WO2017107025A1 - Dispositif de détection - Google Patents

Dispositif de détection Download PDF

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Publication number
WO2017107025A1
WO2017107025A1 PCT/CN2015/098146 CN2015098146W WO2017107025A1 WO 2017107025 A1 WO2017107025 A1 WO 2017107025A1 CN 2015098146 W CN2015098146 W CN 2015098146W WO 2017107025 A1 WO2017107025 A1 WO 2017107025A1
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WIPO (PCT)
Prior art keywords
micro
detecting device
substrate
sensing
sample
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PCT/CN2015/098146
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English (en)
Chinese (zh)
Inventor
黄荣堂
Original Assignee
黄荣堂
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Publication date
Application filed by 黄荣堂 filed Critical 黄荣堂
Priority to CN201580085443.8A priority Critical patent/CN108474802A/zh
Priority to PCT/CN2015/098146 priority patent/WO2017107025A1/fr
Publication of WO2017107025A1 publication Critical patent/WO2017107025A1/fr

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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/08—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a stream of discrete samples flowing along a tube system, e.g. flow injection analysis

Definitions

  • the invention relates to a detecting device, in particular to a portable device and the test process is carried out without additional force, and the heavier molecules in the sample are separated from the lighter molecules and the related tests are simultaneously carried out. Detection device.
  • the sample can flow in the microchannel by the capillary phenomenon formed by the difference between the adhesion between the sample and the microchannel and the cohesive force of the sample itself.
  • the micro-sensing chip in the test zone can be detected for the sample.
  • the researchers transmitted the detection signals read by the micro-sensing chip to an external analytical instrument for related research and data analysis.
  • today's detection devices must be powered to drive the flow of microfluids in the microchannels, thus greatly reducing the portability of the detection device.
  • the researchers need to first screen the specimen to obtain specific molecules in the specimen, and then analyze and study the specific molecule.
  • the sample is blood
  • the conventional detection method utilizes characteristics in which the blood cell and the plasma have different qualities, and the blood is separated into blood cells and plasma by a centrifugal separator. Therefore, the above-mentioned conventional technique is not only complicated, but also has a long detection time, and it is more necessary to provide the centrifugal separator power for detection, which is inconvenient.
  • an object of the present invention is to provide a detecting device capable of directly separating a sample into a mass-heavy molecule and a light-weight molecule, and detecting the sample of the separated molecule, so that centrifugation is not required
  • the separator separates the sample, which not only simplifies the convenience of the detection procedure, but also has the concept of green energy saving.
  • Another object of the present invention is to provide a detecting device which is highly portable and does not require additional power during the detection of the sample.
  • the detecting apparatus of the present invention comprises: a substrate having a first surface, the first surface having a recessed portion, the recessed portion including a bottom portion and a slope, the bottom portion being embedded in the substrate, and the slope is connected to the first surface and a bottom portion and disposed at one end of the recess; a cover having a second surface facing the first surface; a micro-sensing chip embedded in the substrate; and a micro-channel structure embedded in the second surface, wherein the first surface and the second surface are mutually dense after the cover covers the substrate
  • the microchannel structure is coupled to the first surface to form a microchannel comprising at least one injection port and a volume control slot for controlling the flow rate of the sample in the microchannel, the specimen entering the recess through the microchannel from the inlet
  • the sample is separated into a lower layer liquid and an upper layer liquid in the depressed portion, the lower layer liquid stays at the bottom portion, and the upper layer liquid flows from the concave portion to the micro sensing chip;
  • the sample is blood
  • the lower layer is blood cells
  • the upper layer is plasma
  • one end of the micro flow channel has a capacity control slot for controlling the flow rate of the sample in the micro flow channel.
  • the slope is disposed in an end of the recess adjacent to the injection port.
  • the micro-sensing chip has at least one detecting structure for detecting bio-particles or bio-polymers in the structure to energize the sample.
  • the detecting device further includes a plurality of terminals disposed on the substrate and connected to the micro sensing chip, and the plurality of terminals are coupled to a reading device.
  • the plurality of terminals are connected to the micro-sensing chip by wire bonding.
  • the detecting structure is a resistive type, a capacitive type, an impedance type, or a transistor type, or an electrochemical type, a counting type, or a photoelectric type based on a nano sensing material.
  • the sensor, the nanomaterial is functionalized by a biopolymer selected from the group consisting of an antibody, an aptamer or a sugar molecule or an enzyme.
  • the detection structure can also be selected from purely electrochemical or optoelectronic sensors.
  • the nano-sensing material is selected from the group consisting of carbon nanotubes, graphene, reduced graphene oxide (rGO), graphene oxide (graphene oxide, GO), nanoribbon graphene, nano silicon wire, nano InP wire, nano GaN wire, nano semiconductor wire or nano semiconductor film.
  • the material of the substrate is polymethylmethacrylate (PMMA), polyethylene terephthalate (PET), polycarbonate (PC), and porosity.
  • PMMA polymethylmethacrylate
  • PET polyethylene terephthalate
  • PC polycarbonate
  • porosity Polydimethylsiloxane Polydimethylsilicon (PDMS), porous silica gel, rubber, plastic or glass.
  • the cover body is made of polymethylmethacrylate (PMMA), porous polyethylene terephthalate (PET), polycarbonate (polycarbonate, PC). ), porous polydimethylsilicon (PDMS), porous silica gel, rubber or plastic.
  • PMMA polymethylmethacrylate
  • PET porous polyethylene terephthalate
  • PC polycarbonate
  • PDMS porous polydimethylsilicon
  • a pretreatment portion is provided between the recess and the injection port, and is adapted to separate the sample or mix with other reagents.
  • the edge of the second surface when the second surface is assembled with the first surface, the edge of the second surface is located inside the side line of the first surface.
  • the detecting means after the completion of the vacuuming process is packaged in a vacuum packaging bag.
  • the first surface and the top surface of the micro-sense chip are in the same plane.
  • the micro flow channel is located in a region between the micro sensing chip and the recess, and the channel cross-sectional area in the micro channel is reduced.
  • a detecting device of the present invention comprises: a substrate having a first surface comprising a recess and at least one reaction tank; a cover having a second surface covering the first surface of the cover; a micro-sensing chip embedded in the substrate, comprising at least one sensing region; a first injection port; a second injection port; and a micro-channel system formed between the substrate and the cover body, comprising a first micro-flow channel formed on a first surface of the substrate and connecting the reaction grooves and the second injection port, a second micro flow channel formed on the second surface of the cover body, and a capacity control groove formed on the second surface of the cover body and communicating with the second micro flow And a third micro flow channel connecting the reaction grooves to at least one sensing area of the micro sensing chip; wherein the second micro flow channel comprises a first portion and a second portion, the first portion is the first portion The injection inlet extends to the capacity control tank and communicates with the recess, and the second portion extends from the
  • a detecting apparatus of the present invention includes: a substrate having a first surface including a recessed portion and a disintegrating groove; a cover having a second surface covering the first surface of the cover;
  • the micro-sensing chip is embedded in the substrate and includes a sensing region; a micro-channel is formed between the substrate and the cover, and communicates with the sensing portion of the recess and the micro-sensing chip; and a heating component is formed under a portion of the micro-channel
  • At least one of the substrate and the cover body comprises a porous material; wherein a decomposition liquid containing a sample having DNA fills the decomposition groove and the depressed portion, and then flows through the micro flow channel Above the hot component, the heated component is heated by circulation and copied in large quantities, and then flows through the microchannel to the sensing area of the micro sensing chip.
  • FIG. 1 is a perspective view of a detecting device according to an embodiment of the present invention.
  • FIG. 2 is a perspective view of a substrate of a detecting device according to an embodiment of the present invention.
  • FIG 3 is a perspective view of a recessed portion of an embodiment of the present invention.
  • FIG. 4 is a perspective exploded view of a substrate and a cover of a detecting device according to an embodiment of the invention.
  • FIG. 5 is a perspective exploded view of a substrate and a cover of a detecting device according to another embodiment of the present invention.
  • Fig. 6 is a schematic view showing a sample in a depressed portion according to an embodiment of the present invention.
  • FIG. 7 is a schematic diagram showing the reduction of the cross-sectional area in the microchannel according to an embodiment of the present invention.
  • FIG. 8 is a schematic diagram of a pre-processing unit according to an embodiment of the present invention.
  • Fig. 9 is a table showing an experimental record of a detecting device according to an embodiment of the present invention.
  • Figure 10 is a perspective view of another embodiment of the present invention.
  • FIG. 11A and 11B are schematic top views of another embodiment of the present invention.
  • 12 to 16 are different embodiments showing a depressed portion of a substrate according to another embodiment of the present invention.
  • Figure 17 is a top perspective view showing another embodiment of the present invention.
  • Figure 18 is a top perspective view showing another embodiment of the detecting device of the present invention.
  • a refers to an amount of at least one (one or more).
  • FIG. 1 is a perspective view of a detecting device according to an embodiment of the present invention
  • FIG. 2 is a perspective view of a substrate of a detecting device according to an embodiment of the present invention
  • FIG. 3 is a perspective view of a recessed portion according to an embodiment of the invention
  • FIG. 4 is a perspective exploded view of the substrate and the cover of the detecting device according to an embodiment of the present invention
  • FIG. 5 is a perspective exploded view of the substrate and the cover of the detecting device according to another embodiment of the present invention. Referring to FIG. 1 , FIG. 2 , FIG. 3 , FIG. 4 and FIG.
  • the detecting device 10 of the present invention includes a substrate 100 , a cover 200 , a micro sensing chip 300 , and a micro flow channel structure 400 .
  • a substrate 100 On the substrate 100, there is a first surface 101, and on the first surface 101, there is a recess 102.
  • the recess 102 is composed of a bottom portion 103 and a slope 104, wherein the bottom portion 103 is embedded in the substrate 101, and the slope 104 is located at one end of the recess portion 102 near the injection port 402.
  • At least one of the substrate 100 and the cover 200 comprises a porous material, and the cover 200 has a second surface 201 thereon.
  • the cover 200 covers the substrate 100
  • the first surface The 101 faces the second surface 201 and is in close contact with each other.
  • the micro-channel structure 400 is disposed on the second surface 201.
  • the cover 200 covers the substrate 100
  • the micro-channel structure 400 is combined with the first surface 101 to form a micro-channel 401, at least the substrate 100 and the cover 200.
  • the sample 600 is placed in the injection port 402 of the microchannel 401, and the sample 600 is driven from the injection by the suction generated by the vacuum in the microchannel 401.
  • the inlet 402 enters the recess 102 via the microchannel 401, and the sample 600 is separated into the lower layer 601 and the upper layer 602 (shown in FIG. 6) in the recess 102.
  • the lower layer 601 stays at the bottom 103, and the upper layer 602
  • the recessed portion 102 flows from the micro-sense chip 300.
  • the sample 600 may be a body fluid, including blood, cerebrospinal fluid, gastric juice and various digestive juices, semen, saliva, tears, sweat, urine, vaginal secretions, etc. or It is a solution containing the sample 600.
  • blood is taken as an example.
  • the heavier blood cell the lower layer 601 precipitates at the bottom 103 of the depressed portion 102, and the lighter plasma ( The supernatant liquid 602) will exit from the recess 102 and enter the micro-sensor chip 300 along the micro-channel 401.
  • an anticoagulant may be applied to the bottom and/or the side wall of the injection port 402.
  • the slope 104 of the recess 102 of the present invention ensures that the specimen 600 can be concave.
  • the trap 102 performs the function of separating.
  • the sample 600 tends to have a misjudgment result when the separated sample 600 is interpreted by the micro-sensing chip 300 because the separation effect is not good.
  • the slope 104 of the depressed portion 102 near one end of the injection port 402 has a function of smoothing the flow of the sample 600 in the micro flow path 401 when the sample 600 is in the micro flow path 401.
  • an array of micropiles may be formed at an interface between the recessed portion 102 and the microchannel 401 at a distance of less than 3 micrometers to intercept a suspension of 3 micrometers or more.
  • microcylinders spaced between 10 and 100 micrometers apart and then complexing a plurality of microspheres having a size larger than the spacing of the plurality of microcylinders to form a plurality of voids to intercept suspended matter larger than the void size, or may increase
  • the slope and/or surface roughness of the slope 104 of the recess 102 intercepts more suspended matter.
  • the surfaces of the bottom portion 103 and the slope 104 of the depressed portion 102 may be treated with oxygen plasma or an intervening agent or the like to increase hydrophilicity and increase the probability of sedimentation of the suspended matter in the sample 600.
  • a blood coagulant such as calcium chloride (CaCl) may be applied to the bottom portion 103 and the slope 104 of the depressed portion 102 to promote coagulation and aggregation of the blood cells to settle in the depressed portion 102.
  • a non-blood sample such as a somatic cell in raw milk
  • it may be applied to the bottom portion 103 and the slope 104 of the depressed portion 102 or a mixture containing the thrombin (Thrombin) and fibrinogen may be added to the sample 600.
  • Thrombin thrombin
  • fibrinogen fibrinogen
  • fibrinogen calcium ions
  • fibrin mesh increasing the probability that the suspended matter settles in the depressed portion 102.
  • the research project usually also includes quantitative analysis of the separated sample.
  • a volume control slot 405 is provided within the microchannel 401 relative to the other end of the injection port 402 for the purpose of analyzing the designed structure for the quantitative sample 600.
  • the sample 600 enters the microchannel 401 from the injection port 402, it passes through the recess 102 and the micro-sensing chip 300, and finally the sample 600 is stored in the capacity control slot 405.
  • the sample 600 at the injection port 402 does not enter the microchannel 401 again, so the signal detected by the micro-sensing chip 300 is controlled by the capacity control slot 405.
  • the signal generated by the quantitative sample 600 is generated by the quantitative sample 600.
  • the capacity control slot 405 has a capacity of 0.5 cc.
  • the sample 600 applied to the injection port 402 is much larger than 0.5 cc, the signal sample 600 that can be detected by the micro-sense chip 300 is only 0.5. Cc. If the signal detected by the micro-sensing chip 300 is divided by 0.5 cc, the unit of the signal is presented in a concentration manner.
  • the micro-sensing chip 300 is embedded in the substrate 100, and the top surface of the micro-sensing chip 300 and the first surface 101 must be in the same plane to ensure that the sample 600 in the micro-channel 401 can be Flowing into the micro-sensing chip 300.
  • the micro flow channel 401 passes through at least one detecting structure of the micro sensing chip 300 from above, and in another embodiment, the micro flow channel 401 may also pass through at least one detecting structure of the micro sensing chip 300 from below. .
  • Each detection structure can be quantified by bio-coupling modification, or can be further quantified by bio-particles or bio-polymers in the sample 600, or further via the micro-sensing chip 300, for example, a resistive type, a capacitive type, an impedance type, or a transistor type. Or electrochemical type comprising nano or non-nano, or counting type, photoelectric type comprising nano or non-nano sensing elements, converted into electrical signals, and finally the I/O pads of the micro sensing chip 300 are electrically connected to the plurality of terminals 501.
  • the plurality of terminals 501 are electrically connected to the external reading device, and the detection signals are output to provide related research and analysis.
  • the plurality of terminals 501 may also be connected to the micro-sensing chip 300 by wire bonding.
  • the micro-sensing chip 300 can also include an amplifier circuit to amplify the weak electronic signals detected.
  • the present invention designs the micro-channel 401 in a region where the micro-channel 401 is located between the micro-sensing chip 300 and the depressed portion 102.
  • the cross-sectional area of the inside is reduced, so that the flow rate of the sample 600 entering the micro-sensing chip 300 is lowered, so that the time during which the sample 600 stays in the micro-sensing chip 300 can be increased, and the majority of the sample 600 can be brought closer to the micro-sensing chip. 300, in order to facilitate the detection of low concentration sample 600. As shown in FIG.
  • the flow path depth of the micro flow channel 401 is originally 60 ⁇ m, and the flow path depth between the micro sensing chip 300 and the recess portion 102 can be gently reduced by a slope. Up to 10 ⁇ m, so that the biomarker 603 of the deep flow channel (60 ⁇ m) upstream of the microchannel 401 can thus pass through the slope, slow down its flow rate, and limit its suspension range, and thus rush to the aptamer 604 at the bottom of the microchannel 401, Most of the biomarkers 603 are captured by the aptamer 604 at the bottom of the microchannel 401. Since the flow rate is low, the captured biomarkers 603 are fixed to the aptamer 604.
  • the detecting structure is a resistive type, a capacitive type, an impedance type, or a transistor type, an electrochemical type, a counting type sensor based on a nano sensing material, and a nano sensing material.
  • the biopolymer in particular, refers to at least one of an antibody, or an aptamer, or a sugar molecule, or an enzyme molecule.
  • the sensors can be of a plurality or array type to provide a quantitative test of a plurality of objects within the sample 600.
  • the nano sensing material described above may be a material having semiconductor characteristics such as nanowires such as carbon nanotubes, nano silicon wires, nano InP wires, nano GaN wires, or nano semiconductor wires, which are suitable for sensing, Or a nano-semiconductor film, or graphene, reduced graphene oxide (rGO), graphene oxide (GO), nanoribbon graphene, and the like.
  • the detection structure can also be selected from purely electrochemical or optoelectronic sensors.
  • the material of the substrate 100 may be polymethylmethacrylate (PMMA), polyethylene terephthalate (PET), polycarbonate (PC). Porous polydimethylsilicon (PDMS), porous silica gel, rubber, plastic or glass; the material of the cover 200 may be polymethylmethacrylate (PMMA), polyethylene terephthalate Polyethylene terephthalate (PET), polycarbonate (PC), porous polydimethylsilicon (PDMS), porous silica gel, rubber or plastic.
  • PMMA polymethylmethacrylate
  • PET polyethylene terephthalate
  • PC polycarbonate
  • PDMS porous polydimethylsilicon
  • the material of the substrate 100 and the cover 200 it is necessary to consider the material properties between the substrate 100 and the cover 200.
  • the cover 200 covers the substrate 100
  • the inside of the microchannel 401 must be evacuated to form a vacuum state to provide a suction force for driving the sample 600 to flow in the microchannel 401. Therefore, at least one of the substrate 100 and the cover 200 must be a porous material.
  • the material hardness characteristic between the substrate 100 and the cover 200 can be a hard and a soft one.
  • the substrate 100 is made of a plastic having a higher hardness
  • the cover 200 is made of a porous polydimethylsilicon (PDMS) having a lower hardness and is more rigid.
  • the microchannel structure 400 is formed on the low cover 200, so when the microchannel 401 is evacuated, the porous polydimethylsilicon (PDMS) having a lower hardness is attached to the hardness.
  • the air in the pores of the PDMS is simultaneously removed to maintain the vacuum state in the microchannel 401.
  • the pore vacuum state of the porous polydimethylsilicon (PDMS) is gradually filled by the outside air, but as long as it is not balanced with the external pressure,
  • the microchannel 401 is provided with a negative pressure to drive the sample 600 to flow.
  • the substrate 100 is made of a plastic material having a relatively high hardness
  • the material of the cover 200 is a polydimethylsilicon (PDMS) having a low hardness and a porosity.
  • the present invention is not limited thereto, and the substrate 100 may also be made of a material having a lower hardness, and the cover 200 is a material having a higher hardness.
  • the present invention is specifically designed to laminate the first surface 101 and the second surface 201 to each other, and the edge of the second surface 201 is Located inside the side of the first surface 101 (as shown in Figure 1). Since the first surface 101 and the second surface 201 are seam-finished when they are attached to each other, in the mass production, the automatic device only needs to seal the slit with a sealant, and the vacuum can be applied to the injection port to make the micro-injection A vacuum state is formed inside the flow path.
  • the detection device 10 after completion of the vacuuming process is packaged in a vacuum package.
  • the recess 102, the micro-sense chip 300, the micro-channel structure 400, and the quantitative control structure 403 are disposed on the substrate 100.
  • the recess 102, the micro-feel The test chip 300, the micro flow channel structure 400, and the quantitative control structure 403 may also be disposed on the cover 200.
  • a plurality of microchannels 401, a plurality of recesses 102, a plurality of micro-sensing chips 300, and a plurality of quantitative control structures 403 may be disposed on the substrate 100 via the special substrate 100.
  • the single detecting device 10 can simultaneously process a plurality of test samples, which is not only efficient but also saves time and cost; and in another preferred embodiment of the present invention, between the recess 102 and the injection port 402 There is a pre-processing portion 404 (shown in Figure 8) that is adapted to separate the sample 600 or to mix with other reagents. Some special specimens 600 must be removed from the original specimen 600 prior to actual detection, or mixed with other materials, and the prior treatment portion 404 of the present invention has the function of providing the above separation and mixing.
  • the detecting device 10 of the present invention utilizes a vacuuming method, and one of the substrate 100 and the cover 200 is made of a porous material, and the micro flow channel 401, the recess portion 102 and the capacity control slot 405 are formed inside.
  • a negative pressure is generated with respect to the external atmospheric pressure.
  • Sensing chip 300 to capacity control slot 405 completes this detection and does not require additional power to drive sample 600 to flow during the detection process using a power component such as a pump or valve member.
  • 9 is an experimental recording table of the detecting device 10 according to an embodiment of the present invention.
  • the sample 600 is dropped to the injection port 402. After one day, the sample 600 still cannot flow to the depressed portion 102; in the test samples 2 to 6, after the vacuuming treatment of the detecting device 10 for 6 minutes and 30 seconds to 7 minutes, the sample 600 takes about 14 to 17 minutes. Flows to the entrance of the micro-sensing chip 300. Therefore, it has been experimentally found that after the vacuuming process of the detecting device 10 of the present invention is performed for a certain period of time, the flow pattern of the sample 600 in the detecting device 10 has consistency and repeatability.
  • a plurality of terminals of the detecting device 10 of the present invention may be formed.
  • the terminal carrier 500 is formed on the first surface 101 of the substrate 100 and protrudes from the side of the substrate 100.
  • the micro-sensing chip 300 of the present embodiment can be similar to the foregoing embodiment; the cover 200, the capacity control slot 405, the injection port 402, the recess 102, and the micro flow channel 401 can also be similar to the foregoing embodiments.
  • the detecting apparatus 10 of the foregoing embodiments of the present invention may further include: a first-class choke 408 is formed in the micro-channel 401; and a reaction tank 409 is connected to the micro-sensing chip 300, wherein the flow resistance is
  • the flow path 408 is formed between the capacity control tank 405 and the reaction tank 409 to further delay the time during which the sample 600 flows to the quantitative control structure 403, and increase the reaction time of the sample 600 and the micro-sensing chip 300, thereby improving the accuracy of the detection. .
  • the sample 600 is filled with the sample liquid and the object to be tested is suspended in the sample liquid, it is necessary to have sufficient analyte to be precipitated on the micro-sensing chip 300 to make the most accurate analysis, and the flow resistance channel 408 can be used. After the sample 600 is filled in the reaction tank 409, the sample 600 is allowed to stay in the reaction tank 409 for 3 to 7 minutes, and in one embodiment, up to about 5 minutes. The effect of the flow resistance flow path 408 slowing down the flow rate of the sample 600 allows a certain amount of the sample 600 to fully react with the micro-sensing chip 300.
  • the flow restricting flow path 408 continues to flow to the capacity control tank 405, but the volume of the flow restricting flow path 408 is very small relative to the reaction tank 40, so the sample 600 in the reaction tank 409 before the sample 600 flows to the capacity control tank 405 It can be regarded as a state of being stationary, that is, the micro-sensing chip 300 is reacted with a certain amount of the sample 600 in a unit time, and therefore the volume of the cavity in which the reaction tank 409 is combined with the substrate 100 can be used as a unit of a certain amount of analysis.
  • the flow resistance flow path 408 may have a meandering pattern, as shown in FIG.
  • the number of times of meandering is short, the meandering amplitude is short, and the width of the flow path is narrow, or the number of times of zigzag in FIG. 11B is small, the meandering amplitude is long, and the width of the flow path is wide. .
  • the recess 102 of the substrate 100 of the detecting device 10 of the present invention there are shown variations in the recess 102 of the substrate 100 of the detecting device 10 of the present invention.
  • the flat bottom 103 of the recess 102 is closer to the injection port 401 than the slope 104.
  • the recess 102 may have only the ramp 104 without a flat bottom, and the depth of the ramp 104 is deeper the further away from the injection port 401.
  • the recess 102 may have only the ramp 104 without a flat bottom, and the depth of the ramp 104 is shallower as it is farther from the injection port 401.
  • the width of the recessed portion 102 may be narrower as it is farther from the injection port 401.
  • the width of the recessed portion 102 may be wider as it is farther from the injection port 401.
  • the detecting device 10 of the present invention can separate the heavier molecules and the lighter molecules in the sample 600 by the design of the recess 102. Since it is not necessary to use a centrifugal separator, and the sample 600 can be directly separated, the detecting device 10 of the present invention has a green and environmentally friendly concept of convenience and energy saving.
  • the detecting device 10 of the present invention is electrically connected to the external device In the device, the separated sample 600 can upload the detection signal to the external device while the detection is performed, so that the researcher can perform subsequent related research and analysis, so the detection device 10 of the present invention also has the advantages of rapid detection and simple operation. The advantages.
  • the detecting device 20 of the present invention comprises: a substrate 700 comprising a recess 702, a microchannel 704 and at least one reaction tank, for example, comprising a first reaction tank 706, a second reaction tank 708, a third reaction tank 710 and A fourth reaction tank 712, wherein the first to fourth reaction tanks are connected by the micro flow passage 704; a cover 900 includes a plurality of injection ports such as a first injection port 810, a second injection port 812, and a micro flow channel 802.
  • a first sensing cavity 814, the at least one sensing cavity can include a second sensing cavity 816, a third sensing cavity 818, and a fourth sensing cavity 820, and a certain amount of control structure 803;
  • the micro-sensing chip 900 is embedded in the substrate 700; and a terminal carrier 720 is connected to the micro-sensing chip 900 and a plurality of terminals 721 are formed on the surface.
  • the microchannel 802 can include a first portion between the first injection port 810 and the quantitative control structure 803 and a second portion substantially parallel to the first portion and extending from the quantitative control structure 803 toward the second injection port 812, wherein the micro flow channel
  • the first portion and the second portion of 802 are two different locations that are in communication with the quantitative control structure 803.
  • the cover 800 can further include a first-stage choke 808 formed in the first portion of the micro flow channel 802.
  • the quantitative control structure 803 can be formed on the substrate 700 in addition to the cover 800.
  • the material of the substrate 700 can be similar to the plastic or hydrophilic material with higher hardness in the foregoing embodiment, and the material of the cover 800 can be similar to the porous PDMS or other hydrophobic material with soft hardness, that is, the cover.
  • the body 800 is more hydrophobic than the substrate 700.
  • the third reaction tank 710 and the fourth reaction tank 712 are closed by the cover 800 and respectively communicated by the branches of the second portion of the micro flow passage 802, and the quantitative control structure 803 of the cover 800 forms a Capacity control slot 805.
  • the cover 800 covers the substrate 700, the first sensing cavity 814, the second sensing cavity 816, the third sensing cavity 818, and the fourth sensing cavity 820 are respectively covered in the second of the micro sensing chip 900.
  • the four different sensing portions of the sensing region, the first sensing cavity 814, the second sensing cavity 816, the third sensing cavity 818, and the fourth sensing cavity 820 are respectively connected to each other through a micro flow channel 804
  • the first portion of the microfluidic channel 802 is selectively widened at the corresponding micro-sensing chip 900.
  • the microchannels 802, 804, 704 and the capacity control slot 805 can be considered as a microchannel system.
  • the detecting device 20 of the embodiment has four reaction tanks and four sensing chambers, in other embodiments, the detecting device 20 may have only one counter.
  • the detecting device 20 of the embodiment has two sensing regions, in other embodiments, only one sensing region may be provided. Since the cover 800 has hydrophobicity and the substrate 700 has hydrophilicity, when a sample is introduced into the microchannel 802 from the first injection port 810, the sample is automatically taken by one side of the substrate 700 in the micro flow channel 802. The sample is adsorbed until the substrate 700 adsorbs the sample beyond its hydrophilic saturation value, and the sample fills the microchannel 802. Therefore, when the sample flows to a tank such as the recess 702 or the volume control slot 805, After filling the tank, the microchannel 802 flows out and flows to the next tank.
  • a tank such as the recess 702 or the volume control slot 805
  • the detecting device 20 of the present embodiment can be applied to drug resistance detection, such as the following steps:
  • Step 1 The first reaction tank 706, the second reaction tank 708, the third reaction tank 710, and the fourth reaction tank 712 are prefilled with four antibiotics (not shown) for one bacteria, and are attached to the patch form. The bottom of each tank.
  • Step 2 The first injection port 810 is dropped into the sample (not shown), and the sample enters the depressed portion 702 through the first portion of the micro flow channel 802 to filter impurities. It can be seen from the foregoing embodiment that the vacuum state of the microchannel 802 of the detecting device 20 can automatically flow the sample in the direction of the capacity control slot 805. If necessary, the cover 800 can press the capacity control slot 805 to generate a deformation to form a negative pressure to drive the detection. The flow of the body.
  • Step 3 After the recessed portion 702 is filled, the filtered sample reaches the first sensing region of the micro-sensing chip 900 via the first portion of the micro-flow channel 802. At this time, the micro-sensing chip 900 first determines whether the sample is in the sample. Have bacteria to detect drug resistance.
  • Step 4 The culture solution is dropped from the second injection port 812. Since the first reaction tank 706, the second reaction tank 708, the third reaction tank 710, and the fourth reaction tank 712 are connected by the micro flow passage 704, the communication can be utilized.
  • the tube principle controls the liquid level of the four reaction tanks to a height of 95% of the reaction tank.
  • Step 5 The filtered sample is injected into the capacity control slot 805 after being initially interpreted by the micro-sensing chip 900. After the volume control slot 805 collects the filtered sample, the filtered sample begins to pass through the microflow. The four branches of the second portion of the track 802 are injected into the first reaction tank 706, the second reaction tank 708, the third reaction tank 710, and the fourth reaction tank 71, respectively, and after the four reaction tanks are filled, the filtered The sample then fills the first sensing cavity 814, the second sensing cavity 816, the third sensing cavity 818, and the fourth sensing cavity 82 via the microchannel 804.
  • Step 6 Read four electrical signals of the four sensing portions of the second sensing area of the micro-sensing chip 900.
  • Step 7 After the bacteria in the first reaction tank 706, the second reaction tank 708, the third reaction tank 710, and the fourth reaction tank 71 are cultured for about half an hour, the fourth sensing region of the micro-sensing chip 900 is read again. The four electrical signals of the sensing department.
  • Step 8 Compare the electrical signals of Step 6 and Step 7. If there is a significant change, you can judge the corresponding Antibiotic resistance. For example, in Step 7, if the electrical signal corresponding to the first sensing cavity 814 of the micro-sensing chip 900 is increased compared to Step 6, it means that the bacteria are resistant to the antibiotics in the first reaction tank 706, and vice versa in Step 7 if the micro-sensing chip 900 corresponds. The electrical signal of the first sensing cavity 814 has no significant increase compared to Step 6, and the antibiotic in the first reaction tank 706 has an effect of inhibiting the growth of the bacteria.
  • the detecting device 20 of the present embodiment can also be applied to detecting exosomes in blood, as follows:
  • Step 1 The blood with the extracellular chromosome is dropped from the first injection port 810 (not shown). After the blood enters the depressed portion 702 through the first portion of the microchannel, the blood cell is intercepted by the depressed portion 702, and the plasma continues to proceed.
  • the micro-sensing chip 900 flows. It can be seen from the foregoing embodiment that the vacuum state of the microchannel 802 of the detecting device 20 can automatically flow the plasma toward the volume control tank 805. If necessary, the lid 800 can press the capacity control tank 805 to form a negative pressure to drive the flow of plasma.
  • Step 2 The cell decomposition solution (1ysis buffer) is dropped from the second injection port 812, and the first reaction tank 706, the second reaction tank 708, the third reaction tank 710, and the fourth reaction tank 712 are subjected to the micro flow channel 704. Connected, based on the principle of the communication tube, the liquid level of the four reaction tanks is controlled to a height of 95% of the reaction tank. Since the detecting device 20 is applied to detect the foreign body in the blood, it is not necessary to determine whether the foreign body is a preset type. Therefore, the micro sensing chip 900 of the detecting device 20 may have only one sensing region, one reaction tank, and communication with the micro device. One of the sensing chips 900 senses the cavity.
  • Step 3 The volume control tank 805 collects the plasma from the first portion of the microchannel 802, and the plasma is injected into the first reaction tank 706 and the second reaction tank 708 from the four branches of the second portion of the microchannel 803, respectively.
  • the third reaction tank 710 and the fourth reaction tank 712 react with the cell decomposition liquid, and the cell decomposition liquid can decompose the cell wall of the foreign body to expose the protein of the foreign body.
  • the reacted plasma then fills the first sensing chamber 814, the second sensing chamber 816, the third sensing chamber 818, and the fourth sensing chamber 82 via the microchannel 804. .
  • Step 4 Read four electrical signals of the four sensing portions of the second sensing region of the micro-sensing chip 900.
  • Step 5 After the external reaction in the four reaction tanks starts to react for about half an hour, the four electrical signals of the four sensing portions of the second sensing region of the micro-sensing chip 900 are read again.
  • Step 6 Compare the electrical signals of Step 5 and Step 4, and estimate the concentration of the foreign body from the change of the two-step electrical signal.
  • the detecting device 30 includes a substrate 700 including a recessed portion 702 and a decomposition groove 760; a cover 800 includes a micro flow channel 802, a sensing cavity 809, a first injection port 810 and a second injection port 812; A micro-sensing chip 900 is embedded in the substrate 700 and has a sensing region connected by the sensing cavity 809 A heating module 750 includes a heating chip 751 and a resistor wire 752 formed on the heating chip 751 in a meandering manner; and a terminal carrier 720 is connected to the micro sensing chip 900 and a plurality of terminals 721 are formed on the surface.
  • the recessed portion 702 may be a recessed portion of the foregoing embodiments, such as different forms of FIGS. 12 to 16, and/or formed with arrays of micropillars (not shown) at the interface with the microfluidic channel 802. Or other disclosed structures may increase the sediment retention probability of the specimen.
  • the electric resistance wire 752 of the heating assembly 750 has two conductive ends 752a, 752b electrically connected to two contacts of a power supply (not shown), and the temperature of the electric resistance wire 752 rises to heat the upper micro flow channel 802 to heat.
  • the chip 751 can regulate the temperature of the resistor line 752.
  • the detecting device 30 may include a capacity control slot 805.
  • the quantitative control structure may be formed on the cover 800 or the substrate 700.
  • the first-class choke 808 is formed in the micro flow channel 802 and located in the capacity control slot 805 and the sensing cavity 809. between.
  • the detecting device 30 of the present embodiment can be applied to the detection of DNA extracted by Polymerase Chain Reaction (PCR), and a sample having DNA such as blood (not shown) can be injected into the decomposition tank 760 by the first injection port 810. A cell decomposing liquid can be injected from the second injection port 812.
  • PCR Polymerase Chain Reaction
  • the sample can flow from the micro flow channel 802 to the depressed portion 702, and the sample can be filtered in the concave portion 702, and then heated by the micro flow channel 802 to the heating assembly 750, and the micro flow
  • the track 802 is meander-shaped on the heating assembly 750 and its meandering direction is substantially perpendicular to the meandering direction of the electric resistance wire 752, so that the sample can be uniformly heated.
  • the micro-sensing chip 900 may also have a plurality of sensing portions for different detection of DNA.
  • the flow restricting flow path 808 is combined with the capacity control groove 805 to allow the detecting device 30 to quantitatively analyze the sample.

Abstract

L'invention concerne un dispositif de détection (10, 20, 30), comprenant une plaque de base (100, 700), un corps formant couvercle (200, 800), une micropuce de détection (300, 900) et une structure de microcanal (400), au moins un élément parmi la plaque de base (100, 700) et le corps formant couvercle (200, 800) contenant un matériau poreux. La plaque de base (100, 700) comporte une première surface (101), une rainure (102, 702) ménagée dans la première surface (101), ladite rainure (102, 702) comportant une partie inférieure (103) et une pente (104), caractérisée en ce que ladite partie inférieure (103) est intégrée à la plaque de base (100, 700), et en ce que la pente (104) relie la première surface (101) à la partie inférieure (103) et se trouve à une extrémité, proche d'un orifice d'injection (402, 810), de la rainure (102, 702). Le corps formant couvercle (200, 800) comporte une seconde surface (201) en regard de la première. La micropuce de détection (300, 900) est intégrée à la plaque de base (100, 700). La structure de microcanal (400) est intégrée entre la seconde surface (201) et la première surface (101) pour former un microcanal (401, 802). Une substance à détecter (600) pénètre à partir de l'orifice d'injection (402, 810) dans la rainure (102, 702) par l'intermédiaire du microcanal (401, 802), et est séparée en un liquide de couche inférieure (601) et un liquide de couche supérieure (602), le liquide de couche inférieure (601) étant retenu dans la partie basse (103), et le liquide de couche supérieure (602) s'écoulant depuis la rainure (102, 702) jusqu'à la micropuce de détection (300, 900), sans qu'il soit nécessaire d'appliquer un courant supplémentaire au dispositif de détection (10, 20, 30) pendant le processus de détection de la substance à détecter (600).
PCT/CN2015/098146 2015-12-21 2015-12-21 Dispositif de détection WO2017107025A1 (fr)

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PCT/CN2015/098146 WO2017107025A1 (fr) 2015-12-21 2015-12-21 Dispositif de détection

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