KR20090120584A - Method of measuring reaction temperature of bio fluids, microcalorimeter using the same and method of manufacturing the microcalorimeter - Google Patents

Abstract

PURPOSE: A method of measuring reaction temperature of bio fluids, a micro calorimeter using the same, and a method of manufacturing the micro calorimeter are provided to promote the mixing of bio fluids for reaction without a separate temperature control system. CONSTITUTION: A method of manufacturing a micro calorimeter(100) comprises following steps. A protective layer and an insulating layer are formed on a substrate. A part of a lower surface of the substrate is etched. An adhesive layer is formed on the upper side of the substrate. A first wiring layer is formed on the upper side of the adhesive layer. A first wiring layer pattern is formed by etching the first wiring layer. A second wiring layer is formed on the upper side of the substrate. A thermopile(200) is made of first wiring layer patterns and second wiring layer patterns. A polymer pattern defines a first fluid path(110), a second fluid path(120), a third fluid path(130), a fourth fluid path(140), and a fifth fluid path(150).

Description

METHOD OF MEASURING REACTION TEMPERATURE OF BIO FLUIDS, MICROCALORIMETER USING THE SAME AND METHOD OF MANUFACTURING THE MICROCALORIMETER}

The present invention relates to a method for measuring a reaction temperature of a biofluid, a microcalorimeter using the same, a method for producing a microcalorimeter, and a reaction temperature measuring system for a biofluid. More specifically, the new design of the thermocouple to measure the temperature difference enables accurate measurement of the heat of reaction between the biofluids without the need for an additional temperature control system. The present invention relates to a method for measuring a reaction temperature of a biofluid so as to obtain a smoother and faster than a diffusion method, a microcalorimeter using the same, a method for preparing a microcalorimeter, and a reaction temperature measuring system for a biofluid.

Micro-calorimeter is a device for measuring the heat of reaction of different biological samples, it operates by injecting and mixing the biological sample and measuring the heat.

Conventional microcalorimeters use natural sample mixing (diffusion) in wide (> 1 mm) and long (> 50 mm) channels to achieve a reaction between different biological samples. This requires a large amount of sample and has the disadvantage that the time taken for the reaction is very long.

In addition, since the temperature of the external atmospheric environment can affect the measurement of the reaction heat, an additional external temperature control system is required to measure the heat of reaction between the samples. This greatly reduces the ease of use and mobility of the microcalorimeter.

An object of the present invention for solving the above problems is to measure the heat of reaction accurately without the influence of the external environment without an additional temperature control system, the reaction temperature of the biological fluid that can promote the mixing of the biological fluids to react To provide a measuring method.

It is also an object of the present invention to provide a microcalorimeter suitable for the reaction temperature measurement method of the biofluid described above.

It is also an object of the present invention to provide a method for producing the microcalorimeter described above.

It is also an object of the present invention to provide a biological fluid reaction temperature measuring system using the microcalorimeter described above.

According to an aspect of the present invention for achieving the above object, in the method for measuring the reaction temperature of the biofluid, the first biological fluid and the second biological fluid are introduced into a state separated from each other. Branching the introduced second biological fluid so that a part of the branched second biological fluid is joined to the flow of the first biological fluid to react with the first biological fluid to react with the branched second biological fluid; Others continue to flow separately from the first biological fluid. The temperature difference between the mixed flow of the first biological fluid and the second biological fluid and the second biological fluid flowing separately from the first biological fluid is measured.

According to an embodiment of the present invention, upon joining a part of the flow of the branched second biological fluid into the flow of the first biological fluid, the reaction by mixing between the first biological fluid and the second biological fluid is promoted. In order to do so, the first biological fluid and the second biological fluid are mixed while being rotated with respect to the advancing direction thereof.

According to an embodiment of the present invention, the measurement of the temperature difference between the mixed flow of the first biological fluid and the second biological fluid and the other part of the flow of the second biological fluid flowing separately from the first biological fluid It is done in multiple times.

According to one embodiment of the invention, the measurement of the temperature difference is by thermopile.

According to an embodiment of the present invention, the method may further include measuring a temperature difference between the first biofluid fluid and the second biofluid fluid introduced in a state separated from each other.

According to an aspect of the present invention for achieving the above object, a microcalorimeter is formed on the substrate, the upper surface of the substrate and a plurality of thermocouples for measuring the temperature difference between two connection points and the substrate and the Is formed on a plurality of thermocouples, the first flow path for introducing the first biological fluid, the second flow path for introducing the second biological fluid, the third flow path connecting the second flow path and the first flow path, the A fourth flow passage connected to a second flow passage for distilling the second biological fluid, and a fifth flow passage for discharging the first biofluid and the second biofluid connected to the first flow passage and the third flow passage; A polymer pattern defining a flow path, wherein a portion of the plurality of thermocouples is connected to the first flow path and the second flow path, and another portion of the plurality of thermocouples is connected to the fifth flow path and the fourth flow path. It is determined.

According to an embodiment of the present invention, the fifth flow path further includes a plurality of structures for promoting mixing of the first biological fluid and the second biological fluid therein.

According to one embodiment of the present invention, an angle formed between a direction in which the plurality of structures extends and a traveling direction of the fifth flow path is an acute angle.

According to an aspect of the present invention for achieving the above object, in the method of manufacturing a microcalorimeter, a protective film and an insulating film are formed on a substrate. A portion of the lower surface of the substrate is etched. An adhesive layer is formed on the upper surface of the substrate. A first wiring layer is formed on the upper surface of the adhesive layer. The first wiring layer is etched to form a first wiring layer pattern. A second wiring layer is formed on the upper surface of the substrate. The second wiring layer is etched to form a second wiring layer pattern, thereby forming thermocouples including the first wiring layer pattern and the second wiring layer pattern. A first flow path for introducing a first biological fluid, a second flow path for introducing a second biological fluid, a third flow path connecting the second flow path and the first flow path, and connected to the second flow path Forming a polymer pattern defining a fourth flow path for flowing out of the biofluid and a fifth flow path for flowing out the mixed first and second biological fluids connected to the first flow path and the third flow path; . The polymer pattern is laminated on the upper surface of the substrate.

According to an embodiment of the present invention, the first flow path for introducing the first biological fluid, the second flow path for introducing the second biological fluid, the third flow path connecting the second flow path and the first flow path, A fourth flow passage connected to the second flow passage for distilling the second biological fluid and a second flow passage for discharging the first biofluid and the second biofluid connected to the first flow passage and the third flow passage; Forming a polymer pattern defining five euros forms a first photosensitive layer on the top surface of the wafer. The first photosensitive layer is exposed in the shape of the first passage, the second passage, the third passage, the fourth passage, and the fifth passage. A second photosensitive layer is formed on an upper surface of the first photosensitive layer. The second photosensitive layer is exposed. The first photosensitive layer and the second photosensitive layer are developed to form a photosensitive layer pattern. A polymer pattern is formed on the upper surface of the wafer. The polymer pattern is separated from the wafer.

According to an aspect of the present invention for achieving the above object, a biofluid reaction temperature measurement system is formed on the substrate, the upper surface of the substrate and a plurality of thermocouples (thermopile) for measuring the temperature difference between the two connection points and It is formed on the substrate and the plurality of thermocouples, a first flow path for introducing a first biological fluid, a second flow path for introducing a second biological fluid, a third connecting the second flow path and the first flow path A flow path, a fourth flow path connected to the second flow path for outflowing the second biological fluid, and a first flow fluid mixed with the first flow path and the third flow path and the second biofluid flow out; A polymer pattern defining a fifth flow path, wherein a portion of the plurality of thermocouples is connected to the first flow path and the second flow path, and another portion of the plurality of thermocouples is the fifth flow path and the A fifth flow path connected to the fourth flow path, wherein the fifth flow path includes a plurality of structures for facilitating mixing of the first biological fluid and the second biological fluid, The angle formed is a micro-calorimeter acute angle, the biological fluid supply unit connected to the first channel and the second channel, respectively, to supply the first biological fluid and the second biological fluid to the micro-calorimeter, the plurality of The fourth flow path and the fifth flow path to discharge the first biological fluid and the second biological fluid from the analysis unit and the microcalorimeter connected to the plurality of thermocouples to analyze the temperature measurement result by the thermocouples. And a biofluid discharge part connected to each of the flow paths.

As described above, according to a preferred embodiment of the present invention, the temperature measurement by the thermocouple is made even before the biofluid reacts, and because there is a reference flow separate from the flow in which the reaction occurs, the reaction between the two flows By measuring the temperature difference, accurate reaction heat can be measured by eliminating the influence of the external environment without any additional temperature control device.

In addition, the present invention can form a rotating vortex of the biological sample in the flow path by installing structures (micromixers) such as irregularities in the flow path in which the reaction takes place, the mixing between the samples compared to the conventional method that only depends on diffusion The time can be greatly shortened, the amount of sample used can be reduced, and the length of the channel required for sufficient mixing can be reduced.

 Therefore, the microcalorimeter manufactured according to the present invention can quickly mix the sample by using the micromixer in the flow path, and it is possible to measure the heat of reaction accurately using a very small amount of the biological sample. Based on these characteristics, it can be useful for measuring the heat of reaction of various samples in basic research fields such as chemistry, biochemistry and bio, as well as applied research fields for diagnosis and sample search. In addition, the advantage of accurate measurement of reaction heat without additional temperature control system greatly enhances the mobility and versatility as a diagnostic sensor, and ensures the accuracy and ease of diagnosis when used for actual medical and diagnostic purposes. . Based on these advantages, various demands for future medical diagnostic sensors are expected, and commercialization will be possible based on this.

For example, the microcalorimeter proposed in the present invention can be applied to a drug search system for various inducers applied in the development of new drugs, especially for early diagnosis of cancer using the detection of specific proteins that react with cancer cells. Can be applied. Based on this application possibility, various demands are expected, and commercialization research based on this can be realized through government agencies, medical institutions, and pharmaceutical companies.

Hereinafter, preferred embodiments of the present invention will be described in detail with reference to the accompanying drawings, but the present invention is not limited to the following embodiments, and those skilled in the art will appreciate the technical spirit of the present invention. The present invention may be embodied in various other forms without departing from the scope of the present invention. In the accompanying drawings, the dimensions of the substrate, film, region, pad or patterns are shown to be larger than the actual for clarity of the invention. In the present invention, each film, region, pad or pattern is referred to as being formed on the "on", "top" or "top surface" of the substrate, each film, region or pads. It means that the pad or patterns are formed directly on the substrate, each film, region, pad or patterns, or that another film, another region, another pad or other patterns are additionally formed on the substrate. In addition, where each film, region, pad, region or pattern is referred to as "first," "second," "third," and / or "preliminary," it is not intended to limit these members, but only the cornea, To distinguish between areas, pads, regions or patterns. Thus, "first", "second", "third" and / or "preparation" may be used selectively or interchangeably for each film, region, pad, site or pattern, respectively.

Hereinafter, a method for measuring a reaction temperature of a biological fluid according to a preferred embodiment of the present invention, a method for preparing a microcalorimeter and a microcalorimeter for performing the same, and a biofluid reaction temperature measuring system using the same will be described in detail. .

Method for measuring reaction temperature of biofluid

1 is a plan view illustrating a method for measuring a reaction temperature of a biological fluid according to an embodiment of the present invention.

Referring to FIG. 1, the microcalorimeter 100 for performing a reaction temperature measurement method of a biological fluid may include a first flow path 110, a second flow path 120, a third flow path 130, and a fourth flow path 140. ), A fifth flow path 150, a first thermocouple 200, a second thermocouple 210, a third thermocouple 220, and a fourth thermocouple 230.

The first passage 110 and the second passage 120 are separated from each other to introduce the first biological fluid and the second biological fluid, respectively.

The second flow path 120 branches into the third flow path 130 and the fourth flow path 140, and the third flow path 130 is connected to the first flow path 110 and the fifth flow path 150.

The first thermocouple 200 is installed in the first passage 110 and the second passage 120, and the second thermocouple 210, the third thermocouple 220, and the fourth thermocouple 230 are the fourth passage 140. ) And the fifth flow path 150.

The number of thermocouples is not necessarily four, and even if the number is different, between the first passage 110 and the second passage 120, and between the fourth passage 140 and the fifth passage 150, respectively. As long as it is installed, those skilled in the art will readily know that the present invention is within the scope of meeting the technical idea of the present invention.

In order to measure the reaction temperature of the biofluid according to the present invention, the first biological fluid and the second biological fluid to be reacted are introduced into the first channel 110 and the second channel 120, respectively. As an example, the temperature difference between the first biological fluid and the second biological fluid separated by the first thermocouple 200 may be measured.

The first biological fluid and the second biological fluid may be anything as long as the amount of calories included in the reaction is changed. For example, the first biological fluid and the second biological fluid may be animal blood, cell fluid, test drug, and the like.

The second biological fluid introduced through the second channel 120 branches and the part of the branched second biological fluid flows into the fifth channel 150 along the third channel 130 and the branched second fluid flows through the second channel 120. The other part of the biological fluid continues to flow in a state separated from the first biological fluid along the fourth passage 140.

At this time, the first biological fluid flows from the first flow path 110 and the second biological fluid flows from the third flow path 130 flows together in the fifth flow path 150 to be mixed and reacted. In one embodiment, the first biological fluid and the second biological fluid may be mixed while rotating in a spiral with respect to the traveling direction in the fifth flow path 150 in order to promote the reaction during the mixing. The rotation may be based on a plurality of structures included in the fifth flow path 150, and the principle of the rotation occurring by the plurality of structures will be described in more detail with reference to FIG.

The mixed flow of the first living fluid and the second living fluid flowing through the fourth flow path 140 by the second thermocouple 210, the third thermocouple 220, and the fourth thermocouple 230 and the fifth flow path ( The temperature difference with the second biological fluid flowing through 150 is measured.

The temperature difference is not necessarily a plurality of times, and the temperature difference is measured by means by which the mixed flow of the first biological fluid and the second biological fluid and the temperature difference of the second biological fluid can be measured even though not necessarily by thermocouples. If it can be seen that it satisfies the technical idea of the present invention.

Hereinafter, a method for measuring reaction temperature of a biological fluid according to the present invention will be described in more detail.

Method 1: The first biological fluid flows through the first flow path 110. After all thermocouples 200, 210, 220, and 230 have reached a steady state (signal is 0V) in the state of continuously supplying the first biological fluid, the second biological fluid is supplied through the second channel 120. do. Only the second biological fluid flows in the fourth flow path 140, and in the fifth flow path 150, the first biological fluid and the second biological fluid mix with each other to generate heat of reaction. In this case, in the fourth flow passage 140, the temperature of the second biological fluid supplied serves as a reference temperature. Therefore, the temperature difference between the fourth flow path 140 and the fifth flow path 150 measured through the thermocouples 210, 220, and 230 may be referred to as a temperature rise value due to the pure heat of reaction between the two biofluids. That is, in the fourth flow path 140, since the temperature of the second biological fluid supplied serves as a reference temperature, the heat of reaction can be measured without being affected by the temperature change caused by the external environment.

Method 2: The first biological fluid is supplied to the first channel 110, and the second biological fluid is supplied to the second channel 120 without reaching a steady state. In this case, the signal measured by the thermocouples 210, 220, and 230 due to the temperature value of each of the biofluids supplied may not be a temperature rise value due to pure reaction heat. However, since the first thermocouple 200 measures the temperature difference of each of the biofluids to be supplied, the value measured by the thermocouple 200 is subtracted from the temperature difference values respectively measured by the thermocouples 210, 220, and 230. The value is pure heat of reaction. That is, since the temperature difference is measured by the first thermocouple 200 even before the reaction occurs, even if the steady state is not reached, the reaction heat can be measured without being affected by the temperature change caused by the external environment.

Microcalorimeter

2 is a perspective view showing a micro-calorimeter according to an embodiment of the present invention.

Referring to FIG. 2, the microcalorimeter 100 includes a substrate 400, a plurality of thermocouples 200, 210, and 220, and a polymer pattern 300.

The substrate 400 supports the plurality of thermocouples 200, 210, and 220 and the polymer pattern 300. The substrate 400 may include a heat dissipation part 410 which is a region in which thickness is reduced so that minute reaction heat is not lost to the side through silicon having high thermal conductivity. In an embodiment, the substrate 400 may be a silicon wafer on which silicon dioxide and silicon nitride thin films are deposited.

A plurality of thermocouples 200, 210, and 220 are formed on the upper surface of the substrate 400. In an embodiment, each of the plurality of thermocouples 200, 210, and 220 may be formed of two kinds of metals, or polysilicon and aluminum implanted with BF + ions.

The polymer pattern 300 is formed on the substrate 400 and the plurality of thermocouples 200, 210, and 220, and a first flow path (not shown) and a second flow path (not shown) inside the polymer pattern 300. ), A third passage (not shown), a fourth passage 140, and a fifth passage 150 are defined.

A connection relationship between the first passage (not shown), the second passage (not shown), the third passage (not shown), the fourth passage 140, and the fifth passage 150 and a plurality of thermocouples 200 and 210. , And the arrangement relationship of 220 is the same as that described with reference to FIG.

As an example, the fifth passage 150 may include a plurality of structures 152 that form concavities and convexities to promote mixing of the fluids flowing through the fifth passage 150. An angle formed between a direction in which the plurality of structures 152 extends and a traveling direction of the fifth channel 150 may be an acute angle. Since the angle between the direction in which the plurality of structures 152 extends and the traveling direction of the fifth flow path 150 is an acute angle, the fluid traveling in the fifth flow path 150 is subjected to lateral pressure with respect to the traveling direction. And consequently spiral movement with respect to the direction of travel, thereby facilitating mixing of the fluid flowing therein. Meanwhile, in FIG. 2, the plurality of structures 152 are formed on the upper surface of the fifth flow path 150, but need not necessarily be the upper surface and may be formed on the other surface. In addition, it may not necessarily be an oblique diagonal shape, for example, may be a V-shape in the middle, two or more square walls separated from each other.

Manufacturing method of micro calorimeter

3 is a cross-sectional view sequentially showing a method of manufacturing a polymer pattern for use in a microcalorimeter according to an embodiment of the present invention.

Referring to the upper left of FIG. 3, after forming the first photosensitive layer 510 on the upper surface of the silicon wafer 500, the first to fifth to fifth channels (not shown) are formed using a mask. It exposes in shape. After the exposure is subjected to a Post Exposure Bake (PEB) step. In an embodiment, the first photosensitive layer 510 may be SU-8 2050, the thickness of the first photosensitive layer 510 may be 70 μm, and the exposure may be performed by UV.

3, the second photosensitive layer 520 is formed on the upper surface of the first photosensitive layer 510, and then exposed in the shape of a plurality of structures (not shown) using a mask. After the exposure is subjected to a Post Exposure Bake (PEB) step. In an embodiment, the second photosensitive layer 520 may be SU-8 2050, the thickness of the second photosensitive layer 520 may be 30 μm, and the exposure may be performed by UV.

Referring to the lower left of FIG. 3, the first photosensitive layer 510 and the second photosensitive layer 520 are developed to form a photosensitive layer pattern 530.

Referring to the upper right of FIG. 3, the polymer pattern 300 is formed on the upper surface of the wafer 500. In one embodiment, the polymer pattern 300 may be formed by pouring and heating the PDMS.

Referring to the bottom right of FIG. 3, the polymer pattern 300 is separated from the wafer 500 and the photosensitive layer pattern 530.

4 is a cross-sectional view sequentially showing a method of manufacturing a microcalorimeter according to an embodiment of the present invention.

Referring to the first left figure of FIG. 4, the passivation layer 602 and the insulating layer 604 are formed on the upper surface of the substrate 400. In one embodiment, the substrate 400 may be a silicon wafer, the protective film 602 may be a silicon nitride film to protect the substrate 400 against bulk etching, and the insulating film 604 may be silicon to electrically insulate. It may be silicon dioxide. The formation of the protective film 602 and the insulating film 604 may be by chemical vapor deposition (CVD).

Referring to the second left picture of FIG. 4, a portion of the protective film 602 and the insulating film 604 formed on the lower surface of the substrate 400 is removed. In one embodiment, the removal may be by Reactive Ion Etching (RIE) technology.

Referring to the third left picture of FIG. 4, a portion of the lower surface of the substrate 400 is etched to form the heat dissipation part 410. The heat dissipation part 410 is for preventing the minute reaction heat from being lost to the side through the silicon having high thermal conductivity. In one embodiment, the etching may be a bulk etching by potassium hydroxide (KOH) solution, the thickness may be 400-450μm and the width may be 800μm.

Referring to the fourth left picture of FIG. 4, the adhesive layer 702 is formed on the upper surface of the substrate 400, and the first wiring layer 700 is formed on the upper surface of the adhesive layer 702. In an embodiment, the adhesive layer 702 may be titanium having a thickness of 500 μm, and the first wiring layer 700 may be polysilicon, a metal, or the like having a thickness of 3000 μm.

Referring to the fifth figure on the left side of FIG. 4, ions are implanted into the first wiring layer 700. In one embodiment, the ions implanted into the first wiring layer 700 may be BF + ions, and may be implanted at a density of 5E 15. However, this can be easily understood by those skilled in the art that the first rewiring layer 700 corresponds to polysilicon, and in the case of a metal, since the process of injecting ions is unnecessary, the technical features of the present invention are still satisfied even if omitted. .

Referring to the first drawing on the right side of FIG. 4, the first wiring layer 700 is etched to form a first wiring layer pattern 710. The etching may be by Reactive Ion Etching (RIE) technology.

Referring to the second right picture of FIG. 4, the second wiring layer 800 is formed on the upper surface of the substrate 400. The second wiring layer 800 includes a metal. In one embodiment, the second wiring layer 800 may be formed by depositing aluminum to about 5000μm by sputtering.

Referring to the third drawing on the right side of FIG. 4, the second wiring layer 800 is etched to form the second wiring layer pattern 810. The etching may be by Reactive Ion Etching (RIE) technology. Accordingly, the thermocouple 200 including the first wiring layer pattern 710 and the second wiring layer pattern 810 is formed.

4, the polymer pattern 300 manufactured according to the method of FIG. 3 is laminated on the upper surface of the substrate 400. The polymer pattern 300 is stacked on the substrate 400 and the thermocouple 200, and the first to fifth channels (not shown) are defined in the polymer pattern 300. In one embodiment, the coupling between the polymer pattern 300 and the thermocouple 200 may be by plasma bonding technology.

5 is a cross-sectional view illustrating a flow of a fluid in a fifth flow path of a polymer pattern according to an embodiment of the present invention.

Referring to FIG. 5, the fifth flow path 150 includes a plurality of structures 152 that form irregularities therein. According to an embodiment, an angle formed between a direction in which the plurality of structures 152 extends and a traveling direction of the fifth channel 150 may be an acute angle. Since the angle formed between the direction in which the plurality of structures 152 extends and the traveling direction of the fifth flow path 150 is an acute angle, the fluid traveling in the fifth flow path 150 generates a transverse pressure with respect to the traveling direction. And consequently spiral movement with respect to the direction of travel, thereby facilitating mixing of the fluid flowing therein. The plurality of structures 152 may not necessarily have an acute diagonal shape, for example, may have various shapes such as a V-shape in the middle and two or more rectangular wall shapes separated from each other. That is, those skilled in the art will readily appreciate that any form satisfies the technical idea of the present invention as long as pressure is applied in the transverse direction with respect to the advancing direction to allow the fluid to proceed spirally.

Therefore, when the first biological fluid and the second biological fluid introduced into the first flow path 110 and the third flow path 130 respectively pass through the fifth flow path 150, they are helically rotated by the plurality of structures 152. Will proceed, thus facilitating mixing.

The photographs of FIG. 5 show that as the flow of fluid increases the degree of vortex increases, further facilitating mixing.

Biofluid Reaction Temperature Measurement System

6 is a block diagram illustrating a biofluid reaction temperature measuring system according to an exemplary embodiment of the present invention.

The biofluid reaction temperature measuring system includes a microcalorimeter 100, a biofluid supply unit 910, a biofluid discharge unit 920, and an analysis unit 930.

The micro-calorimeter 100 is a substrate, a plurality of thermocouples, a first flow path for introducing the first biofluid, a second flow path for introducing the second biofluid, and connecting the second flow path and the first flow path. A third flow passage, a fourth flow passage connected to the second flow passage to allow the second biological fluid to flow out, and the first biofluid and the second biofluid connected to the first flow passage and the third flow passage and mixed; A polymer pattern defining a fifth flow path for outflow. Some of the plurality of thermocouples are connected to the first flow path and the second flow path, and other portions of the plurality of thermocouples are connected to the fifth flow path and the fourth flow path, and the fifth flow path is internally provided with the first flow path. It may include a plurality of structures for promoting the mixing of one biological fluid and the second biological fluid, the direction in which the plurality of structures extend and the angle formed by the fifth flow path may be an acute angle. Detailed descriptions of the components of the microcalorimeter 100 are the same as those described with reference to FIGS. 1 and 2, and thus repeated descriptions thereof will be omitted.

The biofluid supply unit 910 is connected to the first channel and the second channel to supply the first biological fluid and the second biological fluid to the microcalorimeter, respectively. The first biological fluid and the second biological fluid may be anything as long as the amount of heat included in the reaction is changed. For example, the first biological fluid and the second biological fluid may be animal blood, cell fluid, test drug, and the like.

The biofluid discharge part 920 is connected to the fourth flow path and the fifth flow path, respectively, in order to discharge the first biofluid and the second biofluid from the microcalorimeter.

The analyzer 930 is connected to the plurality of thermocouples in order to analyze the temperature measurement results by the plurality of thermocouples.

Biofluid reaction temperature measurement system according to the present invention can be applied to the drug screening system for a variety of inducers applied in the development of new drugs in the future, in particular for early diagnosis of cancer using the detection of specific proteins that react with cancer cells Can be.

1 is a plan view illustrating a method for measuring a reaction temperature of a biological fluid according to an embodiment of the present invention.

2 is a perspective view showing a micro-calorimeter according to an embodiment of the present invention.

3 is a cross-sectional view sequentially showing a method of manufacturing a polymer pattern for use in a microcalorimeter according to an embodiment of the present invention.

4 is a cross-sectional view sequentially showing a method of manufacturing a microcalorimeter according to an embodiment of the present invention.

5 is a cross-sectional view showing the flow of the fluid in the fifth flow path of the polymer pattern according to an embodiment of the present invention.

6 is a block diagram illustrating a biofluid reaction temperature measuring system according to an exemplary embodiment of the present invention.

Explanation of symbols on the main parts of the drawings

100: microcalorimeter 110: the first euro

120: second euro 130: third euro

140: fourth euro 150: fifth euro

200: first thermocouple 210: second thermocouple

220: third thermocouple 230: fourth thermocouple

Claims (9)

Introducing a first biological fluid and a second biological fluid in a state separated from each other; Branching the introduced second biological fluid so that a part of the branched second biological fluid is joined to the flow of the first biological fluid to react with the first biological fluid to react with the branched second biological fluid; Allowing the other to continue to flow separately from the first biological fluid; And Measuring a temperature difference between the mixed flow of the first biological fluid and the second biological fluid and the second biological fluid flowing separately from the first biological fluid and measuring the reaction temperature of the biological fluid; Way. The method of claim 1, wherein when the part of the branched second fluid flow is joined to the flow of the first biological fluid, the reaction is performed to promote a reaction by mixing between the first biological fluid and the second biological fluid. A method for measuring a reaction temperature of a biofluid, wherein the first biofluid and the second biofluid are mixed while being rotated with respect to a traveling direction thereof. The method of claim 2, wherein the measurement of the temperature difference between the mixed flow of the first biological fluid and the second biological fluid and another part of the flow of the second biological fluid flowing separately from the first biological fluid is performed at a plurality of times. Across, And measuring a temperature difference between the first biological fluid and the second biological fluid introduced in a state in which they are separated from each other. The method of measuring a reaction temperature of a biofluid according to claim 2, wherein the temperature difference is measured by a thermopile. Board; A plurality of thermocouples formed on an upper surface of the substrate and for measuring a temperature difference between two connection points; And A first flow path formed on the substrate and the plurality of thermocouples, a first flow path for introducing a first biological fluid, a second flow path for introducing a second biological fluid, and a second connection connecting the second flow path and the first flow path; A third flow passage, a fourth flow passage connected to the second flow passage to discharge the second biological fluid, and a first flow passage mixed with the first flow passage and the third flow passage and the second biological fluid flow out A polymer pattern defining a fifth flow path for And a portion of the plurality of thermocouples is connected to the first flow path and the second flow path, and another portion of the plurality of thermocouples is connected to the fifth flow path and the fourth flow path. 6. The microcalorimeter of claim 5, wherein the fifth flow path further includes a plurality of structures for promoting mixing of the first biofluid and the second biofluid. The microcalorimeter of claim 6, wherein an angle formed between a direction in which the plurality of structures extends and a traveling direction of the fifth flow path is an acute angle. Forming a protective film and an insulating film on the substrate; Etching a portion of the lower surface of the substrate; Forming an adhesive layer on an upper surface of the substrate; Forming a first wiring layer on an upper surface of the adhesive layer; Etching the first wiring layer to form a first wiring layer pattern; Forming a second wiring layer on an upper surface of the substrate; Forming thermocouples formed of the first wiring layer pattern and the second wiring layer pattern by etching the second wiring layer to form a second wiring layer pattern; A first flow path for introducing a first biological fluid, a second flow path for introducing a second biological fluid, a third flow path connecting the second flow path and the first flow path, and connected to the second flow path Forming a polymer pattern defining a fourth flow path for flowing out of the biofluid and a fifth flow path for flowing out of the mixed first and second biological fluids connected to the first flow path and the third flow path; step; And laminating the polymer pattern on the upper surface of the substrate. A substrate, formed on an upper surface of the substrate and formed on the substrate and the thermocouples for measuring a temperature difference between two connection points and on the substrate and the plurality of thermocouples; 1 euro, a second flow path for introducing a second biological fluid, a third flow path connecting the second flow path and the first flow path, a fourth flow path connected to the second flow path for flowing out the second biological fluid And a polymer pattern connected to the first flow path and the third flow path and defining a fifth flow path for flowing out the first biological fluid and the second biological fluid, wherein some of the plurality of thermocouples are disposed in the thermocouple. A first passage and a second passage, the other portion of the plurality of thermocouples is connected to the fifth passage and the fourth passage, and the fifth passage has the first living body and the second living body therein. Mixing of fluids Each comprises a number of structures and the direction and the fifth flow path extends to a plurality of the structures for forming Truesilver acute micro calorimeter; A biofluid supply unit connected to the first channel and the second channel to supply the first biological fluid and the second biological fluid to the microcalorimeter; An analysis unit connected to the plurality of thermocouples to analyze the temperature measurement results by the plurality of thermocouples; And Biofluid reaction temperature measurement system comprising a biofluid discharge unit connected to the fourth flow path and the fifth flow path to discharge the first biofluid and the second biofluid from the microcalorimeter, respectively. .

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