The present disclosure relates to a relates to a cylinder channel having a sawtooth-shaped cross section, a method for manufacturing same, a coaxial channel including same and a method for manufacturing a microfiber or a microparticle having a sawtooth-shaped cross section using same.
Many biochips and microchips have been developed based on the micro technology. Among them, microfluidic chips are used extensively in cell researches and chemical engineering researches and the application is extending toward sensors, cell culture chips, tissue production, or the like. As the use of the microfluidic chips increases, the shape of the channels of the microchips becomes more complicated and diverse. Accordingly, to provide better research environment, it is of great importance to provide 3-dimensional channels having various cross sections.
Basically, since the channels are mostly manufactured in top-down or down-top fashion, microchannels having only round, tetragonal or polygonal cross sections can be manufactured with the current technique. Accordingly, there is a need to develop channels having more complicated and various shapes for wider application of microchips.
The present disclosure is directed to providing a method for manufacturing a cylinder channel having a sawtooth-shaped cross section (hereinafter, also referred to as ‘sawtooth groove’), a method for manufacturing a coaxial channel including the cylinder channel and a method for manufacturing a microfiber having an opposite sawtooth-shaped cross section using same.
In an aspect, the present disclosure provides a cylinder channel having a sawtooth-shaped cross section.
In another aspect, the present disclosure provides a method for manufacturing a cylinder channel having a tapered sawtooth-shaped cross section.
In another aspect, the present disclosure provides a molded part of a cylinder channel having a sawtooth-shaped cross section prepared by the above-described method.
In another aspect, the present disclosure provides a coaxial channel including a cylinder channel having a sawtooth-shaped cross section.
In another aspect, the present disclosure provides a method for manufacturing a coaxial channel including a cylinder channel having a sawtooth-shaped cross section.
In another aspect, the present disclosure provides a molded part including a coaxial channel including a cylinder channel having a sawtooth-shaped cross section which is prepared by the above-described method.
In another aspect, the present disclosure provides a method for manufacturing a microfiber having a sawtooth-shaped cross section using the microfluidic chip including the coaxial channel including the cylinder channel having a sawtooth-shaped cross section and a method for aligning cells using same.
In another aspect, the present disclosure provides a method for manufacturing a microparticle having a sawtooth-shaped cross section using the coaxial channel including the cylinder channel having a sawtooth-shaped cross section.
The fiber and particle synthesized according to present disclosure will find various applications in the fields of biomedicine, tissue engineering and drug delivery.
The present disclosure allows development of various microfluidic chips by diversifying the kinds of microfluidic channels by providing a cylinder channel having a sawtooth-shaped cross section.
Further, the present disclosure allows improvement of the performance of a mixer or a blender by inducing an unstable fluid flow by modifying the angle of the sawtooth-shaped groove of a cylinder channel.
A microfiber having a sawtooth-shaped cross section manufactured using the cylinder channel having a sawtooth-shaped cross section according to the present disclosure may have enhanced strength.
Using the microfiber having a sawtooth-shaped cross section according to the present disclosure, it is possible to align tissues (or fibrils) and also to directly align cells on the channel.
Also, fibers of various shapes and functions can be manufactured using patterned coaxial channels.
a shows an actually manufactured microfluidic chip.
b shows production of a fiber by a spider.
a schematically shows a method for manufacturing a coaxial channel including a cylinder channel having a sawtooth-shaped pattern.
b is an SEM image of a fiber manufactured using a coaxial channel including a cylinder channel having a sawtooth-shaped cross section.
c shows a result of testing strength of a fiber manufactured according to the present disclosure and a fiber without a sawtooth-shaped pattern.
a is a top view of a cylinder channel having a sawtooth-shaped sawtooth groove pattern according to the present disclosure which is bonded to a coaxial channel.
b is a side view of a cylinder channel having a sawtooth-shaped sawtooth groove pattern according to the present disclosure which is bonded to a coaxial channel.
c is an optical microscopic image of a master mold according to the present disclosure.
a is an electron microscopic image of a fiber manufactured according to the present disclosure and
As described above, microfibers having only round or polygonal cross sections can be manufactured with the current technique and a microfiber having a sawtooth-shaped cross section cannot be manufactured.
Accordingly, the present disclosure provides a cylinder channel having a sawtooth-shaped cross section to obtain fibers similar to spider silk.
Hereinafter, various aspects and embodiments of the present disclosure will be described in detail.
In an aspect, the present disclosure provides a cylinder channel of a microfluidic chip including a plurality of sawtooth grooves having a tapered or regular sawtooth-shaped cross section.
Specifically, the sawtooth groove may have a thickness of 3-15 μm and a width of 5-15 μm and the gap between the sawtooth grooves may be 10-20 μm. Outside this range, it is difficult to obtain a microfiber or microparticle desired by the present disclosure.
In another aspect, the present disclosure provides a method for manufacturing a cylinder channel, including positioning and bonding a membrane including a sawtooth groove on a base mold having a mold groove formed on an upper portion thereof and a hole for pressure control formed on a lower portion thereof such that the membrane including the sawtooth groove faces upward and controlling pressure such that the pressure at the upper portion of the membrane is lower than the lower portion and the membrane is deformed toward the lower portion at the mold groove, wherein the membrane has a plurality of sawtooth grooves having a sawtooth-shaped cross section at the upper portion and said controlling of the pressure is carried out using the hole for pressure control.
In the present disclosure, the deformation of the membrane means a deformation whereby the membrane is deformed to have a naturally curved surface by pressure difference as a result of the pressure control by the hole for pressure control at the lower portion of the base mold.
In another aspect, the present disclosure provides a method for manufacturing a coaxial channel including the cylinder channel having a sawtooth groove, including: 1) forming a mold layer on a wafer and forming a plurality of sawtooth grooves on an upper portion of the mold layer using a photoresist; 2) coating a membrane on the upper portion of the mold layer and curing same to obtain a membrane having a sawtooth-shaped surface; 3) bonding a base mold having a mold groove formed on an upper portion thereof and a hole for pressure control formed on a lower portion thereof on the membrane and positioning the membrane such that the plurality of sawtooth grooves of the membrane face upward; 4) controlling pressure using the hole for pressure control such that the pressure at the upper portion of the membrane is lower than the lower portion and the membrane is deformed toward the lower portion at the mold groove; 5) positioning a photosensitive material on the deformed membrane, positioning a light-transmitting material on the photosensitive material and irradiating light onto the light-transmitting material to prepare a master mold including the photosensitive material; 6) preparing a molded part including a semicylindrical channel having a sawtooth-shaped cross section using the master mold; and 7) bonding two molded parts each including a semicylindrical channel having a sawtooth-shaped cross section to prepare a molded part including a cylinder channel having a sawtooth-shaped cross section.
In the method for manufacturing a coaxial channel according to the present disclosure, in 1), the thickness of the mold layer is not particularly limited but may be specifically 1-60 μm. The sawtooth-shaped sawtooth groove may have a thickness of 3-15 μm and a width of 5-15 μm and the gap between the sawtooth grooves may be 10-20 μm. Outside this range, it is impossible to manufacture a fiber having a desired sawtooth-shaped cross section.
In 2), the sawtooth-shaped surface may be formed by a photolithography process using a fine sawtooth groove pattern and a positive photoresist (see
In 2), specifically, the membrane may be an elastomer selected from polydimethylsiloxane (PDMS), rubber, polybutadiene, polyisobutylene, polyurethane, etc., but is not limited thereto.
The membrane may be any one as long as it has a molecular weight in the range commonly used in the art to which the present disclosure belongs.
In 2), the thickness of the membrane may be selected appropriately in order to achieve the effect desired by the present disclosure. Specifically, a thickness of 1-60 μm may be desired to effectively achieve the effect desired by the present disclosure.
In 3), the base mold may be selected from PDMS, PMMA, plastic and cast metal such as gold or iron, but is not limited thereto.
In 3), the base mold having the mold groove formed on the upper portion thereof and the hole for pressure control formed on the lower portion thereof is bonded on the membrane and, after the mold layer formed in 1) is separated from the wafer by removing using a solvent, the membrane is positioned such that the sawtooth-shaped pattern faces upward.
In 3), the mold groove of the base mold may have a tapered or regular cross section and the base mold may be positioned on the membrane so as to form a coaxial channel according to the present disclosure.
In 4), the pressure control may be performed using the hole for pressure control such that the membrane is deformed toward the lower portion. The pressure control may be performed continuously or intermittently with time intervals.
In 5), the photosensitive material may be selected from SU-8, AZ PR and Norland Optical Adhesive (NOA), although not being limited thereto. More specifically, it may be SU-8. The light-transmitting material may be selected from glass, quartz, plastic, polystyrene, polyethylene, etc., although not being limited thereto. More specifically, it may be glass or quartz.
The SU-8 refers to a material having the following chemical formula.
The photosensitive material or the light-transmitting material may be any one as long as it has a molecular weight in the range commonly used in the art to which the present disclosure belongs.
The light may be UV or visible light. Specifically, the effect desired by the present disclosure may be achieved effectively when the light is UV.
In 6), the molded part including the semicylindrical channel may be selected from PDMS, NOA, PMMA and acryl, but is not limited thereto.
In 7), the bonding of the two molded parts each including a semicylindrical channel having a sawtooth-shaped cross section may be performed using oxygen plasma, but is not limited thereto.
In another aspect, the present disclosure provides a coaxial channel including a cylinder channel having a sawtooth-shaped cross section, which includes (A) a main channel, (B) a sample channel and (C) one or more external channel. At least one of the main channel, the sample channel and the one or more external channel may be a cylinder channel having a circular or oval cross section. A terminal end of the sample channel may be connected to an initial end of the main channel. (i) The sample channel may be tapered toward the terminal end portion or (ii) only the terminal end portion of the sample channel may be tapered toward the portion connected with the main channel and the remaining portion may be constant in size and shape of the cross section, with at least a part of the sample channel having a sawtooth-shaped cross section. The one or more external channel may be connected to a side of the main channel.
In the present disclosure, the initial end and the terminal end of the channel refer to an end portion where the flow of a medium in the channel begins and an end portion where the flow of the medium ends, respectively.
The main channel is connected to the sample channel and the external channel. A material flowing out of the sample channel enters the main channel, is cured after meeting with a material flowing out of the external channel and is discharged as a microfiber or a microparticle.
The sample channel refers to a channel through which a sample (fluid) flows. And, the external channel refers to a channel which is connected to the side of the main channel and through which a material that cures a sample flowing out of the sample channel passes.
The coaxial channel (i) may be constant in size along a longitudinal direction, (ii) may decrease or increase linearly in size along the longitudinal direction or (iii) may be a combination of thereof.
The sample channel may be tapered toward the terminal end portion and the remaining portion may be constant in size and shape of the cross section, with at least a part of the sample channel having a sawtooth-shaped cross section.
A longitudinal axis in the main channel may be in line with a longitudinal axis in the sample channel, a longitudinal axis in the external channel may cross with a longitudinal axis in the main channel, and all the longitudinal axes in the main channel, the sample channel and the one or more external channel may be in the same plane. In this case, the effect desired by the present disclosure may be achieved effectively.
In another aspect, the present disclosure provides a molded part including the cylinder channel having a sawtooth-shaped cross section according to the present disclosure. Any molded part satisfying the structure and function described above is included in the scope of the present disclosure. However, a molded part manufactured according to the method of the present disclosure is advantageous over a molded part manufactured according to a different method in that the effect desired by the present disclosure can be achieved more effectively.
In another aspect, the present disclosure provides a method for manufacturing a microfiber having a sawtooth-shaped cross section using the coaxial channel including the cylinder channel having a sawtooth-shaped cross section, which includes: (A) injecting a sample material into the sample channel; and (B) injecting an external material into the external channel.
Specifically, (A) and (B) may be carried out simultaneously. Alternatively, they may be carried out sequentially, continuously or intermittently with time interval.
In another exemplary embodiment, the sample material may be (i) a non-UV-curable material selected from PLGA, alginate, chitosan and collagen, (ii) a UV-curable material selected from 4-HBA, PNIPAAM, Norland Optical Adhesive (NOA) and PEG or (iii) a mixture thereof. The mixing ratio is not particularly limited but may be 1:9-9:1.
The content of the sample material is not particularly limited. For example, the content of the sample material may be 1-5 wt % and the content of a solvent may be 95-99 wt %. If the content of the sample material is less than 1 wt %, a microfiber may not be manufactured. And, if the content of the sample material exceeds 5 wt %, the sample material may not be dissolved.
The solvent is not particularly limited. For example, water, brine, cell culture medium, etc. may be used.
In another exemplary embodiment, the external material may be a solution wherein (i) a first external material selected from calcium chloride, sodium chloride and a mixture thereof is dissolved in (ii) a second external material selected from water, cell culture, PBS and a mixture thereof. In this case, the effect desired by the present disclosure can be achieved effectively.
Specifically, the external material may include 1-5 wt % of the first external material and 95-99 wt % of the second external material. If the content of the first external material is less than 1 wt %, the microfiber may not be cured. And, if the content of the second external material exceeds 5 wt %, the first external material may not be dissolved.
In another aspect, the present disclosure provides a method for controlling the diameter of a microfiber having a sawtooth-shaped cross section manufactured using the coaxial channel including the cylinder channel having a sawtooth-shaped cross section according to the present disclosure, which includes controlling (i) the injection rate of the sample material into the sample channel and (ii) the injection rate of the external material into the external channel.
In an exemplary embodiment, (i) the injection rate of the sample material into the sample channel may be controlled in the range of 0.6-1.8 mL/h and (ii) the injection rate of the external material into the external channel may be controlled in the range of 20-40 mL/h. In this case, the effect desired by the present disclosure can be achieved effectively.
In another aspect, the present disclosure provides a method for manufacturing a microparticle having a sawtooth-shaped cross section using the coaxial channel including the cylinder channel having a sawtooth-shaped cross section, which includes: (A) injecting a sample material into the sample channel; and (B) injecting an external material into the external channel.
Specifically, (A) and (B) may be carried out simultaneously. Alternatively, they may be carried out sequentially, continuously or intermittently with time interval.
In another exemplary embodiment, the sample material may be (i) a non-UV-curable material selected from PLGA, alginate, chitosan and collagen, (ii) a UV-curable material selected from 4-HBA, PNIPAAM, NOA and PEG or (iii) a mixture thereof. The mixing ratio is not particularly limited but may be 1:9-9:1.
The content of the sample material is not particularly limited. For example, the content of the sample material may be 1-5 wt % and the content of a solvent may be 95-99 wt %. If the content of the sample material is less than 1 wt %, a microfiber may not be manufactured. And, if the content of the sample material exceeds 5 wt %, the sample material may not be dissolved.
The solvent is not particularly limited. For example, water, brine, cell culture medium, etc. may be used.
In another exemplary embodiment, the external material may be a solution wherein (i) a first external material selected from calcium chloride, sodium chloride, etc. is dissolved in (ii) a second external material selected from organic solvents such as oleic acid, soybean oil, methanol, dodecane, etc.
In particular, when the external material is prepared by: (a) preparing a first external material solution by dissolving the first external material in (iii) a third external material selected from 2-methyl-1-propanol, isopropyl alcohol and a mixture thereof; (b) preparing a mixture solution by mixing the first external material solution with the third external material; and (c) distilling the mixture solution, the effect desired by the present disclosure can be achieved effectively.
The external material may include 1-5 wt % of the first external material alone or a mixture thereof with the second external material and 95-99 wt % of the third external material. If the content of the first external material alone or the mixture thereof with the second external material is less than 1 wt %, the microfiber may not be cured. And, if the content of the first external material alone or the mixture thereof with the second external material exceeds 5 wt %, the first external material alone or the mixture thereof with the second external material may not be dissolved.
In another aspect, the present disclosure provides a method for controlling the diameter of a microparticle having a sawtooth-shaped cross section manufactured using the coaxial channel including the cylinder channel having a sawtooth-shaped cross section according to the present disclosure, which includes controlling (i) the injection rate of the sample material into the sample channel and (ii) the injection rate of the external material into the external channel.
In an exemplary embodiment, (i) the injection rate of the sample material into the sample channel may be controlled in the range of 0.6-1.8 mL/h and (ii) the injection rate of the external material into the external channel may be controlled in the range of 5-35 mL/h. In this case, the effect desired by the present disclosure can be achieved effectively.
Hereinafter, the present disclosure will be described in detail through examples. However, the following examples are for illustrative purposes only and it will be apparent to those of ordinary skill in the art that the scope of the present disclosure is not limited by the examples.
Manufacturing of Coaxial Channel Including Cylinder Channel Having Sawtooth-Shaped Cross Section
In order to manufacture a cylinder channel having a sawtooth-shaped cross section, a mold layer was formed on a silicon wafer and a part of the mold layer was patterned into fine sawtooth grooves by a photolithography process (
A quadrangular PDMS membrane channel having a degassing port (hole for pressure control) was bound to the replicated membrane using oxygen plasma and the mold was removed using acetone to prepare a channel wherein the replicated membrane was separated from the Si wafer and bound to the quadrangular PDMS membrane channel (
The coaxial channel included a main channel, two sample channels and one or more external channels and had various shapes and dimensions such as pseudo-rectangular structure, combined structure, tapered structure and coaxial structure as shown in
For example, the combined structure was formed using base molds having different depths. The shallow portion has a pseudo-rectangular shape as the deformed membrane spreads out at the bottom of the channel, whereas the membrane is deformed to form a cylindrical structure at the deep portion.
<Manufacturing of Spider Mimicking Chip (Fiber Generating Chip)>
As an example of a microfluidic chip, a spider mimicking chip capable of producing microfibers of various shapes and functions was manufactured.
The spider mimicking chip has a thin sample injecting channel portion that produces a microfiber from different samples (artificial spigot).
a shows a microfluidic chip manufactured based on the same principle.
Referring to
<Generation of Fiber Using Coaxial Channel Including Cylinder Channel Having Sawtooth-Shaped Cross Section>
The scanning electron microscopic (SEM) image at the right top of
To prepare the fiber having sawtooth grooves, 3 wt % alginate aqueous solution and 2.8 wt % calcium chloride aqueous solution were used. The injection rate of the alginate solution and the calcium chloride solution was set at 1.3 mL/h and 23 mL/h, respectively, to decrease the gelling time of the alginate solution.
The strength of the obtained fiber having sawtooth grooves was tested as follows. The fiber was connected to a 0.1-g basket (aluminum, DuPont) and water was added to the basket in 0.1-g increments until the fiber was snapped.
As seen from
And, when two fibers of the same thickness were fixed and pulled downward, the patterned fiber exhibited about 1.5 times stronger ultimate strength as compared to the general fiber without patterns.
This result can be compared to the I-beam exhibiting better strength than a general beam in civil engineering or construction.
<Alignment of Cells for Reconstruction of Muscle Tissue>
The technical feature of the present disclosure may be utilized to align cells by forming fine patterned grooves in the order of 2-10 μm on a microfiber, as shown in
A result of measuring angles between the cells and the groove is shown in
Number | Date | Country | Kind |
---|---|---|---|
10-2010-0134507 | Dec 2010 | KR | national |
Filing Document | Filing Date | Country | Kind | 371c Date |
---|---|---|---|---|
PCT/KR2011/009780 | 12/19/2011 | WO | 00 | 8/14/2013 |