KR101061159B1 - Low temperature bonding method of biochip using direct atmospheric pressure plasma - Google Patents

Abstract

The present invention uses a direct pressure atmospheric plasma to modify the surface of plastics used in the manufacture of microchips such as biochips, lap on a chip, etc. without changing the characteristics of the pattern and the top plate and The present invention relates to a method of manufacturing a chip by bonding two substrates uniformly and stably by enhancing the adhesion of the lower plate. According to the present invention, a method of manufacturing a microchip by bonding two substrates of plastics, each of which consists of a top plate and a bottom plate, having a micro-pattern, includes: modifying the two substrates by plasma treatment at atmospheric pressure, one by one, and by modifying the two substrates. Compressing and bonding the two substrates so that the two surfaces adhere to each other.

Microchip, biochip, lab-on-a-chip, direct atmospheric plasma, bonding

Description

Biochip Low-Temperature Bonding Method using Direct Atmospheric Plasma}

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for manufacturing a microchip, and more particularly, to plastics used for manufacturing a microchip such as a biochip or a lap on a chip using a direct pressure atmospheric plasma. The present invention relates to a method of manufacturing a chip by bonding two substrates uniformly and stably by strengthening the adhesion between the upper and lower plates without changing the characteristics of the pattern by changing the surface.

Today, in order to observe and measure the microparticles contained in the liquid sample, a variety of microchips such as biochips, lap on a chip, and the like are used. For example, blood cell populations such as red blood cells, white blood cells or platelets, or cell populations in urine, saliva or spinal fluid, yeast groups in fermented foods such as beer, bacterial groups in aqueous solution, microplankton, juice, ketchup, Particles from several micrometers to several tens of micrometers, such as cells and impurities in suspensions such as milk, reproductive cell populations in mammals, impurities in incompletely dissolved turbidity, and various metal and nonmetallic crystals in aqueous solutions or solvents Injecting the sample containing the microchip into the microchip can be observed and measured through the analysis equipment equipped with an optical microscope or CCD camera.

Plastics are widely used today for the production of such microchips, and microchips are manufactured by forming and bonding appropriate microchannels or other patterns to upper and lower plates made of plastic as shown in FIG. 1. In general, the two substrates may be bonded to each other by a method such as heating, using an adhesive, coating, pressing, vibration, or ultrasonic bonding for manufacturing the plastic microchip. However, such a general bonding method is inferior in the uniformity of the adhesion and productivity is a problem when performing in a vacuum. In order to solve this problem, a solvent bonding method for forming a solvent channel at the boundary between two substrates and injecting an adhesive is being tried. However, due to the lack of uniformity and productivity, a new substrate bonding method for manufacturing a microchip has been developed. It is required.

The present invention is to solve the above problems, an object of the present invention is to modify the plastics used in the manufacture of the microchip by using a direct pressure atmospheric plasma surface of the upper plate and the lower plate without changing the characteristics of the pattern The present invention provides a method for manufacturing a microchip capable of fabricating a chip by pressing two substrates uniformly and stably by strengthening.

According to an aspect of the present invention for achieving the above object, a method of manufacturing a microchip by joining two substrates of plastics consisting of the upper plate and the lower plate, the step of surface modification by plasma treatment of the two substrates one by one at normal pressure; And pressing and bonding the two substrates such that modified surfaces of the two substrates adhere to each other.

The surface modification step is characterized in that using a direct plasma.

The direct plasma is characterized by forming a plasma sheath to a predetermined distance from the substrate.

It is preferable that the said plasma sheath is formed to the distance of 1 mm or less from a board | substrate.

The surface modification may include using an inert gas of argon or helium for plasma generation at the atmospheric pressure.

In order to generate plasma at the atmospheric pressure, 0.2% to 10% of oxygen may be used as compared to the inert gas.

Before the surface modification by plasma treatment at atmospheric pressure, it is preferable to wash the two substrates using any one or more alcohols such as ethanol or isopropyl.

The bonding step is characterized in that the two substrates are pressed and adhered at a temperature lower than the transition temperature range of the plastic, the pressure is within 1.25 to 5 atm, and the time is within 5 to 30 minutes.

Here, the plastics are light transmissive plastics such as polymethyl methacrylate (PMMA), cyclone olefin (COC) resin, polyethylene terephthalate (PET), polycarbonate (PC), polyethylene (PE), polypropylene (PP), polystyrene (PS) or polyolefin (POC) resin.

In addition, the microchip according to another aspect of the present invention includes a microchip, such as a biochip, a lap on a chip, and the like, which are manufactured through the plasma treatment and bonding at the above normal pressure.

As described above, according to the method of manufacturing a microchip according to the present invention, the surface of the plastics is modified by using a direct pressure atmospheric plasma to enhance the adhesion between the upper and lower plates without pressing the two substrates, thereby compressing the two substrates. By attaching, it is possible to provide a microchip in which two substrates are uniformly and stably bonded together.

In order to fully understand the present invention, the operational advantages of the present invention, and the objects achieved by the practice of the present invention, reference should be made to the accompanying drawings which illustrate preferred embodiments of the present invention and the contents described in the accompanying drawings.

Hereinafter, exemplary embodiments of the present invention will be described in detail with reference to the accompanying drawings.

2 is a flowchart illustrating the manufacture of a plastic microchip according to an embodiment of the present invention.

Referring to FIG. 2, first, an upper plate and a lower plate of plastics are prepared (S110). Here, the upper and lower plates each have a thickness of 0.2 to 1.5 millimeters or less, and preferably have a thickness of about 0.5 mm in order to improve adhesion as described below. Here, the upper plate and the lower plate are bonded to each other and are made of a microchip such as a bio chip or a lap on a chip, and the upper plate or the lower plate is a microchip for observing and measuring microparticles contained in a liquid sample. Patterns such as channels may be formed. Here, the plastic substrate used as the upper plate and the lower plate is a light transmissive plastic, polymethyl methacrylate (PMMA), cyclone olefin (COC) resin, polyethylene terephthalate (PET), polycarbonate (PC), polyethylene (PE), polypropylene (PP), polystyrene (PS), or a polyolefin (POC) resin, such as a high molecular compound.

When the upper and lower plates are prepared as described above, each of the two substrates may be manually or automatically transferred to the atmospheric pressure plasma reactor as shown in FIG. 3 or 4 (S120). At this time, it is preferable to wash the two substrates using alcohols such as ethanol or isopropyl before each of the two substrates is transferred to the atmospheric plasma reactor and subjected to plasma treatment.

3 illustrates a remote plasma scheme, and FIG. 4 illustrates a direct plasma. Although the present invention mainly assumes the use of a direct plasma, the present invention is not limited thereto, and a remote plasma may be used as necessary.

Referring to FIG. 3, a remote plasma method generates a plasma by applying RF (Radio Frequency) power between two plates while injecting a predetermined gas, and is placed on a lower stage using a plasma generated between two plates. The plasma is exposed to the substrate perpendicularly to the substrate. As shown in the upper image of FIG. 5, in the remote plasma method, a sheath, which is a region in which light emission is poor, is large at the interface between the substrate and the plasma, and high energy radicals or ions are hardly formed between the substrate and the reactor. Therefore, the corresponding energy of the activated radical is only enough to break the binding chain of OO, CN, C-Cl, CC, CO, CH, etc. of the plastic polymer compound, and H-Cl, HH, OH, O = O Since the bond chains of C, C, and C are difficult to break, the material of the plastic substrate that can be applied may be limited. In Fig. 5, the solid circle means activated high energy radicals or ions, and the dashed circle means unactivated radicals or ions.

On the other hand, referring to FIG. 4, the direct plasma generates a plasma while injecting a gas between the ground plate 25 under the stage 26 and the RF power plate 27 on the upper side to hold the substrate, thereby generating the stage ( And plasma treatment in parallel to the substrate placed on the substrate. As shown in the right figure of FIG. 5, in the direct plasma method, a sheath, which is a region in which light emission is poor, is very small at the interface between the substrate and the plasma, and high energy radicals or ions are formed between the substrate and the reactor. Surface chemical reactions can be induced.

As shown in FIG. 6, a positive space charge region corresponding to the substrate from about 0.6 of the electron density n _eo in the bulk having a quasi neutral region of the electron density n _s to the substrate. ), Most of the potential of the RF power drops, and the ion density n _ion is greater than the electron density n _s .

The surface treatment of the substrate is performed in such a sheath region, and in direct plasma, such a sheath region is formed only by a very small distance from the substrate, for example, up to a distance of 1 mm or less from the substrate. Energy radicals and ions are not only bound to chains of plastic polymer compounds, such as OO, CN, C-Cl, CC, CO, CH, but also H-Cl, HH, OH, O = O, C = C, C = O, etc. It can be applied to almost all of the above plastic polymer compounds by allowing the bond chain to be sufficiently broken.

In addition, since the remote plasma may be affected by the grounding treatment under the stage and the like and may form a non-uniform plasma, it is preferable to form a uniform and stable plasma at normal pressure (atmospheric pressure) using such a direct plasma. In particular, the direct plasma is capable of uniform and stable plasma processing even for large area substrates of 30 cm or more in width and length.

When the upper plate or the lower plate is transferred to the atmospheric pressure plasma reactor of the direct plasma method as described above, each substrate is subjected to plasma treatment according to the direct plasma method as described above (S130). Plasma generation at this time is processed under the conditions of 50 to 300W of the RF power, and a strong and appropriate RF power having a surface modification effect is required to the extent that the patterns of channels and the like formed on each substrate are not damaged. In some cases, it is also possible to obtain a desired surface modification effect by repeating the treatment twice or more, for example, about five times at about 100W for each substrate.

For example, in the case of polymethyl methacrylate (PMMA), CH, CC, O = CO chains are broken by the direct plasma treatment as described above, and a large amount of OH (Hydroxyl) and C = O (Carbonyl) chains are produced. As a result, the movement of molecules is free, thereby lowering the contact angle (hydrophilicity) with water, thereby increasing the surface adhesion. Similar principles for other plastics allow surface modification to hydrophilicity.

In addition, at this time, an atmosphere of argon gas or helium gas as an oxygen gas and an inert gas is formed between the stage holding the substrate for plasma generation and the plate to which RF power is applied. These oxygen gases, argon gas, or helium gas are injected at a flow rate of 0.01 to 2 liters per minute, preferably inert gas (argon / helium gas) is injected at a flow rate of 1-2 liters per minute, and oxygen gas is injected into the inert gas ( Argon / helium gas) is preferably injected at a flow rate of 0.01 to 2 liters per minute at 0.2 to 10% by weight, for example 2% by weight. Thus, by modifying the surface of the plastics using a plasma formed at atmospheric pressure, the two substrates are uniform by pressing and bonding the two substrates by strengthening the adhesion between the upper plate and the lower plate without changing the characteristics of the substrate pattern such as the microchannel. It can be made to adhere stably.

After the plasma treatment is performed on each substrate, the two substrates that have been plasma-treated and are surface-modified are transferred to a predetermined press (S140), and the two substrates are stacked by pressing each other so that the modified surfaces face each other, and then bonding them together. Attach (S150). The bonding condition at this time is a transition temperature of 60 to 150 degrees Celsius or less, for example, 80 degrees Celsius (for example, for PMMA), a pressure of 1.25 atmospheres to 5 atmospheres, for example, 3 atmospheres, And within two to five minutes of time, for example, ten minutes. In particular, the bonding temperature here may vary depending on the type of plastic, since the intermediate transition temperature before proceeding from the solid phase to the liquid phase may vary from plastic to plastic. For example, in the case of polymethyl methacrylate (PMMA), it is possible to bond at a low temperature of about 80 degrees Celsius which is below the transition temperature range by the direct plasma treatment as described above, and in the case of cyclone olefin (COC), It is possible to bond at a low temperature of about 130 degrees Celsius which is below the temperature range. In the conventional thermocompression bonding method, the plastic state is modified by raising the temperature above the transition temperature, but in the present invention, the microchannel or the like is patterned even at a low temperature below the transition temperature range according to the surface modification by the atmospheric pressure plasma of the direct method. It is possible to achieve a stable bonding while preventing the deformation.

As such, the upper plate and the lower plate may be bonded together, and as shown in FIG. 7, a microchip of a predetermined purpose may be completed. For example, a microchip sample inlet, a blood cell group such as red blood cells, white blood cells or platelets, a cell group in urine, saliva or spinal fluid, a yeast group in fermented foods such as beer, a bacterial group in an aqueous solution, and a microorganism. Micros such as cells and impurities in suspensions such as plankton, juice, ketchup and milk, germ cell populations in mammals, impurities in incompletely dissolved turbidity, and various metal and nonmetallic crystals in aqueous solutions or solvents. Inject a sample containing several tens of micrometers from the meter, and observe the microparticles moving through the microchannel to a predetermined outlet through an analysis equipment equipped with an optical microscope or a CCD camera. Can be.

As described above, optimal embodiments have been disclosed in the drawings and the specification. Although specific terms have been used herein, they are used only for the purpose of describing the present invention and are not intended to limit the scope of the invention as defined in the claims or the claims. Therefore, those skilled in the art will understand that various modifications and equivalent other embodiments are possible from this. Therefore, the true technical protection scope of the present invention will be defined by the technical spirit of the appended claims.

1 is a view for explaining the manufacture of a general plastic microchip.

2 is a flowchart illustrating the manufacture of a plastic microchip according to an embodiment of the present invention.

3 is a view for explaining a remote plasma method according to an embodiment of the present invention.

4 is a view for explaining a direct plasma method according to an embodiment of the present invention.

5 is a view for comparing the substrate surface chemical reaction and the sheath between the remote plasma method and the direct plasma method according to an embodiment of the present invention.

6 is a view for explaining the formation of the sheath between the substrate and the plasma according to an embodiment of the present invention.

7 is a view for explaining an example of a microchip manufactured according to an embodiment of the present invention.

Claims (10)

In a method of manufacturing a microchip by bonding two substrates of plastics consisting of an upper plate and a lower plate, Surface modification of the two substrates, one by one, at atmospheric pressure; And Pressing and bonding the two substrates such that modified surfaces of the two substrates adhere to each other at a temperature lower than a plastic transition temperature range, And modifying the surface by forming a plasma sheath up to a distance of 1 mm or less from the substrate using the direct plasma in the surface modifying step. delete delete delete The method of claim 1, wherein the surface modification step, Microchip manufacturing method characterized in that for generating the plasma at the atmospheric pressure, at least one of an inert gas of argon or helium. The method of claim 5, wherein 0.2% to 10% oxygen is used in comparison with the inert gas to generate plasma at the atmospheric pressure. According to claim 1, Before the surface modification by plasma treatment at atmospheric pressure, Washing the two substrates using alcohols of at least one of ethanol or isopropyl Microchip manufacturing method characterized in that it further comprises. The method of claim 1, wherein the bonding step, A method of manufacturing a microchip, comprising: bonding two substrates by pressing the substrate at a pressure of 1.25 atmospheres to 5 atmospheres and a time of 5 to 30 minutes. The method of claim 1, wherein the plastics are light transmissive plastics such as polymethyl methacrylate (PMMA), cyclone olefin (COC) resin, polyethylene terephthalate (PET), polycarbonate (PC), polyethylene (PE), polypropylene ( PP), polystyrene (PS), or polyolefin (POC) resin comprising a microchip manufacturing method. Microchip manufactured according to the method of claim 1.

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