KR100566370B1 - Micropump utilizing gas generation and production method thereof - Google Patents

Abstract

The present invention discloses a micropump and a small cell incubator used to transport materials in a microstructure, including a lab-on-a-chip (LOC), and includes a series of micro-electro-mechanical systems (MEMS) processes. An oxygen generator consisting of an H ₂ O ₂ solution isolated from the treatment and MnO ₂ as a catalyst or a carbon dioxide generator that generates carbon dioxide by heating NaHCO ₃ or reacting with HOC (COOH) (CH ₂ COOH) ₂ . do. The gas generated by the micropump using oxygen or carbon dioxide generation according to the present invention exhibits sufficient purity to be used in subsequent processes and reactions and provides sufficient pressure and amount to repel liquid samples in reservoirs or microchannels. . In addition, the micropump using oxygen or carbon dioxide generation according to the present invention can be applied to a small cell incubator that is greatly limited in mobility due to the supply of carbon dioxide can realize a portable small cell incubator.

Description

Fine pump using gas generation and its manufacturing method {MICROPUMP UTILIZING GAS GENERATION AND PRODUCTION METHOD THEREOF}

1 is a cross-sectional perspective view of a fine pump using gas generation according to a first embodiment of the present invention;

2 is a cross-sectional view taken along line AA ′ of FIG. 1 according to the first embodiment of the present invention;

3A to 3F are manufacturing process diagrams of a fine pump using gas generation according to the first embodiment of the present invention;

4 is a sectional perspective view of a fine pump using gas generation according to a second embodiment of the present invention;

5 is a cross-sectional view taken along line B-B 'of FIG. 4 according to a second embodiment of the present invention;

6A to 6E are manufacturing process diagrams of a fine pump using gas generation according to a second embodiment of the present invention;

7 is a sectional perspective view of a fine pump using gas generation according to a third embodiment of the present invention;

8 is a cross-sectional view taken along line C-C 'of FIG. 7 according to a third embodiment of the present invention;

9 is a sectional perspective view of a fine pump using gas generation according to a fourth embodiment of the present invention;

10 is a cross-sectional view taken along the line D-D 'of FIG. 9 according to the fourth embodiment of the present invention;

11 is a top cross-sectional perspective view of a small cell incubator using gas generation according to a fifth embodiment of the present invention,

12 is a bottom cross-sectional perspective view of a small cell incubator using gas generation according to a fifth embodiment of the present invention,

13 is a cross-sectional view taken along the line E-E 'of FIG. 11 according to the fifth embodiment of the present invention;

14 is a schematic view showing the shape of an airline of a small cell incubator using gas generation according to a fifth embodiment of the present invention;

15 is a schematic view showing the shape of a media line of a small cell incubator using gas generation according to a fifth embodiment of the present invention.

 <Description of Symbols for Main Parts of Drawings>

One ; Silicon substrate 2; SiO ₂ thin film

3; Si ₃ N ₄ thin film 4; H ₂ O ₂ solution storage

5; MnO ₂ storage 6; Fine Channel

7; Polydimethyl siloxane (PDMS) 8; Sample reservoir

9; Pipeline 10; Sample inlet

11; Glass plate 12; Silicon substrate

13; SU-8 layer 21; Glass plate

23; Hot wire 24; H ₂ O ₂ solution storage

25; Paraffin 26 mixed with MnO ₂ powder; Fine Channel

27; PDMS 28; Sample reservoir

29; Pipeline 30; Inlet

51; Glass plate 53; thermic rays

54; NaHCO ₃ storage 56; Airlines

57; PDMS 58; PDMS membrane

59; PDMS cover 61; Media line

The present invention relates to micropumps and small cell incubators used in microstructures, including LOCs, and more particularly to a small amount of gas generated by a series of treatments including a MEMS (Micro-Electro-Mechanical Systems) process. This relates to a micropump, a small cell incubator using gas generation used in a chemical reaction or a separate process, and a method for producing the same.

Lab-on-a-chip (LOC) is a device for sample analysis (sample pretreatment, reaction) on a chip made of glass, plastic or silicon of several cm2 size using micromachining techniques such as optical etching and etching techniques. Micro-total analysis systems (μ-TAS) are a typical application for micro-analysis, which is designed to integrate and separate and detect devices, and to perform automated analysis at high speed and efficiency.

Separation analysis using LOC has advantages in medical, diagnostic applications and biological applications where it is difficult to collect large amounts of samples, because experiments can be performed with only a few samples. Currently, it is mainly used for the analysis of biological materials such as separation of amino acids and peptides, DNA sequencing, immunoassay, etc., but it is also expanding the scope of application to other research fields, among others, real-time analysis in the field. It can be used in the field of separation and analysis of environmental pollutants required, or in the field of mobile small laboratory where results can be checked on-site, so that it can be applied to next-generation diagnosis, measurement field, and new drug search field requiring high-speed analysis of many analytes. This is attracting attention.

However, the operation of the LOC requires an external power for transporting materials in the chip. The transport methods developed to date include electric methods such as electroosmosis and electrophoresis and pump methods using a fine motor. In the above conventional transportation method, an external continuous power source is required, so that the overall size of the chip is increased or additional equipment is involved. Therefore, the actual commercialization of LOC and field application requires the development of miniaturized power sources and pumps or the replacement of existing pumps.

In addition, in order to develop a cell chip, which is an advanced field of LOC, into a portable cell incubator, temperature and pH control must be accompanied, and temperature control is possible through a fine heating wire. However, the pH of the culture medium of the cells is controlled by the action of carbon dioxide supplied into the culture medium. Therefore, the continuous supply of carbon dioxide is required, there is a disadvantage that the existing large cell incubator is connected to a compressed carbon dioxide gas cylinder that weighs several tens of kilograms. Therefore, the development of miniaturized carbon dioxide sources must precede the emergence of portable small cell incubators.

In order to achieve the above object, the present invention provides a silicon substrate having a storage space for storing a H ₂ O ₂ solution, a SiO ₂ / Si ₃ N ₄ thin film formed on the silicon substrate, and a storage for storing MnO ₂ . A space is formed and a sample reservoir, a sample inlet, and a microchannel communicating with the storage space are formed by a conduit, and a fine pump using gas generation including PDMS coupled to the SiO ₂ / Si ₃ N ₄ thin film. to provide.

According to another aspect of the present invention, a glass plate for securing a storage space, a heating wire formed in the storage space, and an air line coupled to the glass plate to form the storage space and communicate with the storage space by a pipeline A small cell incubator having the formed PDMS, a gas-permeable thin PDMS membrane placed on the PDMS, a channel through which the culture medium bound on the PDMS membrane flows, and a PDMS cover in which the culture surface of the cell is engraved To provide.

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

Example 1

1 and 2 are cross-sectional perspective views of a micropump using oxygen generation in which H ₂ O ₂ solution and MnO ₂ are separated by a SiO ₂ / Si ₃ N ₄ thin film according to the first embodiment of the present invention, and FIG. A 'cross section.

As shown in FIG. 1 and FIG. 2, the micropump using gas generation according to the first embodiment of the present invention is H ₂ on the silicon substrate 1 on which the SiO ₂ / Si ₃ N ₄ thin films ₂ and ₃ are formed. PDMS having a storage space (4) for the O ₂ solution and a space (5), a microchannel (6), a sample reservoir (8), a conduit (9) and a sample inlet (10) for storing MnO ₂ (polydimethyl siloxane) 7 is covered. When a light physical shock or pressure is transmitted from the outside of the PDMS (7), the SiO ₂ / Si ₃ N ₄ thin film (2,3) is broken into pieces and the upper MnO ₂ mixes with the lower H ₂ O ₂ solution. do. The oxygen gas generated in this way is discharged through the microchannel 6 to push out the liquid sample used for the subsequent reaction or present in the front.

As shown in FIG. 1, a conduit 9 is formed between the H ₂ O ₂ solution storage space 4 and the MnO ₂ storage space 5 and the sample reservoir 8 to communicate with each other. At one end of (8), a sample inlet 10 for injecting a sample is formed. The microchannel 6 is formed after the sample reservoir 8.

3A to 3F are manufacturing process diagrams of the micropump using gas generation according to the first embodiment of the present invention, and FIGS. 3A to 3C are MnO ₂ storage spaces 5, microchannels 6, and sample reservoirs 8. ), The conduit 9 and the sample inlet 10, etc. are formed in the PDMS, and FIGS. 3D to 3F form the H ₂ O ₂ solution storage space 4 on the silicon substrate and prepare the PDMS prepared in FIG. 3C. The covering process is shown.

The process according to FIGS. 3A-3F proceeds as follows.

(a) As shown in FIG. 3A, SU-8, a negative photosensitive material, is spin-coated and patterned on the silicon substrate 12 to form a layer having a thickness of about 65 μm.

(b) As shown in FIG. 3B, a space for MnO ₂ is formed by repeating the same process as (a) with SU-8 thereon to raise the layer thereon.

(c) PMS is poured and solidified onto the silicon substrate 12 and the patterned SU-8 layer 13, as shown in FIG. 3C.

(d) As shown in FIG. 3D, SiO ₂ film 2 and Si ₃ N ₄ film 3 are sequentially formed on and under the silicon substrate 1.

(e) As shown in FIG. 3E, HMDS (hexamethyldisilazane) and AZ 9260 photoresist are sequentially applied to the bottom surface of the silicon substrate on which the SiO ₂ / Si ₃ N ₄ thin films ₂ and ₃ are formed, and then etched. The part to be exposed is subjected to ultraviolet exposure using a mask and developed. Then, the Si ₃ N ₄ film is removed by reactive ion etching (RIE), and the SiO ₂ film is removed with a buffered HF (BHF) solution. It is etched with tetramethylammonium hydroxide (TMAH), a silicon etching solution, to secure the H ₂ O ₂ solution storage space 4, and a vinyl film or glass plate 11 is attached thereto.

(f) As shown in FIG. 3F, the PDMS prepared in (c) is removed from the silicon substrate and the SU-8 pattern and covered with the substrate prepared in (e) to complete a fine pump using gas generation.

Example 2

4 and 5 are cross-sectional perspective views of the micropump using oxygen generation to which the structure for isolating H ₂ O ₂ solution and MnO ₂ using paraffin according to the second embodiment of the present invention and B-B 'of FIG. Line cross section.

According to the second embodiment of the present invention, when paraffin is melted by an externally applied heating wire, oxygen gas is generated when MnO ₂ is released into the H ₂ O ₂ solution, which pushes and moves the fluid in the microchannel. Once released into the H ₂ O ₂ solution, MnO ₂ remains in the H ₂ O ₂ solution to continue the reaction even after the current is interrupted.

4 and 5, in the micro pump using gas generation according to the second embodiment of the present invention, the storage space 24 for the H ₂ O ₂ solution is secured on the glass plate 21, and the storage space Heat wires 23 are arranged in parallel or irregularities in 24, and paraffin 25 mixed with MnO ₂ powder is formed thereon. Outwardly, the storage space 24 is formed, and the PDMS 27 in which the microchannel 26, the sample reservoir 28, the conduit 29, and the injection port 30 are formed is covered.

In FIG. 4, a conduit 29 is formed between the storage space 24 and the sample reservoir 28 to communicate with each other. The H ₂ O ₂ solution storage space 24 and one end of the sample reservoir 28 are H _2. Injection holes 30 for injecting O ₂ and a sample are respectively formed. The microchannel 26 is formed after the sample reservoir 28. The total size of the micropump using gas generation according to the second embodiment is approximately 2 cm x 1 cm (width x length).

6A to 6E illustrate a manufacturing process of a micropump using oxygen generation in which H ₂ O ₂ solution and MnO ₂ are separated using paraffin according to the second embodiment of the present invention.

The process according to FIGS. 6A-6E proceeds as follows.

(a) As shown in Fig. 6A, an aluminum layer is thermally deposited to a thickness of about 0.2 mu m to form a hot wire on the glass plate 21. The hot wire is formed with a line width of 30 μm in an area of about 2 mm × 2 mm.

(B) As shown in FIG. 6B, after HMDS and AZ 5214 photoresist are sequentially applied in rotation, ultraviolet rays are exposed using a hot-wire pattern mask. After etching aluminum outside the hot wire 23, the photoresist is removed with acetone.

(c) As shown in FIG. 6C, PDMS is attached to form a storage space of H ₂ O ₂ solution and MnO ₂ .

(d) As shown in FIG. 6D, paraffin is dissolved and mixed with MnO ₂ powder, and about 2 μl is injected into the storage space to form a layer 25.

(e) As shown in FIG. 6E, the oxygen generator is completed by covering 5 μl of a H ₂ O ₂ solution covering the PDMS 27 where the microchannels and the like are formed.

Example 3

7 and 8 are cross-sectional perspective views of a fine pump using carbon dioxide generation using NaHCO ₃ and a cross-sectional view taken along line C-C 'of FIG. 7 according to a third embodiment of the present invention.

According to a third embodiment of the present invention, NaHCO ₃ is heated by a micro heating wire applied with an external current and decomposed into Na ₂ CO ₃ and water and carbon dioxide by the following formula.

2 NaHCO ₃ ( s )-> Na ₂ CO ₃ ( s ) + H ₂ O ( l ) + CO ₂ ( g )

The generated carbon dioxide pushes and moves the fluid in the reservoir or microchannel.

As shown in FIG. 7 and FIG. 8, in the micro pump using gas generation according to the third embodiment of the present invention, a fine hot wire 33 is formed on the glass plate 31 by using a metal thin film such as aluminum, and PDMS. The storage space 34 of NaHCO ₃ is secured using the PDMS, in which the microchannel 36, the sample reservoir 38, the conduit 39, the inlet 40, etc. are formed after the NaHCO ₃ is placed in the space. 37) is covered.

In the manufacturing process of the micropump using carbon dioxide generation using NaHCO ₃ according to the third embodiment of the present invention, H ₂ O ₂ solution and MnO ₂ are prepared using paraffins according to the second embodiment shown in FIGS. 6A to 6E. It is the same as the manufacturing process of the micropump using oxygen generation with the isolation structure, but the process of forming the paraffin (25) layer mixed with MnO ₂ powder is omitted, and NaHCO ₃ is injected instead of H ₂ O ₂ solution. .

Example 4

9 and 10 are cross-sectional perspective views and views of a micropump using carbon dioxide generation produced using a mixture of NaHCO ₃ and HOC (COOH) (CH ₂ COOH) ₂ and fine water droplets according to a fourth embodiment of the present invention. 9 is a sectional view taken along the line D-D '.

According to the fourth embodiment of the present invention, the mixture of NaHCO ₃ and HOC (COOH) (CH ₂ COOH) ₂ is stable in its state, but HOC (COOH) (CH ₂ COOH) ₂ is added as water is added thereto. When present in aqueous solution, it reacts with NaHCO ₃ to generate HOC (COOH) (CH ₂ COONa) ₂ , water and carbon dioxide as shown in the following chemical formula.

3 NaHCO ₃ ( s ) + HOC (COOH) (CH ₂ COOH) ₂ ( s )

-> HOC (COOH) (CH ₂ COONa) ₂ ( s ) + 3 H ₂ O ( l ) + 3 CO ₂ ( g )

The generated carbon dioxide pushes and moves the fluid in the reservoir or microchannel.

9 and 10, in the fine pump using gas generation according to the fourth embodiment of the present invention, a fine hot wire 43 is formed on the glass plate 41 by using a thin metal film such as aluminum, Using PDMS, a mixture of NaHCO ₃ and HOC (COOH) (CH ₂ COOH) ₂ and droplet storage 44 are secured. Parafilm (manufactured by Pechiney Plastic Packaging, Chicago, water-proof, moisture-proof film, can be easily recorded by heating). Put a small droplet of water (45) on the heating wire (43) and put NaHCO ₃ and HOC (COOH) (CH ₂ COOH After adding the mixture of ₂ ), the microchannel 46, the sample reservoir 48, the conduit 49, the inlet 50, and the like are formed to cover the PDMS 47. Then, when heated with a fine hot wire 43, the parafilm melts and the water droplets 45 are expelled to release the water and the reaction of HOC (COOH) (CH ₂ COOH) ₂ and NaHCO ₃ begins to generate carbon dioxide.

The manufacturing process of the micropump using carbon dioxide generation using a mixture of NaHCO ₃ and HOC (COOH) (CH ₂ COOH) ₂ and fine water droplets according to the fourth embodiment of the present invention is shown in FIGS. 6A to 6E. Process of forming a fine layer of paraffin (25) mixed with MnO ₂ powder is the same as the manufacturing process of the micropump using oxygen generation applied to the structure to isolate the H ₂ O ₂ solution and MnO ₂ using paraffin according to the second embodiment Is omitted and a water drop 45 is placed instead, and a mixture of NaHCO ₃ and HOC (COOH) (CH ₂ COOH) ₂ is injected instead of the H ₂ O ₂ solution.

Example 5

11-13 are top and bottom cross-sectional perspective views of a small cell incubator with a carbon dioxide source according to a fifth embodiment of the present invention, and a cross-sectional view taken along line E-E 'of FIG.

According to the fifth embodiment of the present invention, carbon dioxide generated by pyrolysis of NaHCO ₃ is passed through a thin PDMS film 58 formed thereon while flowing through an air line (microchannel) 56 and formed thereon. CO ₂ is supplied to the placed cell culture to enable pH adjustment.

11 to 13, the small cell incubator using gas generation according to the fifth embodiment of the present invention has a fine hot wire 53 formed on the glass plate 51 using a metal thin film such as aluminum, NaHCO ₃ storage 54 is secured using PDMS. The PDMS 57 having the air line 56 formed thereon is put thereon and NaHCO ₃ is injected. Then, after the permeable thin PDMS membrane 58 is placed, a small cell incubator is completed by covering the PDMS cover 59 in which the media line is engraved. After the culture medium and the cells are injected into the completed small cell incubator through the media inlet, current is supplied to the micro heating wire to decompose NaHCO ₃ to supply carbon dioxide. At this time, it is possible to control the amount of carbon dioxide supplied by adjusting the current supplied to the fine hot wire.

The manufacturing process of the small cell incubator using gas generation according to the fifth embodiment of the present invention is as follows.

(a) Aluminum is thermally deposited on the glass plate 51 to a thickness of about 0.2 μm.

(b) After rotationally applying the HMDS and the AZ 5214 photoresist, they are exposed to ultraviolet rays using a hot-wire pattern mask. After etching aluminum outside the hot wire 53, the photoresist is removed with acetone.

(c) Attach PDMS to secure storage 54 for storing NaHCO ₃ .

(d) After SU-8 is rotated on the wafer, ultraviolet light is exposed and developed to form an embossed frame of the air line 56 having the shape of FIG.

(e) Pour the PDMS into the mold prepared in (d) and solidify it to produce a PDMS 57 in which the airline 56 is engraved to cover the structure prepared in (c).

(f) After PDMS is poured onto the wafer and spun on, it is hardened by storing it for more than 3 hours at 70 degrees Celsius or more. (Through this, the PDMS film 58 is formed to a thickness of 300 µm or more and 500 µm or less.)

(g) After NaHCO ₃ is injected into the structure prepared in (e), the PDMS film 58 prepared in (f) is covered.

(h) PDMS cover in which the culture surface (media line) 61 of the channel and the cell through which the culture fluid flows is engraved by performing the same process as in (d) and (e) using the mask having the shape of FIG. 59).

(i) The PDMS cover 59 prepared in (h) is covered with the structure completed in (g) to complete a small cell incubator.

At this time, when used for the culture of cells requiring adhesion culture, the process of inducing the adsorption of cells by adding a poly-L-lysine solution at room temperature for at least 10 minutes to the surface where the cells reach may be added immediately after (g). .

In the present embodiment, a cell incubator having a carbon dioxide source has been described, but a cell incubator using gas generation according to a fifth embodiment of the present invention may have an oxygen source at the same time as a carbon dioxide source, and in this case, separate oxygen It can be used for experiments in environments that require a source.

In the above description, it should be understood that those skilled in the art can only make modifications and changes to the present invention without changing the gist of the present invention as it merely illustrates a preferred embodiment of the present invention.

The gas generated by the micropump and small cell incubator using gas generation in accordance with the present invention exhibits sufficient purity to be used in subsequent processes and reactions and provides sufficient pressure and amount to push the liquid sample in the reservoir or microchannel. to provide. At this time, when using a H ₂ O ₂ solution of 30% (w / w) concentration, oxygen of more than 100 times the volume of H ₂ O ₂ solution is generated, depending on the amount of catalyst used, the oxygen generation time is in minutes It can be adjusted up to several tens of minutes. In addition, it can be manufactured inexpensively and simply so that it is suitable for single-use use, and its dependence on external devices is very low so that it can be easily integrated into many other LOCs or small devices. In addition, the by-products have the advantage of being environmentally friendly and biocompatible as water and oxygen. In addition, in the case of the carbon dioxide generator is applied to a small cell incubator that is greatly limited in mobility due to the supply problem of carbon dioxide can realize a portable small cell incubator.

Claims (8)

In a fine pump using gas generation, A silicon substrate having an H ₂ O ₂ solution storage space formed therein; SiO ₂ / Si ₃ N ₄ thin film formed on the silicon substrate, Comprising a PDMS coupled to the SiO ₂ / Si ₃ N ₄ thin film, The PDMS includes a MnO ₂ storage space facing the H ₂ O ₂ solution storage space with the SiO ₂ / Si ₃ N ₄ thin film interposed therebetween, the sample reservoir communicating with the MnO ₂ storage space by a pipeline; A micro pump using gas generation comprising a sample inlet connected to one end of the sample reservoir and a micro channel communicating from the other end of the sample reservoir to the outside of the micro pump. In the method of producing a fine pump using gas generation, Forming and patterning a SU-8 layer, which is a negative photosensitive material, on a silicon substrate, a MnO ₂ storage space, a sample reservoir communicating with the MnO ₂ storage space by a conduit, a sample inlet connected to one end of the sample reservoir, and the sample storage Forming a microchannel communicating from another end of the device to the outside of the micropump, Forming a PDMS on the SU-8 layer; Sequentially forming a SiO ₂ film and a Si ₃ N ₄ film on a separate silicon substrate, Etching a lower surface of the silicon substrate on which the SiO ₂ film and the Si ₃ N ₄ film are formed to form a storage space of an H ₂ O ₂ solution; Attaching a lower plate under the storage space of the H ₂ O ₂ solution; Removing the PDMS from the silicon substrate and the SU-8 template and coupling the PDMS onto the silicon substrate on which the storage space for the H ₂ O ₂ solution is formed. In a fine pump using gas generation, A bottom plate forming the bottom surface, A heating wire formed in the storage space on the lower plate, It includes a PDMS coupled to the bottom plate, The PDMS includes the storage space and includes a sample reservoir connected to the storage space by a pipeline, a sample inlet connected to one end of the sample reservoir, and another end of the sample reservoir to the outside of the fine pump. Fine pump using gas generation including a communicating microchannel. The method of claim 3, wherein H ₂ O ₂ solution is stored in the storage space, Fine pump using gas generation further comprises a paraffin layer mixed with MnO ₂ powder formed on the hot wire. The method of claim 3, wherein The fine pump using the gas generation in which the NaHCO ₃ solution is stored in the storage space. delete In the method of producing a fine pump using gas generation, Forming a hot wire in the storage space on the lower plate; Coupling the PDMS on which the storage space is formed on the lower plate; A sample reservoir communicating with the storage space, an inlet connected to one end of the storage space and the sample reservoir by a conduit, and a microchannel communicating from the other end of the sample reservoir to the outside of the fine pump; A method of manufacturing a micropump using gas generation comprising coupling a separate PDMS to the PDMS in which the storage space is formed. delete

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