WO2023088184A1 - 微流控芯片及微流控芯片检测系统 - Google Patents
微流控芯片及微流控芯片检测系统 Download PDFInfo
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- WO2023088184A1 WO2023088184A1 PCT/CN2022/131391 CN2022131391W WO2023088184A1 WO 2023088184 A1 WO2023088184 A1 WO 2023088184A1 CN 2022131391 W CN2022131391 W CN 2022131391W WO 2023088184 A1 WO2023088184 A1 WO 2023088184A1
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- microfluidic chip
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- 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
- B01L3/502738—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 integrated valves
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- 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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- 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
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- B01L3/50273—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the means or forces applied to move the fluids
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- B01L7/52—Heating 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
Definitions
- the present disclosure relates to the field of in vitro diagnosis, in particular to a microfluidic chip and a microfluidic chip detection system.
- Nucleic acid detection technology is a technology that directly detects the genetic material of living organisms, such as DNA and RNA. Its specificity and sensitivity are extremely high, the window period is short, and it has multiple detection capabilities. However, the nucleic acid detection process is very complicated, with many steps, and has high requirements for the detection environment, laboratory conditions, and technical level of personnel. Therefore, the development trend of nucleic acid detection is fully automatic integration, high integration, bedside detection, and real-time detection. , Check anywhere.
- nucleic acid detection based on microfluidic technology has the advantages of complete automation, high integration, simplicity and speed, avoiding cross-contamination, independent use in various environments, and no need for highly skilled professionals. concepts and requirements.
- a microfluidic chip comprising:
- a storage member with a groove on it, and at least two storage bins around the groove;
- a base located at one end of the storage member away from the groove, and a reaction chamber is arranged on the base;
- a valve is disposed in the groove, the valve is configured to operably communicate any one of the at least two storage chambers with the reaction chamber.
- At least two first storage member inner flow passages are provided in the storage member, and each first storage member inner flow passage is correspondingly connected to a storage chamber, and the valve is provided with a valve connected to the reaction chamber.
- the valve is configured to operatively communicate the valve flow channel with any one of the first reservoir internal flow channels.
- the first end of the flow channel in each first reservoir passes through the bottom wall of the groove, and the valve is configured to operably connect the flow channel in the valve with the first
- the first end of the flow channel in the storage part communicates with each other, and the second end of the flow channel in each first storage part communicates with the storage bin through a side of the storage bin adjacent to the base.
- the second end of the flow channel in the first storage part communicates with the lowest part of the storage bin.
- both the first end and the second end of the flow channel in the valve pass through an end of the valve adjacent to the bottom wall of the groove, and the first end of the flow channel in the valve is connected to the The reaction chamber is connected, the second end of the flow channel in the valve is operatively connected with the flow channel in any first storage member, the first end of the flow channel in the valve is located in the middle of the valve, and the flow channel in the valve The second end of the flow channel is adjacent to the outer edge of the valve.
- the valve comprises:
- a rotor rotatably arranged in the groove, the rotor includes a valve seat and a valve stem, the valve stem is connected to the valve seat;
- the valve cover is connected to the circumferential side wall of the groove, and abuts against the valve seat, and the valve seat is limited between the valve cover and the bottom wall of the groove, and the valve cover is A first through hole is provided, the operating portion of the valve stem passes through the first through hole, and the operating portion of the valve stem is configured to be connected with an external operating member.
- valve cover abuts against a circumferential edge of the valve seat.
- the microfluidic chip further includes a sealing film
- the at least two storage compartments include a reagent compartment
- the sealing film is configured to seal the reagent compartment
- the microfluidic chip further includes a top cover and A puncture needle, the top cover is arranged at one end of the storage part provided with the groove, the puncture needle is connected to the top cover, and the puncture needle is configured to be pressed to the the sealing film to puncture the sealing film.
- the top cover includes a first rib, the piercing needle is connected to the first rib, and the first rib is configured to be broken under the action of an external force, so that the The piercing needle disengages from the cap and presses against the sealing membrane.
- the middle part of the top cover is provided with a second through hole, and the second through hole is configured to allow an external operating member to pass through to operate the valve.
- the puncture needle is provided with an airway inside the needle, and a hole connecting the outside of the puncture needle and the airway inside the needle is provided near the part where the puncture needle is connected to the top cover. third via.
- the microfluidic chip further includes a cover sheet, the cover sheet is arranged in the top cover, and the cover sheet is provided with a fourth through hole that allows the piercing needle to pass through.
- the breaking needle is configured to press against the sealing film under the action of external force, and continue to press against the sealing film after piercing the sealing film, so that the third through hole is sealed by the cover sheet.
- the reaction compartment protrudes toward a side away from the storage member.
- the microfluidic chip further includes an expansion part, the expansion part is provided with an amplification chamber, and the side of the storage part is provided with slots, and the slots are located between the adjacent two Between the storage chambers, the amplification member is plugged into the slot, and the valve is configured to operably communicate the reaction chamber with the amplification chamber.
- the storage part is provided with a second storage part inner flow channel, the first end of the second storage part inner flow channel passes through the slot, and the second storage part inner flow channel
- the second end passes through the groove
- the expansion part is provided with an inner flow channel of the expansion part that communicates with the expansion chamber, and the inner flow channel of the expansion part is connected with the inner flow channel of the second storage part.
- the first end is connected, and the valve is configured to be operatively connected to the second end of the flow channel in the second storage member, so as to pass the solution in the reaction chamber through the flow channel in the second storage member and the second end of the second storage member.
- the flow channel in the amplification piece leads to the amplification chamber.
- the storage part is provided with a third storage part inner flow channel, the first end of the third storage part inner flow channel passes through the slot, and the third storage part inner flow channel
- the second end passes through the groove
- the expansion part is provided with an internal air channel of the expansion part that communicates with the expansion chamber, and the air channel in the expansion part is connected to the inner flow channel of the third storage part.
- the first end communicates, and the valve is configured to operatively communicate with the second end of the flow channel in the third storage member, so as to pass the gas of the amplification chamber through the air channel in the expansion member and the The flow passage in the third storage member leads to a storage bin.
- the valve is provided with an in-valve flow passage communicating with the reaction chamber, and the valve is also provided with an in-valve air passage, and the valve is configured to operatively connect the flow in the valve
- the channel connects the reaction chamber and the amplification chamber, and connects the air passage in the valve with the amplification chamber and a storage chamber.
- the storage part is provided with an internal air channel of the storage part, the internal air channel of the storage part communicates with the reaction chamber, and the internal air channel of the storage part is configured to communicate with an external air pump.
- the first end of the air passage in the storage part passes through one end of the groove in the storage part, and the first end of the air passage in the storage part is located between two adjacent storage bins.
- the top cover is fixed on an end of the storage element where the groove is provided, and the base is fixed on an end of the storage element away from the top cover.
- a detection system for a microfluidic chip including a detection device and the above-mentioned microfluidic chip, the detection device includes an operating platform for accommodating the microfluidic chip, and a The operating part of the valve.
- the present disclosure at least has the following beneficial effects:
- a groove is arranged on the storage member, at least two storage chambers are arranged around the circumference of the groove, a valve is arranged in the groove, and a reaction chamber is arranged below the valve, and any storage chamber can be closed by operating the valve.
- the solution in the reaction chamber is directed to the reaction chamber, or the solution in the reaction chamber is directed to any storage chamber to realize solution transfer.
- the structure is simple and compact, which can greatly shorten the length of the flow channel and improve the detection efficiency.
- FIG. 1 is a schematic diagram of the overall structure of a microfluidic chip provided according to some embodiments of the present disclosure
- Fig. 2 is a schematic diagram of an exploded structure of a microfluidic chip provided according to some embodiments of the present disclosure
- FIG. 3 is a schematic structural view of a top cover of a microfluidic chip provided according to some embodiments of the present disclosure
- FIG. 4 is a schematic structural view of a top cover and a cover sheet of a microfluidic chip provided according to some embodiments of the present disclosure
- Fig. 5 is a schematic structural diagram of storage elements and valves of a microfluidic chip provided according to some embodiments of the present disclosure
- Fig. 6 is a schematic top view of a storage part of a microfluidic chip provided according to some embodiments of the present disclosure
- Fig. 7 is a schematic bottom view of a storage part of a microfluidic chip provided according to some embodiments of the present disclosure.
- FIG. 8 is a schematic cross-sectional view of a storage part of a microfluidic chip provided according to some embodiments of the present disclosure
- FIG. 9 is a schematic diagram of an exploded structure of a valve of a microfluidic chip provided according to some embodiments of the present disclosure.
- FIG. 10 is a schematic cross-sectional view of a valve of a microfluidic chip provided according to some embodiments of the present disclosure
- Fig. 11 is a schematic structural diagram of a base of a microfluidic chip provided according to some embodiments of the present disclosure.
- FIG. 12 is a schematic top view of a base of a microfluidic chip provided according to some embodiments of the present disclosure
- Fig. 13 is a schematic diagram of the bottom structure of the base of the microfluidic chip provided according to some embodiments of the present disclosure
- FIG. 14 is a schematic cross-sectional view of a base of a microfluidic chip provided according to some embodiments of the present disclosure.
- Fig. 15 is a schematic diagram of an amplification part of a microfluidic chip provided according to some embodiments of the present disclosure.
- Fig. 16 is a schematic diagram of the microfluidic chip before the expansion part, the second gasket and the storage part are connected according to some embodiments of the present disclosure
- Fig. 17 is a schematic diagram of the microfluidic chip before the amplification part is inserted into the slot of the storage part according to some embodiments of the present disclosure.
- Some embodiments of the present disclosure provide a microfluidic chip and a microfluidic chip detection system, which are suitable for rapid detection in vitro.
- a groove 11 is provided on the storage member 1 , and at least two storage bins 12 are arranged around the groove 11 .
- the groove 11 includes a bottom wall and a circumferential side wall.
- the base 2 is disposed at the end of the storage element 1 away from the groove 11 , and the base 2 is provided with a reaction chamber 21 .
- the valve 3 is disposed in the groove 11 , and the valve 3 is configured to operably connect any one of the at least two storage chambers 12 with the reaction chamber 21 .
- the at least two storage bins 12 include at least one sample bin and at least two reagent bins 121.
- the reagent bins 121 are used to store different detection reagents, which can be solid or liquid reagents.
- the number of reagent bins 121 can be flexibly increased or decreased according to demand.
- One sample compartment can be provided, or two can be provided as required, and the sample compartment is used for adding samples to be tested, and the samples to be tested include blood or saliva.
- the reaction chamber 21 is a reagent reaction place for nucleic acid extraction.
- Valve 3 is a key component of liquid flow control in the microfluidic chip, which controls the connection and closure of the flow channel.
- the base 2 is used to ensure the stable flat placement of the microfluidic chip, and also has positioning and limiting functions to improve detection stability.
- a groove 11 is provided on the storage member 1, at least two storage chambers 12 are arranged around the circumference of the groove 11, a valve 3 is arranged in the groove 11, and a reaction chamber 21 is arranged below the valve 3, by operation
- the valve 3 can lead the solution in any storage bin 12 to the reaction bin 21, or direct the solution in the reaction bin 21 to any storage bin 12 to realize solution transfer.
- the structure is simple and compact, and the length of the flow channel can be greatly shortened, improving detection efficiency.
- At least two first storage member internal flow channels 13 are provided in the storage member 1, and each first storage member internal flow channel 13 is correspondingly connected to a storage bin 12.
- An in-valve flow channel 31 communicating with the reaction chamber 21 is provided, and the valve 3 is configured to operably communicate the in-valve flow channel 31 with any one of the first storage member internal flow channels 13 .
- the flow channel 31 in the valve is always in communication with the reaction chamber 21, and the flow channel 31 in the valve can be selectively communicated with the flow channel 13 in any one of the first storage parts by operating the valve 3, so as to guide the solution in the storage chamber 12 to the reaction chamber. Bin 21, or guide the solution in the reaction bin 21 to the storage bin 12.
- the first end 131 of the channel 13 in each first storage member passes through the bottom wall of the groove 11 , and the valve 3 is configured to operably connect
- the channel 31 communicates with the first end 131 of the channel 13 in the first storage part, and the second end 132 of the channel 13 in each first storage part communicates with the storage bin 12 through the side of the storage bin 12 adjacent to the base 2 .
- the second end 132 of the flow channel 13 in the first storage member communicates with the lowest position of the storage bin 12 and the closest to the groove 11 .
- the second end 132 of the flow channel 13 in the first storage member communicates with the lowest position of the storage compartment 12 and the part closest to the groove 11 , so as to shorten the length of the flow channel.
- the first end 311 and the second end 312 of the flow channel 31 in the valve pass through the end of the valve 3 adjacent to the bottom wall of the groove 11 , and the flow channel 31 in the valve
- the first end 311 of the valve internal flow channel 31 communicates with the reaction chamber 21, the second end 312 of the flow channel 31 in the valve is operatively communicated with the internal flow channel 13 of any first storage member, and the first end 311 of the flow channel 31 in the valve is located in the valve 3
- the second end 312 of the flow channel 31 in the valve is close to the outer edge of the valve 3 .
- the storage element 1 has a cylindrical shape as a whole.
- the valve 3 includes a rotor 32 and a valve cover 33 .
- the rotor 32 is rotatably disposed in the groove 11 , the rotor 32 includes a valve seat 321 and a valve stem 322 , and the valve stem 322 is connected to the valve seat 321 .
- the valve cover 33 is connected to the circumferential side wall of the groove 11, and abuts against the valve seat 321, and the valve seat 321 is limited between the valve cover 33 and the bottom wall of the groove 11, and the valve seat 321 abuts against the bottom of the groove 11.
- the valve cover 33 is provided with a first through hole 331 , the operating portion of the valve stem 322 passes through the first through hole 331 , and the operating portion of the valve stem 322 is configured to be connected with an external operating member.
- the valve seat 321 includes a valve seat body 3211 and a first gasket 3212.
- the first gasket 3212 is in the same shape as the bottom of the valve seat body 3211.
- the valve seat body 3211 and the first gasket 3212 are fixedly arranged.
- the flow channel 31 in the valve is formed in the valve seat 321 .
- the valve seat body 3211 is made of hard material, and the first gasket 3212 is made of elastic material.
- valve cover 33 By adjusting the valve cover 33, an appropriate abutment pressure is applied to the valve seat 321 of the rotor 21, so that the valve seat 321 and the bottom of the groove 11 The wall abuts against each other, so that the flow channel 31 in the valve has the airtightness required for detection, and avoids liquid leakage at the connection between the flow channel 31 in the valve and the flow channel in the storage member.
- valve cover 33 abuts against the peripheral edge of the valve seat 321 .
- the first end 131 of the flow channel 13 in each first storage member passes through the bottom wall of the groove 11 and is arranged around the central axis of the groove 11.
- the valve cover 33 abuts against the peripheral edge of the valve seat 321, enabling the valve seat to 321 abuts against the bottom wall of the groove 11 to seal the connection between the flow channel 31 in the valve and the flow channel in the storage part to avoid liquid leakage.
- the radial dimension of the valve stem 322 is smaller than the radial dimension of the valve seat body 3211, one end of the valve stem 322 is fixedly connected to the valve seat body 3211, and the other end of the valve stem 322 is an operating part for passing through the first through hole 331, And it is connected with an external operating part.
- the valve stem 322 is rotated by the operating member, thereby driving the valve seat body 3211 and the first washer 3212 to rotate, so as to selectively connect the second end 312 of the valve internal flow channel 31 with a first storage member internal flow channel 13 .
- the circumferential direction of the valve seat body 3211 is provided with a boss 324, and the boss 324 has an arc-shaped outer contour to reduce the circumferential direction of the valve seat body 3211 and the circumference of the groove 11 during the rotation of the valve seat body 3211 relative to the groove 11. Friction against the side walls.
- the microfluidic chip further includes a sealing film
- at least two storage chambers 12 include a reagent chamber 121
- the sealing film is configured to seal the reagent chamber 121
- the microfluidic chip further includes The top cover 4 and the puncture needle 41, the top cover 4 is arranged on the end of the storage part 1 provided with the groove 11, the puncture needle 41 is connected to the top cover 4, and the puncture needle 41 is configured to press against the sealing film under the action of an external force , to puncture the sealing membrane.
- the top cover 4 includes a first rib 421, the piercing needle 41 is connected to the first rib 421, and the first rib 421 is configured to be broken under the action of an external force. , so that the piercing needle 41 is detached from the top cover 4 and pressed against the sealing film.
- the middle part of the top cover 4 is provided with a second through hole 43 , and the second through hole 43 is configured to allow an external operating member to pass through to connect the operating part of the valve 3 , for turning valve 3.
- the puncture needle 41 is provided with an inner needle airway 411 , and the part where the puncture needle 41 is connected to the top cover 4 is provided with a third through hole 412 , and the third through hole 412 communicates The outside of the needle 41 and the needle airway 411 are pierced.
- the microfluidic chip further includes a cover sheet 6, which is arranged in the top cover 4, and is provided with a cover sheet 6 that allows external operating parts to pass through to connect the rotor 32.
- the cover sheet 6 is also provided with a fourth through hole 61 that allows the puncture needle 41 to pass through.
- the puncture needle 41 is configured to press against the sealing film under the action of an external force, and continue to press against the sealing film after puncturing the sealing film, so as to The third through hole 412 is sealed by the cover sheet 6 .
- the piercing needle 41 includes a first needle segment and a second needle segment, and the radial dimension of the second needle segment is larger than that of the first needle segment.
- the second needle section is connected to the first rib 421 , the first needle section is configured as a pointed needle for piercing the sealing membrane, and the third through hole 412 is provided in the second needle section.
- the puncture needle 41 is pressed against the sealing film under the action of external force, and punctures the sealing film, so that the reagent chamber 121 communicates with the atmosphere through the needle inner airway 411 and the third through hole 412 on the puncture needle 41, which is convenient for subsequent extraction of reagents.
- the first needle segment passes through the fourth through hole 61 .
- the puncture needle 41 is further pressed against the sealing film under the action of external force, and the third through hole 412 is sealed by the cover sheet 6, thereby sealing the reagent chamber 121 to prevent waste liquid from flowing out.
- a sealing film is disposed on the cover sheet 6 to seal the reagent compartment 121 .
- the sealing film is directly disposed on the reagent compartment 121 to seal the reagent compartment 121 .
- reaction chamber 21 protrudes toward the side away from the storage element 1 .
- the reaction chamber 21 has a spherical crown structure.
- the reaction chamber 21 is used as a reagent reaction site for nucleic acid extraction, and the extraction step is completed in a short time through the cooperation of the spherical crown chamber structure and the ultrasonic transducer.
- the microfluidic chip further includes an amplification part 5, and the amplification part 5 is provided with an amplification chamber 51, as shown in Figures 5 and 6, the side of the storage part 1 There is a slot 14 at the top, the slot 14 is located between two adjacent storage bins 12, the amplification part 5 is plugged into the slot 14, and the valve 3 is configured to operably communicate the reaction bin 21 with the amplification bin 51 .
- the amplification part 5 is a sheet structure with a large heating surface and is easy to collect sample fluorescence.
- the expansion part 5 adopts a separate design, and can be connected or separated from the main structure of the microfluidic chip (including the storage part 1 ) by plugging and unplugging, which improves the versatility.
- the storage part 1 is provided with a second storage part inner channel 15, the first end 151 of the second storage part inner flow channel 15 passes through the slot 14, and the second The second end 152 of the internal flow channel 15 of the storage part passes through the groove 11, as shown in Figure 15, the expansion part 5 is provided with the expansion part internal flow channel 52 communicated with the amplification chamber 51, and the expansion part internal flow channel 52 communicates with the first end 151 of the flow channel 15 in the second storage part, and the valve 3 is configured to operatively communicate with the second end 152 of the flow channel 15 in the second storage part, so as to pass the solution in the reaction chamber 21 through the second storage part.
- the flow channel 15 in the two storage parts and the flow channel 52 in the expansion part lead to the expansion chamber 51 .
- the storage part 1 is provided with a third storage part inner flow channel 16, the first end 161 of the third storage part inner flow channel 16 passes through the slot 14, and the third storage part inner flow channel 16 passes through the slot 14, and the third The second end 162 of the internal flow channel 16 of the storage part passes through the groove 11, as shown in Figure 15, the expansion part 5 is provided with an expansion part internal air channel 53 communicated with the expansion chamber 51, and the expansion part internal air channel 53 communicates with the first end 161 of the flow channel 16 in the third storage part, and the valve 3 is configured to be operatively connected to the second end 162 of the flow channel 16 in the third storage part, so that the gas in the amplification chamber 51 passes through the expansion chamber.
- the air passage 53 in the extension part and the flow passage 16 in the third storage part lead to a storage chamber 12 to keep the air pressure balance in the amplification chamber 51.
- the above-mentioned connected air channel and flow channel discharge excess liquid in the amplification chamber 51 to the storage chamber 12 to avoid leakage pollution.
- the extension part 5 includes a main body and a plug-in part, the expansion chamber 51 is arranged on the main body, and the plug-in part is mated with the slot 14 for plug-in connection.
- the valve 3 is connected to the second end 152 of the flow channel 15 in the second storage part, so that the solution in the reaction chamber 21 is guided to the expansion chamber 51 through the flow channel 15 in the second storage part and the flow channel 52 in the amplification part.
- the valve 3 is also connected to the second end 162 of the flow channel 16 in the third storage part, so as to guide the gas in the expansion chamber 51 to a storage chamber through the air passage 53 in the expansion part and the flow channel 16 in the third storage part.
- the storage compartment 12 is adjacent to the slot 14 .
- the valve 3 is provided with an in-valve channel 31 communicating with the reaction chamber 21, and an in-valve air channel 32 is also provided in the valve 3, and the valve 3 is configured to be operable
- the flow passage 31 in the valve is connected to the reaction chamber 21 and the amplification chamber 51
- the air passage 32 in the valve is connected to the amplification chamber 51 and a storage chamber 12 .
- the storage part 1 is provided with an internal air passage 17 in the storage part. air pump. Suction force is provided by the air pump to guide the solution in the storage chamber 12 to the reaction chamber 21 through the valve 3, or the air pump provides blowing force to guide the solution in the reaction chamber 21 to the storage chamber 12 through the valve 3 Inside.
- the first end 171 of the air channel 17 in the storage part passes through one end of the groove 11 of the storage part 1 , and the first end 171 of the air channel 17 in the storage part is located at Between two adjacent storage bins 12.
- the top cover 4 is fixed on the end of the storage element 1 provided with the groove 11
- the base 2 is fixed on the end of the storage element 1 away from the top cover 4 .
- the storage part 1 is a cylindrical structure
- the cover surface of the top cover 4 covering the storage part 1 is circular
- the surface connecting the base 2 and the storage part 1 is circular
- the cover sheet 6 is round.
- the groove 11 provided in the storage member 1 is a cylindrical groove.
- the base 321 and the first gasket 3212 of the rotor 32 of the valve 3 are circular.
- microfluidic chip Some specific embodiments of the microfluidic chip will be described in detail below in conjunction with FIGS. 1 to 17 .
- the microfluidic chip includes a storage part 1 , a base 2 , a valve 3 , a top cover 4 , an amplification part 5 and a cover sheet 6 .
- the top cover 4 is fixed on the top of the storage part 1, and covers part of the top of the storage part 1, and the cover sheet 6 is arranged between the top cover 4 and the top of the storage part 1.
- the base 2 is fixedly arranged on the bottom of the storage part 1 .
- the middle position of the top of the storage part 1 is provided with a groove 11 which is concave to the bottom, and the valve 3 is arranged in the groove 11, and the operation part of the valve 3 protrudes from the groove 11 and extends to the top cover 4, and the top cover 4 is provided with a valve allowing
- the through hole through which the operating part of the valve 3 passes, or the external operating part extends into the through hole to connect the operating part of the valve 3 to operate the valve 3.
- the extension part 5 is pluggably arranged on the side of the storage part 1 , and the side part of the top cover 4 is provided with a gap for avoiding the extension part 5 .
- the top cover 4 includes a circular cover plate 47, the middle part of the cover plate 47 is provided with a second through hole 43, the second through hole 43 is used to pass through the operating part of the valve 3, or the external The operating part extends into the second through hole 43 and is connected to the operating part of the valve 3 .
- a circumferential sidewall 48 extending towards the storage part 1 is provided on the circumference of the cover plate 47 , and the circumferential sidewall 48 of the top cover 4 encloses the top part of the storage part 1 .
- the circumferential side wall 48 of the top cover 4 is provided with a clamping block, and the top of the storage part 1 is provided with a clamping slot, and the top cover 4 and the storage part 1 are fixedly connected through the clamping block and the clamping slot structure.
- the cover plate 47 of the top cover 4 is provided with a sample loading port 46, and the sample loading port 46 corresponds to the position of a storage bin 12 in a plurality of storage bins 12. Add the sample to be tested in the sample adding chamber.
- the cover plate 47 of the top cover 4 is also provided with a fifth through hole 44, the fifth through hole 44 is used to communicate with the air channel 17 in the storage part of the storage part 1, and the air channel 17 in the storage part communicates with the reaction chamber 21.
- the gas in the warehouse 21 communicates with the outside through the air channel 17 in the storage part and the fifth through hole 44.
- the fifth through hole 44 can be used as a pump interface, connected to an air pump, and the suction force is provided by the air pump to make the solution in the storage bin 12 pass through.
- the valve 3 leads into the reaction chamber 21 ; the blowing force is provided by an air pump, so that the solution in the reaction chamber 21 is led into the storage chamber 12 through the valve 3 .
- the storage part 1 is provided with a plurality of storage compartments 12 around the groove 11, therefore, correspondingly, a plurality of piercing needles 41 are connected to the cover plate 47 of the top cover 4, and each piercing needle 41 is arranged at intervals around the center line of the groove 11 , each puncture needle 41 corresponds to a storage bin 12 .
- Each piercing needle 41 can be connected to the ring part 45, the outer edge of the ring part 45 is connected to the cover plate of the top cover 4 through a plurality of first ribs 421, and the inner edge of the ring part 45 can be connected to the cover plate of the top cover 4 through a plurality of second ribs.
- the rib 422 is connected to a cylindrical member 49 .
- the puncture needle 41 is a hollow structure, that is, there is an air passage 411 inside the needle, and a third through hole 412 is provided on the puncture needle 41, and the third through hole 412 communicates with the air passage 411 inside the needle and the outside atmosphere.
- the piercing needle 41 comprises a first needle segment and a second needle segment, the radial dimension of the second needle segment being larger than the radial dimension of the first needle segment.
- the second needle section is connected to the ring member 45 , the first needle section is configured as a pointed needle for piercing the sealing membrane, and the third through hole 412 is provided on the second needle section.
- the cover sheet 6 is circular, and a fourth through hole 61 , a sixth through hole 62 and a seventh through hole 63 are formed in the middle thereof.
- the sixth through hole 62 is aligned with the second through hole 43 on the cover plate 47.
- the sixth through hole 62 is used to pass through the operating part of the valve 3, or allow an external operating member to extend into the sixth through hole 62 to connect to the valve 3. operation department.
- There are multiple fourth through holes 61 and each fourth through hole 61 corresponds to a piercing needle 41 .
- the seventh through hole 63 is aligned with the fifth through hole 44 on the top cover 4 and is used for communicating with the air channel 17 in the storage part.
- the radial dimension of the second needle section of the puncture needle 41 is greater than the radial dimension of the first needle section.
- the piercing needle 41 on the top cover 4 is used to pierce the sealing film on the storage bin 12, so that the storage bin 12 communicates with the atmosphere.
- the cover sheet 6 is used to cooperate with the puncture needle 41 of the top cover 4, and seal the storage bin 12 after the detection is completed.
- the storage member 1 is cylindrical, and a groove 11 is formed in the middle of the top end, and a plurality of storage bins 12 are arranged around the groove 11 .
- the storage bin 12 can be used as a sample loading bin and a reagent bin 121 .
- the multiple storage bins 12 include a sample loading bin and a plurality of reagent bins 121, the sample adding bin is used to add samples to be tested, the reagent bin 121 is used to store reagents for biochemical reactions, and the upper part of the reagent bin 121 The surface is sealed with a sealing film, and the lower surface is sealed.
- the second end 132 of the inner channel 13 of the first storage member communicates with the reagent chamber 121 through the lowest position of the reagent chamber 121 .
- the reagent compartment 121 selects an appropriate bonding method according to requirements to ensure that the packaging of the reagent is airtight and convenient for transportation and storage.
- the section of the storage bin 12 is oval.
- the section of the storage compartment 12 is narrow near the centerline of the groove 11 and wide at the part away from the centerline of the groove 11 .
- the size and distribution of storage bins 12 can be adjusted according to requirements.
- the storage part 1 is provided with an internal storage part air passage 17 , and the first end of the storage part internal air passage 17 is located between two adjacent storage bins 12 .
- the air channel 17 in the storage part communicates with the reaction chamber 21 .
- a slot 14 is provided on the side of the storage element 1 for inserting the expansion element 5 .
- the storage part 1 is provided with at least two first storage part inner flow channels 13 , and each first storage part inner flow channel 13 communicates with one storage bin 12 correspondingly.
- the first end 131 of each internal flow channel 13 of the first storage member passes through the bottom wall of the groove 11 for communicating with the internal flow channel 31 of the valve 3 .
- the second end 132 of the flow channel 13 in each first storage part communicates with the storage bin 12 through the side of the storage bin 12 adjacent to the base 2, and the second end 132 of the flow channel 13 in the first storage part communicates with the bottom of the storage bin 12. site to avoid reagent residue.
- the second end 132 of the flow channel 13 in the first storage part communicates with the position of the storage chamber 12 closest to the groove 11, so as to shorten the communication distance with the valve 3 and improve the detection efficiency.
- the storage part 1 is provided with a second storage part internal flow channel 15 , and a first end 151 of the second storage part internal flow channel 15 passes through the slot 14 for communicating with the expansion part internal flow channel 52 .
- the second end 152 of the inner channel 15 of the second storage member passes through the groove 11 for communicating with the inner channel 31 of the valve 3 .
- the storage part 1 is provided with a third storage part internal flow channel 16 , and the first end 161 of the third storage part internal flow channel 16 passes through the slot 14 for communication with the expansion part internal air channel 53 .
- the second end 162 of the inner channel 16 of the third storage member passes through the groove 11 for communicating with the inner valve air channel 34 of the valve 3 .
- the slot 14 is provided with a first buckle 141 for mating connection with the second buckle 54 on the extension part 5 .
- valve 3 is used to control the closure of the liquid circuit and communicate with each chamber.
- the valve 3 includes a rotor 32 and a valve cover 33 .
- the rotor 32 is rotatably disposed in the groove 11 .
- the rotor 21 includes a valve seat body 3211, a valve stem 322 and a first washer 3212.
- the first gasket 3212 is in the same shape as the bottom of the valve seat body 3211, both of which are circular.
- the valve seat body 3211 and the first gasket 3212 are fixedly arranged.
- the flow channel 31 in the valve is formed in the combined structure of the valve seat body 3211 and the first gasket 3212 .
- the radial dimension of the valve stem 322 is smaller than the radial dimension of the valve seat body 3211, one end of the valve stem 322 is fixedly connected to the valve seat body 3211, and the other end of the valve stem 322 is an operating part for passing through the first through hole 331, And it is connected with an external operating part.
- the valve 3 is provided with an in-valve channel 31 and an in-valve air channel 32 .
- the first end 311 of the flow channel 31 in the valve is located in the middle of the valve 3, and is aligned with the first end 181 of the flow channel 18 of the fourth storage part on the groove 11, and the flow channel 31 in the valve always passes through the fourth storage part
- the inner flow channel 18 communicates with the reaction chamber 21, and the second end 312 of the valve inner flow channel 31 can be selectively connected with any first storage member inner flow channel 13 or the second storage member inner flow channel during the rotation of the rotor 32. 15, and the second end 312 of the flow channel 31 in the valve is close to the outer edge of the valve 3 .
- the first end 32 of the air channel 32 in the valve communicates with the second end 162 of the flow channel 16 in the third storage part, and the air in the valve
- the second end of the channel 32 communicates with the first end 131 of the flow channel 13 in the first storage part
- the second end 132 of the flow channel 13 in the first storage part communicates with a storage bin 12 .
- the inner flow channel 13 of the storage part communicates with or communicates with the inner flow channel 15 of the second storage part to complete the liquid flow transfer during the detection process.
- the operating portion of the valve rod 322 is configured as a hexagonal structure.
- the circumferential direction of the valve seat body 3211 is provided with a boss 324, and the boss 324 has an arc-shaped outer contour to reduce the circumferential direction of the valve seat body 3211 and the circumference of the groove 11 during the rotation of the valve seat body 3211 relative to the groove 11. Friction against the side walls.
- the base 2 includes a chassis 22 , a support member 23 and a positioning member 24 .
- the surface of the chassis 22 is circular, and the chassis 22 is provided with a positioning protrusion 27 for connecting the storage part 1 .
- the supporting member 23 is disposed under the chassis 22 for supporting the chassis 22 and the entire microfluidic chip.
- the support member 23 is used as a supporting structure of the microfluidic chip, so that the microfluidic chip can be placed stably.
- the bottom of the support member 23 is also provided with a positioning groove 28, and the positioning groove 28 is used to cooperate with the placement platform on the detection equipment to complete the initial positioning of the microfluidic chip.
- a clamping groove 25 is formed between the support member 23 and the chassis 22. When the microfluidic chip is pushed into the detection device, the clamping groove 25 is used for positioning with the structure on the detection device, and then the microfluidic chip is Fixed to avoid the detection error caused by the movement of the microfluidic chip during the detection process and improve the detection consistency.
- the reaction chamber 21 is located at the bottom of the chassis 22 and protrudes downwards. It has a spherical crown structure. This structure can be coupled with the ultrasonic head to quickly achieve resonance and assist in sample lysis and magnetic bead mixing.
- the chassis 22 is provided with an inner flow passage in the chassis that communicates with the reaction chamber 21 .
- the first end 261 of the inner flow passage in the chassis is located in the middle of the chassis 22 , and the second end 262 of the inner flow passage in the chassis communicates with the reaction chamber 21 .
- the first end 261 of the inner channel of the chassis communicates with the inner channel 18 of the fourth storage member, and is aligned with the first end 311 of the inner channel 31 of the valve, so that the inner channel 31 of the valve communicates with the reaction chamber 21 all the time.
- the second end 262 of the flow channel in the chassis communicates with the reaction chamber 21 through the lowest part of the reaction chamber 21, so as to avoid the formation of a dead zone and cause the reagents to be exhausted.
- the positioning part 24 is arranged on the supporting part 23, and is used for positioning when installing the microfluidic chip on the detection device.
- the above-mentioned top cover 4 is fixed on the end of the storage part 1 provided with the groove 11 , the base 2 is fixed on the end of the storage part 1 away from the top cover 4 , and the valve 3 is set in the groove 11 .
- the top cover 4, the storage part 1, the base 2 and the valve 3 form the main structure of the microfluidic chip.
- the amplification member 5 is a thin-sheet structure, which is used to realize rapid heating and cooling amplification.
- the expansion part 5 is pluggably connected to and detachable from the slot 14 of the storage part 1 .
- the amplification part 5 can be separated from the main structure of the microfluidic chip, and can be produced and bonded with a material different from the main structure.
- the expansion part 5 is provided with an expansion chamber 51, and the amplification chamber 51 is in the shape of a sheet, so that it can have a larger contact surface with the heat source and thermal conductivity.
- the expansion part 5 is provided with an expansion part internal flow channel 52 communicating with the amplification chamber 51 , and the expansion part internal flow channel 52 is in communication with the first end 151 of the second storage part internal flow channel 15 .
- the expansion part 5 is provided with an internal air channel 53 of the expansion part communicating with the expansion chamber 51 , and the internal air channel 53 of the expansion part is in communication with the first end 161 of the internal flow channel 16 of the third storage part.
- connection between the main structure of the microfluidic chip and the expansion part 5 can be fixed by secondary injection molding or bonding, etc., to fix the soft rubber second gasket 7 to ensure that the internal flow channel 52 of the expansion part and the air in the expansion part at the connection Airtightness of Road 53.
- the cross sections of the first buckle 141 provided in the slot 14 and the second buckle 54 provided on the expansion part 5 can be triangular. After the expansion part 5 is inserted into the slot 14, the first buckle 141 and the second buckle The buckles 54 limit each other to prevent the expansion part 5 from being pulled out from the slot 14 .
- Some embodiments also provide a microfluidic chip detection system, which includes a detection device and the above-mentioned microfluidic chip, and the detection device includes an operating table for accommodating the microfluidic chip, and an operating member for operating the valve 3 .
- the microfluidic chip detection system provided by the embodiments of the present disclosure has low requirements for operators. It only needs to add the sample to be tested, put the microfluidic chip into the detection device, and click the start button to start including extraction and amplification. detection process.
- the operator pays attention to the positioning structure corresponding to the base 2 of the microfluidic chip and the detection equipment, and lays it flat on the tray of the detection equipment to complete the initial positioning. After clicking the start button, the tray enters the working area of the detection device, and at the same time, the clamping groove 25 of the base 2 cooperates with the structure on the detection device to clamp and fix the microfluidic chip.
- the detection process starts, the air pump is connected to the air pump interface on the microfluidic chip, the puncture needle 41 on the top cover 4 of the microfluidic chip is under downward pressure, the first rib 421 breaks, and the puncture needle 41 is separated from the top cover 4. Puncture the sealing film on the storage compartment 12, and the storage compartment 12 communicates with the air through the needle airway 411 and the third through hole 412 in the puncture needle 41 to prepare for the reagent release.
- the magnetic bead method is used for nucleic acid extraction.
- the ultrasonic head will couple and resonate with the reaction compartment 21.
- the spherical crown structure of the reaction compartment 21 can provide better support. Avoid wall deformation during the ultrasonic process, and at the same time, the contact surface has good consistency. Under the effect of ultrasound, the vibration of the wall surface drives the reagents and magnetic beads in the reaction chamber 21 to oscillate, and the auxiliary lysis of the sample and the mixing of the magnetic beads can be completed within a few seconds.
- the waste liquid after reaction will be transferred from the reaction chamber 21 back to the storage chamber 12, and then sealed by the rotary valve 3.
- the pressing module in the testing device will act on the piercing needle 41 on the top cover 4 of the microfluidic chip again, and the downward pressure will cause the second rib 422 to break, and the piercing needle 41 will continue to move down, piercing
- the second needle section of the needle 41 forms an interference fit with the cover piece 6, and the cover piece 6 covers the third through hole 412 on the second needle section, so that the storage bin 12 is isolated from the atmosphere, and the reaction waste liquid in the storage bin 12 is prevented from leaking .
- the flow channel in the present disclosure can be used for liquid transmission or gas transmission, and similarly, the air channel can be used for gas transmission or liquid transmission.
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Abstract
Description
Claims (22)
- 一种微流控芯片,包括:储存件(1),其上设有凹槽(11),围绕所述凹槽(11)设有至少两个储存仓(12);底座(2),设于所述储存件(1)背离所述凹槽(11)的一端,所述底座(2)上设有反应仓(21);以及阀(3),设于所述凹槽(11)内,所述阀(3)被配置为可操作地将至少两个储存仓(12)中的任一个与所述反应仓(21)连通。
- 根据权利要求1所述的微流控芯片,其中所述储存件(1)内设有至少两个第一储存件内流道(13),每个第一储存件内流道(13)对应连通一个储存仓(12),所述阀(3)内设有连通所述反应仓(21)的阀内流道(31),所述阀(3)被配置为可操作地将所述阀内流道(31)与任一第一储存件内流道(13)连通。
- 根据权利要求2所述的微流控芯片,其中每个第一储存件内流道(13)的第一端(131)穿过所述凹槽(11)的底壁,所述阀(3)被配置为可操作地将所述阀内流道(31)与所述第一储存件内流道(13)的第一端(131)连通,每个第一储存件内流道(13)的第二端(132)经所述储存仓(12)邻近所述底座(2)的一侧与所述储存仓(12)连通。
- 根据权利要求3所述的微流控芯片,其中所述第一储存件内流道(13)的第二端(132)连通所述储存仓(12)的位置最低的部位。
- 根据权利要求3或4所述的微流控芯片,其中所述阀内流道(31)的第一端(311)和第二端(312)均穿过所述阀(3)邻近所述凹槽(11)的底壁的一端,所述阀内流道(31)的第一端(311)与所述反应仓(21)连通,所述阀内流道(31)的第二端(312)可操作地与任一第一储存件内流道(13)连通,所述阀内流道(31)的第一端(311)位于所述阀(3)的中部,所述阀内流道(31)的第二端(312)靠近所述阀(3)的外缘。
- 根据权利要求1至5任一项所述的微流控芯片,其中所述阀(3)包括:转子(32),可转动地设于所述凹槽(11)内,所述转子(32)包括阀座(321)和阀杆(322),所述阀杆(322)连接所述阀座(321);以及阀盖(33),连接所述凹槽(11)的周向侧壁,且抵接所述阀座(321),将所述 阀座(321)限位在所述阀盖(33)与所述凹槽(11)的底壁之间,所述阀盖(33)上设有第一通孔(331),所述阀杆(322)的操作部穿出所述第一通孔(331),所述阀杆(322)的操作部被配置为与外部的操作件连接。
- 根据权利要求6所述的微流控芯片,其中所述阀盖(33)与所述阀座(321)的周向边缘抵接。
- 根据权利要求1至7任一项所述的微流控芯片,还包括密封膜,所述至少两个储存仓(12)包括试剂仓(121),所述密封膜被配置为密封所述试剂仓(121),所述微流控芯片还包括顶盖(4)和刺破针(41),所述顶盖(4)设于所述储存件(1)设有所述凹槽(11)的一端,所述刺破针(41)连接于所述顶盖(4),所述刺破针(41)被配置为在外力作用下压向所述密封膜,以刺破所述密封膜。
- 根据权利要求8所述的微流控芯片,其中所述顶盖(4)包括第一筋条(421),所述刺破针(41)连接于所述第一筋条(421),所述第一筋条(421)被配置为在外力作用下断开,以使所述刺破针(41)脱离所述顶盖(4)压向所述密封膜。
- 根据权利要求8或9所述的微流控芯片,其中所述顶盖(4)的中部设有第二通孔(43),所述第二通孔(43)被配置为允许外部的操作件穿过,以操作所述阀(3)。
- 根据权利要求8至10任一项所述的微流控芯片,其中所述刺破针(41)内设有针内气道(411),所述刺破针(41)与所述顶盖(4)连接的部位附近设有连通所述刺破针(41)外部和所述针内气道(411)的第三通孔(412)。
- 根据权利要求11所述的微流控芯片,还包括盖片(6),所述盖片(6)设于所述顶盖(4)内,所述盖片(6)上设有允许所述刺破针(41)穿过的第四通孔(61),所述刺破针(41)被配置在外力作用下压向所述密封膜,且在刺破密封膜后继续压向密封膜,以使所述第三通孔(412)被所述盖片(6)密封。
- 根据权利要求1至12任一项所述的微流控芯片,其中所述反应仓(21)向远离所述储存件(1)的一侧凸起。
- 根据权利要求13所述的微流控芯片,其中所述反应仓(21)为球冠状结构。
- 根据权利要求1至14任一项所述的微流控芯片,还包括扩增件(5),所述扩增件(5)设有扩增仓(51),所述储存件(1)的侧部设有插槽(14),所述插槽(14)位于所述相邻两个储存仓(12)之间,所述扩增件(5)与所述插槽(14)插接,所述阀(3)被配置为可操作地将所述反应仓(21)与所述扩增仓(51)连通。
- 根据权利要求15所述的微流控芯片,其中所述储存件(1)设有第二储存件内流道(15),所述第二储存件内流道(15)的第一端(151)穿过所述插槽(14),所述第二储存件内流道(15)的第二端(152)穿过所述凹槽(11),所述扩增件(5)设有连通所述扩增仓(51)的扩增件内流道(52),所述扩增件内流道(52)与所述第二储存件内流道(15)的第一端(151)连通,所述阀(3)被配置为可操作地连通所述第二储存件内流道(15)的第二端(152),以将所述反应仓(21)内的溶液通过所述第二储存件内流道(15)和所述扩增件内流道(52)引向所述扩增仓(51)。
- 根据权利要求16所述的微流控芯片,其中所述储存件(1)设有第三储存件内流道(16),所述第三储存件内流道(16)的第一端(161)穿过所述插槽(14),所述第三储存件内流道(16)的第二端(162)穿过所述凹槽(11),所述扩增件(5)设有连通所述扩增仓(51)的扩增件内气道(53),所述扩增件内气道(53)与所述第三储存件内流道(16)的第一端(161)连通,所述阀(3)被配置为可操作地连通所述第三储存件内流道(16)的第二端(162),以将所述扩增仓(51)的气体通过所述扩增件内气道(53)和所述第三储存件内流道(16)引向一储存仓(12)。
- 根据权利要求15至17任一项所述的微流控芯片,其中所述阀(3)内设有连通所述反应仓(21)的阀内流道(31),所述阀(3)内还设有阀内气道(32),所述阀(3)被配置为可操作地将所述阀内流道(31)连通所述反应仓(21)和所述扩增仓(51),且将所述阀内气道(32)连通所述扩增仓(51)和一储存仓(12)。
- 根据权利要求1至18任一项所述的微流控芯片,其中所述储存件(1)设有储存件内气道(17),所述储存件内气道(17)连通所述反应仓(21),所述储存件内气道(17)被配置为连通外部的气泵。
- 根据权利要求19所述的微流控芯片,其中所述储存件内气道(17)的第一端(171)穿过所述储存件(1)设置凹槽(11)的一端,所述储存件内气道(17)的第一端(171)位于相邻两个储存仓(12)之间。
- 根据权利要求8至12任一项所述的微流控芯片,其中所述顶盖(4)固定设于所述储存件(1)设有所述凹槽(11)的一端,所述底座(2)固定设于所述储存件(1)远离所述顶盖(4)的一端。
- 一种微流控芯片检测系统,包括检测设备和根据权利要求1至21任一项所述的微流控芯片,所述检测设备包括用于容纳所述微流控芯片的操作台,以及用于操作 所述阀(3)的操作件。
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| US18/697,740 US20240408594A1 (en) | 2021-11-17 | 2022-11-11 | Microfluidic chip and microfluidic chip detection system |
| AU2022390503A AU2022390503B2 (en) | 2021-11-17 | 2022-11-11 | Microfluidic chip and microfluidic chip detection system |
| CA3232120A CA3232120A1 (en) | 2021-11-17 | 2022-11-11 | Microfluidic chip and microfluidic chip testing system |
| JP2024523643A JP7733884B2 (ja) | 2021-11-17 | 2022-11-11 | マイクロ流体チップ及びマイクロ流体チップ検出システム |
| EP22894720.6A EP4434626A4 (en) | 2021-11-17 | 2022-11-11 | MICROFLUIDIC CHIP AND MICROFLUIDIC CHIP TESTING SYSTEM |
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| CA3232120A1 (en) | 2023-05-25 |
| AU2022390503A1 (en) | 2024-03-28 |
| JP2024538204A (ja) | 2024-10-18 |
| EP4434626A1 (en) | 2024-09-25 |
| KR20240066173A (ko) | 2024-05-14 |
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| AU2022390503B2 (en) | 2025-06-26 |
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