WO2018179841A1 - Dispositif de piégeage de microparticules, système de piégeage de microparticules et procédé de piégeage de microparticules - Google Patents

Dispositif de piégeage de microparticules, système de piégeage de microparticules et procédé de piégeage de microparticules Download PDF

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Publication number
WO2018179841A1
WO2018179841A1 PCT/JP2018/003822 JP2018003822W WO2018179841A1 WO 2018179841 A1 WO2018179841 A1 WO 2018179841A1 JP 2018003822 W JP2018003822 W JP 2018003822W WO 2018179841 A1 WO2018179841 A1 WO 2018179841A1
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Prior art keywords
shape
flow path
flow
particles
wall surface
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PCT/JP2018/003822
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English (en)
Japanese (ja)
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健介 小嶋
渡辺　俊夫
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ソニー株式会社
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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D35/00—Filtering devices having features not specifically covered by groups B01D24/00 - B01D33/00, or for applications not specifically covered by groups B01D24/00 - B01D33/00; Auxiliary devices for filtration; Filter housing constructions
    • B01D35/02—Filters adapted for location in special places, e.g. pipe-lines, pumps, stop-cocks
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B81—MICROSTRUCTURAL TECHNOLOGY
    • B81B—MICROSTRUCTURAL DEVICES OR SYSTEMS, e.g. MICROMECHANICAL DEVICES
    • B81B1/00—Devices without movable or flexible elements, e.g. microcapillary devices
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M1/00—Apparatus for enzymology or microbiology
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00—Sampling; Preparing specimens for investigation
    • G01N1/02—Devices for withdrawing samples
    • G01N1/04—Devices for withdrawing samples in the solid state, e.g. by cutting
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N37/00—Details not covered by any other group of this subclass

Definitions

  • the present invention relates to a fine particle capturing apparatus, a fine particle capturing system, and a fine particle capturing method.
  • cells are the smallest functional units that make up living organisms, and even cells that look morphologically identical are not actually uniform, but the amount and type of genomes, expressed proteins, sugar chains / lipids and various metabolites, It is considered that there is a great difference between individual cells when discriminating at the molecular level including the modification mode.
  • comprehensive and quantitative analysis of molecular information carried by a diverse group of biomolecules at the level of one cell greatly increases the current state in which cell characteristics at the molecular level can only be evaluated as the average value of a cell population. It is a new approach to life science research that breaks down.
  • Patent Document 1 discloses a structure in which a well having a size into which a cell enters is engraved in a flow path in which a cell-containing sample flows, and a cell or bead is sucked by providing a slit in the well ( FIG. 23, FIG. 25, etc.).
  • the liquid flow in the micro flow channel is a laminar flow, and the flow rate at the center of the flow channel is always faster than the vicinity of the side surface of the flow channel.
  • particles are routed around the center of the flow path, they pass through vigorously, and there is a possibility that the cells or beads do not reach the vicinity of the microwell on the side wall where the slit is arranged.
  • the present technology has been made in view of such a situation, and an object thereof is to provide a particulate trapping device that improves the trapping efficiency of particulates that pass through the center of a flow path.
  • a particulate trapping apparatus as an example of the present technology includes a flow path for flowing fine particles, a recess formed in an inner wall surface of the flow path, and a drawing passage for drawing the fine particles, The lead-in passage is communicated, and a structure for guiding the flow of fine particles in the direction of the inner wall surface is formed on the inner wall surface.
  • the structure of the particulate trapping apparatus that is an example of the present technology can have a protrusion.
  • a particulate trapping system that is an example of the present technology includes a channel for flowing particulates on a substrate, a recess formed on the inner wall surface of the channel, and a passage for drawing in the particulates.
  • the passage for communication can include a fine particle trapping portion in which a structure for guiding the flow of fine particles in the direction of the inner wall surface is formed on the inner wall surface, and a liquid feeding portion connected to the fine particle trapping portion.
  • the fine particle capturing method as an example of the present technology includes a flow path for flowing the fine particles on the base material, a recess formed on the inner wall surface of the flow path, and a drawing passage for drawing the fine particles.
  • the sample passage containing the particles to be trapped is supplied to a fine particle capturing device in which a structure for guiding the flow of fine particles in the direction of the inner wall surface is formed on the inner wall surface, and the sample is sent to the inner passage.
  • the particles to be captured can be captured from the recess through the drawing-in passage to the outside.
  • the present technology it is possible to provide a particle capturing apparatus that improves the efficiency of capturing particles passing through the center of the flow path.
  • the effects of the present technology are not necessarily limited to the above effects, and may be any of the effects described in the present disclosure.
  • Embodiment 1 Particle capturing device Embodiment (1) Embodiment 1 (2) Embodiment 2 (3) Embodiment 3 (4) Embodiment 4 (5) Embodiment 5 (6) Embodiment 6 (7) Embodiment 7 (8) Embodiment 8 (9) Embodiment 9 2.
  • Particle capture system Particulate capture method4. Flow path shape of particle trap
  • Fine particle capture device [Configuration example of particulate trap]
  • the type of particles to be captured by the particulate capturing device of the present technology is not particularly limited.
  • a cell, a bead, a semiconductor chip, a micro bump as a terminal of a semiconductor connection portion, a bead type solar cell, and the like can be given.
  • the size and shape of the particles are not particularly limited.
  • hybrid bio / inorganic materials for example, hybrid bio / inorganic materials, nano-hybrid environmental sensors, environmental sensors: sensor array formation technology, concentrating materials for solar cells, and high-density mounting modules.
  • Forming technology using self-organized pattern as a template organic light switching device with periodic uneven structure of sub-wavelength (sub- ⁇ m) size necessary for self-organizing arrangement of chip-shaped parts, improving light extraction efficiency of light-emitting device, etc.
  • Formation of quasi-phase-matching structure by optical poling of non-linear organic dyes for self-assembly, self-assembly of metal or semiconductor nanoparticles for quantum dot memory, and polymer self-assembly material for nanocrystal memory .
  • the fine particle capturing apparatus 10 of the present technology includes a flow path 12 in a base material 11.
  • the substrate 11 is not particularly limited, and polyethylene, polypropylene, vinyl chloride resin, polystyrene, polyethylene terephthalate, acrylic resin, polycarbonate, fluororesin, polybutylene terephthalate, phenol resin, melamine resin, epoxy resin, unsaturated polyester resin, polydimethyl It is formed of a resin such as siloxane, glass, metal or the like.
  • the flow channel 12 can determine the width and height of the flow channel based on the size, shape, and type of particles to be captured, the amount of sample flowing through the flow channel, the viscosity, and the like.
  • the flow path 12 On the flow path 12, it has a corrugated structure having a peak portion 13 and a valley portion 14, and a concave portion 16 is formed on the top portion 15 of the peak portion 13. Particles in the sample are captured in the recess 16.
  • the flow path 12 has a top surface 19 on the opposite side of the corrugated structure.
  • the liquid flow of the sample is a laminar flow in the flow channel 12, and there is a characteristic that the flow velocity at the center of the flow channel 12 is always faster than the vicinity of the side surface of the flow channel (FIG. 3). 4 arrows at the top left). Therefore, the flow velocity of the top portion 15 is increased by providing the concave portion 16 in the corrugated top portion 15 of the corrugated structure. Therefore, by providing the concave portion 16 in the top portion 15, it is possible to prevent doublets in which two or more particles try to enter the concave portion 16 (dotted circle).
  • the flow rate is fast, so it is thought that the second and subsequent cells are less likely to enter the central laminar flow.
  • the central laminar flow is about 20% faster than the overall flow rate of the liquid flow.
  • the recess 16 further has a retracting passage 17.
  • a valve (not shown) is opened and proceeds downstream
  • the flow path 12 is formed by the presence of the drawing-in path 17 that communicates the recess 16 and the outside (downstream flow path) 18.
  • a pulling force is generated by positive pressure from the side toward the outside 18. Due to the pressure difference between the inside and outside of the flow path 12, the particles easily enter the recess 16.
  • the external 18 is a downstream flow path 12 and is in a series with the flow path 12.
  • valve installation is not limited to this.
  • a valve for flowing the sample liquid may be installed upstream of the flow path 12 where the recesses 16 are connected, and a valve for sucking the sample liquid may be installed downstream.
  • the shape of the recess 16 can be determined in accordance with the shape of the particles to be captured.
  • the shape of the concave portion 16 is, for example, a cylindrical shape, a truncated cone shape, an inverted truncated cone shape, an elliptical column shape, an elliptical truncated cone shape, an inverted elliptical truncated cone shape, a tapered shape, an inverted tapered shape, a polygonal column having a triangular shape or more. Can be mentioned.
  • the depth of the concave portion 16 is equal to or smaller than the particle size of the particles to be captured. With such a depth, it is possible to prevent doublets of particles in the recesses 16 and other particles from accumulating on the captured particles.
  • the “particle size” of the particles refers to the average value of the major axis diameter and minor axis diameter of the fine particles. Specifically, in the case of fine particles, the particle diameter can be calculated by measuring a considerable number (for example, 100) of arbitrary fine particles using image processing software or the like using a microscope and obtaining the number average.
  • the depth of the recess 16 can be preferably 2 or less, more preferably 1 or less, as a ratio to the particle size of the particles to be captured.
  • the depth of the recess 16 can be preferably 2 or less, more preferably 1 or less, as a ratio to the diameter of the inscribed circle in the opening of the recess 16.
  • the depth of the concave portion 16 is preferably 1 or less, more preferably 0.8 or less, in a ratio with the height from the valley portion 14 to the mountain portion 13.
  • the diameter of the recessed portion 16 is set to be a particle to be captured. It is preferable that the particle size is 1 time or more and less than 2 times the particle size. Further, in the case where the opening of the recess 16 is a polygon of a triangle or more, if it is an odd-numbered n-gon, the vertical line can be regarded as a perpendicular line, and if it is an even-numbered n-angle, a diagonal line can be regarded as a diameter. If the diameter is less than 1 time, it is difficult for a single cell to enter the recess 16, and if it is 2 times or more, a plurality of cells may enter.
  • the height from the valley 14 to the peak 13 is preferably the same as or higher than the particle size of the particles to be captured.
  • the flow rate of the liquid in the flow path 12 increases as it approaches the center. For this reason, when the height of the crest 13 and the trough 14 is lower than the particle size of the particles, the flow velocity received by the particles also in the vicinity of the crest 13 is slow. When the flow velocity in the vicinity of the mountain portion 13 is slow, particles that have flowed later easily adhere to the particles captured in the recess 16. Due to the low flow velocity, the energy of the particles that flow after the collision also decreases, and the particles adhere to the trapped particles and accumulate.
  • the pitch between the peaks 13 can be set to a length that is not less than 2 times and not more than 20 times the particle size of the particles to be captured. Specifically, the distance from the top 15 of the peak 13 to one valley 14 and the top 15 of the adjacent peak 13 is not less than 2 times and not more than 20 times the particle size of the particles to be captured. It is. If it is less than 2 times, particles may enter the valley 14, and if it exceeds 20 times, depending on the height of the peak 13, the corrugated structure approaches a flat structure, and the effect of the present technology is fully exhibited. There are things that cannot be done.
  • the pitch between the peaks 13 is more preferably 5 times to 15 times the particle size of the particles to be captured.
  • the effect produced by the waveform structure of the present technology can be exhibited.
  • a fine corrugated structure or a concave portion must be formed on the base material. In view of ease of manufacture, the above range can be adopted.
  • left and right pitches of the mountain portion 13 may be the same or different.
  • the channel width of the channel 12 can be relatively small at the peak portion 13 and can be increased at the valley portion 14. .
  • the central laminar flow of the liquid flow is fast, particles staying at the top 15 can be flowed.
  • FIG. 10 An example of the size of each part of the fine particle capturing apparatus 10 described above is shown in FIG. Here, it is assumed that the particle capturing apparatus 10 captures a single cell or bead having a diameter of 10 ⁇ m.
  • the width of the peak 13 is 70 ⁇ m
  • the height of the peak 13 is 15 ⁇ m
  • the width of the top 15 is 20 ⁇ m
  • the diameter of the opening of the recess 16 is 15 ⁇ m
  • the depth of the recess 16 is 10 ⁇ m
  • the drawing passage 17 Has a length of 35 ⁇ m and the width of the pull-in passage is 3 ⁇ m.
  • FIG. 5A shows the fine particle capturing apparatus 10 of the first embodiment.
  • FIG. 5B shows an enlarged plane of the flow path 12 in the particle capturing apparatus 10.
  • the particles to be captured in the microparticle capturing apparatus 10 are 15 ⁇ m ⁇ polystyrene beads.
  • the substrate was made of polydimethylsiloxane (PDMS) as a material, and a chip provided with a flow path and a microwell prepared by molding a PDMS resin in a mold serving as a master.
  • a PDMS substrate as a manufactured chip was subjected to direct plasma (DP) ashing with O 2 : 10 cc, 100 W, 30 sec to make the surface hydrophilic, and bonded to a cover glass in the air.
  • DP direct plasma
  • a flow path 12 is formed at the center of the base plate.
  • the channel 12 is formed with the corrugated structure and the recess 16 described above, and two systems can be operated in parallel with the upper channel and the lower channel.
  • An inlet port IN1 at the upper left of the base plate is connected to the flow path 12, and a particle-containing sample (a cell culture solution containing trypan blue) is introduced into the inlet port IN1.
  • the lower left inlet port IN2 of the base plate is also connected to the flow path 12, and water or D-PBS ( ⁇ ) is introduced into the inlet port IN2. Then, the particle-containing sample passes through the flow path 12 and is sucked into the upper right outlet port OUT1 of the base plate.
  • the particulate trapping apparatus 10 can perform these two systems of operations in parallel.
  • the particle-containing sample and water or D-PBS (-) are the force for introducing them, the force flowing downstream, the force for flowing the sample liquid generated by opening and closing a valve installed in the bypass, etc., from OUT1 and OUT2.
  • the sample liquid can be flowed into the flow path 12 by any one of the force for sucking the sample liquid or a combination thereof.
  • FIG. 6 shows a particulate trapping device 60 in which flow paths are arranged in parallel.
  • the fine particle capturing device 60 of FIG. 6 is formed in a two-layer structure of 1,500 well that can be highly integrated by disposing the flow path of the collecting pipe in the lower layer.
  • FIG. 6A is an enlarged view in which five rows of channels are arranged, and FIG. 6B is enlarged so that the structure at the left end of the channel can be seen.
  • each channel has a corrugated structure, a recess, and a pull-in passage on both sides (the left and right inner sides of the channel).
  • FIGS. 6D, 6F, and 6G show an example of the size of each part of the fine particle capturing apparatus 60 of the present embodiment.
  • the particle capturing device 60 captures a single cell or bead having a diameter of 10 ⁇ m.
  • the width of the peak is 70 ⁇ m
  • the height of the peak is 15 ⁇ m
  • the width of the top is 20 ⁇ m
  • the diameter of the opening of the recess is 15 ⁇ m
  • the depth of the recess is 10 ⁇ m
  • the length of the lead-in passage 17 is 70 ⁇ m.
  • the width of the drawing-in passage is 3 ⁇ m.
  • the width of the external groove on both sides of the flow path is 500 ⁇ m.
  • the width of the channel is 70 ⁇ m and the height of the channel is 100 ⁇ m.
  • the particle-containing sample is supplied from the introduction part on the left side of FIG. 6A, passes through each flow path, and the flow is divided into two at the right end, so that the sample liquid flows outside.
  • a positive pressure is generated by the presence of the use passage, and the particles are trapped in each recess.
  • FIG. 7 shows an experimental configuration example in which a bead capturing experiment was performed using the particle capturing apparatus 60 of FIG.
  • one end of the first PEAK tube is connected to the outlet port OUT1 of the jig, and the other end of the first PEAK tube is connected to the Alternative Pump (AP) via the drain bottle.
  • one end of the second PEAK tube is connected to the outlet port OUT2 of the jig, and the other end of the second PEAK tube is connected to the Primming Pump (PP) via the drain bottle.
  • a stock solution of 15 ⁇ m ⁇ polystyrene beads was diluted 1000 times to prepare a particle-containing sample.
  • the fine particle capturing device 60 is mounted on a jig, and PBS and sheath liquid (water) for replacing the inside of the flow path of the fine particle capturing device 60 are prepared in each reservoir tank.
  • PBS and sheath liquid (water) for replacing the inside of the flow path of the fine particle capturing device 60 are prepared in each reservoir tank.
  • one of each reservoir tank and each inlet PEAK tube was connected, and the other of each inlet PEAK tube was connected to each inlet port IN1 and IN2 of the jig.
  • the inside of the flow path is decompressed by the suction pumps PP-line and AP-line from each of the outlet ports OUT1 and OUT2 (the right side portion of the particulate trapping device 60), thereby facilitating the flow of the sheath liquid and expelling bubbles in the flow path.
  • the inside of the channel was completely replaced with liquid.
  • the diluted solution of beads was loaded into a reservoir tank of PBS solution, and inserted into the particle capturing device 60 from the
  • the suction was -5 kPa on the PP side and -2 kPa on the AP side.
  • the height of the liquid surface was set to 10 cm above the surface of the fine particle capturing apparatus 60 on the sheath liquid side, and 1 cm above the PBS side on which the particle-containing sample was loaded.
  • FIG. 8 shows a particle trapping device 80 that realizes 3,500 wells, which is more than twice as many as the number of flow paths, with respect to the 1,500 well particle trapping device 60 of FIG. 8A shows an upper layer 81 that distributes sheath fluid, FIG. 8B shows a lower layer 82 that distributes cell fluid, and FIG. 8C shows a two-layer structure 83 in which the upper layer 81 and the lower layer 82 are laminated.
  • FIG. 8D is an enlarged view of the region A8 into which the sheath liquid in FIG. 8A is injected
  • FIG. 8E is an enlarged view of the region D8 in FIG. 8D.
  • the fine particle capturing device 80 forms an upper and lower two-layer structure 83, but the cell fluid flows in the lower layer 82 through the through-hole by switching the sheath fluid piping and the cell channel piping up and down, and the cell channel in the channel of the upper layer 81 Designed to be transported to
  • the lower layer 91 and the upper layer 81 shown in FIG. 9A are stacked to form a two-layer structure 92 shown in FIG. 9B.
  • a two-layer structure 92 In the two-layer structure 92, a plurality of main flow paths are arranged in parallel. In this case, cell utilization efficiency is lowered.
  • the two-layer structure 102 has a continuous main flow path. In this case, the flow path resistance is large and bubbles cannot be removed.
  • the lower layer 111 and the upper layer 81 shown in FIG. 11A are stacked to form a two-layer structure 112 shown in FIG. 11B.
  • a plurality of main flow paths are parallel and continuous.
  • the flow path resistance becomes appropriate and bubbles are easily removed. Therefore, it can be seen that the two-layer structure 112 is the configuration that increases the cell utilization efficiency most.
  • Embodiment 4 A particulate trapping apparatus according to Embodiment 4 will be described with reference to FIGS.
  • a concave array that captures particulates is formed on both sides of the inner wall surface of the flow path, and a structure that guides the flow of particulates toward the inner wall surface on the bottom surface of the inner wall surface of the flow path. Is formed.
  • FIG. 12A is a perspective view showing a structure formed in the particle capturing apparatus 120 of the present embodiment
  • FIG. 12B is a center in the width direction (vertical direction in FIG. 12B) of the structure formed in the particle capturing apparatus 120.
  • It is sectional drawing which shows the cross section which cut
  • a prism shape 121 is formed as a structure on the bottom surface of the inner wall surface of the flow path.
  • FIG. 13A is a perspective view showing a structure formed in the particle trapping apparatus 130 of Modification 1 of the present embodiment
  • FIG. 13B shows a structure formed in the particle trapping apparatus 130 as in FIG. 12B. It is sectional drawing shown.
  • a single diamond shape 131 as a structure is formed near the inlet of the flow channel on the bottom surface of the inner wall surface of the flow channel.
  • FIG. 14A is a perspective view showing a structure formed in the particle trapping apparatus 140 of Modification 2 of the present embodiment
  • FIG. 14B shows a structure formed in the particle trapping apparatus 140 as in FIG. 12B. It is sectional drawing shown.
  • an array of pole shapes 141 as structures is periodically arranged in the center of the bottom surface of the inner wall surface of the flow path in the extending direction of the flow path. Has been. Note that these arrangements may be random, not periodic.
  • FIG. 15A is a perspective view showing a structure formed in the particle trapping apparatus 150 of Modification 3 of the present embodiment
  • FIG. 15B shows a structure formed in the particle trapping apparatus 150 as in FIG. 12B. It is sectional drawing shown.
  • the particulate trapping apparatus 150 of Modification 3 has an array of pyramid shapes 141 as periodic structures periodically arranged in the extending direction of the flow channel on the bottom surface of the inner wall surface of the flow channel. Yes.
  • FIG. 16A is a perspective view showing a structure formed in the particle trapping device 160 of Modification 4 of the present embodiment
  • FIG. 16B shows a structure formed in the particle trapping device 160 as in FIG. 12B
  • FIG. 16C is a plan view showing a structure formed in the fine particle capturing device 160.
  • an array of torus shapes 161 as structures are periodically arranged in the extending direction of the flow path on the bottom surface of the inner wall surface of the flow path. Yes.
  • FIG. 17A is a perspective view showing a structure formed in the particle capturing device 170 of Modification 5 of the present embodiment
  • FIG. 17B shows a structure formed in the particle capturing device 170 in the same manner as FIG. 12B. It is sectional drawing shown.
  • an array of octagon (octagonal) shape 171 as a structure on the bottom surface of the inner wall surface of the flow path is periodically arranged in the extending direction of the flow path. Is arranged.
  • FIG. 18A is a perspective view showing a structure formed in the particle trapping apparatus 180 of Modification 6 of the present embodiment
  • FIG. 18B shows a structure formed in the particle trapping apparatus 180 similarly to FIG. 12B. It is sectional drawing shown.
  • the particle trapping device 180 of Modification 6 has an array of dome-shaped 181 as a structure periodically arranged in the extending direction of the flow channel on the bottom surface of the inner wall surface of the flow channel. Yes.
  • the dome shape 181 can make the height of a top part equivalent to the height of the recessed part which capture
  • FIG. 19A is a perspective view illustrating a structure formed in the particle capturing apparatus 190 according to Modification 7 of the present embodiment
  • FIG. 19B illustrates a structure formed in the particle capturing apparatus 190 as in FIG. 12B. It is sectional drawing shown.
  • an array of phase-shifted dome-shaped (Phase (shift) 191 is extended on the bottom surface of the inner wall surface of the flow path. It is periodically arranged in the direction.
  • the shape of the structure is not limited to the shape of the present embodiment, and may be a shape having a protrusion such as an elliptical shape, a conical shape, or a combination of these shapes.
  • FIG. 20 shows the tendency of particle induction when the flow rate is 4E-4 m / sec.
  • FIG. 21 shows the tendency of particle induction when the flow rate is 2E-3 m / sec. 22 and 23 show the relationship between the shape, flow velocity and pressure of the structure and the number of trapped particles.
  • the shape of the structure is a dome shape 181, the number of trapped particles is the highest. It was also found that the default number of trapped particles was the lowest.
  • the “default shape” refers to a shape in which a recess is formed only on one side surface of the flow path and no structure is formed on the bottom surface of the flow path.
  • the particulate trapping device of the present embodiment has a structure on the inner wall surface (bottom surface) of the flow path so that the concave portion for trapping particulates is formed in the direction of the inner wall surface compared to the conventional particulate trapping device. Since the flow of the fine particles can be induced, the capture efficiency of the fine particles passing through the center of the flow path can be improved.
  • FIG. 24A is a perspective view showing a structure formed in the particle trapping apparatus 240 of the present embodiment
  • FIG. 24B is a cross-sectional view showing the structure formed in the particle trapping apparatus 240 similarly to FIG. 12B
  • FIG. 24C is a plan view showing the structure formed in the particulate trapping device 240.
  • an array of oval shapes 241 as structures is periodically formed on the bottom surface of the inner wall surface of the flow path in the extending direction of the flow path. Has been placed.
  • FIG. 25A shows the tendency of particle induction when the flow rate is 4E-4 m / sec
  • FIG. 25B shows the tendency of particle induction when the flow rate is 2E-3 m / sec.
  • the shape of the structure is the oval shape 241
  • the number of trapped particles is higher especially when the flow velocity is 4E-4 m / sec, compared to the case of the default shape. I understood.
  • the particulate trapping device 240 of the present embodiment can improve the trapping efficiency of particulates passing through the center of the flow path, as compared with the conventional particulate trapping device, like the particulate trapping devices 120 to 190 of the fourth embodiment. it can.
  • FIG. 26A is a perspective view showing a structure formed in the particle trapping apparatus 260 of the present embodiment
  • FIG. 26B is a cross-sectional view showing the structure formed in the particle trapping apparatus 260 similarly to FIG. 12B
  • FIG. 26C is a plan view showing a structure formed in the particulate trapping device 260.
  • the particulate trapping apparatus 260 of the present embodiment has a protrusion that is lower than the height of the protrusion of the torus shape 161 of FIG. 16 on the bottom surface of the inner wall surface of the flow path.
  • An array of thin torus shapes 261 is periodically arranged in the extending direction of the flow path.
  • FIG. 27A shows the tendency of particle induction when the flow rate is 4E-4 m / sec
  • FIG. 27B shows the tendency of particle induction when the flow rate is 2E-3 m / sec.
  • the number of trapped particles is higher in the case of the thin torus shape 261 as compared with the default shape, particularly when the flow velocity is 4E-4 m / sec. I understood it.
  • the particulate trapping device 260 of the present embodiment can improve the trapping efficiency of particulates passing through the center of the flow path, as compared with the conventional particulate trapping device, as in the particulate trapping devices 120 to 190 of the fourth embodiment. it can.
  • FIG. 28A is a perspective view showing a structure formed in the particle trapping device 280 of this embodiment
  • FIG. 28B is a cross-sectional view showing a structure formed in the particle trapping device 280 similarly to FIG. 12B
  • FIG. 28C is a plan view showing the structure formed in the particle capturing device 280.
  • the fine particle capturing apparatus 280 of the present embodiment has a structure on the bottom surface of the inner wall surface of the flow path in the arrangement direction of the torus shape 281 in addition to the torus shape 281 as shown in FIG.
  • An array of pole-shaped torus shapes 283 having pole shapes 282 formed on both side surfaces is periodically arranged in the extending direction of the flow path.
  • FIG. 29A shows the tendency of particle induction when the flow rate is 4E-4 m / sec
  • FIG. 29B shows the tendency of particle induction when the flow rate is 2E-3 m / sec.
  • the shape of the structure is the torus shape with a pole 281
  • the number of trapped particles is high particularly when the flow velocity is 4E-4 m / sec, compared to the case of the default shape.
  • the particulate trapping device 280 of the present embodiment can improve the trapping efficiency of the particulates passing through the center of the flow path, as compared with the conventional particulate trapping device, similarly to the particulate trapping devices 120 to 190 of the fourth embodiment. it can.
  • Embodiment 8 [Example of mounting technology for self-aligning IC chips] A fine particle capturing apparatus of the present technology was manufactured from an on-chip IC (SoC: system on silicon) substrate.
  • SoC system on silicon
  • a high-density IC chip fabricated on a silicon wafer by a semiconductor process is cut out from the wafer into a 100 ⁇ m square using a dicer.
  • the number of IC chips depends on the size to be cut out and the width of the margin for cutting, the number of IC chips is prepared as many as 7 million on a 300 mm wafer.
  • the IC chip placed in the concave portion at the top of the corrugated structure can be combined with another chip for subsequent wiring by a subsequent process.
  • another electrical circuit board is built around the top of the corrugated flow path, and when the IC chip is captured in the recess, the wiring is expanded with a wire bonder or the like, and integrated with the flow path board. Can be produced. Further, by cutting out, an on-chip IC device can be efficiently manufactured.
  • Embodiment 9 [Application to fabrication of micro LED display] A fine particle capturing apparatus shown in FIG. 30 was produced. Three independent lanes having a corrugated structure are prepared, and different micro LED chips are dispersed in the liquid in each lane, and are fed in the direction of the arrow on the left side of FIG. By flowing the LED and the green LED, the LEDs can be mounted at equal intervals of 150 ⁇ m pitch.
  • the LED chip captured at the top of the corrugated structure 31 can be used as a micro LED display by wiring with a wire bonder to the captured concave portion and the global electrode 27 disposed below the concave portion.
  • this mounting technique can be applied to mount an IC circuit currently made of polysilicon on each pixel at an equal interval pitch. . Therefore, an active matrix polysilicon circuit that is expensive and has a poor yield can be replaced with an IC chip that operates stably.
  • the particulate trapping system of the present technology includes a liquid feeding section in the particulate trapping device.
  • FIG. 31 shows an example of the particle capturing system 301.
  • the fine particle capturing unit 302 is connected to the liquid feeding unit 303 via the valve 307.
  • the liquid feeding unit 303 supplies the particle-containing sample to the fine particle capturing unit 302.
  • Sample flow can be controlled by opening and closing valve 307. This control can be performed by the liquid feeding control unit 306.
  • a control program may be provided in a computer to automatically control liquid feeding. By controlling the liquid feeding, not only can the sample flow / stop, but also a reverse flow and a pulsating flow that changes the flow at regular intervals can be generated.
  • the particle capturing system 301 may include a particle observation unit 305.
  • the particle observation unit 305 is not particularly limited, but the flow path and particles flowing and captured may be magnified with a microscope or the like and observed with the naked eye, or data processing may be performed with an image processing apparatus or the like without depending on the naked eye. It may be. The observation result here is fed back to the liquid feeding control unit 306 to further control the flow of the sample.
  • the particulate trapping system 301 may include a waste liquid portion 304 on the downstream side, and can collect a sample liquid having a reduced particle content as a waste liquid.
  • a valve or a pump may be further provided on the upstream side or the downstream side of the waste liquid unit 304, and a suction force may be applied to the flow path of the particle capturing unit 302.
  • Fine particle capture method The fine particle capture method of this technology supplies the sample containing the particles to be captured to the particle capture device and feeds the sample, while sucking it out from the recess through the pull-in passage to capture the particles to be captured. It is a method to do.
  • a fine particle capturing method as an example of the present technology includes a flow path for flowing fine particles on a substrate, a recess formed on an inner wall surface of the flow path, and a drawing passage for drawing the fine particles. Then, the recess and the lead-in passage are communicated with each other, and a sample containing particles to be captured is supplied to a fine particle capturing device in which a structure for guiding the flow of fine particles in the direction of the inner wall surface is formed on the inner wall surface. While feeding the sample, the sample can be sucked out from the recess through the drawing-in passage to capture the target particles.
  • connection flow path from the INLET to the main flow path where the microwell array is arranged was connected with a steep curve.
  • polystyrene beads of ⁇ 20.000.10 ⁇ 0.10 um are used, there is a possibility that traffic congestion will increase if a 1000-fold diluted bead can be caught.
  • the flow path has a shape having a gentle slope obliquely from INLET (IN1 and IN2) toward the flow paths 321 and 322, and the connection portion is It is close to a straight line. Furthermore, the shapes of the flow paths 321 and 322 are tapered toward the direction in which the fine particles flow (direction from IN to OUT).
  • the particle trapping device avoids accumulation due to sudden deceleration of particles by connecting the connection channel from INLET to the main channel where the microwell array is arranged with a gentle curve. can do. Furthermore, the particle trapping device according to the present technology has a tapered asymmetry channel shape, and the pressure decreases toward the back side of the microwell array. The pressure distribution by tapering the flow path can be made uniform.
  • this technique can take the following structures.
  • a structure for guiding the flow of fine particles in the direction of the inner wall surface is formed on the inner wall surface. Particulate trap.
  • a particulate trapping system comprising a liquid feeding section connected to the particulate trapping section.
  • a particle capturing device in which a structure for guiding the flow of particles in the inner wall direction is formed In the inner wall surface, a particle capturing device in which a structure for guiding the flow of particles in the inner wall direction is formed, A fine particle capturing method, wherein a sample containing particles to be captured is supplied and the sample is sucked to the outside through the pull-in passage from the recess to capture the particles to be captured.

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Abstract

La présente technique fournit un dispositif de piégeage de microparticules qui améliore l'efficacité de piégeage des microparticules passant au milieu d'un trajet d'écoulement. A cet effet, la présente technique concerne un dispositif de piégeage de microparticules qui comporte : un trajet d'écoulement à travers lequel s'écoulent des microparticules ; des évidements situés à la surface de la paroi interne du trajet d'écoulement ; et un trajet d'attraction pour attirer les microparticules. Les évidements et le trajet d'attraction communiquent. Une structure visant à diriger le flux de microparticules vers la surface de la paroi interne est présente à la surface de la paroi interne.
PCT/JP2018/003822 2017-03-31 2018-02-05 Dispositif de piégeage de microparticules, système de piégeage de microparticules et procédé de piégeage de microparticules WO2018179841A1 (fr)

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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2006094783A (ja) * 2004-09-29 2006-04-13 Fujitsu Ltd 細胞給排・捕捉装置及び細胞給排・捕捉方法
JP2009125635A (ja) * 2007-11-21 2009-06-11 Foundation For The Promotion Of Industrial Science 再セット可能な微小液滴の配列装置
US20130078163A1 (en) * 2011-09-22 2013-03-28 Georgia Tech Research Corporation Deterministic High-Density Single-Cell Trap Array
WO2016073486A1 (fr) * 2014-11-03 2016-05-12 The General Hospital Corporation Concentration de particules dans un dispositif microfluidique
WO2018037788A1 (fr) * 2016-08-23 2018-03-01 ソニー株式会社 Appareil de capture de particule unique, système de capture de particule unique et procédé de capture de particule unique

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2006094783A (ja) * 2004-09-29 2006-04-13 Fujitsu Ltd 細胞給排・捕捉装置及び細胞給排・捕捉方法
JP2009125635A (ja) * 2007-11-21 2009-06-11 Foundation For The Promotion Of Industrial Science 再セット可能な微小液滴の配列装置
US20130078163A1 (en) * 2011-09-22 2013-03-28 Georgia Tech Research Corporation Deterministic High-Density Single-Cell Trap Array
WO2016073486A1 (fr) * 2014-11-03 2016-05-12 The General Hospital Corporation Concentration de particules dans un dispositif microfluidique
WO2018037788A1 (fr) * 2016-08-23 2018-03-01 ソニー株式会社 Appareil de capture de particule unique, système de capture de particule unique et procédé de capture de particule unique

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