all annular.
Preferably, the two opposite sides of the bearing plate 1 and the fixing plate 3 are integrally formed with the anti-slip protrusions 101, thereby facilitating the assembly of the microfluidic device by a user.
In a specific embodiment, the conductive member is manufactured by vacuum evaporation, printing, electroplating or ink-jet.
In the present embodiment, the conductive electrode 33 may be manufactured by a process of vacuum evaporation or printing or electroplating or inkjet.
In one embodiment, the conductive member is made of one or more noble metals such as ruthenium, rhodium, palladium, platinum, gold, or silver, or a combination thereof.
In the present embodiment, the conductive electrode 33 is preferably made of platinum material, but it should be understood that the conductive electrode 33 may be made of other noble metal materials at the time of manufacturing, which is not particularly limited in this application.
Embodiment two:
referring to fig. 7, the difference between the present embodiment and the first embodiment is that the conductive member is specifically: the conductive member includes a plurality of sets of negative electrodes 36 and positive electrodes 37 disposed on the nanopore chip 32, wherein the negative electrodes 36 are positioned within the sensing chamber 322 for providing a negative voltage, and the positive electrodes 37 are for providing a positive voltage.
Based on the fact that the conductive electrode 33 is made of precious metal (such as platinum, rhodium, palladium and gold) materials, the manufacturing cost of the microfluidic device is high, so that the negative electrode 36 is used for providing negative voltage, the positive electrode 37 is used for providing positive voltage, and the situation that the existing nano-pore electrode only has a microporous negative electrode is changed (the defect that only has the microporous negative electrode is as follows, when an external reagent completes microporous membrane laying and hole embedding, the external circuit can smoothly read DNA step current only by applying positive pulling voltage to the external electrode) is overcome, that is, the microfluidic device obtained by the embodiment can achieve the effects of low manufacturing cost and strong applicability.
Further, the nanopore chip 32 is provided with an identifier 38 for identifying the position of the pin 323 on the nanopore chip 32.
In this embodiment, the identifier 38 is an identifier groove disposed at a top corner of the nanopore chip 32, and it should be noted that, when manufacturing, the identifier 38 may be a colored identifier sheet according to actual needs, so long as the pin can be positioned, so that the application will not be repeated.
Embodiment III:
with reference to fig. 8, an embodiment of the present invention further provides an assembly method of a microfluidic device for a nanopore sensor as described above, comprising the steps of:
s101, fixing the pre-installed nanopore sensing assemblies on the lower side of the fixing plate 3 in a bolting way;
s102, fixing the fixing plate 3 on the lower side of the bearing plate 1 in a bolting way;
s103, embedding the conductive electrode 33 from the upper side of the bearing plate 1, and enabling one end of the conductive electrode 33 to extend into the sensing chamber 322 and the other end to be connected with the printed circuit board 31;
and S104, fixing the cover plate 2 on the upper side of the bearing plate 1 in an adhesive manner to form a micro-fluid cavity 13 with a fluid inlet 11 and a fluid outlet 12.
In this embodiment, the nanopore chip 32 is fixed at the corresponding position of the printed circuit board 31, it should be noted that, a plurality of contacts 311 are arranged on the underside of the printed circuit board 31 facing away from the nanopore chip 32 in advance for connecting with pins 323 of the nanopore chip 32, and then the printed circuit board 31 is fixedly mounted on the underside of the carrier board 1 by using the locking bolt 35, wherein the fixing board 3 is provided with a relief hole 10 for the chip to pass through; then utilize fixing bolt 34 with fixed plate 3 and loading board 1 fixed connection again, then insert corresponding position with conductive electrode 33, finally utilize shadowless glue with apron 2 and loading board 1 fixed connection to accomplish the assembly of micro-fluidic device, in general, the structure of this application realizes simply, equipment and dismantles conveniently to the quick mass production of nanopore chip 32 itself, simple process manufacturing, low price.
While the invention has been described with reference to certain preferred embodiments, it will be understood by those skilled in the art that various changes and substitutions of equivalents may be made and equivalents will be apparent to those skilled in the art without departing from the scope of the invention. Therefore, the protection scope of the invention is subject to the protection scope of the claims.
Claims (7)
1. A microfluidic device for a nanopore sensor, comprising:
the sequencing device comprises a bearing plate (1), wherein a microfluidic cavity (13) which is provided with a fluid inlet (11) and a fluid outlet (12) and is used for flowing sequencing liquid is arranged on the upper side of the bearing plate (1);
the cover plate (2) is connected with the bearing plate (1) and is used for sealing a micro-fluid cavity (13) between the fluid inlet (11) and the fluid outlet (12);
a nanopore sensing assembly located in a fluid path, the nanopore sensing assembly comprising:
a printed circuit board (31), wherein the printed circuit board (31) is connected with the lower side of the bearing plate (1) through a fixed plate (3);
a nanopore chip (32), wherein the nanopore chip (32) is arranged on the upper side of the printed circuit board (31), penetrates through the fixed plate (3) and is in airtight contact with the lower side of the bearing plate (1), and the nanopore chip (32) is provided with a sensing chamber (322) which is provided with a plurality of nanopores (321) and is communicated with the microfluidic cavity (13) and is used for receiving at least one part of sequencing liquid;
a conductive member connected to the printed circuit board (31) and extending into the sensing chamber (322);
the conductive member is a conductive electrode (33) comprising a contact part (331), a joint part (332) and a connection part (333) which are connected in sequence;
wherein, a part of the connecting part (332) is embedded on the upper side of the bearing plate (1) and is exposed from the upper side of the bearing plate (1);
the contact part (331) penetrates through the bearing plate (1) and extends into the sensing chamber (322);
the connecting part (333) penetrates through the bearing plate (1) and is connected with the printed circuit board (31);
the contact part (331), the connecting part (332) and the connecting part (333) which are sequentially connected form a U-shaped structure;
the conductive piece comprises a plurality of groups of negative electrodes (36) and positive electrodes (37) which are arranged on the nanopore chip (32), wherein the negative electrodes (36) are positioned in the sensing chamber (322) and used for providing negative voltage, and the positive electrodes (37) are used for providing positive voltage;
the upper side of the fixed plate (3) is provided with a plurality of groups of positioning sinking tables (9), and the lower side of the bearing plate (1) is provided with positioning grooves for embedding the positioning sinking tables (9);
further comprises:
-a first seal (4), the first seal (4) being connected to the carrier plate (1) for sealing the fluid inlet (11);
-a second seal (41), the second seal (41) being connected to the carrier plate (1) for sealing the fluid outlet (12);
all the nanopores (321) are surrounded into a ring shape, the geometric center line of the contact part (331) coincides with the geometric center line formed by all the nanopores (321), and the tail end of the contact part (331) and the bottom of the sensing chamber (322) have a preset gap;
the nanopore (321) is arranged on the bottom wall of the sensing chamber (322);
a third sealing piece (5) for sealing the sensing chamber (322) is arranged between the sensing chamber (322) and the bearing plate (1);
a waterproof and breathable film (73) is arranged at the position of the fluid outlet (12).
2. The microfluidic device for a nanopore sensor according to claim 1, wherein: the conductive member is manufactured by vacuum evaporation or printing or electroplating or ink-jet.
3. The microfluidic device for a nanopore sensor according to claim 1, wherein: the conductive member is made of one or more noble metals of ruthenium, rhodium, palladium, platinum, gold or silver, or a compound thereof.
4. The microfluidic device for a nanopore sensor according to claim 1, wherein: the cover plate (2) is provided with a drip hole (6) communicated with the fluid inlet (11), and the first sealing piece (4) is tightly matched with the drip hole (6) for sealing the drip hole (6);
the liquid dropping hole (6) comprises a guiding part and a communicating part which are communicated, the bottom surface of the guiding part is inclined and extends downwards, 2 side surfaces of the guiding part are contracted towards the communicating part, the upper end of the communicating part is located at the lowest end of the guiding part, and the lower end of the communicating part is communicated with the fluid inlet (11).
5. The microfluidic device for a nanopore sensor according to any of claims 2-4, wherein: the novel fluid inlet device is characterized by further comprising a fourth sealing piece (7), wherein a liquid inlet column (71) is arranged on the lower side of the bearing plate (1), a liquid inlet hole (72) communicated with the fluid inlet (11) is formed in the liquid inlet column (71), and the fourth sealing piece (7) is used for sealing the liquid inlet hole (72).
6. The microfluidic device for a nanopore sensor according to claim 1, wherein: the nanopore chip (32) is provided with an identifier (38) for identifying the position of a pin (323) on the nanopore chip (32).
7. A method of assembling a microfluidic device for a nanopore sensor according to any of claims 1 to 4, comprising the steps of:
s101, fixing the pre-installed nanopore sensing assemblies on the lower side of the fixing plate (3) in a bolting way;
s102, fixing the fixing plate (3) on the lower side of the bearing plate (1) in a bolting way;
s103, embedding the conductive electrode (33) from the upper side of the bearing plate (1), and enabling one end of the conductive electrode (33) to extend into the sensing chamber (322) and the other end to be connected with the printed circuit board (31);
s104, fixing the cover plate (2) on the upper side of the bearing plate (1) in an adhesive mode to form a micro-fluid cavity (13) with a fluid inlet (11) and a fluid outlet (12).
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210774477.XA CN115121303B (en) | 2022-07-01 | 2022-07-01 | Microfluidic device for nanopore sensor and method of assembling the same |
| PCT/CN2022/111305 WO2024000739A1 (en) | 2022-07-01 | 2022-08-10 | Microfluid device for nanopore sensor, and assembly method therefor |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
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| CN202210774477.XA CN115121303B (en) | 2022-07-01 | 2022-07-01 | Microfluidic device for nanopore sensor and method of assembling the same |
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| CN115121303A CN115121303A (en) | 2022-09-30 |
| CN115121303B true CN115121303B (en) | 2024-01-02 |
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| CN202210774477.XA Active CN115121303B (en) | 2022-07-01 | 2022-07-01 | Microfluidic device for nanopore sensor and method of assembling the same |
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| WO (1) | WO2024000739A1 (en) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7520164B1 (en) * | 2006-05-05 | 2009-04-21 | E.I. Spectra, Llc | Thin film particle sensor |
| CN109844528A (en) * | 2016-10-26 | 2019-06-04 | 豪夫迈·罗氏有限公司 | For the integrated circuit of nano-pore sequencing and the multi-chip packaging of flow cell |
| CN114636744A (en) * | 2022-03-09 | 2022-06-17 | 中山大学 | Nanoporous membrane-based microelectrode array chip and high-throughput intracellular electrical signal continuous monitoring system |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20120001273A1 (en) * | 2010-07-02 | 2012-01-05 | Siargo Ltd. | Micro-package for Micromachining Liquid Flow Sensor Chip |
| CN103913489B (en) * | 2013-01-09 | 2015-06-10 | 北京怡成生物电子技术股份有限公司 | Micro biochip for real-time detection of substances in body fluids |
| GB201611770D0 (en) * | 2016-07-06 | 2016-08-17 | Oxford Nanopore Tech | Microfluidic device |
| CN207318408U (en) * | 2017-10-25 | 2018-05-04 | 深圳宣泽生物医药有限公司 | High-throughput nano metre hole detection device |
| US20200326325A1 (en) * | 2019-04-12 | 2020-10-15 | Lisa Diamond | Nanosensor chip with compound nanopores |
| GB201917832D0 (en) * | 2019-12-05 | 2020-01-22 | Oxford Nanopore Tech Ltd | Microfluidic device for preparing and analysing a test liquid |
| US20210237079A1 (en) * | 2020-01-31 | 2021-08-05 | Ontera Inc. | Device with Flow Features for Sample Processing and Method of Use |
| EP4240825A1 (en) * | 2020-11-06 | 2023-09-13 | University Of Rochester | Devices and methods for monitoring cells, tissues, or organs-on-a-chip |
-
2022
- 2022-07-01 CN CN202210774477.XA patent/CN115121303B/en active Active
- 2022-08-10 WO PCT/CN2022/111305 patent/WO2024000739A1/en active Application Filing
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7520164B1 (en) * | 2006-05-05 | 2009-04-21 | E.I. Spectra, Llc | Thin film particle sensor |
| CN109844528A (en) * | 2016-10-26 | 2019-06-04 | 豪夫迈·罗氏有限公司 | For the integrated circuit of nano-pore sequencing and the multi-chip packaging of flow cell |
| CN114636744A (en) * | 2022-03-09 | 2022-06-17 | 中山大学 | Nanoporous membrane-based microelectrode array chip and high-throughput intracellular electrical signal continuous monitoring system |
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| CN115121303A (en) | 2022-09-30 |
| WO2024000739A1 (en) | 2024-01-04 |
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