KR100473361B1 - Microchip and method for manufacturing the same - Google Patents

Abstract

A microchip and a method of manufacturing the same are disclosed. A filter part mold is formed on the silicon wafer and a channel part mold is formed on the periphery thereof, and then a first layer is formed on the silicon wafer. After forming the first and second holes in which the channel part mold is partially exposed on one side and the other side of the first layer, and removing the silicon wafer to form the filter part and the channel part in the first layer, the lower part of the first layer The second layer is formed to produce a microchip. Since the layers constituting the microchip are made of an optically transparent material, the physical properties of the red blood cells passing through the microchip through light can be easily measured. The cost for manufacturing the chip can be significantly lowered. In addition, it is possible to easily produce microchips of fine size having dimensions of several μm or less.

Description

Microchip and method for manufacturing the same

The present invention relates to a microchip and a method for manufacturing the same, and more particularly, to a microchip and a method for manufacturing the same, which are made of a light-transmissive plastic or glass to enable easy measurement of blood properties.

In general, red blood cells that form human blood together with leukocytes and platelets have a donut shape with a clogged middle, and have a diameter of about 8 to 12 μm and a thickness of about 1 to 2 μm, but are very flexible. Narrow filters can pass through at high speed. As such, information about the erythrocytes, such as the degree, shape, and rate of passage of the erythrocytes as they deform during the passage of the filter, is used to diagnose hematological diseases. For example, information about erythrocytes generally relates to the number of red blood cells per unit volume (RBC) in the blood, the amount of hemoglobin per unit volume, the volume of erythrocytes, and the concentration of hemoglobin per erythrocyte. .

Currently, many studies have demonstrated that the RBC deformability of red blood cells, which is a characteristic of changing the shape of red blood cells under stress, is associated with necrosis of cells that develop diseases such as cancer. For example, in Cohen's "Influence of tumor burden on red cell deformability by tumor growth," L1210 leukemia cells and Lewis lung carcinoma cells were transplanted into experimental rats, resulting in cancer cell death and reduced red blood cell deformability. Was observed at the same time, and Dintefass's "Dome aspects of hemorheology of metastasis in malignant melanoma" reported an increase in blood viscosity with respect to melanoma and a decrease in erythrocyte deformability. Sevick and Jain reported that "Effect of Red blood cell rigidity on tumor blood flow: increase in viscous rigidity during hyperglycemia "showed that when blood cells were artificially hardened, blood flow in the cells was impaired and blood flow decreased.

In addition, in Korea, Park Seok-won's "Study on Blood Viscosity and Erythrocyte Deformation in Patients with Malignant Tumors" measured the filtration time of red blood cells and compared the blood of control blood, urethral cancer patients, and gastric cancer patients. The difference was statistically confirmed. Also, the result of using the filtering method to measure the erythrocyte deformability through Oh Do Hoon's "Influence of Ginkgo biloba extract on the deformability of mouse erythrocytes." The average filtering time is about 11.8 seconds, compared to 33.1 seconds in the case of cancer mice.

As described above, the deformability of red blood cells is deeply related to diseases such as cancer, and the method of enabling the early diagnosis of cancer as well as blood-related diseases such as diabetes and malaria through the study of the deformity of these red blood cells is possible. Is being studied.

On the other hand, International Patent Application Publication No. 93-701749 (name of the blood test apparatus of the examinee) proposes a blood test apparatus that can measure the number of red blood cells, white blood cells or platelets in the blood and diagnose the disease based thereon It is. However, the blood test apparatus disclosed in the international patent does not have a device such as a microchip for measuring the characteristics of the red blood cells, and applies an electromagnetic field to the blood to move blood cells in the autonomous system and consists of a plurality of pumps and valves. Since it detects through, because the configuration of the device is too complicated to determine the presence or absence of the disease by measuring only the number of red blood cells, etc., the disease related to the deformability of the red blood cells is difficult to determine.

In addition, US Pat. No. 6,187,592 to Paul L. Gourley is provided with a device capable of measuring the properties of red blood cells having microchips through which red blood cells pass.

1 is a cross-sectional view of a microcavity portion of the apparatus for measuring the properties of red blood cells shown in the US Patent No. 6,187,592, Figure 2 is a schematic plan view of the microcavity shown in FIG.

Referring to FIG. 1, the device for measuring the characteristics of the red blood cells includes an upper mirror 10, a lower mirror 15, an acquisition medium 20, and an analysis region 25, in which the red blood cells 30 are located. Has a resonant optical cavity 40 to be analyzed. Although not shown, a laser pump is arranged to activate the obtaining medium 20, and the light rays emitted from the laser pump are irradiated to the red blood cells 30 located in the analysis region 25 through the beam splitter and the lens.

Referring back to FIG. 1, the lower mirror 10, which is a multiple reflective layer, and the obtaining medium 20 are provided on the semiconductor substrate 50 to form a laser obtaining region. The upper mirror 15 and the insulating layer pattern 60, which are multiple dielectric layers formed under the upper substrate 55, together form the analysis region 20 in which the red blood cells 30 are analyzed.

1 and 2, a tube 70 through which red blood cells 30 pass is formed across the analysis region 25, and a gate 80 positioned at the end of the tube 70 and the analysis region 20. ), The flow of red blood cells 30 is controlled. In this way, the red blood cells 30 passing through the analysis region 25 is irradiated with light, and the difference between the longitudinal and horizontal axis wavelengths of the light scattered from the red blood cells 30 is analyzed to measure the degree of anemia.

On the other hand, in recent years, in order to specify the shape of blood cells in blood such as red blood cells, a silicon chip is mainly processed finely to manufacture a microchip having an input part, a filter part, and an output part.

3 is a schematic plan view of a microchip formed by microfabricating a silicon wafer according to the prior art.

Referring to FIG. 3, the conventional microchip 100 forms a filter unit 120 formed of a metal pattern on a silicon wafer 140, and an input unit 110 and an output unit are respectively formed at the periphery of the filter unit 120. The unit 130 was disposed. Generally, in this case, the microchip 100 includes a filter portion 120 having a width of about 4 μm and a length of about 90 μm, and the velocity and volume profile of red blood cells passing through the microchip 100 ( profile).

As described above, in the case of the microchip made of the conventional silicon wafer, the cost of manufacturing the microchip including the silicon wafer is increased because the price of the silicon wafer is relatively high and the time required to process the silicon wafer is increased. have.

In addition, when manufacturing a microchip by microfabricating a silicon wafer as in the prior art, it is very difficult to manufacture a microchip having a dimension of several μm or less.

Moreover, in the case of a microchip manufactured by microfabricating a silicon wafer as in the related art, a problem arises in that integration of a small channel portion and a large channel portion formed in the microchip is very difficult.

Accordingly, an object of the present invention is to provide a microchip and a method of manufacturing the same, which include an upper and a lower layer made of an optically transparent material, which can easily measure physical properties of blood passing through the light by transmitting light directly to the microchip. To provide.

Another object of the present invention is to provide a microchip and a method for manufacturing the same, which can reduce the manufacturing cost of the microchip by constructing the microchip made of a light transmitting material such as transparent plastic and glass.

In addition, another object of the present invention is to provide a microchip and a method for manufacturing the same, which can be easily manufactured in a micro dimension of several micrometers or less through a plastic micromachining process.

In order to achieve the above objects of the present invention, according to the present invention, a first layer, a second layer corresponding to the first layer, a filter portion formed between the first layer and the second layer, and a peripheral portion of the filter portion There is provided a microchip comprising a channel portion.

Preferably, the first layer is made of a light transmissive plastic such as PDMA (polydiallylmethylamine) or PMMA (polymethylmethacrylate, polymethylmethacrylate), and the second layer is made of a light transmissive plastic or It is made of the same material as glass. The filter part is formed to have a height of about 1 to 4 μm and a width of about 3 to 7 μm, respectively, and the first and second channels of the channel part are each formed to a height of about 25 to 100 μm. Inlet and outlet holes are formed in the first layer to partially expose the first and second channels.

According to one embodiment of the invention, the inlet hole is inserted into the connection tube of the sample injection member, such as chickenpox or syringe pump for the inflow of blood.

According to another embodiment of the present invention, a connection tube of a sample discharge member such as a suction pump or a syringe is inserted into the discharge hole for the outflow of blood.

Further, according to a preferred embodiment of the present invention in order to achieve the above object of the present invention, forming a filter mold on a silicon wafer, forming a channel mold on the periphery of the filter mold on the silicon wafer Forming a first layer on the silicon wafer, forming a first hole in which the channel part mold is partially exposed on one side of the first layer, and forming the channel part mold on the other side of the first layer. Forming a partially exposed second hole, removing the silicon wafer to form a filter portion and a channel portion in the first layer, and forming a second layer below the first layer. A method for manufacturing a microchip is provided.

In this case, the forming of the filter unit may include forming a thin film on the silicon wafer, patterning the thin film to form a plurality of thin film patterns parallel to each other on the silicon wafer, and removing the thin film pattern. Forming a filter part including a plurality of fine channels spaced apart from each other in parallel to one layer, wherein the forming of the channel part comprises applying a photoresist to the entire surface of the silicon wafer on which the filter part mold is formed; Patterning the photoresist to form first and second photoresist patterns on both sides of the filter part mold; and removing the first and second photoresist patterns to form first and second channels in the first layer. Forming a step.

Preferably, the first layer is formed using PDMA or PMMA, which is a light transmissive plastic, and the second layer is formed using PDMA, PMMA or glass. In this case, the first hole is an inflow hole through which the blood cells are introduced, and the second hole is a discharge hole through which the blood cells are discharged.

Further, according to another preferred embodiment of the present invention in order to achieve the above objects of the present invention, forming a filter mold on a silicon wafer, forming a channel mold on the periphery of the filter mold on the silicon wafer Forming a first layer on the silicon wafer; inserting a tube in contact with the channel portion mold on one side of the first layer; removing the silicon wafer to remove the filter portion and the channel in the first layer. Forming a portion, forming a first hole in which the channel portion is partially exposed on the other side of the first layer, and forming a second layer under the first layer. This is provided.

In this case, the tube is inserted into the first layer with a tube inserting member positioned at the end of the tube, and the inserting of the tube removes the tube inserting member to remove the tube inserting member from the first layer. And forming two holes. In this case, the second hole is an inflow hole through which the blood cells flow, and the first hole is a discharge hole through which the blood cells are discharged.

In the case of a microchip made of a conventional silicon wafer, since the silicon wafer is an optically opaque material, it is difficult to determine the characteristics of erythrocytes by transmitting light to the chip. Therefore, the characteristics of erythrocytes are analyzed by analyzing the difference in wavelengths scattered from the erythrocytes. Was analyzed. However, according to the microchip according to the present invention, since the first and second layers, which constitute the microchip, are formed of an optically transparent material such as transparent plastic or glass, such as PDMA or PMMA, respectively, The physical properties of the red blood cells passing through the microchip through light can be easily measured. In addition, in the case of the conventional silicon wafer chip, the overall cost of manufacturing the microchip has increased because the silicon wafer is expensive and takes a long time to process, but as in the present invention, the microchip is made of a transparent material such as transparent plastic and glass. In the construction, the cost for manufacturing the microchip can be significantly lowered. Moreover, although it is almost impossible to manufacture a microchip having a dimension of several micrometers or less by the conventional plastic processing process, as described above, according to the present invention, a microchip having a small size having a dimension of several micrometers or less can be easily manufactured. have.

Hereinafter, a microchip and a method of manufacturing the same according to preferred embodiments of the present invention will be described in detail with reference to the accompanying drawings, but the present invention is not limited or limited to the following embodiments.

4 is a schematic diagram illustrating a disease diagnosis apparatus using physical properties of red blood cells to which a microchip for measuring physical properties of blood according to an embodiment of the present invention is applied.

Referring to FIG. 4, the disease diagnosis apparatus 200 using the physical characteristics of the red blood cells generally has a fixed plate 255, a microchip 250 located on the fixed plate 255, and a sample on the microchip 250. Analyze the characteristics of the blood detected by the sample injection member 265 for injecting the light, the optical detection member 270 for measuring the characteristics of the blood passing through the microchip 250, and the optical detection member 270. It is composed of an analysis device 280 for.

The fixing plate 255 on which the microchip 250 is mounted is installed to be movable up and down with respect to the optical detection member 270 while the measurement is performed. The fixing plate 255 may be provided with a fixing member 260 for fixing the microchip 250 to the fixing plate 255 in order to improve the mounting stability of the microchip 250.

The sample is injected from the sample injection member 265, such as a chickenpox or syringe pump, to the microchip 250 positioned on the fixed plate 255, and the sample injected into the microchip 250 is disposed inside the microchip 250. As it passes, physical properties such as shape, deformability, and velocity of red blood cells are detected by the optical detection member 270 such as a lens array or a microscope. A light source (not shown) may be installed under the fixing plate 255 to irradiate light to the microchip 250 so that the optical detection member 270 may perform a function smoothly. The physical properties of blood detected from the optical detection member 270 are analyzed by an analysis device 280 such as a computer to determine the presence or absence of a particular disease from the properties measured on the blood of the examinee.

5 is a cross-sectional view of the microchip illustrated in FIG. 4.

As shown in FIG. 5, the microchip 250 according to the present invention includes a first layer 205 as an upper layer and a second layer 210 as a lower layer. The first layer 205 is made of a light transmissive plastic, and the second layer 210 is made of a light transmissive plastic or glass to allow light to pass through the microchip 250.

On the second layer 210, a filter part 215 including a plurality of microchannels formed by molding a plurality of thin film patterns spaced apart from each other at predetermined intervals as a mold is formed, and a peripheral part of the filter part 215 is formed on the second layer 210. A channel portion consisting of the first and second channels 220 and 221 is formed. Each of the thin film patterns serving as a mold for forming the filter unit 215 is made of a metal, a metal oxide, or an insulator, and the first and second channels 220 and 221 are formed using a photoresist as a mold. In this case, the thin film patterns are formed to have a thickness of about 1 to 4 μm and a width of about 3 to 7 μm, so that the microchannels constituting the filter unit 215 are each about 1 to 4 μm thick. And a width of about 3 to 7 μm. In addition, the photoresist serving as a mold for forming the first and second channels 220 and 221 is formed to have a thick height of about 25 to 100 μm, and thus the first and second channels 220 and 221 are also formed. It will have a height of about 25 ~ 100㎛.

A first hole 240 exposing a part of the first channel 220 is formed from an upper portion of the first layer 205 and a second channel 221 from an upper portion of the other layer of the first layer 205. A second hole 231 exposing a part of the cavities is formed. In this case, each of the first hole 230 or the second hole 231 may be an inlet hole for selectively introducing the sample into the microchip 250 or a discharge hole for discharging the sample from the microchip 250. That is, when the first hole 230 is an inlet hole, the second hole 231 becomes an outlet hole, and when the first hole 230 becomes an outlet hole, the second hole 231 becomes an inlet hole.

First and second connection tubes 240 and 241 may be connected to the first and second holes 230 and 231, respectively. For example, when the first hole 230 is an inflow hole and the sample is introduced into the microchip 250, the first connection tube 240 is inserted into the first hole 230 and the sample injection member 265 is inserted into the first hole 230. The sample is introduced into and discharged from the microchip 250. On the other hand, when the second hole 231 is the discharge hole and the sample which has been measured is discharged from the microchip 250, the second connection tube 241 is inserted into the second hole 231 and the syringe or the suction pump is used. The same sample discharge member (not shown) is used to introduce and discharge the sample from the microchip 250.

Hereinafter, a method of manufacturing a microchip according to the present invention will be described in detail with reference to the drawings.

First, a process of forming a silicon mold for forming a microchip according to the present invention will be described. 6A to 6C illustrate enlarged cross-sectional views for explaining a process of forming a silicon mold according to the present invention.

Referring to FIG. 6A, first, a metal such as platinum (Pt), tantalum (Ta), titanium (Ti), aluminum (Al), or tungsten (W) or an oxide of such metal, that is, platinum on a silicon wafer 300 Thin films made of metals or metal oxides by depositing oxides, tantalum oxides, aluminum oxides, titanium oxides, or tungsten oxides by chemical vapor deposition (CVD), vacuum evaporation or sputtering 305 is formed. In this case, the thin film 305 is formed to a thickness of about 1 to 4㎛, and is subsequently patterned into a plurality of thin film patterns 310 (filter) to filter (red blood cells). In addition, since the thin film 305 composed of the metal or metal oxide essentially performs the filter portion of the microchip, silicon nitride, TEOS (Si (OCH ₂ CH ₃ )) instead of the metal or metal oxide thin film for this function. ₄ may be formed using an insulator such as tetraethylorthosilicate or Low Temperature Oxide (LTO).

Referring to FIG. 6B, the thin film 305 formed on the silicon wafer 300 is etched by photolithography or reactive ion etching to form a thin film pattern on the silicon wafer 300. 310). In this case, a plurality of thin film patterns 310 uniformly spaced at a predetermined distance are formed on the silicon wafer 300 to serve as a mold to the filter unit for filtering blood later. Preferably, each of the thin film patterns 310 has a width of about 3 to 7 μm, but the width of the thin film patterns 310 may be fixed to about 4 μm, about 5 μm, or about 6 μm.

Subsequently, a photoresist is coated on the entire surface of the silicon wafer 300 on which the thin film pattern 310 is formed by spin coating to obtain a thickness of about 25 to 100 μm, preferably about 50 μm. A photoresist layer 315 is formed. Accordingly, the photoresist layer 315 is stacked at a predetermined height while covering the plurality of thin film patterns 310 formed on the silicon wafer 300 to serve as a mold for forming a channel portion of the microchip 250 later. .

Referring to FIG. 6C, the photoresist layer 315 is etched to expose the thin film pattern 310 by a photolithography method or a reactive ion etching method, thereby forming each of the thin film patterns 310 formed on the silicon wafer 300. First and second photoresist patterns 320 and 321 may be formed on both sides to serve as molds of the channel part. That is, the first and second photoresist patterns 320 on the silicon wafer 300 are positioned between the first and second photoresist patterns 320 and 321 so that a plurality of thin film patterns 310 serving as a mold of the filter unit are positioned. , 321.

FIG. 7A illustrates a perspective view of a silicon mold formed according to the present invention, and FIG. 7B is an enlarged perspective view of part 'A' of the silicon mold illustrated in FIG. 7A.

7A and 7B, the silicon mold 330 formed according to the above-described method may be formed on the plurality of thin film patterns 310 formed on the center of the silicon wafer 300 and on both sides of the thin film patterns 310. The first and second photoresist patterns 320 and 321 may be formed. In this case, the plurality of thin film patterns 310 serves as a mold for forming a filter unit for filtering blood, and the first and second photoresist patterns 320 and 321 respectively positioned at both sides of the thin film pattern 310 are formed. It serves as a mold for forming the channel portion through which blood passes.

Hereinafter, a process of forming a microchip according to the present invention using the silicon mold 330 will be described in detail with reference to the accompanying drawings.

8A to 8D are cross-sectional views illustrating a process of forming a microchip according to an embodiment of the present invention.

Referring to FIG. 8A, a silicon mold having a thin film pattern 310 functioning as a mold of a filter part formed on the silicon wafer 300 and first and second photoresist patterns 320 and 321 functioning as a mold of a channel part are formed. The first layer 340 is formed on the front surface of the 330 by applying a light-transmitting plastic having excellent light transmittance with good processability such as polydiallylmethylamine (PDMA) or polymethylmethacrylate (PMMA). The first layer 340 maintains the structure of the thin film pattern 310 functioning as a mold of the filter part and the first and second photoresist patterns 320 and 321 serving as a mold of the channel part, and at the same time the inlet hole 345. ) And a discharge hole 346 is formed to support the inlet tube 350 and the discharge tube 351 to be formed later.

Referring to FIG. 8B, the silicon wafer 300 is removed while the first layer 340 is formed thereon. In this case, the thin film pattern 310 which is a mold of the filter part formed on the silicon wafer 300 and the first and second photoresist patterns 320 and 321 which are a mold of the channel part are also removed. Accordingly, the first and second channels 320 and 320 having the shape of the filter unit 310 and the first and second photoresist patterns 321 and 321 may be formed in the first layer 340. A channel portion including 321 is formed.

Subsequently, the first and second channels 320 and 321 constituting the channel part may be formed by drilling a portion in which the first and second channels 320 and 321 are positioned below the center of the first layer 340, respectively. ) Forms a plurality of holes consisting of the inlet hole 345 and the outlet hole 346 so as to partially expose. At this time, the inlet hole 345 is formed so that the first channel 320 is exposed, the outlet hole 346 is formed so that the second channel 321 is exposed.

Even if the silicon wafer 300 under the first layer 340 is removed, the shape of the filter unit 310 and the first and second photoresist patterns 320 and 321 according to the shape of the thin film patterns 310 may be obtained. The first and second channels 320 and 321 are formed in the first layer 340. The plurality of holes formed in the first layer 340 serve as inlet holes 345 through which the sample is supplied and outlet holes 346 through which the sample is discharged.

Referring to FIG. 8C, as described above, the second layer 360 made of a transparent material having a predetermined strength, such as glass, below the first layer 340 having the inflow hole 345 and the discharge hole 346 formed therein. ), And then the inlet tube 350 and the outlet tube 351 are inserted into the plurality of inlet and outlet holes 345 and 346 formed in the first layer 340 to detect the sample, respectively. The microchip 370 according to one embodiment is completed. In this case, the second layer 360 may be formed of a light transmitting plastic such as PDMA or PMMA, which is the same material as the first layer 340.

9 is a cross-sectional view for explaining a process of detecting physical properties of red blood cells using a microchip according to an embodiment of the present invention. In Figure 9, the small arrows indicate the flow of the sample through the microchip, 'B' refers to the point where the optical detection is performed on the red blood cells.

As shown in FIG. 9, blood components such as red blood cells pass through the microchip 370 along the small arrow direction. That is, the sample is first formed in the first layer 340 and into the microchip 370 through an inlet hole 345 connected to a sample injection member (not shown), such as a chickenpox or syringe pump, through an inlet tube 350. It is introduced to the filter unit 310 through the first channel 320 constituting the channel portion. The sample passing through the filter unit 310 is again formed in the second channel 321 and the first layer 340 is discharged to the outside through the discharge hole 346 connected to the outside through the discharge tube 351. At this time, the sample passes through the filter portion 310 of the microchip 370 and physical properties such as the length and velocity of the red blood cells are detected by an array optical detection member such as a microscope or a lens at a point indicated by an arrow 'B'. .

10A to 10C are cross-sectional views illustrating a process of forming a microchip according to another exemplary embodiment of the present invention.

Referring to FIG. 10A, a thin film pattern 310 functioning as a mold of a filter part and a first and second photoresist pattern 320 and 321 functioning as a mold of a channel part are formed on the silicon wafer 300 as illustrated in FIG. 6C. The first layer 380 is formed by coating a light-transmissive plastic such as PDMA or PMMA on the silicon mold 330 on which is formed.

Subsequently, an inflow tube 390 in which the tube support member 385 is mounted is inserted into a portion in which the first photoresist pattern 320 serving as a mold of the channel portion is positioned below the center of the first layer 380. The tube support member 385 allows the tube 390 to maintain its structure while inserting the inlet tube 390 into the first layer 380. Such a tube support member 385 is made of a material such as metal, but may be made of a synthetic resin having a predetermined hardness. In the present embodiment, the inlet tube 390 is formed first, but the same result can be obtained by inserting the discharge tube 391 described later.

Referring to FIG. 10B, the silicon wafer 300 formed on the first layer 380 is removed, and the filter unit 310 and the first and the first layers 380 having the shape of the thin film pattern 310 are formed on the first layer 380. The first and second channels 320 and 321 having the shapes of the second photoresist patterns 320 and 321 are formed. Subsequently, when the tube support member 385 is pulled out from the inlet tube 390, an inlet hole 395 through which a sample is introduced is formed in the first layer 380 so that a part of the first channel 320 constituting the channel part is formed. Exposed.

Subsequently, a hole in which the second channel 321 is positioned below the first layer 380 is drilled through micromachining to form the discharge hole 396 exposing a portion of the second channel 321.

Referring to FIG. 10C, after attaching a second layer 400 made of a transparent material such as glass to the lower portion of the first layer 380, the sample passing through the microchip 410 in the discharge hole 396 is attached. When the discharge tube 391 is discharged, the microchip 410 according to the present embodiment is completed.

In the present embodiment, the inlet hole 395 is first formed in the first layer 380, and then the outlet hole 396 is formed, but the outlet hole 396 and the discharge tube 391 are formed in the first layer 380. ), The inlet hole 395 and the inlet tube 390 may be formed in the first layer 380. In addition, the inlet hole 395 and the outlet hole 396 may be simultaneously formed in the first layer 380, and the inlet tube 390 and the outlet tube 391 may be installed. Since the process of measuring the physical characteristics of the blood using the microchip 410 according to the present embodiment is as described above, a description thereof will be omitted.

Hereinafter, a method of injecting a sample into the microchip according to the present invention described above will be described.

11A and 11B are schematic perspective views and cross-sectional views illustrating a method of injecting a sample into a microchip according to an embodiment of the present invention, respectively. In FIGS. 11A and 11B, the configuration of the microchip is the same as that of the microchip shown in FIGS. 8C and 10C, and thus description thereof will be omitted. In FIG. 11B, the arrow shows the flow of the sample supplied from the sample supply device and injected into the microchip.

11A and 11B, the microchip 450 is placed on a fixed plate 425 such as a substrate, and then a sample injection member 430 such as a syringe pump is inserted into the inlet hole of the microchip 450. ). At this time, the inlet hole of the microchip 450 and the sample injection member 430 are connected to each other through a connection tube 435, so that the mounting stability of the fixing plate 425 of the microchip 450 can be improved. The fixing member 420 may be formed on the fixing plate 425.

Subsequently, the sample is first injected into the sample injection member 430 such as a syringe pump, and then the sample injected into the sample injection member 430 is supplied to the microchip 450 while applying a constant pressure to the sample injection member 430. do. According to this method, since the sample can be injected into the microchip 450 at a constant speed, there is an advantage that the speed of the red blood cells passing through the microchip 450 can be kept constant. On the contrary, in order to supply the sample to the microchip 450, first, the sample must be filled in the sample injection member 430 in a predetermined amount so that the consumption of the sample increases, and the size of the device for supplying the sample also increases. have.

12A and 12B are schematic perspective views and cross-sectional views illustrating a method of injecting a sample into a microchip according to another embodiment of the present invention, respectively. Also in FIGS. 12A and 12B, the configuration of the microchip 550 is the same as the microchip illustrated in FIGS. 8C and 10C, and thus description thereof will be omitted. In FIG. 12B, the arrows indicate the flow of the sample supplied from the sample supply device and injected into the microchip, and the hatched ellipses represent the blood supplied to the microchip.

12A and 12B, the microchip 550 is seated on the fixing plate 500, and then a drop of blood 530 of the person being examined is dropped into the inlet hole of the microchip 550. . As described above, the fixing member 510 may be formed on the fixing plate 500 in consideration of mounting stability of the microchip 550. Subsequently, a syringe is connected to the outlet of the microchip 550 and blood 530 positioned in the inlet hole of the microchip 550 is manually or using a sample discharge member 520 such as a suction pump. Introduced into the microchip 550 to measure physical characteristics such as the size of red blood cells and the moving speed. In this case, a sample discharge member 520 such as a suction pump is installed in the discharge hole of the microchip 550 through a connection tube 525 in order to smoothly introduce the blood 530 of the examiner into the microchip 550. do. In addition, instead of such a suction pump, a simple syringe may be connected to introduce blood 530 in the microchip 550. In the above-described method, it is easy to adjust the speed of the blood 530 passing through the microchip 550 to be slow or fast, even when the amount of sample required to measure the physical characteristics of the red blood cells is minute. The advantage is that measurement is possible. In addition, since the sample can be flowed into the microchip 550 even without an additional device, the configuration of the device is simplified.

When diagnosing a disease using the microchip according to the present invention described above, undiluted general blood may be directly used, and when used in a hospital, only red blood cells may be separated to measure physical properties of the microchip. In addition, the extracted red blood cells may be diluted to a specific concentration, such as about 1: 1 or about 1: 2, and the red blood cells may be separated on a microchip according to the present invention, or other desired predetermined blood cells may be separated using a concentration adjusting element. Can be used to adjust the concentration of. Moreover, the microchip may be processed so that other microchannels having a structure similar to the microchip according to the present invention are added to the microchip in order to adjust the concentration of the sample.

In the case of a microchip made of a conventional silicon wafer, since the silicon wafer is an optically opaque material, it is difficult to determine the characteristics of the red blood cells by transmitting light to the chip, so the characteristics of the red blood cells are analyzed by analyzing the difference in the wavelengths scattered from the red blood cells. Was analyzed. However, according to the microchip according to the present invention, since the upper and lower layers constituting the microchip are each made of an optically transparent material such as transparent plastic or glass such as PDMA or PMMA, the microchip can transmit light to the microchip. Physical properties of the red blood cells passing through can be easily measured.

In addition, in the case of the conventional silicon wafer chip, the overall cost of manufacturing the microchip has increased because of the high price of the silicon wafer. However, when the microchip is made of transparent plastic and glass as in the present invention, The cost can be significantly lowered.

Moreover, although it is almost impossible to manufacture a microchip having a dimension of several micrometers or less by the conventional plastic processing process, as described above, according to the present invention, a microchip having a small size having a dimension of several micrometers or less can be easily manufactured. have.

As described above, although described with reference to preferred embodiments of the present invention, those skilled in the art will be variously modified and modified without departing from the spirit and scope of the invention described in the claims below. It will be appreciated that it can be changed.

1 is a cross-sectional view of a microcavity portion of a device capable of measuring the properties of a conventional red blood cell.

FIG. 2 is a schematic plan view of the microcavity shown in FIG. 1.

3 is a schematic plan view of a microchip formed by microfabricating a conventional silicon wafer.

4 is a schematic configuration diagram illustrating an example of a disease diagnosis apparatus using physical properties of red blood cells to which a microchip according to the present invention is applied.

5 is a cross-sectional view of the microchip illustrated in FIG. 4.

6A to 6C are enlarged cross-sectional views illustrating a process of forming a silicon mold according to the present invention.

7A is a perspective view of a silicone mold formed in accordance with the present invention.

FIG. 7B is an enlarged perspective view of part 'A' of the silicon mold illustrated in FIG. 7A.

8A to 8D are cross-sectional views illustrating a process of forming a microchip according to an embodiment of the present invention.

9 is a cross-sectional view for explaining a process of detecting physical properties of red blood cells using a microchip according to an embodiment of the present invention.

10A to 10C are cross-sectional views illustrating a process of forming a microchip according to another exemplary embodiment of the present invention.

11A and 11B are schematic perspective views and cross-sectional views illustrating a method of injecting a sample into a microchip according to an embodiment of the present invention, respectively.

12A and 12B are schematic perspective views and cross-sectional views illustrating a method of injecting a sample into a microchip according to another embodiment of the present invention, respectively.

<Description of the code | symbol about the principal part of drawing>

200: Disease diagnosis apparatus 205, 340, 380: The first layer

210, 360, 400: 2nd layer 215, 310: Filter part

220, 320: First channel 221, 321: Second channel

230: First hall 231: Second hall

250, 370, 410, 450, 550 ： Microchip

255, 425, 500: fixing plate 260, 420, 510: fixing member

265 and 430: sample injection member 270: optical detection member

280: analyzer 300: silicon wafer

305: thin film 315: photoresist layer

330: Silicon mold 345, 395: Inflow hole

346, 396: discharge hole 350, 390: inlet tube

351, 391: discharge tube 385: tube support member

435, 525: connection tube 520: sample discharge member

530 ： Blood

Claims (29)

In the microchip for the measurement of physical properties of blood, Top layer: A lower layer attached below the upper layer; A filter unit formed between the upper layer and the lower layer and configured of a plurality of fine channels spaced apart from each other in parallel to each other; And And a channel part formed between the upper layer and the lower layer, the channel part including first and second channels respectively formed on both sides of the filter part. The method of claim 1, The upper layer is a microchip, characterized in that made of a light-transmissive plastic. The method of claim 2, The upper layer is a microchip, characterized in that made of PDMA (polydiallylmethylamine, polydiallylmethylamine) or PMMA (polymethylmethacrylate, polymethylmethacrylate). The method of claim 2, The lower layer is a microchip, characterized in that consisting of a transparent plastic or glass. The method of claim 4, wherein The lower layer is a microchip, characterized in that composed of any one selected from the group consisting of glass, PDMA (polydiallylmethylamine), and PMMA (polymethylmethacrylate, polymethylmethacrylate). delete The method of claim 1, The microchannels each having a width of 3 to 7 μm and a height of 1 to 4 μm. delete The method of claim 1, And the first and second channels each have a thickness of 25-100 μm. The method of claim 1, And the inlet and outlet holes through which the first and second channels are partially exposed are formed in the upper layer. The method of claim 10, The inlet hole is a microchip, characterized in that the connection tube of the sample injection means for the inlet of the blood cells is inserted. The method of claim 11, The sample injection means is a microchip, characterized in that the head or syringe pump. The method of claim 10, The discharge hole is a microchip characterized in that the connection tube of the sample discharge means for the discharge of the blood cells is inserted. The method of claim 13, The sample dispensing means is a microchip, characterized in that the suction pump or syringe. In the method of manufacturing a microchip for the measurement of physical properties of blood cells contained in blood, Forming a filter mold on the silicon wafer; Forming channel part molds on both sides of the filter part mold on the silicon wafer; Forming an upper layer on the silicon wafer; Forming a first hole in which the channel part mold is partially exposed on one side of the upper layer; Forming a second hole in which the channel part mold is partially exposed on the other side of the upper layer; Removing the silicon wafer to form a filter part and a channel part in the upper layer; And Forming a lower layer below the upper layer manufacturing method of a microchip. The method of claim 15, Forming the filter unit, Forming a thin film on the silicon wafer; Patterning the thin film to form a plurality of thin film patterns parallel to each other on the silicon wafer; And Removing the thin films to form a filter part including a plurality of fine channels parallel to each other on the upper layer. The method of claim 16, The thin film is a microchip, characterized in that composed of any one metal selected from the group consisting of platinum, tantalum, titanium, aluminum and tungsten. The method of claim 16, The thin film is a microchip, characterized in that composed of any one metal oxide selected from the group consisting of platinum oxide, tantalum oxide, titanium oxide, aluminum oxide and tungsten oxide. The method of claim 16, The thin film is a microchip, characterized in that composed of any one of the insulating material selected from the group consisting of silicon nitride, TEOS and low temperature oxide. The method of claim 16, Forming the channel portion, Applying a photoresist to the entire surface of the silicon wafer on which the filter part mold is formed; Patterning the photoresist to form first photoresist patterns and second photoresist patterns on both sides of the filter part mold; And And removing the first and second photoresist patterns to form a channel portion including first and second channels around the filter portion. The method of claim 15, Wherein the first hole is an inflow hole into which the blood cells flow, and the second hole is a discharge hole through which the blood cells are discharged. The method of claim 21, And inserting a connection tube of a sample injection means for introducing the blood cells into the inlet hole. The method of claim 15, And inserting a connection tube of a sample discharge means for outflow of the blood cells into the discharge hole. In the method of manufacturing a microchip for the measurement of physical properties of blood cells contained in blood, Forming a filter mold on the silicon wafer; Forming channel part molds on both sides of the filter part mold on the silicon wafer; Forming an upper layer on the silicon wafer; Inserting a tube in contact with the channel part mold on one side of the upper layer; Removing the silicon wafer to form a filter part and a channel part in the upper layer; Forming a first hole in which the channel part is partially exposed on the other side of the upper layer; And Forming a lower layer below the upper layer manufacturing method of a microchip. The method of claim 24, Forming the filter unit in the upper layer, Forming a thin film on the silicon wafer; Patterning the thin film to form a plurality of thin film patterns parallel to each other on the silicon wafer; And Removing the thin film patterns to form a channel part including a plurality of fine channels parallel to each other on the upper layer. The method of claim 25, Forming the channel portion in the upper layer, Applying a photoresist to the entire surface of the silicon wafer on which the filter part mold is formed; Patterning the photoresist to form first photoresist patterns and first photoresist patterns on both sides of the filter part mold; And And removing the first and second photoresist patterns to form first and second channels around the filter unit. The method of claim 24, And the tube is inserted into the top layer with tube insertion means located at the end of the tube. The method of claim 27, Inserting the tube further comprises the step of removing the tube inserting means to form a second hole in the upper layer where the tube is located. The method of claim 28, And the second hole is an inflow hole into which the blood cells flow, and the first hole is a discharge hole through which the blood cells are discharged.