WO2022071883A1 - Dispositif microfluidique, trousse de réactifs et leur procédé de préparation - Google Patents

Dispositif microfluidique, trousse de réactifs et leur procédé de préparation Download PDF

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Publication number
WO2022071883A1
WO2022071883A1 PCT/SG2021/050587 SG2021050587W WO2022071883A1 WO 2022071883 A1 WO2022071883 A1 WO 2022071883A1 SG 2021050587 W SG2021050587 W SG 2021050587W WO 2022071883 A1 WO2022071883 A1 WO 2022071883A1
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WO
WIPO (PCT)
Prior art keywords
input
channel
output
blocking body
wall
Prior art date
Application number
PCT/SG2021/050587
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English (en)
Chinese (zh)
Inventor
唐晓燕
Original Assignee
新加坡正煦诊断有限公司
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 新加坡正煦诊断有限公司 filed Critical 新加坡正煦诊断有限公司
Priority to BR112023005584A priority Critical patent/BR112023005584A2/pt
Priority to EP21876105.4A priority patent/EP4223418A1/fr
Publication of WO2022071883A1 publication Critical patent/WO2022071883A1/fr

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Classifications

    • 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
    • B01L3/502738—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
    • 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
    • B01L2200/12—Specific details about manufacturing devices
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/16—Reagents, handling or storing thereof
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/12—Specific details about materials
    • B01L2300/123—Flexible; Elastomeric
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/06—Valves, specific forms thereof
    • B01L2400/0633—Valves, specific forms thereof with moving parts
    • B01L2400/0655—Valves, specific forms thereof with moving parts pinch valves

Definitions

  • the present invention relates to a microfluidic device, and more particularly, to a microfluidic kit that can be used for polymerase chain reaction and a preparation method thereof.
  • Microfluidic devices are used for microfluidic experiments and sample detection in the biological or medical fields, for example, as a container for liquid samples, for carrying out polymerase chain reaction. With the development of detection technology, the demand for microfluidic detection is increasing day by day, and the application of microfluidic devices in microfluidic experiments is more and more extensive.
  • the microfluidic devices used in the current polymerase chain reaction include various types of microfluidic valves, such as pinch valves that close the microfluidic channel through a stopper such as a thimble, and control the opening and closing of the membrane in the microfluidic channel to control the microfluidic channel.
  • Valve devices for fluid passages, etc. Known microfluidic devices for biological and medical sample detection have complex structures, low valve closure reliability, and high costs. Therefore, it is necessary to provide a microfluidic device with convenient operation, high reliability and low cost, so as to improve the detection efficiency of biological and medical samples.
  • the present invention provides a kit for the detection of biological samples or medical samples, such as for polymerase chain reaction.
  • the kit of the present invention includes a plurality of reagent containing and carrying units, and at least one reagent containing and carrying unit includes a substrate, formed in A fluid containing cavity in the substrate, an input channel and an output channel formed in the substrate, and a reagent contained in the fluid containing cavity.
  • the input channel and the output channel are respectively communicated with the fluid accommodating cavity.
  • the first inner wall of the input channel at one input segment abuts the second inner wall of the input channel at the input shut-off segment, so that the input channel is closed.
  • the first inner wall at one output segment abuts the second inner wall of the output segment so that the output channel is closed. Closure of the input channel and closure of the output channel seal the reagent within the fluid containment cavity.
  • the input channel is located on the first inner wall of the segment to form an input end blocking body in the input channel, the input end blocking body is located against the input channel on the second inner wall of the segment and closes the input a channel;
  • the output channel is located on the first inner wall of the segment to form an output end blocking body in the output channel, the output end blocking body abuts the output channel on the second inner wall of the segment and closes the output channel.
  • the input end blocking body is integrated with the second inner wall of the input channel located in the segment and blocks the input channel.
  • the blocking body at the input end and the second inner wall of the input channel located in the segment can be melted in a heated state and fused together after plastic deformation under the action of external pressure.
  • the fused input end plugging body and the second inner wall of the input channel located in the segment are solidified into one body when the temperature returns to normal temperature, so as to form the input end plugging body in the input channel.
  • the output end blocking body is integrated with the second inner wall of the output channel at the segment and blocks the output channel.
  • the blocking body of the output end and the second inner wall of the output passage located in the segment can be melted in a heated state and fused together after plastic deformation under the action of external pressure.
  • the fused output end plugging body and the second inner wall of the output channel located in the segment are solidified into one body when the temperature returns to normal temperature, so as to form the output end plugging body in the output channel.
  • the input end blocking body includes a first blocking body and a second blocking body arranged at intervals, and the first blocking body and the second blocking body cut the input channel into a first input section, a second input section and a third input section, the second input section is enclosed between the first blocking body and the second blocking body, and the third input section communicates with the fluid accommodating chamber .
  • the first blocking body and the second blocking body of the input end are respectively integrated with the second inner wall of the input channel and block the input channel.
  • the first blocking body and the second blocking body of the input end and the second inner wall of the input channel can be melted in a heated state and merged into one after plastic deformation under the action of external pressure.
  • the first blocking body and the second blocking body of the input end and the second inner wall of the input channel, which are respectively fused into one, are solidified into one body when the temperature returns to normal temperature, so as to form the input end in the input channel.
  • the output end blocking body includes a first blocking body and a second blocking body arranged at intervals, and the first blocking body and the second blocking body cut the output channel into a first output section and a third output section, so The first output section communicates with the fluid accommodating cavity, and the second output section is enclosed between the first blocking body and the second blocking body.
  • the first blocking body and the second blocking body of the output end are respectively integrated with the second inner wall of the output channel and block the output channel.
  • the first blocking body and the second blocking body of the output end and the second inner wall of the output channel can be melted in a heated state and fused into one after plastic deformation under the action of external pressure.
  • the first blocking body and the second blocking body of the output end and the second inner wall of the output channel which are respectively integrated into one, are solidified into one body when the temperature returns to normal temperature, so as to form the output end in the output channel.
  • the present invention provides a microfluidic device for containing and carrying liquid biological samples or medical samples for detection operations, such as polymerase chain reaction detection.
  • the microfluidic device of the present invention includes a plurality of microfluidic units, at least one microfluidic unit includes a substrate, a fluid containing cavity formed in the substrate, an input channel and an output channel formed in the substrate, and inlets and outlets formed on the substrate. Both sides of the input channel respectively have a first inner wall and a second inner wall spaced apart from each other. Both sides of the output channel respectively have a first inner wall and a second inner wall spaced apart from each other.
  • An input passage communicates between the inlet and the fluid containing chamber.
  • the output channel communicates between the fluid containing chamber and the outlet.
  • the substrate is located in the A segment of the input channel can be plastically deformed under the action of external pressure, so that the first inner wall of the input channel located in the segment abuts the second inner wall of the input channel located in the segment to close the said input channel input channel.
  • a segment of the base plate located in the output channel can undergo plastic deformation under the action of external pressure, so that the first inner wall of the output channel located in the segment abuts against the second inner wall of the output channel located in the segment an inner wall to close the output channel, thereby closing the fluid containment cavity.
  • the plastic deformation of the first inner wall of the input channel located in the segment in the direction of the input channel toward the second inner wall can form an input end blocking body in the input channel.
  • the input end plug is located against the input channel on the second inner wall of the segment to close the input channel.
  • the plastic deformation of the first inner wall of the output channel located in the segment in the direction of the output channel toward the second inner wall can form an output end blocking body in the output channel.
  • the output end plug is located against the output channel on the second inner wall of the segment, thereby closing the output channel.
  • the input end blocking body cuts the input channel into a first input section and a second input section and blocks the liquid flow between the first input section and the second input section.
  • the first input section communicates with the inlet, and the second input section communicates with the fluid containing chamber.
  • the output end blocking body cuts the output channel into a first output section and a second output section and blocks the liquid flow between the first output section and the second output section.
  • the first output section communicates with the fluid accommodating chamber, and the second input section communicates with the outlet.
  • the input end blocking body includes a first blocking body and a second blocking body arranged at intervals. The first blocking body and the second blocking body cut the input channel into a first input section, a second input section and a third input section. A first input section communicates with the inlet. The second input section is enclosed between the first blocking body and the second blocking body. The third input section communicates with the fluid containing chamber.
  • the output end blocking body includes a first blocking body and a second blocking body arranged at intervals. The first blocking body and the second blocking body cut the output passage into a first output section, a second output section and a third output section.
  • the present invention provides a method for preparing a kit for the detection of biological samples or medical samples, eg, for polymerase chain reaction.
  • the method includes filling a fluid containing chamber with reagents and test samples, squeezing the input channel, causing plastic deformation of the input channel, so that the first inner wall of the input channel abuts the second inner wall to close the input channel, and squeezing the output channel, causing the output channel to plastically deform, so that the first inner wall of the output channel abuts the second inner wall to close the output channel, thereby sealing the reagent and the sample in the inside the fluid holding chamber.
  • like numerals refer to structurally identical or functionally similar components or method steps.
  • FIG. 1 is a perspective view of a microfluidic device according to one embodiment of the present invention
  • FIG. 2A is an enlarged perspective view of an exemplary microfluidic unit of the microfluidic device shown in FIG. 1
  • FIG. 2B is a cross-sectional perspective view along AA and BB of FIG. 2A
  • FIG. 3A 2A is a perspective view of the state before the local plastic deformation of the microfluidic unit shown in FIG. 2A
  • FIG. 3B is a state perspective view of the microfluidic unit shown in FIG.
  • FIG. 3A before receiving the local plastic deformation treatment, showing the indenter and the anvil for the plastic deformation treatment;
  • Fig. 3C is a perspective view of the microfluidic unit shown in Fig. 3A after receiving local plastic deformation treatment, showing the indenter and anvil used for plastic deformation treatment;
  • Fig. 3D is the microfluidic unit shown in Fig. 3A after receiving local plastic deformation treatment;
  • Fig. 3E is a longitudinal sectional view of Fig. 3D;
  • Fig. 4A is a partially enlarged perspective view of parts 4A and 4B of Fig. 3C;
  • Fig. 4B is a perspective view of the indenter of Fig. 4A;
  • Fig. 5 is a partially enlarged perspective view of part 5 of Fig.
  • FIG. 10A is a perspective view of a microfluidic device according to another embodiment of the present invention
  • Figure 12A is an enlarged view of an example microfluidic unit of the microfluidic device shown in Figure 11 12B is a cross-sectional perspective view of FIG. 12A along CC and DD;
  • FIG. 12A is a perspective view of a microfluidic device according to another embodiment of the present invention
  • Figure 15 is a partial enlarged perspective view of the part 15 of Figure 13E;
  • Figure 16 is a partial cross-sectional view of Figure 14A;
  • Figure 17 is a partial enlarged perspective view of the part 17 of Figure 15;
  • Fig. 18 is a partial cross-sectional view of Fig. 14A;
  • Fig. 19 is a partial enlarged perspective view of portion 18 of Fig. 13E;
  • Fig. 20A is a partial enlarged perspective view of portion 20A of Fig. 19;
  • Fig. 20B is a further or alternative schematic view of the example shown in Fig. 20A;
  • Fig. 21 is a perspective view of a kit according to an embodiment of the present invention;
  • Fig. 21 is a perspective view of a kit according to an embodiment of the present invention;
  • Fig. 21 is a perspective view of a kit according to an embodiment of the present invention;
  • Fig. 21 is a perspective view of a kit according to an embodiment of the present invention;
  • FIG. 22A is an enlarged perspective view of an exemplary reagent accommodating and carrying unit of the kit shown in Fig. 21;
  • Fig. 22B is a schematic diagram of the kit with an additional enlarged part of Fig. 22A;
  • Fig. 23A Fig. 22A is an enlarged partial cross-sectional view along EE;
  • Fig. 23B is a further or alternative schematic view of the example shown in Fig. 23A;
  • Fig. 24 is a partial cross-sectional enlarged view along FF of Fig. 22A.
  • Figure 25 is a flow chart of a method for preparing a kit according to an embodiment of the present invention.
  • FIG. 1 is a perspective view of a microfluidic device according to one embodiment of the present invention.
  • FIG. 2A is an enlarged perspective view of an exemplary microfluidic unit in the microfluidic device shown in FIG. 1
  • FIG. 2B is an enlarged perspective view of a cross-section taken along the AA direction of FIG. 2A.
  • the microfluidic device 100 includes a plurality of microfluidic units 102 o having the same structure.
  • Each microfluidic unit 102 includes a substrate 110 , a fluid accommodating cavity 150 formed in the substrate 110 , and a The input channel 130 and the output channel 170 in 150 , and the fluid inlet 120 and the fluid outlet 180 formed on the substrate 110 .
  • the input channel 130 has a first inner wall 113a and a second inner wall 113bo spaced apart from each other.
  • the output channel 170 has a first inner wall 117a and a second inner wall 117bo spaced apart from each other.
  • the output channel 170 is communicated between the fluid containing chamber 150 and the outlet 180 .
  • the substrate 110 may be made of solid light-transmitting or non-light-transmitting materials such as transparent plastic, plexiglass, and the like.
  • the fluid containing chamber 150, the input channel 130 and the output channel 170 are formed by injection molding, molding or Other processing processes form holes inside the substrate 110 .
  • the fluid holding chamber 150, the input channel 130 and the output channel 170 can contain liquids, such as for polymerase chain reaction
  • the microfluidic device 100 After being filled with liquid biological samples or medical samples and reagents, the microfluidic device 100 is used to carry the samples and reagents to detect the samples under certain reaction conditions.
  • the material from which the substrate 110 is made has the property of being plastically deformed when subjected to a certain external pressure and/or temperature. For example, when a segment 135 of the substrate 110 located in the input channel 130 is squeezed by external pressure, plastic deformation may occur, so that the inner wall of the input channel 130 located in this segment 135 is deformed and moved toward the interior of the input channel 130, resulting in the input channel.
  • the cross-section of the input channel 130 is reduced until the cross-section is reduced to zero, thereby closing the cross-section of the input channel 130 .
  • a segment 175 of the substrate 110 located in the output channel 170 is squeezed by external pressure, plastic deformation may occur, resulting in the reduction of the cross-section of the output channel 170 until the cross-section of the output channel 170 is reduced to zero, reducing the cross-section of the input channel 170 Section is closed.
  • indenter 50F is applied by indenter 50 to segment 135 of one input channel 130 of microfluidic device 100 placed on anvil 60 .
  • the front end of the indenter 50 has a convex portion 52 .
  • the pressing head 50 presses the upper surface 111 of the substrate 110 .
  • the external pressure 50F reaches the plastic deformation threshold of the substrate 110 , as shown in FIG. 2A , FIG. 2B , FIG. 5 , FIG. 6 and FIG.
  • the depression 112 corresponding to the shape of the convex portion 52 of the indenter 50, and at the same time, the substrate material at the lower part of the depression 112 is pressed toward the inside of the input channel 130, so that the first inner wall 113a of the input channel 130 located in the segment 135 abuts the input channel 130 is located on the second inner wall 113b of the segment 135 and forms an input end blocking body 132o in the input channel 130.
  • the input end blocking body 132 occupies the cross section of the input channel 130, thereby blocking and closing the input channel 130o Similarly, as shown in FIG. 2A , FIG. 2B , FIG. 8 , FIG. 9 and FIG.
  • the external pressure 50F is applied to an output channel 170 of the microfluidic device 100 placed on the anvil 60 through the pressure head 50 One segment 175. Under the supporting action of the anvil 60 , the pressing head 50 presses the upper surface 111 of the substrate 110 .
  • the indenter 50 causes local plastic deformation of the substrate 110 , presses the depression 162 on the upper surface 111 of the substrate 110 , and at the same time pushes the substrate material in the lower part of the depression 162 toward the inside of the output channel 170 Extrusion, so that the first inner wall 117a of the output channel 170 at the segment 175 abuts the second inner wall 117b of the input channel 170 at the segment 175 and forms an output end blocking body 172o in the output channel 170.
  • the output end blocking body 172 occupies the output channel The cross-section of 170, thereby blocking and closing the output channel 170o After the input channel 130 and the output channel 170 are closed in the above manner, the fluid accommodating cavity 150 connected between the input channel 130 and the output channel 170 is blocked by the input end blocking body 132 and the output channel 170, respectively.
  • the output end blocking body 172 is sealed, so that the reagent filled in the fluid containing chamber 150 and the gas that may exist are sealed in the fluid containing chamber 150 without leakage.
  • the pressure of the indenter 50 can be set correspondingly according to the plastic deformation characteristics of the substrate material.
  • the indenter can also apply pressure to the substrate 110 in a heated state, so as to more effectively achieve local plastic deformation of the substrate, so that the input channel and the output channel are affected by their respective opposite inner side walls. Abut against each other and close to seal the fluid containing chamber 150o.
  • the input end blocking body 132 cuts the input channel 130 into a first input section 131 and a second input section 133o
  • the first input section 131 communicates with the inlet 120
  • the second input section 133 communicates with the fluid containing chamber 150 .
  • the input end blocking body 132 forms a fluid flow barrier between the first input section 131 and the second input section 133 .
  • the output end blocking body 172 divides the output channel 170 into a first output section 171 and a second output section 173 .
  • the output end blocking body 172 forms a flow barrier between the first output section 171 and the second output section 173 .
  • the temperature of the indenter can be set to cause local melting of the part where the substrate is in contact with the indenter, so that the indenter applies pressure to the substrate 110 to squeeze the input channel 130 and the output channel 170 process, will pass through segments 135 respectively located in
  • the input end blocking body 132 and the output end blocking body 172 formed by the deformation of the first inner walls 113a and 117a of the segment 175 are partially melted, and at the same time, the second inner wall 113b, The contact parts 113d and 117d of 117b are partially melted.
  • the partially melted input end blocking body 132 and the output end blocking body 172 are respectively fused with the partially melted contact parts 113d and 117d.
  • the partially melted input end blocking body 132 and the output end blocking body 172 are respectively fused and solidified with the contact parts 113d and 117d.
  • Integral closed ends 132a and 172a are respectively formed at the positions of the input channel 130 and the output channel 170 pressed by the indenter, thereby blocking the input channel 130 and the output channel 170 respectively, as shown in FIG. 10B .
  • the input channel 130 and the output channel 170 have a Local plastic deformation occurs under the extrusion of the pressure head set at temperature and pressure, and the formed input end plug body 132, output end plug body 172 and contact parts 113d, 117d are then heated and melted at the preset temperature, and at the same time the pressure head is heated and melted.
  • the pressure head Under the pressing action of the pressure head, they are respectively integrated into one body, so that integrated closed ends 132a and 172a are formed at the positions where the input channel 130 and the output channel 170 are pressed by the pressure head, and the samples, reagents and reactants are sealed in the fluid accommodating cavity. Since they are all made of the same material, that is, made of the material of the substrate 110, the integrated closed ends 132a and 172a formed after being melted by heat and deformed under pressure and the substrate 110 constitute the input channel 130, the fluid accommodating chamber 150 and the output channel 170 The other parts have the same structural strength.
  • the closed ends 132a and 172a of the microfluidic device 100 of this embodiment which are deformed under pressure and melted by heat, are fused to the liquid filled in the fluid chamber 150, such as samples, reagents and reactions for polymerase chain reaction.
  • the agent provides the same sealing effect as the rest of the input channel 130 , the fluid containment chamber 150 and the output channel 170 .
  • the anvil may be a bar-shaped anvil slightly wider than segments 135/175 as shown in Figures 6 and 9
  • the present invention provides a microfluidic device.
  • the microfluidic device 200 As shown in FIG. 11 , FIG. 12A and FIG. 12B , the microfluidic device 200 according to the present embodiment includes a plurality of microfluidic units 202 with the same structure.
  • Each microfluidic unit 202 includes a substrate 210, a fluid containing chamber 250 formed in the substrate, an input channel 230 and an output channel 270 formed in the substrate 210, and an inlet 220 and an outlet 280 formed on the substrate 210.
  • the input channel 230 has The first inner wall 213a and the second inner wall 213b are spaced apart from each other.
  • the output channel 270 has a first inner wall 217a and a second inner wall 217b spaced apart from each other.
  • the input channel 230 is communicated between the inlet 220 and the fluid containing cavity 250 .
  • the output channel 270 is communicated between the fluid containing chamber 250 and the outlet 280 .
  • the substrate 210 may be made of solid light-transmitting or non-light-transmitting materials such as transparent plastic, organic glass, and the like.
  • the fluid accommodating cavity 250 , the input channel 230 and the output channel 270 are holes formed inside the substrate 210 by injection molding, molding or other processing processes.
  • the fluid containing chamber 250, the input channel 230, and the output channel 270 may contain liquids, such as biological or medical samples, reagents, and the like for polymerase chain reaction. After being filled with liquid biological or medical samples and reagents, the microfluidic device 200 is used to carry the samples and reagents to detect the samples and reagents.
  • the material from which the substrate 210 is made has the property of plastically deforming when subjected to a certain external pressure and/or temperature. For example, when a segment 235 of the substrate 210 located in the input channel 230 is squeezed by external pressure, plastic deformation may occur, so that the inner wall of the input channel 230 located in the segment 235 is deformed and moved toward the interior of the input channel 230, thereby causing the input The cross section of the channel 230 decreases until the cross section decreases to zero, closing the cross section of the input channel 230 .
  • the external pressure The force 70F is applied by the indenter 70 to a segment 235o of an input channel 230 of the microfluidic device 200 placed on the anvil 60.
  • the front end of the indenter 70 has two protrusions 74, 76 spaced apart.
  • the pressing head 70 presses the upper surface 211 of the substrate 210 .
  • the external pressure 70F reaches the plastic deformation threshold of the substrate 210 , as shown in FIG. 12A , FIG. 12B , FIG. 15 , FIG. 16 and FIG.
  • the spaced recesses 212, 218 correspond to the shapes of the protrusions 74, 76 of the indenter 70 while simultaneously pressing the substrate material below the recesses 212, 218 in a direction inside the input channel 230 so that the input channel 230 is located at the segment 235
  • the first inner wall 213 a of the first inner wall 213 a of the input channel 230 is located at the second inner wall 213 b of the segment 235 and forms the input end first blocking body 232 and the input end second blocking body 238 in the input channel 230 .
  • the first blocking body 232 of the input end and the second blocking body 238 of the input end occupy the cross section of the input channel 230, thereby blocking and closing the input channel 230o.
  • an external pressure 70F is applied through a pressure head 70 to a segment 275 of an output channel 270 of the microfluidic device 200 placed on the anvil 60 .
  • the pressing head 70 presses the upper surface 211 of the substrate 210 .
  • the indenter 70 causes local plastic deformation of the substrate 210, presses the depressions 262, 268 on the upper surface 211 of the substrate 210, and simultaneously pushes the substrate material under the depressions 262, 268 to the output channel 270 inside the direction of extrusion, so that the first inner wall 217a of the output channel 270 at the segment 275 abuts the second inner wall 217b of the input channel 270 at the segment 275 and forms the output end blocking body 272, 278o in the output channel 170.
  • the blocking bodies 272 and 278 occupy the cross section of the output channel 270, thereby blocking and closing the output channel 270.
  • the fluid containing cavity 250 communicated between the input channel 230 and the output channel 270 They are sealed by the input end blocking bodies 212 and 218 and the output end blocking bodies 272 and 278 respectively, so that the reagents and samples filled in the fluid containing chamber 250 and possible gas are sealed in the fluid containing chamber 250 without leakage.
  • the pressure of the indenter 70 can be set correspondingly according to the plastic deformation characteristics of the substrate material. If necessary, or according to the plastic deformation characteristics of the substrate material, the indenter can also apply pressure to the substrate 210 in a heated state to more effectively achieve localized plastic deformation of the substrate, so that the input channel and the output channel are affected by their respective opposite inner side walls. close against each other, sealing the fluid holding chamber
  • the input end blocking bodies 232 and 238 cut the input channel 230 into a first input section 231 , a second input section 233 and a third input section 234 .
  • the first input section 231 communicates with the inlet 220 .
  • the second input section 233 is enclosed between the input end blocking bodies 232 and 238 .
  • the third input section 234 is in communication with the fluid containment chamber 250 .
  • the blocking bodies 232 and 238 at the input end form a double barrier of liquid flow between the first input section 231 and the third input section 234 .
  • the output end blocking bodies 272 and 278 cut the output channel 270 into a first output section 271 , a second output section 273 and a third output section 274 .
  • the first output section 271 communicates with the fluid containing chamber 250 .
  • the second output section 273 is enclosed between the output end blocking bodies 272 and 278 .
  • the third output section 274 communicates with the outlet 280 .
  • the blocking bodies 272 and 278 at the output end form a double barrier of liquid flow between the first output section 271 and the third output section 274 .
  • the temperature of the indenter can also be set to be able to locally melt the part where the substrate is in contact with the indenter, so that the indenter applies pressure to the substrate 210 to squeeze the input channel 230 and the output channel
  • the input end blocking bodies 232, 238 and the output end blocking bodies 272, 278 are partially melted, and at the same time, the second inner walls 213b, 217b of the corresponding positions of the input end blocking bodies 232, 238 and the output end blocking bodies 272, 278 are melted.
  • the contact parts 213d, 213e, 217d, 217e of the contact parts are partially melted.
  • the partially melted input end blocking bodies 232, 238 and the output end blocking bodies 272, 278 are respectively fused with the partially melted contact parts 213d, 213e and 217d, 217e.
  • the indenter is removed from the substrate 210 and the temperature of the substrate 210 returns to normal temperature, for example, to the room temperature state
  • the partially melted input end plugging bodies 232, 238 and output end plugging bodies 272, 278 contact the contact parts 213d, 213e and 217d and 217e are fused and solidified into one, and the pressed head of the input channel 230 and the output channel 270
  • the extruded parts form integral closed ends 232a, 238a, 272a and 278a, respectively, as shown in FIG.
  • the input channel 230 and the output channel 270 have a preset temperature and Local plastic deformation occurs under the pressing of the pressure head, and the formed input end blocking bodies 232, 238, output end blocking bodies 272, 278 and contact parts 213d, 213e, 217d, 217e are then heated and melted at the preset temperature
  • the pressure head under the pressing action of the pressure head, they are respectively integrated into one body, so that integrated closed ends 232a, 238a, 272a and 278a are formed at the parts of the input channel 230 and the output channel 270 pressed by the pressure head, and the samples and reagents are sealed in the in the fluid holding chamber.
  • the integrated closed ends 232a, 238a, 272a, 278a formed after being melted by heat and deformed by pressure and the substrate 210 constitute the input channel 230 and the fluid accommodating chamber 250 and other parts of the output channel 270 have the same structural strength.
  • the closed ends 232a, 238a, 272a, and 278a of the microfluidic device 200 in this embodiment are deformed under pressure and melted by heat, and the closed ends 232a, 238a, 272a, and 278a are used for the liquid filled in the fluid holding chamber, such as samples for polymerase chain reaction and
  • the reagent provides the same sealing effect as the rest of the input channel 230 , the fluid containment chamber 250 and the output channel 270 .
  • the present invention provides a kit for the detection of biological samples or medical samples, such as for polymerase chain reaction. As shown in FIGS.
  • the reagent kit 300 includes a plurality of reagent and sample accommodating and carrying units 302o with the same structure.
  • Each reagent and sample accommodating and The carrier unit 302 includes a substrate 310, a fluid accommodating chamber 350 formed in the substrate 310, an input channel 330 and an output channel 370 formed in the substrate, and is filled and filled through the input channel 330 in preparation for the polymerase chain reaction.
  • Reagents and samples 360 contained in the fluid holding chamber 350 .
  • the reagents and samples 360 may include liquids such as samples, reagents, and solvents for polymerase chain reaction.
  • the input channel 330 and the output channel 370 communicate with the fluid containing chamber 350, respectively.
  • the first inner wall 330 a of the input channel 330 located at an input segment 335 abuts against the first inner wall 330 a located at the input segment 335 .
  • the second inner wall 330b of the input channel 330 makes the input channel 330 closed.
  • the first inner wall 370a of one output segment 375 abuts against the second inner wall 370b of the output segment 375, so that the output channel 370 is closed.
  • the closed input channel 330 and the closed output channel 370 seal the reagent 360 within the fluid containment chamber 350 .
  • the position of the input channel 330 on the first inner wall 330 a of an input segment 335 can be realized by applying external pressure on the upper surface 311 of the base plate 310 corresponding to the segment 335 .
  • the external pressure presses the upper surface 311, so that the substrate 310 is plastically deformed and one or more depressions are formed on the upper surface 311, for example, two mutually spaced depressions 312, 316o shown in FIG.
  • the first inner wall 330a of the input channel 330 moves to the second inner wall 330b on the opposite side along with the deformation of the substrate 310 and the formation of the depressions 312 and 316 to form the input end blocking bodies 332 and 338, and Finally, it abuts against the second inner wall 330b, thereby closing the cross section of the input channel 330 at the input segment 335.
  • the location of the output channel 370 on the first inner wall 370a of an input segment 375 can be achieved by applying external pressure on the upper surface 311 of the base plate 310 corresponding to the segment 375 .
  • the external pressure presses the upper surface 311, so that the substrate 310 is plastically deformed and one or more depressions are formed on the upper surface 311, for example, the two spaced depressions 362, 366o shown in FIG.
  • the first inner wall 370a of the output channel 370 moves to the second inner wall 370b on the opposite side with the deformation of the substrate 310 and the formation of the depressions 362 and 366 to form the output end blocking bodies 372 and 378, and finally Abutting against the second inner wall 370b, thereby closing the output channel 370 at the cross-section of the output segment 375.
  • the closure of the input channel 330 and the output channel 370 seals the reagent and sample 360 to the fluid containment chamber 350 .
  • the sample and reagents sealed in the fluid containment chamber 350 react under certain conditions, such as typically 65 . (Polymerase chain reaction under the condition of temperature cycle of 2 to 95°C.
  • the sample sealed in the fluid holding chamber 350 can be tested.
  • the sample is always in a safe and sealed state, making the detection operation safe and convenient.
  • the kit can be destroyed while the sample is always in a safe and sealed state. The possible contamination of the sample to the surrounding environment is effectively prevented.
  • the input end blocking body 332>338 and the second inner wall 313b of the input channel 330 can be integrated, for example, by local melting of the substrate 310 under the action of appropriate external pressure and temperature. , the plastic deformation is integrated into one, and the input channel 330 is blocked.
  • the output end blocking bodies 372, 378 and the second inner wall 370b of the output channel 370 can be integrated into one body, for example, under the action of appropriate external pressure and temperature, the local melting and plastic deformation of the substrate 310 can be integrated, and the blocking The output channel 370o is removed from the external heat source, and the temperature of the substrate 310 returns to normal temperature, for example, after returning to room temperature, the partially melted input end blocking bodies 332, 338 and the output end blocking bodies 372, 378 are respectively connected to the second side of the input channel 330.
  • the present invention provides a method for preparing a kit for biological samples or medical samples.
  • the method 400 for preparing a kit according to the present embodiment includes, in block 410, filling a reagent into a fluid containing chamber.
  • the liquid inlet channel is squeezed in a direction intersecting the liquid inlet channel connected to the reagent and sample containing chambers, causing the liquid inlet channel to be plastically deformed, so that the first inner wall of the liquid inlet channel is deformed Abutting against the second inner wall to close the liquid inlet channel.
  • the liquid outlet is squeezed in a direction intersecting with the liquid outlet channel connected to the reagent and sample accommodating chambers channel, causing the liquid outlet channel to plastically deform, so that the first inner wall of the liquid outlet channel abuts the second inner wall, so as to close the liquid outlet channel.

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Dispersion Chemistry (AREA)
  • Analytical Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Hematology (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)
  • Physical Or Chemical Processes And Apparatus (AREA)

Abstract

L'invention concerne une trousse de réactifs comprenant une pluralité d'unités contenant et transportant un réactif. Au moins une unité contenant et transportant un réactif et un échantillon comprend un substrat, une chambre contenant un fluide formée dans le substrat, un canal d'entrée et un canal de sortie formés dans le substrat, ainsi qu'un réactif contenu dans la chambre contenant un fluide. Le canal d'entrée et le canal de sortie sont respectivement en communication avec la cavité contenant un fluide. Une première paroi interne du canal d'entrée située au niveau d'un segment d'entrée vient en butée contre une seconde paroi interne du canal d'entrée située au niveau du segment d'entrée, de telle sorte que le canal d'entrée est fermé. Une première paroi interne du segment de sortie vient en butée contre la seconde paroi interne au niveau du segment de sortie, de telle sorte que le canal de sortie est fermé. La fermeture du canal d'entrée et du canal de sortie scelle les réactifs dans la chambre contenant un fluide. La présente invention concerne également un dispositif microfluidique dans lequel un segment du canal d'entrée et du canal de sortie est plastiquement déformable sous l'effet d'une pression externe afin de fermer le canal d'entrée et le canal de sortie, respectivement. Les trousses peuvent être utilisées pour la réaction en chaîne par polymérase.
PCT/SG2021/050587 2020-09-30 2021-09-29 Dispositif microfluidique, trousse de réactifs et leur procédé de préparation WO2022071883A1 (fr)

Priority Applications (2)

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BR112023005584A BR112023005584A2 (pt) 2020-09-30 2021-09-29 Dispositivo microfluídico, kit de reagentes e método de fabricação dos mesmos
EP21876105.4A EP4223418A1 (fr) 2020-09-30 2021-09-29 Dispositif microfluidique, trousse de réactifs et leur procédé de préparation

Applications Claiming Priority (2)

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CN202011062253.3A CN114308145A (zh) 2020-09-30 2020-09-30 微流体装置、试剂盒及其制备方法
CN202011062253.3 2020-09-30

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CN114669339B (zh) * 2022-05-27 2022-09-09 湖南冠牧生物科技有限公司 一种核酸提取微流控芯片、核酸提取系统及方法

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WO2006116616A2 (fr) * 2005-04-26 2006-11-02 Applera Corporation Systemes et procedes de detection multiple d'analytes
US20080003145A1 (en) * 2006-06-28 2008-01-03 Applera Corporation Sample Distribution Devices and Methods
US20140272981A1 (en) * 2013-03-14 2014-09-18 Formulatrix, Inc. Microfluidic device
CN106536055A (zh) * 2014-05-27 2017-03-22 伊鲁米那股份有限公司 包括基本仪器和可拆卸盒的用于生物化学分析的系统和方法
EP3248681A1 (fr) * 2016-05-23 2017-11-29 ETH Zurich Dispositif microfluidique définissant un réseau de chambres d'échantillonnage

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006116616A2 (fr) * 2005-04-26 2006-11-02 Applera Corporation Systemes et procedes de detection multiple d'analytes
US20080003145A1 (en) * 2006-06-28 2008-01-03 Applera Corporation Sample Distribution Devices and Methods
US20140272981A1 (en) * 2013-03-14 2014-09-18 Formulatrix, Inc. Microfluidic device
CN106536055A (zh) * 2014-05-27 2017-03-22 伊鲁米那股份有限公司 包括基本仪器和可拆卸盒的用于生物化学分析的系统和方法
EP3248681A1 (fr) * 2016-05-23 2017-11-29 ETH Zurich Dispositif microfluidique définissant un réseau de chambres d'échantillonnage

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EP4223418A1 (fr) 2023-08-09
CN114308145A (zh) 2022-04-12

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