KR101199505B1 - Fabrication Method of Micro-fluidic Chip Using Ultrasonic Bonding - Google Patents

Abstract

The present invention relates to a method of manufacturing a microfluidic chip that separates plasma from blood. More particularly, the present invention relates to a microfluidic chip that efficiently separates plasma from blood by precisely implementing a channel for moving plasma in micro units using micro ultrasonic fusion. The present invention relates to a method for manufacturing a microfluidic chip that can easily make a fluidic chip.
In order to achieve the above object, the present invention provides a method for manufacturing a microfluidic chip 10 of blood using ultrasonic fusion, wherein the microfluidic chip is manufactured by using a photolithography method. Stage 1; A second step of manufacturing the upper substrate 100 and the lower substrate 200 by injection molding using the molding stamp 350; And a third step of bonding the upper substrate 100 and the lower substrate 200 to each other by an ultrasonic fusion method.

Description

Fabrication Method of Micro-fluidic Chip Using Ultrasonic Bonding}

The present invention relates to a method for manufacturing a microfluidic chip using ultrasonic fusion, and more particularly, to easily implement a microfluidic chip for efficiently separating plasma from blood by precisely implementing a channel for moving a plasma in micro units using micro ultrasonic fusion. It relates to a microfluidic chip manufacturing method that can be made.

Recently, a large amount of biosensors that are intended to be used for prognostic management as well as diagnosis of diseases by detecting various biometric information from biological samples such as blood are used.

Biosensors require reproducibility and detection of high sensitivity signals to provide reliable information. For example, a protein chip designed for protein detection is to measure the presence and remaining amount of a specific protein using blood, wherein blood consists of red blood cells, white blood cells, platelets and plasma, and plasma metabolizes fat. As it contains various protein components such as water, sugars, enzymes, antigens, and antibodies, most proteins are mainly contained in blood plasma. Therefore, in order to reduce reproducibility and measurement error, it is necessary to separate plasma from blood. .

A chip-type separation means for separating plasma from blood is a microfluidic chip that separates blood cells by placing a porous medium or membrane on the side or front of the blood flow path, and the blood cells using the sedimentation effect of the blood cells. And microfluidic chips that extract plasma only by forming plasma layers. In addition, separation chips using centrifugal force and separation chips using electrical signals have been proposed.

The non-powered separation chip using a capillary phenomenon is characterized by separating only the plasma by installing a filter in the moving channel to prevent blood cell components from passing while allowing blood to move by the capillary phenomenon.

As an example of separating plasma using centrifugal force, blood sampling means, plasma separation means, and analytical means may be sequentially provided, and the plasma may be automatically separated in the blood flow path by centrifugal operation. Is to extract.

As a separation chip by an electrical signal, a blood passage is provided and a long and short pressure pulse is applied at the inlet to deflect the flow of blood cells as an electrical signal to separate only the plasma from the difference in blood cell mobility.

FIG. 1 briefly illustrates a microfluidic chip 1 using a capillary force driving force as a conventional microfluidic chip (biosensor).

The capillary microfluidic chip 1 is composed of a lower substrate 3 providing channels 4 and 5 through which plasma moves, and an upper substrate 2 covering the plasma substrate, and having an analysis means 6 in a part of the channel. And a signal extraction unit 7 for extracting a signal from the analysis means 6. The moving channels 4 and 5 of the plasma are the blood introduction section 4 dropping blood and the micro channel 5 small enough to impart capillary force to the plasma and have a height small enough to prevent blood cells from passing through. It consists of.

When the sample blood is put into the blood inlet 4, the blood moves by the capillary force of the microchannel 5, and at this time, the blood cell component cannot pass through the microchannel 5, so that only the plasma reaches the analyzing means 6. Therefore, it is possible to precisely measure the bio signals by analyzing only plasma.

However, the microfluidic chip 1 using the conventional capillary force is capable of separating plasma without providing a special driving means, and it is possible to construct a separate chip in a compact manner, despite the advantages of a large number of reliable products. There is a limit to production. The microfluidic chip 1 maintains the height of the microchannel 5 at the level of 5-10 micrometers, which is the size of the blood cells, in order to filter blood cells while exerting the capillary force sufficiently. The thermal bonding method is used in the manufacturing process of joining the upper substrate and the upper substrate 2, because it is difficult to precisely manufacture by thermal deformation (up to 20 to 30 micrometers level).

In order to compensate for these disadvantages, an ultrasonic fusion method capable of bonding the upper substrate 2 and the lower substrate 3 without thermal deformation has been proposed, but it is possible to weld the entire bonding surface of the upper substrate 2 and the lower substrate 3. It has been recognized that it is not suitable for mass production of micro-level microfluidic chips as in the present invention due to the reliability problem of difficulty in delivering sufficient vibration energy evenly and difficult to form the microchannel 5 without leakage.

The present invention is to solve the above problems, to provide a manufacturing method capable of producing a large amount of reliable micro-fluidic chip with a small energy capable of precise measurement.

In order to achieve the above object, the present invention provides a method for manufacturing a microfluidic chip 10 using ultrasonic welding, wherein the method for producing a microfluidic chip is a first step of manufacturing a molding stamp 350 using a photolithography method. ; A second step of manufacturing the upper substrate 100 and the lower substrate 200 by injection molding using the molding stamp 350; And a third step of bonding the upper substrate 100 and the lower substrate 200 to each other by an ultrasonic fusion method.

The first step using the photolithography method may include forming a photoresist (PR) pattern 320 of an internal structure of the microfluidic chip on the substrate 310; Forming a PR welding line 330 to make the welding line 270 of the micro unit for ultrasonic welding; First to third steps of depositing an electroplating seed metal layer 340; First to fourth plating the molding stamp 350 by electroplating using the seed metal layer 340; And the first to fifth steps of stamp release to remove the molding stamp 350 from the PR pattern 320 and the substrate 310.

In addition, in the step 1-2 of forming the PR fusion line 330, it is more preferable that the fusion line 270 of micro units is formed to have an inclination in forming the PR fusion line 330.

Further, the inclination of the fusion line 270 in micro units has a narrower width than that of the base portion 272 of the fusion line 270 in micro units. It is advantageous to be formed and made of.

On the other hand, another embodiment of the present invention provides a microfluidic chip 10 manufacturing method using ultrasonic welding. The microfluidic chip manufacturing method includes a first step of manufacturing a molding stamp 350 using a photolithography method; A second step of manufacturing two fusion line forming substrates 860 by injection molding using the molding stamp 350; And one of the two fusion line formation substrates 860 becomes the lower fusion line formation substrate 860a and the other becomes the upper fusion line formation substrate 860b. It is characterized in that it comprises a third step of joining the upper fusion line forming substrate 860b against each other by an ultrasonic fusion method.

In this case, the first step using the photolithography method may include forming a photoresist (PR) pattern 320 of an internal structure of the microfluidic chip on the substrate 310; Steps 1-2 forming the PR fusion lines 830 and the PR patterns 820 of the plurality of ultrasonic welding micro units; First to third steps of depositing an electroplating seed metal layer 840 on the substrate 310; First to fourth plating the molding stamp 850 by electroplating using the seed metal layer 840; And steps 1-5 of stamp release to remove the molding stamp 850 from the substrate 310.

In this case, steps 1-2 of forming the PR fusion line 830 and the PR pattern 820 may be configured to have a micro unit and have an inclination in forming the PR fusion line 830. 830 is an isosceles rectangle having a height greater than the two PR patterns 820 and positioned between the two PR patterns 820.

In addition, the PR fusion line 330 in which the fusion line 270 of the micro unit is inclined is advantageously formed by an exposure apparatus in which the inclination of the stage holding the substrate 310 is adjusted and rotated.

Meanwhile, a hard bake for drying the PR coating by removing the remaining solvent immediately after the first step 1-2 forming the PR fusion line 330 is completed, and increasing the adhesion of the PR coating to the substrate 310 ( It may be advantageous that additional hard bake processes be performed.

In addition, the second step is preferably vacuum injection molding.

Further, the upper substrate 100 and the lower substrate 200 materials used for the molding are selected from one of cycloolefin copolymer (COC), polycarbonate (PC), polyethylene (PE), and polyflopropylene (PP). More preferred.

In addition, in the first-first step of forming the PR pattern 320, the PR patterns of the filter protrusions 221 and 233 constituting the filters 220 and 230 for filtering blood cells in the internal structure of the microfluidic chip 10. In forming the 320, it is advantageous that the minimum value of the gaps 222 and 234 in the height direction of the filter protrusions 221 and 233 made by the filter protrusions 221 and 233 is at least smaller than the diameter of the blood cells.

In addition, in the first-first step of forming the PR pattern 320, in forming the PR pattern 320 of the internal structure of the microfluidic chip 10, the substrate 100 having the filter protrusions 221 and 233 formed therein is formed. It is much more advantageous to have additional channels 130 formed on the side of the mating substrates 100 and 200 to which the mating substrates 100 and 200 adhere to reduce the flow resistance of plasma.

As another aspect of the present application, the present invention provides a microfluidic chip 10 using micro ultrasonic fusion produced by the manufacturing method described above.

The microfluidic chip manufacturing method using micro ultrasonic fusion provided by the present invention introduces a conventional ultrasonic fusion method suitable for a micro unit manufacturing process to produce a reliable microfluidic chip capable of precise measurement in large quantities with low energy. It can work.

1 is a perspective view of a microfluidic chip using a conventional capillary force
Figure 2 is a perspective view of a microfluidic chip produced by the micro ultrasonic welding method of the present invention
3 is a process chart illustrating a micro ultrasonic welding method according to an embodiment of the present invention
4 is a perspective view and a cross-sectional side view for explaining the structure of the micro fusion line of the present invention;
Figure 5 is a perspective view and a side cross-sectional view for explaining the shape and action mechanism of the filter protrusion of the microfluidic chip produced by the micro ultrasonic welding method of the present invention
6 is a side cross-sectional view of the filter protrusion for explaining the second embodiment of the present invention.
7 is a side cross-sectional view of the filter protrusion for explaining the third embodiment of the present invention.
8 is a process chart illustrating a micro ultrasonic welding method according to another embodiment of the present invention
DESCRIPTION OF REFERENCE NUMERALS
100,860b: upper substrate 110: plasma inlet
120: plasma outlet 130: additional channel
200,860a: lower substrate 220: first filter part
221: first filter projection 220: second filter portion
233: second filter protrusion 240: the first plasma transfer channel
250: second plasma channel 260: plasma extraction unit
270: micro melting line 320,820: PR pattern
340,840: seed metal layer for electroplating
330,830 PR fusion line 350,850 Nickel stamp
851: PR pattern recess for molding 852: PR fusion line forming substrate for molding
860a: lower fusion line formation substrate
860b: upper fusion line formation substrate
890: extra space

Specific embodiments of the present invention will be described in detail with reference to the accompanying drawings. 2 is a perspective view of a microfluidic chip manufactured by the micro ultrasonic welding method of the present invention, FIG. 3 is a process chart illustrating the micro ultrasonic welding method of the present invention, and FIG. 4 is a view illustrating the structure of the micro welding line of the present invention. Perspective and side cross-sectional views. 5 is a perspective view and a side cross-sectional view for explaining the shape and mechanism of action of the filter protrusion of the microfluidic chip manufactured by the micro ultrasonic welding method of the present invention. 6 is a side cross-sectional view of the filter protrusion for explaining the second embodiment of the present invention, and FIG. 7 is a side cross-sectional view of the filter protrusion for explaining the third embodiment of the present invention. Matters that are not required to understand the technical spirit of the invention as parts that are not different from the prior art are excluded from the description, but the technical spirit and protection scope of the present invention are not limited thereto.

First, before describing the method of manufacturing a microfluidic chip using the micro ultrasonic fusion of the present invention, the microfluidic chip of the present invention manufactured by the above manufacturing method will be briefly described with reference to FIG. 2.

In the microfluidic chip 10 of the present invention, the microfluidic chip 10 includes an upper substrate 100 and a lower substrate 200 and has a blood inlet 110 and a plasma outlet 120, by using capillary force. Plasma transfer channels 240 and 250 for moving plasma; A first filter unit 220 for filtering leukocytes; It characterized in that it comprises a second filter unit 230 for filtering red blood cells. The plasma moving channels 240 and 250 maintain the height between the upper substrate 100 and the lower substrate 200 at approximately 10 to 20 micrometers in order to give capillary force, and the first filter unit 220 and the second The filter unit 230 includes first and second filter protrusions 221 and 233 as filters for filtering leukocytes and red blood cells, respectively. In particular, the second filter unit 230 is radially formed around the blood inlet 110 to maximize the filter efficiency, and the flow path forming unit 231 is formed to form the filter channel 232 for improving capillary force. Additionally included.

Blood flowing into the blood inlet 110 moves toward the plasma outlet 120 by capillary forces of the first and second plasma movement channels 240 and 250, and the leukocytes from the first filter unit 220 having a relatively large size. Are filtered out, and the red blood cells are filtered out of the second filter portion having a smaller size. As a result, only the plasma is collected in the plasma deriving unit 260 and is collected through the plasma deriving port 120 and used as a sample for analysis.

Next, a microfluidic chip manufacturing method using micro ultrasonic fusion according to an embodiment of the present invention will be described in detail with reference to FIG. 3.

In the method of manufacturing the microfluidic chip 10 of the present invention, the ultrasonic fusion is performed, but the ultrasonic fusion is strictly performed, and the plasma leveling channels 240 and 250, the first filter unit 220, and the second filter unit 230 of the micro level are strict. Photolithography (photolithography) is introduced in order to precisely form. In addition, injection molding is performed by using a molding stamp 350 made by photolithography to enable mass production.

Microfluidic chip manufacturing method using a micro ultrasonic welding of the present invention comprises the first step of producing a stamping stamp 350 using a photolithography method; A second step of manufacturing the upper substrate 100 and the lower substrate 200 by injection molding using the molding stamp 350; And a third step of bonding the upper substrate 100 and the lower substrate 200 to each other by an ultrasonic fusion method.

The first step of manufacturing the molding stamp 350 is the plasma projection channels 240 and 250, the first filter unit 220 and the filter protrusions 221 and 233 of the second filter unit 230, the second filter unit Step 1-1 to form a photoresist (PR) pattern 320 on the substrate (substrate, wafer, 310) to make the flow path forming means 231 of 230; Steps 1 through 2 forming a PR fusion line 330 on the PR pattern 320 to make the micro fusion line 270 as a core technology of the present invention; First to third steps of depositing a seed metal layer 340 for electroplating on the substrate 310; First to fourth plating the molding stamp 350 by electroplating using the seed metal layer 340; And the first to fifth steps of stamp release to remove the molding stamp 350 from the PR pattern 320 and the substrate 310 thereof.

Step 1-1 is a step of forming a PR pattern 320 for forming an internal structure such as filter protrusions 221 and 233 using PR on a substrate 310 made of Si. First, the liquid PR material sprayed on the substrate 310 is rotated at a high rotational speed to apply the entire substrate 310 in the form of a uniform film, and then baked at a predetermined temperature to vaporize, remove, and solidify the solvent of the PR. . Next, a photo pattern is exposed using a mask on which an internal structure shape is transferred to a coated PR layer, and unnecessary PR is melted with a solvent to develop a PR pattern 320.

Steps 1-2 of forming the PR fusion line 330 also follow the photo-etching detailed process of Step 1-1 as it is, and there is a difference only in that the exposure process is performed differently. The PR fusion line 330 of the present invention is likewise formed to have a slope so that the micro fusion line 270 is configured to have a slope after injection molding (see FIG. 4B further).

An exposure apparatus (not shown) in the photolithography method generally includes a light source unit, and the light emitted through the light lamp is irradiated onto the substrate 310 through a mask through various types of filters, wherein the irradiated light is parallel light. Therefore, the PR patterns 320 irradiated perpendicularly to the substrate 310 and formed on the substrate 310 generally have a two-dimensional quadrangular shape. However, as will be described later, as a unique technical feature of the present invention, the micro fusion line 270 should be formed to have an inclination, and for this purpose, the PR fusion line 330 needs to be inclined. This is made possible by exposing the ramp using an exposure apparatus (see registration number, 10-0930604) already filed separately by the present applicant. The exposure apparatus is characterized in that the inclination of the stage holding the substrate 310 to adjust and rotate, detailed description thereof will be omitted.

Meanwhile, after the development of the PR coating is completed, the solvent remaining after the step 1-2 is removed to dry the PR coating, and additionally a hard bake step for increasing the adhesion of the PR coating to the substrate 310 You can also do it.

Next, steps 1-3 of depositing the seed metal layer 340 for electroplating and steps 1-4 of plating the molding stamp 350 by the electroplating method are performed using the seed metal layer 340. The stamp 350 can be any metal that favors the second step of injection molding, but more preferably nickel (Ni). The seed metal layer 340 may also be selected from any metal for plating nickel easily by electroplating.

The first to fifth steps of the stamp release to remove the molding stamp 350 from the substrate 310 may be performed mechanically, or may use a difference in thermal expansion, and are not particularly limited to any method. It may be selected in an advantageous manner.

In the second step of injection molding the upper substrate 100 and the lower substrate 200 using the molding stamp 350, it is preferable to use a vacuum injection molding according to a conventional molding process. Materials for the upper substrate 100 and the lower substrate 200 used for molding are freely selected from plastic materials. Preferably cycloolefin copolymer (COC) is advantageous, but may be injected into polycarbonate (PC), polyethylene (PE), polyflopropylene (PP) or the like.

A third step of bonding the upper substrate 100 and the lower substrate 200 to each other by the ultrasonic welding method is performed using a conventional ultrasonic welding machine. Ultrasonic fusion machine is a device that can fusion thermoplastic and plastic, film, film, synthetic fiber, etc. quickly and efficiently by using the vibration energy of ultrasonic. The micro fusion line 270 of the present invention, which is provided on the lower substrate 200, is melted by high frictional heat due to strong ultrasonic vibration to have excellent fluidity, and is strictly adhered to the upper substrate 100 to form the joint surface 370. do. Since the micro fusion line 270 is first melted and bonded, unlike the thermal bonding method, thermal deformation does not occur between the upper substrate 100 and the lower substrate 200 such that the channels 240, 250, and 235 of the micro unit are formed. Precisely formed.

Ultrasonic welding in the separation chip manufacturing method of the present invention has an advantage of showing excellent bonding even with a small capacity ultrasonic welding machine is provided with a micro fusion line 270.

The effect of the micro fusion line 270 will be described in more detail with reference to FIG. 4. FIG. 4A is an enlarged view of the blood introduction part 210 of the lower substrate 200 before ultrasonic welding, and the outside of the flow path forming means 231 and the first plasma moving channel 240 to form a flow path through which plasma passes. It can be seen that the micro fusion line 270 is formed along the circumference. Looking at the cross section A-A of Figure 4b it can be seen that the micro-fusion line 270 of the present invention is composed of the interview portion 271 and the base portion 272 having different widths along the height direction.

The size of the micro fusion line 270 is a problem to be determined depending on the capacity of the ultrasonic fusion machine (not shown) used, but the base portion 272 is 40 micrometers, and the interview portion 271 is approximately 30 micrometers. desirable.

As a unique technical feature of the present invention, the interview portion 271 is formed to have a width smaller than the width of the base portion 272. The interview part 271 is the part which starts to melt for the first time when friction heat is generated by the ultrasonic welding machine in contact with the upper substrate 100, and the heat capacity of the interview part 271 is set smaller than that of the base part 272. This has the advantage of minimizing the adhesion even if the ultrasonic welding machine is operated with a small energy or the operating time is set short by mistake. That is, in the case where the fusion machine operates at the rated capacity, the melting point to the base portion 272 is a design specification. Even though the fusion machine has a reduced capacity or a shorter operating time, the interview portion 271 has a small width with only a small amount of energy. Is melted to form an adhesive surface, so minimal adhesion is ensured.

Next, a second embodiment of a method of manufacturing a microfluidic chip using micro ultrasonic fusion of the present invention will be described with reference to FIGS. 5 and 6.

According to a second embodiment of the method of manufacturing a plasma separator, the first filter protrusion constituting the first filter part 220 and the second filter part 230 may be formed in the first-first step of forming the PR pattern 320. The first filter gap 222 and the second filter gap 234 are adjusted by changing the arrangement between the protrusions of the second filter protrusion 233 and the second filter protrusion 233 to improve the filtering efficiency of blood cells.

In the second step of injection molding the lower substrate 200 using COC resin or the like, if the injection is not performed in a vacuum state, the air may be injected into the molding recess 351 (see FIG. 3) of the nickel stamp 350 during the injection process. It is common for the curved filter protrusions 221 and 233 as shown in FIG. 5A to be formed instead of the right angled corners such as the filter protrusion 233 of FIG. 4B. This results in a larger width (W2) of the gap, rather than the width (W1) of the filter gaps (222, 234) of the original design specification, as shown in the BB cross section of FIG. 5B, which is greater than W1 but smaller than W2. There is a problem that blood cells, such as white blood cells or red blood cells, are included in the plasma and are moved to the plasma extraction unit 260 without being filtered.

In order to improve this, in the second embodiment of the present invention, as shown in FIG. 6, in the first-first step of forming the PR pattern 320, the first filter protrusion of the first filter unit 220 for leukocyte removal is performed. The width of the PR pattern 320 for 221 is configured such that the first gap 222 formed by the first filter protrusions 221 is not larger than the normal diameter of the white blood cells anywhere along the height direction. The width of the PR pattern 320 for the second filter protrusion 233 of the second filter unit 230 for the second gap 234 by the second filter protrusions 233 anywhere in the height direction red blood cells It is configured not to be larger than the usual diameter of.

According to the second embodiment of the present invention, even if the second step of the injection molding is not performed in a vacuum state, the filtering efficiency of the blood cells is increased, thereby enabling precise plasma separation.

Next, a third embodiment of a method of manufacturing a microfluidic chip using micro ultrasonic fusion of the present invention will be described in detail with reference to FIG. 7.

The third embodiment of the plasma separator manufacturing method of the present invention is an addition to reduce the flow pressure loss of the plasma on the lower surface of the upper substrate 100, that is, the bonding surface side is bonded to the lower substrate 200 to facilitate the movement of the plasma It is characterized by forming the channel 130. It is sufficient that the width of the additional channel 130 is set such that blood cells do not pass through.

Like the second embodiment of the present invention, when the filter protrusions 221 and 233 have a cut surface of a curved surface rather than a right angle, the width of the filter protrusions 221 and 233 improves the filtering efficiency. . At this time, if the passage for the passage of plasma is provided separately as in the third embodiment of the present invention, the flow pressure loss of the plasma is greatly reduced, so that a sufficient separation efficiency can be obtained by the capillary force without a separate driving means.

Next, a microfluidic chip manufacturing method using micro ultrasonic fusion according to another embodiment of the present invention will be described in detail with reference to FIG. 8.

Referring to FIG. 8, a method of manufacturing a microfluidic chip using micro ultrasonic fusion according to a second embodiment of the present invention may include a first step of manufacturing a molding stamp 350 using photolithography; A second step of manufacturing two fusion line forming substrates 860 by injection molding using the molding stamp 350; And one of the two fusion line formation substrates 860 becomes the lower fusion line formation substrate 860a and the other becomes the upper fusion line formation substrate 860b. And a third step of joining the upper fusion line forming substrates 860b to each other and bonding them by an ultrasonic welding method.

The first step using the photolithography method may include forming a photoresist (PR) pattern 320 of the internal structure of the microfluidic chip on the substrate 310; Steps 1-2 forming the PR fusion lines 830 and the PR patterns 820 of the plurality of ultrasonic welding micro units; First to third steps of depositing an electroplating seed metal layer 840 on the substrate 310; First to fourth plating the molding stamp 850 by electroplating using the seed metal layer 840; And the first to fifth steps of the stamp release to remove the molding stamp 850 from the substrate 310 (see FIGS. 8A to 8D).

Step 1-1 is a step of forming a PR pattern 320 for forming internal structures such as filter protrusions 221 and 233 using PR on a substrate 310 made of Si (FIG. 8A). ) Reference). First, the liquid PR material sprayed on the substrate 310 is rotated at a high rotational speed to apply the entire substrate 310 in the form of a uniform film, and then baked at a predetermined temperature to vaporize, remove, and solidify the solvent of the PR. . Next, a photo pattern is exposed using a mask on which an internal structure shape is transferred to a coated PR layer, and unnecessary PR is melted with a solvent to develop a PR pattern 320.

The first and second steps of forming the PR fusion line 830 and the PR pattern 820 of the present invention also follow the photolithography detailed process of the first to first step, except that the exposure process is partially different. There is. The PR fusion line 830 is formed to have a micro unit and has an inclination, wherein the plurality of PR fusion lines 830 are interposed between two PR patterns 820 and are larger than the two PR patterns 820. It has an isosceles square shape (see FIG. 8B).

An exposure apparatus (not shown) in the photolithography method generally includes a light source unit, and the light emitted through the light lamp is irradiated onto the substrate 310 through a mask through various types of filters, wherein the irradiated light is parallel light. Therefore, the PR pattern 820 irradiated perpendicularly to the substrate 310 and formed on the substrate 310 generally has a two-dimensional quadrangular shape.

Meanwhile, after the development of the PR coating is completed, the solvent remaining after the step 1-2 is removed to dry the PR coating, and additionally a hard bake step for increasing the adhesion of the PR coating to the substrate 310 You can also do it.

Next, steps 1-3 of depositing the electroplating seed metal layer 840 on the substrate 310 and steps 1-4 of plating the molding stamp 850 by electroplating using the seed metal layer 840. (See (c) and (d) of FIG. 8). The stamp 350 can be any metal that favors the second step of injection molding, but more preferably nickel (Ni). The seed metal layer 340 may also be selected from any metal for plating nickel easily by electroplating.

Steps 1-5 of the stamp release (see FIG. 8 (e)) for removing the molding stamp 850 from the substrate 310 may be performed mechanically, or may use a difference in thermal expansion, and are particularly limited to any method. It is not necessary to select in an advantageous manner for the skilled person.

The second step of manufacturing the two fusion line forming substrates 860 by injection molding using the molding stamp 350 may be performed using a vacuum injection molding in accordance with a conventional molding process. The materials for the lower fusion line formation substrate 860a and the upper fusion line formation substrate 860b used for the molding are freely selected from plastic materials. Preferably cycloolefin copolymer (COC) is advantageous, but may be injected into polycarbonate (PC), polyethylene (PE), polyflopropylene (PP) or the like.

A third step of bonding the lower fusion line formation substrate 860a and the upper fusion line formation substrate 860b to each other by the ultrasonic welding method is performed by using a conventional ultrasonic welding machine. Ultrasonic fusion machine is a device that can fusion thermoplastic and plastic, film, film, synthetic fiber, etc. quickly and efficiently by using the vibration energy of ultrasonic. The PR fusion line 830 of the present invention provided on the lower fusion line formation substrate 860a and the upper fusion line formation substrate 860b is melted by high frictional heat caused by strong ultrasonic vibration, and thus these lower fusion line formation substrate 860a is excellent. ) And the upper fusion line forming substrate 860b are bonded to form a channel 235 in micro units (see FIGS. 8E and 8F).

In other words, the process shown in FIG. 8 ameliorates the disadvantages of the process shown in FIG. 3. That is, according to the process illustrated in FIG. 3, the micro fusion line (see 270 in FIG. 3) is melted first to form a bond, and thus, when the fusion line 270 is not melted or residue remains, the lower substrate 200 Gaps may occur between the upper substrates 100.

Accordingly, FIG. 8 shows a plurality of PR fusion lines 830 between two PR patterns 820 so that the PR patterns 820 do not form a channel 235 when these PR fusion lines 830 are melted by ultrasonic waves. Since it is within the extra space 235 therebetween, the lower fusion line formation substrate 860a and the upper fusion line formation substrate 860b may be brought into front contact with each other even when there is no residue, no melting or melting (see FIG. 8G). . Therefore, it becomes possible to finely control the height of the channel 235.

While the present invention has been particularly shown and described with reference to exemplary embodiments thereof, it is to be understood that the invention is not limited to the disclosed embodiments, but, on the contrary, Those skilled in the art will recognize that many modifications and variations are possible in light of the above teachings.

Accordingly, the spirit of the present invention should not be construed as being limited to the embodiments described, and all of the equivalents or equivalents of the claims, as well as the following claims, belong to the scope of the present invention .

The microfluidic chip manufacturing method using the micro ultrasonic fusion according to the present invention can produce a reliable microfluidic chip capable of precise measurement in large quantities with low energy, and thus can be said to have sufficient industrial applicability.

Claims (20)

In the microfluidic chip 10 manufacturing method using ultrasonic welding, the microfluidic chip manufacturing method
A first step of manufacturing a molding stamp 350 using a photolithography method; A second step of manufacturing the upper substrate 100 and the lower substrate 200 by injection molding using the molding stamp 350; And a third step of bonding the upper substrate 100 and the lower substrate 200 by an ultrasonic welding method.
The first step using the photolithography method may include forming a photoresist (PR) pattern 320 of an internal structure of the microfluidic chip on the substrate 310; Steps 1-2 forming a PR fusion line 330 on the PR pattern 320 to make a fusion line 270 of the ultrasonic unit for ultrasonic welding; First to third steps of depositing an electroplating seed metal layer 340 on the substrate 310; First to fourth plating the molding stamp 350 by electroplating using the seed metal layer 340; And a first to fifth step of stamp release to remove the molding stamp 350 from the PR pattern 320 and the substrate 310.
delete The method of claim 1, wherein forming the PR fusion line 330 includes forming the PR fusion line 330 such that the fusion line 270 of the micro unit has an inclination. Microfluidic chip fabrication method using phosphorus ultrasonic welding. The inclination of the fusion line 270 of the micro unit is such that the base portion 272 of the fusion line 270 of the micro unit of the interview portion 271 which is in contact with the fusion target is 270. Method for producing a microfluidic chip using ultrasonic welding, characterized in that formed by a narrower width than). The fusion fusion line 330 of claim 3, wherein the fusion line 270 of the micro unit is inclined is formed by an exposure apparatus in which the inclination of the stage holding the substrate 310 is adjusted and rotated. Microfluidic chip manufacturing method using ultrasonic welding. The method of claim 1, wherein the remaining solvent is removed immediately after the first step 1-2 forming the PR fusion line 330 is completed to dry the PR coating, and to increase the adhesion of the PR coating to the substrate 310. Method for manufacturing a microfluidic chip using ultrasonic fusion characterized in that the hard bake process for the additional. The method of claim 1, wherein the second step is vacuum injection molding. According to claim 7, wherein the upper substrate 100 and the lower substrate 200 used in the molding material of the cycloolefin copolymer (COC), polycarbonate (PC), polyethylene (PE), polyflopropylene (PP) Microfluidic chip manufacturing method using ultrasonic welding characterized in that it is selected from one. The filter protrusions 221 and 233 of claim 1, wherein the first-first step of forming the PR pattern 320 comprises filters 220 and 230 for filtering blood cells in the internal structure of the microfluidic chip 10. In forming the PR pattern 320, the filter protrusions 221 and 233 are configured such that the minimum value of the gaps 222 and 234 in the height direction of the filter protrusions 221 and 233 is at least smaller than the diameter of the blood cells. Microfluidic chip fabrication method using ultrasonic welding. 10. The method of claim 9, wherein forming the PR pattern 320 is a step 1-1 in forming the PR pattern 320 of the internal structure of the microfluidic chip 10, the filter projections (221, 233) A method of manufacturing a microfluidic chip using ultrasonic fusion, characterized in that an additional channel (130) is formed on the side of the formed substrate (100, 200) to which the counter substrate (100, 200) is bonded to reduce the flow resistance of plasma. In the microfluidic chip 10 manufacturing method using ultrasonic welding, the microfluidic chip manufacturing method,
A first step of manufacturing a molding stamp 350 using a photolithography method; A second step of manufacturing two fusion line forming substrates 860 by injection molding using the molding stamp 350; And one of the two fusion line formation substrates 860 becomes the lower fusion line formation substrate 860a and the other becomes the upper fusion line formation substrate 860b. A third step of joining the upper fusion line forming substrates 860b to each other and bonding them by an ultrasonic welding method;
The first step using the photolithography method may include forming a photoresist (PR) pattern 320 of an internal structure of the microfluidic chip on the substrate 310; Steps 1-2 forming the PR fusion lines 830 and the PR patterns 820 of the plurality of ultrasonic welding micro units; First to third steps of depositing an electroplating seed metal layer 840 on the substrate 310; First to fourth plating the molding stamp 850 by electroplating using the seed metal layer 840; And a first to fifth steps of stamp release to remove the molding stamp (850) from the substrate (310).
delete The method of claim 11, wherein the steps 1-2 of forming the PR fusion line 830 and the PR pattern 820 are formed to have a micro unit and have an inclination in forming the PR fusion line 830. The PR fusion line 830 of the microfluidic chip manufacturing method using the ultrasonic welding is characterized in that the two is an isosceles square shape is larger than the PR pattern 820 between the PR patterns (820). The method of claim 13, wherein the PR fusion line 830 is formed by an exposure apparatus in which the inclination of the stage holding the substrate 310 is adjusted and rotated. 12. The method of claim 11, wherein after removing the solvent remaining immediately after the steps 1-2 of forming the PR fusion line 830 and the PR pattern 820 is completed, the PR coating is dried, and the PR to the substrate 310 A method of manufacturing a microfluidic chip using ultrasonic welding, characterized in that a hard bake process is further performed to increase the adhesion of the coating. 12. The method of claim 11, wherein the second step is vacuum injection molding. The method of claim 16, wherein the material of the lower fusion line forming substrate 860a and the upper fusion line forming substrate 860b used for the molding is cycloolefin copolymer (COC), polycarbonate (PC), polyethylene (PE) ), A method for producing a microfluidic chip using ultrasonic fusion, characterized in that it is selected from one of polypropylene (PP). The filter protrusions 221 and 233 of claim 11, wherein the first-first step of forming the PR pattern 320 comprises filters 220 and 230 for filtering blood cells in the internal structure of the microfluidic chip 10. In forming the PR pattern 320, the filter protrusions 221 and 233 are configured such that the minimum value of the gaps 222 and 234 in the height direction of the filter protrusions 221 and 233 is at least smaller than the diameter of the blood cells. Microfluidic chip fabrication method using ultrasonic welding. 19. The method of claim 18, wherein forming the PR pattern 320 includes the filter protrusions 221 and 233 in forming the PR pattern 320 of the internal structure of the microfluidic chip 10. A method for manufacturing a microfluidic chip using ultrasonic fusion, characterized in that an additional channel (130) is formed on the side of the formed substrate (860a, 860b) to which the counter substrate (860a, 860b) is bonded to reduce the flow resistance of plasma. delete

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