JP2005205387A - Continuous particle classification method - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a continuous particle classification method capable of retaining a high classifying accuracy and classifying even extremely small particles when classifying the particles of a synthetic polymer, inorganic powder, metal powder, an animal or a plant cell, emulsion, etc. <P>SOLUTION: A fluid 100P including particles and a fluid 100N not including particles are introduced from inlets 18a and 18b, and, simultaneously, the flow width of the fluid 100P including particles at a section 16 is narrowed to a diameter smaller than the diameter of a particle to be separated thereby to make the position of the particle at the section 16 fixed according to the size of the particle, and utilizing the flow profile 200 enlarging at a wide-width section 17 following, the particle is separated into a direction perpendicular to the flow. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

Detailed Description of the Invention

  The present invention relates to a continuous particle classification method, and more particularly, a continuous particle classification method suitable for use in the continuous classification of particles such as synthetic polymers, inorganic powders, metal powders, animal and plant cells, and emulsions. About.

  In general, the technology for classifying particles such as synthetic polymers, inorganic powders, metal powders, animal and plant cells, and emulsions is not only for basic research but also for specific sizes in the powder industry, electronics industry, food industry, pharmaceutical industry, etc. It is recognized as an important technique in a wide range of fields, such as selection of particle size and analysis of particle size distribution.

  As conventional techniques for classifying particles, for example, a classification method using a liquid cyclone, a classification method using chromatography, or a classification method using field flow fractionation is known.

  However, the classification method using a liquid cyclone can process a large amount at a time, but has problems such as low classification accuracy, difficulty in classifying particles having a very small particle size, and continuous processing.

  In addition, the classification method using chromatography and field flow fractionation has high classification accuracy and is compatible with particles with a particle size of 1 micrometer or less. There are problems that separation takes a long time, the amount that can be processed at one time is small, and continuous processing cannot be performed.

  The present invention has been made in view of the above-mentioned various problems of the prior art, and its object is a synthetic polymer, inorganic powder, metal powder, animal and plant cell, emulsion, etc. Therefore, the present invention is intended to provide a continuous particle classification method that maintains high classification accuracy when classifying particles, and that can classify particles having extremely small particle sizes.

  Another object of the present invention is to provide a continuous particle classification method in which particles can be classified rapidly and in large quantities by continuously introducing particles.

  In order to achieve the above object, the present invention can control the position of particles in a direction perpendicular to the flow by introducing a fluid from a plurality of branches into a channel whose diameter is partially narrowed. This is made by paying attention to the fact that the direction of force applied to particles by the position of the particles varies.

  First, in order to introduce a fluid containing particles and a fluid not containing particles into the flow channel, the flow channel needs to have a plurality of branches at the inlet.

  The invention according to claim 1 of the present invention is a flow channel having a plurality of branches at only one of both ends, and is connected to a portion having a relatively small diameter and a portion having a small diameter in the flow channel. And a structure having a relatively thick portion, wherein a fluid containing particles is continuously introduced from at least one of the plurality of branches, and at least one of the plurality of branches. By continuously introducing a fluid that does not contain particles from two branches, the position in the direction perpendicular to the flow of the particles is made constant according to the size of the particles in the portion with the small diameter, and the diameter is thin. Utilizing the fact that the direction of the force applied to the particles by the flow differs depending on the position in the direction perpendicular to the particle flow at the boundary between the portion and the large diameter portion, the separation is performed at the large diameter portion. It is.

  Therefore, according to the first aspect of the present invention, since the flow path has a plurality of branches only at one end of both ends thereof, a fluid containing particles and a fluid not containing particles from the branches. By introducing each of them continuously, in the part where the diameter of the flow path is small, the particles flow almost in contact with the flow path wall, and the position of the particles in the direction perpendicular to the flow becomes constant depending on the size of the particles. In addition, because the direction of particle movement differs depending on the position of the particle in the direction perpendicular to the flow at the boundary between the portion with a smaller diameter and the portion with a larger diameter, the position of the particle in the direction perpendicular to the flow in the subsequent portion with a larger diameter By increasing the difference, it becomes possible to separate the particles according to the size of the particles, and by using an appropriate detection system, the particle size and particle size distribution of the particles can be measured.

  Moreover, the invention according to claim 2 of the present invention is a flow path having a plurality of branches at both ends, and the diameter of the flow path is small and the diameter connected to the narrow diameter part is A structure having a thick portion, wherein at one end of the flow path, a fluid containing particles is continuously introduced from at least one of the plurality of branches, and of the plurality of branches. By continuously introducing a fluid containing no particles from at least one branch, the position in the direction perpendicular to the flow of the particles is made constant according to the size of the particles in the portion where the diameter is small, and the diameter Using the fact that the direction of the force applied to the particles by the position in the direction perpendicular to the particle flow is different at the boundary between the thin part and the thick part, separation is performed at the thick part. , Respectively to recover the discrete particles at the other end in the flow path, is that.

  Therefore, according to the second aspect of the present invention, since the flow path has a plurality of branches at both ends, the fluid containing particles and the fluid not containing particles are continuously fed from the branch on the inlet side. By introducing, in the portion where the diameter of the flow path is thin, the particles flow while almost in contact with the flow path wall, and the position of the particles in the direction perpendicular to the flow becomes constant depending on the size of the particles, and the diameter further increases. At the boundary between the narrow part and the part with a large diameter, the direction of particle movement differs depending on the position of the particle in the direction perpendicular to the flow. Therefore, the difference in the position of the particle in the direction perpendicular to the flow is enlarged in the part with a large diameter. By doing so, the particles are separated according to size, and further, the separated particles can be recovered at the branch on the outlet side.

  In the continuous particle classification method according to any one of claims 1 and 2, the invention according to claim 3 of the present invention is any one of the width, depth, diameter, and the like of the flow path. Is at least partially in the order of 1 centimeter or less, and the fluid flows in the flow path while maintaining a stable laminar flow.

  Therefore, according to the third aspect of the present invention, each of the introduced fluids flows while maintaining a stable laminar flow, so that more stable control of the particle position is possible, and particle classification and recovery are possible. Can be performed more accurately.

  The invention according to claim 4 of the present invention is that the fluid is a liquid in the continuous particle classification method according to any one of claims 1, 2, or 3. .

  Therefore, according to the invention described in claim 4 of the present invention, it is possible to classify particles suspended in a liquid such as a cell or an emulsion.

  Moreover, invention of Claim 5 among this invention is the continuous particle classification method of any one of Claim 1, Claim 2, Claim 3 or Claim 4, A fluid is gas. That's it.

  Therefore, according to the fifth aspect of the present invention, classification can be performed without suspending particles in a liquid.

  The invention according to claim 6 of the present invention is the continuous particle classification method according to any one of claims 1, 2, 3, 4, or 5. The plurality of flow paths having different scales such as the width, depth, and diameter of the portion with a narrow diameter are connected in series to perform classification in multiple stages.

  Therefore, according to the invention described in claim 6 of the present invention, by connecting in series a plurality of different scales such as the width, depth, diameter, etc. of the portion where the diameter of the flow path is narrow, Stage classification can be performed, and classification with high accuracy is possible even when classifying particles having a wide particle size distribution.

  The invention according to claim 7 of the present invention is the continuous particle classification method according to any one of claims 1, 2, 3, 4, 5, or 6. The channel is a channel formed in the microchip.

  Therefore, according to the seventh aspect of the present invention, the shape of the flow path can be accurately controlled, and the flow path can be easily multistaged and parallelized, so that the classification accuracy is improved. In addition, an improvement in throughput can be expected.

  In addition, according to the seventh aspect of the present invention, since the scale of the flow path is on the order of nanometers to micrometers, it is possible to accurately separate very fine particles.

  Hereinafter, an embodiment of a continuous particle classification method according to the present invention will be described in detail based on the attached documents.

  1A, 1B, and 1C show a microchip 10 that includes an embodiment of a continuous classification method according to the present invention. FIG. 1A is a view taken along an arrow A in FIG. FIG. 1B is a cross-sectional view taken along line BB in FIG. Moreover, FIG.1 (c) is an enlarged view of the part C in Fig.1 (a).

  This microchip 10 is a microchip for measuring the particle size and particle size distribution by separating particles according to their sizes and using an appropriate detection system, such as PDMS (polydimethylsiloxane). It has a flat structure formed by two flat substrates 11 and 12 formed of a polymer material.

  And the flow path 13 is formed in the lower surface 11a of the board | substrate 11, and the depth of a flow path is about 50 micrometers, but this value can be set to arbitrary values from 10 nm to 1 cm. .

  The flow path 13 has inlet-side ports 14a and 14b and an outlet-side port 15. The inlet-side ports 14a and 14b are inlets for a fluid containing particles and a fluid containing no particles, respectively, and the outlet-side port 15 is a fluid. Is the exit.

  In addition, one end of the flow path 13 has two branches (branches 18a and 18b), and the flow path 13 is composed of portions 16 and 17 having two different shapes. The portion 16 corresponds to a portion having a relatively small diameter in claim 1, and the portion 17 corresponds to a portion having a relatively large diameter connected to the portion having a relatively small diameter in claim 1. .

  Here, the branches 18 a and 18 b are connected to the inlet side ports 14 a and 14 b, respectively, and the portion 17 is connected to the outlet side port 15.

  The entire length of the flow path 13, that is, the length from one end where the inlet-side ports 14 a and 14 b are located to the other end where the outlet-side port 15 is located is 19 mm. The lengths are 0.1 mm and 10 mm, respectively, but these values can be set to arbitrary values of 1 μm or more.

  The widths of the portions 16 and 17 are 47 μm and 1 mm, respectively. However, as long as the condition that the width of the portion 16 is less than the width of the portion 17 is satisfied, these values are set to arbitrary values of 10 nm or more, respectively. It is possible.

  The widths of the branches 18a and 18b are 100 μm, but these values can be set to arbitrary values of 10 nm or more, respectively.

  A continuous particle classification method for separating particles such as synthetic polymer, inorganic powder, metal powder, animal and plant cells using the above-described microchip 10 in the above configuration will be described.

  As the particles to be classified, polystyrene-divinylbenzene beads having a diameter of 15 μm and 30 μm were used. However, if the maximum diameter of the particles to be classified is equal to or smaller than the width of the portion 16 in the flow path 13, particles of any size Can be classified.

  As the fluid in which the particles are suspended, a 10 wt% dextran aqueous solution is used, but any liquid or gas can be used.

  Note that the fluid containing particles and the fluid not containing particles may be composed of the same fluid, or may be composed of two or more different fluids.

  The particles introduced into the flow path 13 move in the downstream direction along the flow. At this time, by appropriately adjusting the flow rate of the fluid introduced from the two inlet ports 14a and 14b, the flow path In part 16 at 13, the position of the particles in the direction perpendicular to the flow can be controlled by the size of the particles.

  Hereinafter, a mechanism for controlling the position of the particles will be described. FIG. 2 is an enlarged view of a portion D in FIG. Further, the fluid 100P and the fluid 100N shown by hatching are a fluid containing particles and a fluid not containing particles, respectively, and the particles 300a and 300b are relatively large particles and relatively small particles, respectively. Yes.

  In FIG. 2, an arrow 200 indicates a streamline profile at the boundary between the portion 16 and the portion 17, and arrows 210a and 210b indicate motion vectors of large particles and small particles, respectively.

  First, the fluid 100P including particles and the fluid 100N not including particles are continuously supplied from the two inlet ports 14a and 14b using a syringe pump or the like. At this time, each fluid flows in the flow path 13 while maintaining a stable laminar flow.

  Then, by adjusting the flow rates of the fluid 100P including particles and the fluid 100N not including particles, the width of the fluid 100P in the portion 16 is made smaller than the particle size of the minimum particles to be separated. By this operation, all the particles to be separated flow along one wall 16a in the portion 16, and the position of the particles in the direction perpendicular to the flow in the portion 16 is made constant according to the size of the particles. be able to.

  At the boundary between the portion 16 and the portion 17, the streamline spreads as shown in the profile 200, so that the distance between any streamlines in the portion 16 is further increased in the portion 17.

  Therefore, since the position of the particle in the direction perpendicular to the flow in the portion 16 differs depending on the size of the particle, the motion vector 210a of the large particle 300a and the motion vector 210b of the small particle 300b are at the boundary between the portion 16 and the portion 17. A difference occurs in the direction, and in the subsequent portion 17, the positional difference for each particle size is enlarged, and classification is possible.

  In addition, by observing the separated particles along the detection line 20 in the portion 17 using an appropriate detection system, the particle size of the particles and the particle size distribution of the particle group can be examined.

  Actually, the microchip 10 was used, and a dextran 10 wt% aqueous solution was used as the fluid, and the polystyrene-divinylbenzene bead mixture having a diameter of 15 μm and 30 μm was successfully classified.

  The flow path 13 provided with the embodiment of the continuous classification method according to the invention described above is provided with two inlet-side branches, and a portion 17 for performing classification is directly outlet-side port 15 without branching. However, the present invention is not limited to this, and it is possible to set the number of entrance side branches to 2 or more and the number of exit side branches to any number of 1 or more. 3 (a) and 3 (b) show flow paths 21 and 22 which are modifications thereof.

  In FIG. 3A, the flow path 21 includes three inlet side branches 18a, 18b, 18c for connecting the inlet side ports 14a, 14b, 14c and the part 16, and a part 17 for performing classification. And five outlet side branches 19a to 19e for connecting the five outlet side ports 15a to 15e.

  It is possible to introduce a fluid containing particles from one or two of the three inlet ports 14a, 14b, and 14c into the flow path 21 and introduce a fluid containing no particles from the remaining ports. .

  Further, when classification is performed, the position of the particles in the direction perpendicular to the flow in the portion 17 varies depending on the size of the particles. Therefore, the classified particles flow to separate branches in the subsequent outlet side branches 19a to 19e. Therefore, it is possible to separately collect the classified particles at the respective outlet ports 15a to 15e.

  In FIG. 3B, the flow path 22 includes two inlet-side branches 18a and 18b for connecting the inlet-side ports 14a and 14b and the portion 16, and the classification portion 17 has seven direct portions. It connects with the exit side branch 19a-19g, and each branch 19a-19g is connected with the exit side port 15a-15g.

  It is possible to introduce a fluid containing particles from one of the two inlet ports 14a and 14b into the flow path 22 and introduce a fluid containing no particles from the other port.

  Further, the particles whose position is controlled in the portion 16 can be classified by flowing into the flow channel 17 wider than the portion 16, and the number of the outlet side branches 19a to 19g is equal to the outlet side branch 19a in the flow channel 21. Since it is larger than the number of ~ 19e, more accurate classification and recovery are possible.

  Moreover, in the flow path 13 provided with the embodiment of the continuous classification method according to the invention described above, the shape of the cross section is rectangular, and each of the two fluids flows while contacting the flow path wall in the portion 16. Of course, it is not limited to this.

  That is, when classifying the particles, it is only necessary that the position of the particles be constant depending on the size by using the flow path wall in the portion 16, so that the liquid not containing the particles is not necessarily in contact with the flow path wall. It may be. In FIG. 4, the flow path 23 which is the modification is shown.

  The flow path 23 is a cylindrical flow path having a partially different diameter. FIG. 4A is a cross-sectional view taken along line AA in FIGS. 4B, 4C, and 4D, and FIG. (C) (d) are sectional views taken along lines B1-B1, B2-B2, and B3-B3 in FIG. 4 (a), respectively.

  The flow path 23 has an inlet side flow path 24a and an inlet side flow path 24b disposed inside the inlet side flow path 24a at one end, a portion 25 having a smaller diameter, and a portion 26 having a larger diameter following that. have.

  The portions 25 and 26 of the flow path 23 correspond to the portions 16 and 17 in FIGS. 1 and 2, respectively, and play the same role as described above with reference to FIGS.

  4A, 4B, 4C, and 4D, a fluid 100P and a fluid 100N indicated by hatching are a fluid containing particles and a fluid not containing particles, respectively. At this time, in FIGS. 4A and 4B, the fluid 100P containing particles is introduced from the inlet-side channel 24a, and the fluid 100N not containing particles is introduced from the inlet-side channel 24b.

  The particles introduced into the flow path 23 move downstream along the flow. At this time, by adjusting the flow rates of the fluids 100P and 100N introduced from the two inlet-side flow paths 24a and 24b, In the portion 25, the position of the particle in the direction perpendicular to the flow can be controlled by the size, and the particle flows while contacting the inner wall 25a of the portion 25.

  Subsequently, as the particles flow into the portion 26, the positional difference for each particle size in the portion 25 is enlarged, so that the small particles flow closer to the inner wall 26 a in the portion 26, and the larger particles are more central. It will flow in a close position and particle classification will be possible.

  Further, if a plurality of outlet side branches are connected to the portion 26, it is naturally possible to collect the classified particles separately.

  In the flow paths 13, 21, 22, and 23 having the embodiment of the continuous classification method according to the invention described above, the maximum diameter of the particles to be separated is larger than the width of the portion 16 in FIGS. 1 and 3 or the width of the portion 22 in FIG. Although it must be small, particles of any size, for example 1 nanometer to 1 centimeter, can be classified by changing their width according to the diameter of the particles to be classified.

  Further, when the particle size distribution of the particle group to be separated is wide, the particles recovered from the plurality of outlet ports after the classification are continuously collected in the portion 16 in FIGS. 1 and 3 or the portion 22 in FIG. What is necessary is just to introduce into the flow path which changed width, and to perform further classification.

  Furthermore, since the classification processing amount is proportional to the number of flow paths, the same type of flow paths may be arranged in parallel for the purpose of mass processing, and in the case where the flow path is a microchannel formed on a microchip. Can easily parallelize a large number of the same type of channels on one microchip.

The invention's effect

  Since the present invention is configured as described above, when classifying particles such as synthetic polymer, inorganic powder, metal powder, animal and plant cells, emulsion, etc., high classification accuracy is maintained and the size of the particles is maintained. Even with extremely small particles, an excellent effect that it can be easily and continuously classified is exhibited.

  In addition, since the present invention is configured as described above, it exhibits an excellent effect that it can be classified quickly and in large quantities by the continuous introduction of particles.

1 shows a microchip 10 equipped with an embodiment of a continuous particle classification method according to the present invention, in which FIG. 1 (a) is a view taken in the direction of arrow A in FIG. 1 (b), and FIG. 1 (b) is in FIG. It is sectional drawing by a BB line, FIG.1 (c) is an enlarged view of the part C in Fig.1 (a). FIG. 2 is an explanatory schematic view showing the behavior of fluid introduced from two branches and the state of separation of particles in the microchip 10 shown in FIG. 1, and FIG. 2 is an enlarged view of a portion D in FIG. is there. The other example of the microchip provided with the continuous particle classification method by this invention is shown, Fig.3 (a) (b) is explanatory drawing of the microchips 21 and 22, respectively. FIG. 4 (a) is a cross-sectional view taken along line AA in FIGS. 4 (b), 4 (c), and 4 (d), and shows a flow path 23 equipped with a continuous particle classification method according to the present invention. c) and (d) are cross-sectional views taken along lines B1-B1, B2-B2, and B3-B3 in FIG. 4A, respectively.

Explanation of symbols

DESCRIPTION OF SYMBOLS 10 Microchip 11 Board | substrate 11a Board | substrate 11 lower surface 12 Board | substrate 13 Flow path 14a-14c Inlet side port 15 Outlet side port 15a-15g Outlet side port 16 Portion 13 part 16a Part 16 Inner wall 17 Part 18 part 18a-18c of channel 13 Inlet side branch 19a-19g Outlet side branch 20 Detection line 21 Channel 22 Channel 23 Channel 24a-b Inlet side branch 25 Part 25a of channel 23 Inner wall 26 of part 25 Part 26a of channel 23 Inner wall 100P of part 26 Fluid 100N Fluid 200 Streamline profile 210a-b Vector 300a-b Particle

Claims (7)

A flow path having a plurality of branches at only one of both ends, and a structure having a relatively thin diameter portion and a relatively large diameter portion connected to the thin diameter portion in the flow path Is a method using
The diameter is obtained by continuously introducing a fluid containing particles from at least one of the plurality of branches and continuously introducing a fluid not containing particles from at least one of the plurality of branches. In the thin part, the position of the particle in the direction perpendicular to the flow is made constant according to the size of the particle,
And, at the boundary between the narrow diameter part and the thick diameter part, utilizing the fact that the direction of the force applied to the particle by the flow is different depending on the position of the particle in the direction perpendicular to the flow, the separation is made at the thick part. Perform continuous particle classification method. A flow path having a plurality of branches at both ends, and a method using a structure having a narrow diameter portion and a thick diameter portion connected to the thin diameter portion in the flow path,
At one end of the flow path, a fluid containing particles is continuously introduced from at least one of the plurality of branches, and a fluid not containing particles is continuously supplied from at least one of the plurality of branches. By introducing the particles, the position of the particles in the direction perpendicular to the flow is made constant according to the size of the particles in the portion where the diameter is small,
And, at the boundary between the narrow diameter part and the thick diameter part, utilizing the fact that the direction of the force applied to the particle by the flow is different depending on the position of the particle in the direction perpendicular to the flow, the separation is made at the thick part. A continuous particle classification method in which particles separated at the other end of the flow path are collected. In the continuous particle classification method according to any one of claims 1 and 2,
Continuous particle classification method in which any scale such as width, depth, diameter, etc. of the flow path is at least partially on the order of 1 centimeter or less, and fluid flows in the flow path while maintaining a stable laminar flow . In the continuous particle classification method according to any one of claims 1, 2, or 3,
A continuous particle classification method in which the fluid is a liquid. In the continuous particle classification method according to any one of claims 1, 2, 3, and 4,
A continuous particle classification method in which the fluid is a gas. In the continuous particle classification method according to any one of claims 1, 2, 3, 4, or 5,
A continuous particle classification method in which classification is performed in multiple stages by connecting a plurality of the flow paths having different scales such as the width, depth, and diameter of at least the portion having a small diameter in series. In the continuous particle classification method according to any one of claims 1, 2, 3, 4, 5, or 6,
The flow path is a channel formed in a microchip. Continuous particle classification method.

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