Micromixer, sorter, fiber manufacturing method

Abstract

This disclosure aims to provide a micromixer, sorter apparatus, and a method for manufacturing fibers used therein, which have novel shapes different from conventional microfluidic devices fabricated using lithography, a widely known technology for semiconductor manufacturing. [Solution] The device comprises a first part that provides a first flow path and a second part that provides a second flow path that branches off from the first flow path. The inner wall of the second flow path is spiral in shape along the longitudinal direction of the second part.

Description

Technical Field

[0001] The present disclosure relates to a micromixer, a sorter device, and a method for manufacturing a fiber.

Background Art

[0002] Non-Patent Document 1 discloses designing and manufacturing a 3D microfluidic system in elastomeric polydimethylsiloxane (PDMS) using 3D molding without using photolithography. Design by a CAD program and 3D printing technology are utilized.

[0003] In Non-Patent Document 2, regarding the optimal shape parameters for enhancing the mixing of a twisted-shaped microfluidic mixer, the effects of the number of pitches, cross-sectional shape, and eccentricity ratio on the performance of the twisted micromixer have been investigated. In this document, an estimation of the mixing efficiency has been attempted by calculation, that is, numerical analysis of the flow field.

Prior Art Documents

Non-Patent Documents

[0004]

Non-Patent Document 1

Non-Patent Document 2

[0005] The technology disclosed in Non-Patent Document 1 involves a complex manufacturing method and is limited in the available materials. The technology disclosed in Non-Patent Document 2 concerns theoretical calculations and offers little insight into manufacturing techniques. Many conventional microfluidic devices are fabricated on planar substrates using lithography, a semiconductor manufacturing technique. However, this method presents challenges such as limitations on material selection, complexity of the manufacturing process, and restriction to planar structures.

[0006] This disclosure was made to solve the problems described above and aims to provide a new micromixer, sorting apparatus, and fiber manufacturing method. [Means for solving the problem]

[0007] The micromixer comprises a first portion that provides a first channel and a second portion that provides a second channel that branches off from the first channel, the inner wall of the second channel having a spiral shape along the longitudinal direction of the second portion.

[0008] Other features of this disclosure are outlined below. [Effects of the Invention]

[0009] This can provide new micromixers, sorting devices, and fiber manufacturing methods.

Brief Description of the Drawings

[0010] [Figure 1] It is a perspective view of a micromixer. [Figure 2] It is a view showing an example of the cross-sectional shape of a preform. [Figure 3] It is a view showing a twisted portion. [Figure 4] It is a view showing a twisted portion. [Figure 5] It is a cross-sectional view showing a modification example of the channel shape of a twisted portion. [Figure 6] It is a view showing an example of the production of a micromixer. [Figure 7] It is a perspective view showing an example of a fiber of a sorter device. [Figure 8] It is a perspective view of a sorter device. [Figure 9] It is a plan view of a separator. [Figure 10] It is a view showing a preform and a fiber. [Figure 11] It is a view showing the state of subjecting a preform to rotational heat stretching treatment. [Figure 12] It is a view explaining the mechanism by which a spiral channel is deformed. [Figure 13] It is a view showing a preform having a second base material. [Figure 14] It is a photograph before and after removing the second base material. [Figure 15] It is a photograph showing an example of the production of a fiber having a spiral channel. [Figure 16] It is the result of a CT scan of the created spiral channel. [Figure 17] It is a calculation result showing that two vortices occurred in the spiral channel. [Figure 18] It is an experimental result showing that two vortices occurred in the spiral channel. [Figure 19] It is a view showing the environmental dependence of observation within a spiral channel. [Figure 20]This is a fluorescence photograph of the ROI taken by immersing the fiber in oil.

Embodiments for Carrying Out the Invention

[0011] Embodiment 1. FIG. 1 is a perspective view of a micromixer. The micromixer 70 includes a first portion 71 that provides a first flow path, and a second portion 72 that provides a second flow path branched from the middle of the first portion 71. Both ends of the first portion 71 are Inlet1 and 2, and sample introduction is possible from these into the introduction path 71a. The introduction path 71a provides a flow path with a diameter of 1 mm or less, for example. The sample introduction path 71a is connected to a separator 71b. The separator 71b is a member for guiding the sample introduced from Inlet1 and 2 to the second portion 72. That is, it prevents the sample introduced from Inlet1 from advancing to Inlet2, or the sample introduced from Inlet2 from advancing to Inlet1, and enables these samples to flow into the second portion 72. The second portion 72 includes a straight flow path portion 72a and a twisted portion 72b. According to one example, the flow path of the straight flow path portion 72a is straight, and its inner wall is also uniform without being twisted in the fluid advancing direction. On the other hand, the inner wall of the twisted portion 72b has a spiral shape along the longitudinal direction of the second portion 72. Therefore, the fluid passing through the twisted portion 72b is affected by this inner wall shape. In addition, the outer shape of the twisted portion 72b is also twisted. According to one example, a first sample is provided from Inlet1 and a second sample is provided from Inlet2. The first sample and the second sample are guided to the second portion 72 by the separator 71b, merge in the straight flow path portion 72a, and proceed through the second flow path formed in the second portion 72. Then, through the twisted portion 72b, mixing of the first sample and the second sample is achieved. The mixed sample is taken out from, for example, a tube 73 attached to the second portion 72.

[0012] Figure 1B is an enlarged view of the second section 72. In one example, this second section 72 is a single fiber having a straight channel section 72a and a twisted section 72b. The light-colored part is the tube section, i.e., the base, and the dark-colored part is the channel section. Figure 1B illustrates that the channel is twisted in the twisted section 72b. This twisting makes the inner wall shape of the second channel spiral, which promotes fluid mixing. For example, in a linear micromixer with an inner wall composed only of a flat surface, two types of fluids can hardly be mixed, and this tendency does not change even if the fiber length is increased. In contrast, with the micromixer in Figure 1, two types of fluids can be mixed in the twisted section 72b, where the inner wall has a spiral shape, and the mixing can be improved as the fiber length is increased.

[0013] A method for manufacturing the micromixer 70 is described below. The method for manufacturing the micromixer 70 includes preparing a preform with holes drilled in a substrate, and forming fibers by heat-stretching the preform in one direction while rotating it. Figure 2 shows an example of the cross-sectional shape of the preform. This preform has a substrate 74. A square hole 74a is formed in the central part of the substrate 74. When this preform is processed with a rotary heat stretching device, fibers having channels with spiral-shaped inner walls can be manufactured. Figure 3 shows the channel shape in the twisted portion 72b. The right end of Figure 3 shows that the cross-section of the twisted portion 72b is square. Furthermore, Figure 4 is a perspective view of the twisted portion 72b, and the overall shape is represented by a line diagram. Figure 4 shows that the outer diameter of the substrate 74 is spiral-shaped, and the inner wall of the hole 74a is also spiral-shaped.

[0014] Figure 5 is a cross-sectional view showing the degree of freedom of the channel shape in the twisted portion. Figure 5A shows an example with a rectangular hole 74b. Unlike the approximately square hole in Figure 4, hole 74b has a rectangular cross-sectional shape. Figure 5B shows an example with a triangular hole 74c. Figure 5C shows an example where a circular hole 74d is formed at a position away from the center in a cross-sectional view. In this case, the flow path becomes spiral-shaped. By making the shape of the hole drilled in the substrate during preform formation into a square, triangle, or circle, and by positioning the hole at the center in a cross-sectional view or at a position away from the center in a cross-sectional view, twisted portions with various spiral shapes can be formed. This degree of freedom in the shape of the twisted portion is ensured by using a rotary heat stretching apparatus. Well-known micromixers have been manufactured, for example, by mechanical processing called micro-CNC machining or micro-milling of PMMA plates. With mechanical processing, the channel shapes that can be manufactured tend to be limited. In contrast, when using a rotary thermal stretching apparatus, the shape and position of the holes in the preform can be freely adjusted, making it possible to provide fibers with channel shapes that have not existed before by thermal stretching them.

[0015] After the second part 72 is created by rotary heat stretching, the first part 71 is connected to the second part 72. Figure 6 shows an example of the process for fixing the first part 71 to the second part 72. First, a narrow groove is formed in the second part. Figure 6A shows a narrow groove 72c formed in the straight channel section 72a. Next, a film (thin film) is fitted into this groove 72c. Figure 6B shows a film 72d. The film 72d is, for example, PMMA. By fitting this film 72d into the groove 72c of the straight channel section 72a, the film 72d is fixed to the straight channel section 72a. Where the film 72d is present, the channel of the straight channel section 72a is divided into two by the film 72d. Next, as shown in Figure 6C, a tubular introduction path 71a is placed near the film 72d. Next, as shown in Figure 6D, the separator 71b is fixed to the introduction path 71a and the second part. The method of fixing is not particularly limited, but an adhesive can be used. The separator 71b can have any shape that guides the fluid in the introduction path 71a to the straight flow path section 72a. Next, the tube 73 is fixed to the part of the second section 72 opposite to the separator 71b.

[0016] The aforementioned micromixer enables highly efficient mixing of reagents across various Reynolds number ranges.

[0017] Embodiment 2. Embodiment 2 relates to a sorter apparatus having a fiber. Figure 7 is a perspective view showing an example of the fiber configuration. This fiber 50 comprises an elongated substrate 51 and spiral channels 52 and 53 provided therein. The substrate 51 can be, for example, a thermoplastic polymer or a thermoplastic elastomer. The spiral channels 52 and 53 are channels formed in a helical shape along the side surface of the substrate 51. Figure 7A illustrates that a fluid containing two types of particles is separated into two components as it flows through the spiral channels 52 and 53. The number of spiral channels can be one or more than three. In one example, the fiber 50 is flexible and can be bent. Figure 7B is a schematic diagram of Figure 7A. Figure 7B illustrates that spiral channel 52 has a circular cross-section, and spiral channel 53 has a rectangular cross-section.

[0018] Figure 8 is a perspective view of a sorter apparatus. The sorter apparatus comprises a fiber 54 and a separator 55. Fiber 54 is similar to fiber 50 in Figure 7, except that it has only one spiral channel. Separator 55 comprises a connection section 55a, a branching section 55b, a first channel 55c, and a second channel 55d. Connection section 55a is connected to fiber 54. Branching section 55b is the part that separates the outer and inner components of the spiral channel. For example, the outer component of the spiral channel flows into the first channel 55c, and the inner component of the spiral channel flows into the second channel 55d. In this way, separator 55 is connected to the spiral channel and branches the components of the spiral channel into the first channel 55c and the second channel 55d.

[0019] Figure 9 is a plan view of the separator 55. For ease of explanation, a portion of the branching section 55b is made transparent. The branching section 55b is equipped with a thin film 55e. This thin film 55e is positioned directly above the spiral channel 54a of the fiber 54. In other words, the thin film 55e is provided approximately parallel to the direction of fluid flow in the spiral channel. For example, by forming a cut in the substrate of the fiber 54 that extends into the spiral channel and incorporating the thin film 55e into the cut, the thin film 55e can function as a fluid divider in the spiral channel. This thin film 55e separates the components of the spiral channel 54a into an outer component and an inner component. The outer component is the component that flows in the region of the spiral channel 54a close to the outer edge of the fiber 54. The inner component is the component that flows in the region of the spiral channel 54a close to the center of the fiber 54. The branching section 55b guides the outer component to the first channel 55c and the inner component to the second channel 55d. In this way, the fluid components of the spiral channel are separated.

[0020] Such spiral channels allow for the separation or mixing of cells and particles based on their size using inertial forces. These devices have wide applications in fields such as life sciences, chemistry, and materials science.

[0021] A method for manufacturing such a sorting apparatus will be described. Fibers having spiral channels can be manufactured, for example, by creating a preform and then performing a heat stretching treatment on the preform while rotating it using a rotary heat stretching apparatus. Figure 10A is a cross-sectional view of a preform 56. The preform 56 comprises a substrate 56b and holes 56a located away from the center of the substrate. When such a preform is processed with a rotary heat stretching apparatus, the holes 56a are formed in a helical shape, and spiral channels can be formed in the substrate material. Figure 11 shows the process of rotary heat stretching the preform. In this example, fibers 54 having spiral channels are formed by heating the preform with a heater 58 heated to 260°C and performing a rotary heat stretching treatment. Figure 10B is a photograph of the preform portion and the rotary heat stretched fiber portion. The separator 55 can be manufactured in any shape, for example, using a 3D printer.

[0022] Incidentally, the inventors' research revealed that the cross-sectional shape of the channel sometimes deforms during the heat-stretching process of the preform. Figure 12 illustrates the mechanism by which a spiral channel deforms. Figure 12A shows that the cross-section of the spiral channel before deformation is rectangular. Figure 12B illustrates how such a rectangular spiral channel deforms due to heat stretching accompanied by rotation. In particular, the deformation is significant on the outer side of the fiber, and in that region, the corners of the rectangle disappear, resulting in a rounded cross-sectional shape. Figure 12C discloses the mechanism by which the deformation of the spiral channel occurs. Due to the force exerted on the outer edge of the preform during rotation, particularly large deformation is observed on the outer edge of the fiber.

[0023] This problem can be suppressed by adding a second substrate material to the substrate material. Figure 13 shows a preform having a second substrate material. Figure 13A, a cross-sectional view, shows that the second substrate material 56c has been added to the walls of the holes 56a of the substrate 56b. In one example, the second substrate material 56c is HIPS (high-impact polystyrene) and the substrate 56b is polycarbonate. In another example, both the substrate material 56c and the substrate 56b can be replaced with any polymer. In the example of Figure 13A, the holes 56a have a rectangular shape in cross-section, and the second substrate material 56c has been added to two of the four walls surrounding the holes 56a. Figure 13B is a perspective view of the preform of Figure 13A. When this preform is processed in a rotary thermal stretching apparatus, fibers with spiral channels can be formed while maintaining the shape of the holes 56a.

[0024] After rotary heat stretching, it is necessary to remove the second substrate material 56c. For example, the second substrate material 56c can be dissolved by injecting a limonene solution from a silicone tube into the area where the second substrate material 56c is present. Figure 14A is a cross-sectional photograph of the fiber before the removal of the second substrate material. It was confirmed that HIPS, which is the second substrate material, is present in a part of the spiral channel. Figure 14B is a cross-sectional photograph of the fiber after the removal of the second substrate material. It was confirmed that the second substrate material dissolves when the limonene solution is sprayed onto the second substrate material, and a square spiral channel is obtained in cross-section. According to the inventors' experiments, if the rotation speed of the preform during rotary heat stretching is greater than about 50 rpm, the spiral channel becomes filled with HIPS. Once the spiral channel is filled with HIPS, it becomes difficult to dissolve and remove it, so it is necessary to leave voids without HIPS in the spiral channel. By reducing the rotation speed and setting the spiral channel pitch to, for example, 4 mm or more, the filling of the spiral channel with HIPS can be suppressed, making the HIPS dissolution process easier. In this way, a second substrate material is provided and ultimately removed, allowing the spiral channel to be formed while maintaining the cross-sectional shape of the fiber pore. In this example, the cross-sectional shape of the spiral channel is rectangular, but other cross-sectional shapes can be adopted in other examples.

[0025] Next, we will describe an example of manufacturing a fiber having a spiral channel. By rotating and heat-stretching a preform to which a second substrate material has been added, we were able to manufacture a fiber having a spiral channel that maintains a square cross-sectional shape. Figure 15A is a cross-sectional photograph of the fiber after rotating and heat-stretching. We confirmed that the cross-sectional shape of the spiral channel is maintained to be roughly square. Figure 15B is a front view photograph of the manufactured fiber. We confirmed that the pitch of the spiral channel is 5.8 mm. Figure 16 shows the results of a CT scan of the spiral channel portion of the manufactured fiber. Figure 16A is an overview of the spiral channel. Figure 16B is a top view image of the spiral channel. Figure 16C is a bottom view image of the spiral channel. From these figures, it can be seen that the cross-sectional shape of the spiral channel is maintained to be roughly square. In particular, from the parts indicated by the arrows in Figures 16B and 16C, it can be seen that the amount of deformation of the cross-sectional shape of the spiral channel is minute, and that it was able to maintain a roughly square shape.

[0026] By shifting our approach and actively utilizing the deformation of the channel's cross-sectional shape during the rotational heat-stretching process of the preform, we can realize channel cross-sectional shapes that were previously impossible to produce. In this case, we do not provide a second substrate material, but instead directly adopt the change in the channel's cross-sectional shape caused by rotational heat-stretching. This makes it possible to manufacture, for example, fibers with channels that are elliptical or approximately elliptical in cross-sectional shape, or fibers with channels that are semicircular or approximately semicircular in cross-sectional shape.

[0027] To sort, or separate, sample particles, a pair of vertically symmetrical vortices (Dean vortices) called Dean flow are necessary. According to the inventors' theoretical calculations, it is expected that the spiral channel pitch will need to be reduced to about 0.4 mm in order to generate a Dean flow with sufficient symmetry. Currently, the smallest pitch that can be manufactured while maintaining the channel shape is about 4 mm, so it is necessary to minimize the pitch by selecting materials and optimizing manufacturing conditions.

[0028] Figure 17 shows the theoretical calculation results of the flow profile of a spiral channel. The primary flow, secondary flow, and Q-value (a vortex detection index) are plotted. The theoretical calculation revealed that the maximum flow velocity occurs near the channel wall. Furthermore, as shown by the dashed lines in the figure, the generation of two fluid vortices was confirmed. Figure 18 shows the analysis results using microparticle image velocimetry (PIV). In Figure 18, the distribution of primary and secondary flow and Q-value for a fluid flow rate of 2.0 ml / min in the spiral channel is shown using contour lines and color. Similar to the simulation, the maximum flow velocity occurs near the outer wall. Furthermore, vortices can be observed at the two locations enclosed by the dashed lines. Therefore, the generation of two fluid vortices was confirmed in both theoretical calculations and experiments. From these results, high fluid controllability can be expected in the flow path within the fiber.

[0029] To confirm that the substances to be separated are properly sorted, it is necessary to experimentally determine the equilibrium position of the particles within the channel using fluorescent particles. To determine the radial distribution, observation near the outer edge away from the axis is necessary. When viewing the fiber from the side, observation of the spiral channel is easy in the axial portion of the fiber, but it is difficult to observe the spiral channel near the outer edge away from the axis. Figure 19A illustrates the spiral channel region 60 in the axial portion of the fiber and the spiral channel region 61 near the outer edge away from the axis. In fluorescence observation, where particles are visualized by illuminating them with light of a specific wavelength, observation of the spiral channel region 61 near the outer edge was difficult. In Figure 19A, this spiral channel region 61 is defined as the Region of Interest (ROI). Figure 19B is a photograph of the fiber observed in air. It can be seen that observation is difficult in the ROI. Figure 19C is a photograph of fluorescence observation when the fiber is immersed in oil with a refractive index close to that of PMMA. Figure 19C shows that both the spiral channel in the axial portion and the spiral channel near the outer edge away from the axis can be observed. Figure 20 is a fluorescence image of the ROI taken with the fiber immersed in oil. Figure 20 shows the fluorescence image of the ROI when fluorescent particles were injected, and it can be seen that the trajectory of particles is appropriately captured. Some particle adhesion to the wall surface is observed, but no obstruction to observation was confirmed. In addition, the distribution of fluorescence intensity in the radial direction of the region enclosed by the dotted line is plotted on the right. This is a time-averaged normalized value. From these results, a basis for experimentally determining the equilibrium position of particles within the channel has been established. [Explanation of Symbols]

[0030] 50 Fiber, 55 Separator, 55a Connection, 55b Branch, 55c First channel, 55d Second channel, 70 Micromixer, 71 First section, 72 Second section

Claims

1. A first part that provides a first flow path, The invention comprises a second part that provides a second channel branched off from the middle of the first channel, The inner wall of the second channel is spiral-shaped along the longitudinal direction of the second portion of the micromixer.

2. The second part comprises an elongated base, The micromixer according to claim 1, wherein the second channel is formed in a helical shape along the side surface of the substrate.

3. The micromixer according to claim 1 or 2, wherein the cross-sectional shape of the second channel is square, rectangular, triangular, or circular.

4. A fiber equipped with a spiral channel, A sorting apparatus comprising a separator having a first channel connected to the spiral channel through which components from the outside of the spiral channel flow in, and a second channel through which components from the inside of the spiral channel flow in.

5. The aforementioned fiber comprises a substrate with an elongated shape, The sorter apparatus according to claim 4, wherein the spiral channel is formed in a helical shape along the side surface of the substrate.

6. The separator comprises a thin film provided in the spiral channel, The sorter apparatus according to claim 4 or 5, wherein the thin film guides the component outside the spiral channel to the first channel and the component inside the spiral channel to the second channel.

7. To form a rod-shaped preform having through holes, The process involves forming fibers by thermally stretching the preform in one direction while rotating it, A polymer material is provided in the through-hole of the preform. A method for manufacturing a fiber, comprising dissolving the polymer material after the heat stretching to obtain the spiral-shaped through-hole.

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