KR100961468B1 - Automatic Diagnostic System - Google Patents

Abstract

An automatic diagnostic device is provided. The device is provided with a pretreatment unit provided in the substrate for extracting DNA from a sample, a polymerase chain reaction chamber enclosed in a first rubber plate and sealed in a substrate for amplifying DNA, and a substrate for hybridizing amplified DNA. And a hybridization chamber, which is covered and sealed with a second rubber plate, and a microrobot connected to a substrate to move a solution containing a sample or DNA to a pretreatment unit, a polymerase chain reaction chamber, and a hybridization chamber.

Polymerase Chain Reaction, DNA, Hybridization, Micro Robot, Real Time

Description

Automatic Diagnostic System

The present invention relates to an automatic diagnostic system, and more particularly to an automatic diagnostic system using a micro robot.

The present invention is derived from a study performed as part of the IT source technology development project of the Ministry of Information and Communication and the Ministry of Information and Communication Research and Development [Task Management No .: 2006-S-007-02, Task Name: Ubiquitous Health Management Module System].

As human society develops, chemical-related industries are constantly developing, and chemical analysis technology is necessary to be developed along with the development of these chemical industries. Chemical analytical techniques are commonly referred to as methods used to identify, detect or determine the chemical composition of a substance.

For fast and accurate chemical analysis, development of a chemical analysis device for automatically performing chemical analysis, which was dependent on the experimenter's manual labor, is in progress. These chemical analyzers automatically mix the sample with the reagents, react for a period of time, transfer the reactants to the detector and output a signal proportional to the concentration of the measurement object as an electrical or optical signal, simply by supplying the sample taken. This is done automatically in one measurement system.

The process of analyzing DeoxyriboNucleic Acid (DNA, hereinafter referred to as DNA) in a conventional laboratory will be described using a method of diagnosing Human Papilloma Virus (HPV) as an example.

1. Specimen collection: Samples of the epidermis from the cervix are sampled using a sampling kit such as a medical brush. Collected samples are refrigerated at 2 ~ 10 ℃ until pretreatment for analysis.

2. DNA isolation: (1) After the sample on the medical brush is contained in the microtube containing the storage buffer, the table top vortex to separate the sample into the storage buffer. In a desktop type vortex device, the microtubes are vortexed for 2 minutes and 1 ml of the storage buffer containing the sample is placed in another microtube having a volume of 1.5 ml. (2) In order to precipitate the cells, the microtubes are centrifuged at 3,000 rpm for 10 minutes in a centrifugal apparatus, and the superantant floating on the surface of the microtubes is discarded using a pipette. (3) Add 1.0 ml of washing buffer, swirl the microtube for 10 seconds, centrifuge at 3,000 rpm for 10 minutes, and discard the supernatant. Repeat this process once more. (4) 200 μl of DNA extraction buffer is added, and the microtubes are bathed in a water bath at 90-100 ° C. for 20 minutes. (5) Add 150 μl of the supernatant to another microtube for DNA amplification, and centrifuge the microtube at 13,000 rpm for 10 minutes.

The experimenter can directly switch the desktop vortex and centrifuge devices, insert the various buffers into the microtubes, and discard the supernatant inside the microtubes. The same process is performed.

3. Polymerase Chain Reaction (PCR): (1) 5 μl of DNA extract, 7 μl of 450 base pair premix, 0.3 μl of enzyme and 12.7 μl of distilled water It is placed in a polymerase chain reaction tube of a 0.2 ml tabletop polymerase chain reaction apparatus. (2) The process of sequentially applying three temperatures of 95 ° C., 72 ° C. and 55 ° C., which are the temperature conditions for the polymerase chain reaction, is repeated 35 times.

The process of adding DNA extracts, premixes, enzymes and distilled water to the polymerase chain reaction tube is performed by the experimenter using a pipette by hand and the experimenter directly switching the desktop polymerase chain reaction apparatus. .

4. Secondary polymerase chain reaction: (1) A new polymerase chain with a volume of 0.2 ml containing 2 μl of the first polymerase chain reaction product, 6.5 μl of 450 base pair premix, 0.3 μl of enzyme and 16.2 μl of distilled water. Place in reaction tube. (2) The process of sequentially applying three temperatures of 95 ° C, 72 ° C and 55 ° C, which are the temperature conditions for the polymerase chain reaction, is repeated 20 times.

The process of loading the first polymerase chain reaction product, premix, enzyme and distilled water into a new polymerase chain reaction tube was carried out by the experimenter using the pipette by hand and by the experimenter switching the desktop polymerase chain reaction apparatus directly. The same process is performed.

5. Hybridization process: (1) The 8 μl secondary polymerase chain reaction product is maintained at 95 ° C. for 5 minutes and then in ice water for 5 minutes. (2) 32 [mu] l of the hybridization buffer preheated to 43 [deg.] C. is placed in the hybridization chamber of the hybridization chip slide. (3) 40 microliters of hybridization liquid mixtures are added to a hybridization chamber. (4) The hybridized chip slides are maintained in a heat stabilized oven at 43 ° C. for 1 hour.

The process of placing the secondary polymerase chain reaction product, the hybridization buffer and the hybridization mixture in the hybridization chamber is performed by the experimenter using a pipette by hand and the experimenter directly moving the hybridization chip slide to the oven.

6. Washing: (1) Wash hybridized chip slides twice for 2 minutes in 2X SSC, 0.1% SDS. (2) Wash twice with 0.2X SSC solution for 5 minutes. (3) Wash once for 5 minutes with 0.1X SSC solution. The hybridized chip slides are dried with an air dry and then scanned using a chip scanner to determine genotype and infection of human papillomavirus.

Washing the hybridized chip slides with SSC and SDS solutions and drying the hybridized chip slides with a dry air supply is performed by the experimenter directly using the hands.

As seen in the DNA analysis process as described above, chemical analysis is mostly performed sequentially by pipetting by the experimenter manually, the operation of the table top devices and the movement of by-products. Accordingly, the experimenter cannot leave the experiment site, there may be a mistake of the experimenter, and the time required for the experiment process becomes long.

The problem to be solved by the present invention is to provide an automatic diagnostic system that can perform chemical analysis without depending on the experimenter.

In order to achieve the above object, the present invention provides an automatic diagnostic device. The device is provided with a pretreatment unit provided in the substrate for extracting DNA from a sample, a polymerase chain reaction chamber enclosed in a first rubber plate and sealed in a substrate for amplifying DNA, and a substrate for hybridizing amplified DNA. And a hybridization chamber covered with a second rubber plate and sealed, and a microrobot connected to a substrate to move a solution containing a sample or DNA to a pretreatment unit, a polymerase chain reaction chamber, and a hybridization chamber.

The control unit may further include a control unit for controlling the preprocessor and the micro robot.

The display apparatus may further include a light source and an imaging device, which are respectively provided on the upper and lower portions of the substrate provided with the hybridization chamber. The light source may be a light emitting diode. The imaging device may be a CMOS image sensor or a CD image sensor.

The substrate may be one substrate selected from a silicon substrate, a glass substrate, and a printed circuit board. The substrate may have a size in the range of 20-30 cm in diameter or width.

The pretreatment unit may have a vortex function and a centrifugal function at the same time.

The polymerase chain reaction chamber may be in the form of a lab-on-a-chip. The polymerase chain reaction chamber may be a temperature control chamber. The polymerase chain reaction chamber may be temperature controlled by a hot wire provided inside the substrate.

The first rubber plate may have a thickness in the range of 0.1 to 2 mm, and may have a restoring force close to 100% to maintain the sealed state of the polymerase chain reaction chamber.

The hybridization chamber may be a microarray chip. The hybridization chamber may be a temperature control chamber. The hybridization chamber may be temperature controlled by an internal hot wire electrically connected to the substrate.

The second rubber plate may be a transparent rubber plate. The transparent rubber sheet may have a thickness in the range of 0.1 to 2 mm and may have a restoring force close to 100% to maintain the sealing state of the hybridization chamber.

The microrobot may be programmed to perform a pipetting function to transfer, inject, inhale and discard the solution. The micro robot may further include a dry air supply function.

As described above, according to the problem solving means of the present invention, by using a micro robot, it is possible to perform chemical analysis without depending on the experimenter. As a result, mistakes by the experimenter can be eliminated, and the time required for chemical analysis can be shortened.

Hereinafter, preferred embodiments of the present invention will be described in detail with reference to the accompanying drawings. However, the present invention is not limited to the embodiments described herein but may be embodied in other forms. Rather, the embodiments introduced herein are provided so that the disclosure may be made thorough and complete, and to fully convey the spirit of the invention to those skilled in the art. In addition, since it is in accordance with the preferred embodiment, reference numerals presented in the order of description are not necessarily limited to the order. In the drawings, the thicknesses of films and regions are exaggerated for clarity. In addition, if it is mentioned that the film is on another film or substrate, it may be formed directly on the other film or substrate, or a third film may be interposed therebetween.

FIG. 1A is a schematic conceptual view illustrating an automatic diagnostic apparatus according to an exemplary embodiment of the present invention, and FIG. 1B is a schematic cross-sectional view taken along line II-II ′ of FIG. 1A. 2A and 2B are cross-sectional views taken along the line II ′ of FIG. 1A to describe a preprocessor of the automatic diagnostic apparatus according to the embodiment of the present invention. 3A and 3B are cross-sectional views taken along the line III-III ′ of FIG. 1A to explain the polymerase chain reaction chamber of the automatic diagnostic apparatus according to the embodiment of the present invention. 4A and 4B are cross-sectional views taken along the line II-II 'of FIG. 1A to explain the hybridization chamber of the automatic diagnostic apparatus according to the embodiment of the present invention.

1A and 1B, the automatic diagnostic apparatus 100 includes a substrate 110, a preprocessor 120, a polymerase chain reaction chamber 130, a hybridization chamber 140, and a micro-robot. , 150). In addition, the control unit 160 for controlling the pretreatment unit 120, polymerase chain reaction chamber 130, hybridization chamber 140 and the micro robot 150 may be included. In addition, the light source 180 and the imaging device 190 may be provided on the lower and upper portions of the substrate 110, respectively.

The substrate 110 may have through holes through which the preprocessor 120 and hybridization chamber 140 may be mounted. In addition, the substrate 110 may have a plurality of grooves used as the polymerase chain reaction chamber 130. The substrate 110 may be one substrate selected from a silicon substrate, a glass substrate, and a printed circuit board. The substrate 110 may include internal wires electrically connecting the preprocessor 120, the polymerase chain reaction chamber 130, the hybridization chamber 140, and the micro robot 150 to the controller 160. have. The substrate 110 may have a circular or quadrangular shape. The substrate 110 may have a size having a diameter or width ranging from 20 to 30 cm.

The pretreatment unit 120 may have a reduced shape than a general vortex device or centrifugal device used in a laboratory. The preprocessor 120 may be provided in a circular through hole formed in the substrate 110. The preprocessor 120 may have a plurality of grooves in which the plurality of microtubes may be mounted. The preprocessor 120 may have a vortex function and a centrifugal function at the same time. Accordingly, the preprocessor 120 may be used as a vortex device or a centrifuge device according to the command of the controller 160.

The polymerase chain reaction chamber 130 may be a plurality of grooves formed in the substrate 110. The polymerase chain reaction chamber 130 may be in the form of a lab-on-a-chip. The polymerase chain reaction chamber 130 may have a reduced form than a general polymerase chain reaction apparatus used in a laboratory. The polymerase chain reaction chamber 130 may be a chamber capable of temperature control. The polymerase chain reaction chamber 130 may be temperature controlled by a heat wire (see 132 of FIGS. 3A and 3B) provided in the substrate 110. Accordingly, the temperature of the polymerase chain reaction chamber 130 may be determined according to the command of the controller 160. The polymerase chain reaction chamber 130 may be sealed by a polymerase chain reaction chamber cover 130r covering the plurality of grooves as a whole or each. The polymerase chain reaction chamber cover 130r may be a rubber plate having a high restoring force and having a thickness in the range of 0.1 to 2 mm. The resilience of the rubber sheet can be almost 100%.

The hybridization chamber part 140 may be provided in a rectangular through hole formed in the substrate 110. The hybridization chamber unit 140 may be a microarray chip. The hybridization chamber unit 140 may have a plurality of hybridization chambers 140h. The hybridization chamber unit 140 may be a chamber capable of temperature control. The hybridization chamber unit 140 may be temperature controlled by an internal heating wire electrically connected to the substrate 110. Accordingly, the temperature of the hybridization chamber unit 140 may be determined according to the command of the controller 160. Hybridization chamber portion 140 may be sealed by hybridization chamber portion cover 140r that covers hybridization chambers 140h as a whole or each. The hybridization chamber cover 140r may be a transparent rubber plate having a high restoring force and having a thickness in the range of 0.1 to 2 mm. The resilience of the rubber sheet can be almost 100%.

The micro robot 150 is mechanically and electrically connected to the substrate 110, and includes a preprocessor 120, a polymerase chain reaction chamber 130, and a hybridization chamber 140 provided inside the substrate 110. And a pipette tip providing unit 170, a solution providing unit 172, a solution disposal unit 174, a pipette tip disposal unit 176, and a microtube providing unit 178 provided outside the substrate 110. have. This movement may be extended to the region of the substrate 110 and the outer region by two joints of the micro robot 150. The micro robot 150 may be programmed to perform a pipetting function for transferring, injecting, inhaling and discarding a solution by mounting the pipette tip 155 at the distal end. Accordingly, the micro robot 150 may perform a programmed operation according to a command of the controller 160. The pipette tip 155 may have a reduced shape than that used in the laboratory, and may be sharp enough to penetrate the stopper of the microtube, the polymerase chain reaction chamber cover 130r, and the hybridization chamber cover 140r. Can have an end.

The light source 180 may be provided under the substrate 110 in an area where the hybridization chamber unit 140 is provided. The light source 180 may be a light emitting diode (LED). A lens 185 may be provided between the light source 180 and the substrate 110 to allow light emitted from the light source 180 to be incident in parallel to the hybridization chamber 140. The imaging device 190 may be provided on the substrate 110 in a region where the hybridization chamber 140 facing the light source 180 is provided. The imaging device 140 may be a complementary metal-oxide semiconductor (CMOS) image sensor or a charge-coupled device (CCD) image sensor.

Conventional scanners for measuring DNA microarrays scan DNA microarray chips with laser light sources ranging in size from 2 to 10 μm because the spots of the microarrays range in size from several to several tens of microns. Afterwards, a fluorescence image is formed using software. The fluorescence image by the scanning has a disadvantage in that it is difficult to disseminate due to the high price of the device constituting the scanner. In the case of a DNA microarray chip for diagnosing human papillomavirus, the spot may have a size in the range of tens to hundreds of micrometers when the number of microarrays does not exceed 100. Accordingly, as in the embodiment of the present invention, the CMOS image sensor or the CD image sensor for general photography may be positioned on the hybridization chamber, and the DNA microarray chip may be analyzed by front-side imaging rather than scanning.

The process of analyzing DNA by the automatic diagnosis apparatus 100 according to an embodiment of the present invention will be described with reference to FIGS. 1A to 4B as an example of a method of diagnosing a human papilloma virus.

1. Sampling: Samples of the epidermis can be sampled from the cervix using sampling kits such as medical brushes. Collected samples can be refrigerated at 2 to 10 ° C until pretreatment for analysis.

2. DNA extraction: microtubes 122 containing a sample collected from the cervix and frozen and stored in a plurality of grooves of the pretreatment unit 120 provided in the perforated portion of the substrate 110 of the automatic diagnostic apparatus 100 Is mounted by the experimenter by hand. The preprocessor 120 may have a vortex function and a centrifugal function at the same time. The microtubes 122 may include microtube stoppers 124. The microtube stopper 124 may be made of a rubber material having a high restoring force. The resilience of the rubber material may be about 100%. Accordingly, even if the pipette tip 155 mounted at the end of the micro robot 150 is inserted into the microtube 122 and discharged, the sample contained in the microtube 122 may be protected from the external environment.

Processes that are sequentially performed in the preprocessor 120 are as follows. (1) After the storage buffer is contained in the microtube 122 containing the sample on the medical brush, the microtube 122 is vortexed for 2 minutes in the pretreatment unit 120 to separate the sample into the storage buffer. And 1 ml of the storage buffer containing the sample is placed in another microtube 122 having a volume of 1.5 ml. (2) In order to precipitate the cells, the microtubes 122 are centrifuged at 3,000 rpm for 10 minutes in the pretreatment unit 120, and the supernatant that floats on the surface inside the microtubes 122 is discarded using the microrobot 150. . (3) 1.0 ml of washing buffer was added, the microtube 122 was vortexed for 10 seconds in the pretreatment unit 120, centrifuged at 3,000 rpm for 10 minutes, and the supernatant was discarded. Repeat this process once more. (4) After adding 200 μl of DNA extraction buffer, 150 μl of the supernatant is added to another microtube 122 for DNA amplification, and the microtube is centrifuged at 13,000 rpm for 10 minutes in the pretreatment unit 120.

The vortex processing and centrifugation may be performed by the operation of the preprocessor 120 by a programmed command of the controller 160. In addition, the process of putting a variety of buffers in the microtube 122, the process of transferring the solution to another microtube 122, the process of discarding the supernatant in the microtube 122, the process of replacing the microtube 122, etc. May be performed by the operation of the micro robot 150 by a programmed command of the controller 160.

3. Primary polymerase chain reaction: (1) 5μl of DNA extract, 7μl of 450 base pair premix, 0.3μl of enzyme and 12.7μl of distilled water are contained in the polymerase chain reaction chamber 130. The premix may comprise Cy3 or / and Cy5 phosphors. (2) The process of sequentially applying three temperatures of 95 ° C., 72 ° C. and 55 ° C., which are the temperature conditions for the polymerase chain reaction, is repeated 35 times.

The polymerase chain reaction chamber part 130 may be sealed by the polymerase chain reaction chamber part cover 130r. Accordingly, the pipette tip 155 mounted at the end of the micro robot 150 is inserted into the polymerase chain reaction chamber 130, and even if the sample is discharged, the sample contained in the polymerase chain reaction chamber 130 is stored in the external environment. Can be protected from. In addition, the polymerase chain reaction chamber cover 130r may prevent the solution from being evaporated by the temperature during the polymerase chain reaction.

The process of containing the DNA extract, the pre-mixture, the enzyme and the distilled water in the polymerase chain reaction chamber 130 may be performed by the operation of the micro robot 150 by the programmed command of the controller 160. In addition, temperature control of the polymerase chain reaction chamber 130 may be performed by operation of the heating wire 132 provided in the substrate 110 by a programmed command of the controller 160.

4. Secondary Polymerase Chain Reaction: (1) A polymerase chain reaction chamber 130 containing 2 μl of the first polymerase chain reaction product, 6.5 μl of 450 base pair premix, 0.3 μl of enzyme and 16.2 μl of distilled water. Put in. (2) The process of sequentially applying three temperatures of 95 ° C, 72 ° C and 55 ° C, which are the temperature conditions for the polymerase chain reaction, is repeated 20 times.

The process of storing the first polymerase chain reaction product, the pre-mixture, the enzyme and the distilled water in the extra polymerase chain reaction chamber 130 is performed by the operation of the micro robot 150 by the programmed command of the controller 160. Can be performed. In addition, the temperature control of the excess polymerase chain reaction chamber 130 may be performed by the operation of the heating wire 132 provided on the substrate 110 by a programmed command of the controller 160.

5. Hybridization Process: (1) The 8 μl secondary polymerase chain reaction product is held at 95 ° C. for 5 minutes and then at 0 ° C. for 5 minutes. (2) 32 microliters of the hybridization buffer previously heated at 43 degreeC are contained in the hybridization chamber 140h of the hybridization chamber part 140. FIG. (3) 40 µl of the hybridization mixed solution is added to the hybridization chamber 140h. (4) The hybridization chamber 140 is maintained at a temperature of 43 ° C. for 1 hour.

The hybridization chamber portion 140 may be sealed by the hybridization chamber portion cover 140r. Accordingly, even if the pipette tip 155 mounted at the end of the micro robot 150 is inserted into the hybridization chamber 140 and discharged, the sample contained in the hybridization chamber 140 may be protected from the external environment. In addition, the hybridization chamber cover 140r may prevent the solution from being evaporated by the temperature during the hybridization process. In addition, the hybridization chamber cover 140r may be a transparent rubber plate. This is because it must be able to pass the light emitted from the light source 180 in the process of analyzing the DNA.

The process of containing the secondary polymerase chain reaction product, the hybridization buffer, and the hybridization mixed solution in the hybridization chamber unit 140 may be performed by the operation of the micro robot 150 by the programmed command of the controller 160. In addition, temperature control of the hybridization chamber unit 140 may be performed by operation of a heating wire (not shown) inside the hybridization chamber unit 140 electrically connected to the substrate 110 by a programmed command of the controller 160. have.

6. Cleaning: (1) Wash hybridization chamber (140h) twice for 2 minutes in 2X SSC, 0.1% SDS. (2) Wash twice with 0.2X SSC solution for 5 minutes. (3) Wash once for 5 minutes with 0.1X SSC solution. The hybridization chamber unit 140 is dried using a dry air supply function of the micro robot 150.

Cleaning the hybridization chamber 140h with the SSC solution and the SDS solution and drying the hybridization chamber 140h may be performed by operation of the microrobot 150 by a programmed command of the controller 160.

When the above processes are completed, the light source 180 provided under the substrate 110 in the region where the hybridization chamber unit 140 is provided is turned on, and the imaging device 190 provided thereon is a phosphor present in the hybridization chamber unit 140. Cy3 or / and Cy5 fluorescence images are taken and the fluorescence images are sent to the analysis system. An analytical program embedded in the assay system indicates whether human papillomavirus is infected from the sample taken.

5 is a cross-sectional view for explaining another application of the automatic diagnostic apparatus according to the embodiment of the present invention. The hybridization chamber of FIG. 1 will be described as an example using the protein analysis chamber.

Referring to FIG. 5, the protein analysis chamber unit may include a lower substrate 210a, an upper substrate 210b, an antibody group 212, and a rubber cover 240r.

The lower substrate 210a may correspond to the substrate of FIG. 1 (see 110 of FIG. 1). The lower substrate 210a includes a filtration region (recessed region) for filtering a solution (droplet shape) containing the antigen to be analyzed and a reaction region for antigen-antibody reaction between the antigen contained in the solution and the antibody group 212. It may include. The upper substrate 210b may include an opening for injecting a solution while sealing the filtration region and the reaction region of the lower substrate 210a. The rubber cover 240r may seal the opening of the upper substrate 210b to block contamination sources introduced into the protein analysis chamber from the external environment.

The pipette tip 255 mounted at the end of the micro robot 250 penetrates the rubber cover 240r to inject a solution containing the antigen into the filtration area of the lower substrate 210a. The rubber cover 240r may be a rubber plate having a high restoring force and having a thickness in the range of 0.1 to 2 mm. The resilience of the rubber sheet can be almost 100%. Accordingly, even if the pipette tip 255 mounted at the end of the micro robot 250 is inserted into the protein analysis chamber part and discharged, the sample contained in the protein analysis chamber part may be protected from the external environment.

Specific proteins bound to the antibody group 212 by an antigen-antibody reaction can be analyzed in a similar manner to the process of analyzing DNA in the hybridization chamber. This is because certain proteins are processed to contain phosphors between the filtration and reaction zones. Accordingly, the specific protein captured by the antibody group 212 is irradiated with light to take a fluorescence image, and transmit the fluorescence image to the analysis system. An analytical program built into the assay system indicates the presence or absence of a specific protein from the sample taken. In addition, the automatic diagnostic apparatus of the present invention can be applied to a cell analysis apparatus and the like.

The automatic diagnostic device according to the embodiment of the present invention is a vortex device, a centrifugal device, a dry air supply device, various solution bottles, a polymerase chain reaction device, an oven, and a fluorescence image equipped in an existing laboratory for chemical analysis. By integrating an acquisition device or the like on a small space, most of the process by the hands of the experimenter can be processed by an automated system by a micro robot. Accordingly, an automatic diagnosis system can be provided that can eliminate mistakes made by an experimenter and at the same time reduce the time required for chemical analysis.

1A is a plan conceptual view illustrating an automatic diagnostic apparatus according to an exemplary embodiment of the present invention, and FIG. 1B is a cross-sectional conceptual view taken along line II-II ′ of FIG. 1A;

2A and 2B are cross-sectional views taken along line II ′ of FIG. 1A to illustrate a preprocessor of the automatic diagnostic apparatus according to the embodiment of the present invention;

3A and 3B are cross-sectional views taken along line III-III ′ of FIG. 1A to illustrate a polymerase chain reaction chamber portion of an automatic diagnostic apparatus according to an embodiment of the present invention;

4A and 4B are cross-sectional views taken along the line II-II 'of FIG. 1A to illustrate the hybridization chamber portion of the automatic diagnostic apparatus according to the embodiment of the present invention;

Figure 5 is a cross-sectional view for explaining another use of the automatic diagnostic apparatus according to an embodiment of the present invention.

* Description of the symbols for the main parts of the drawings *

100: automatic diagnostic device 110: substrate

120: pretreatment unit 122: microtube

124: microtube stopper 130: polymerase chain reaction chamber

130r: polymerase chain reaction chamber cover 132: hot wire

140: hybridization chamber portion 140h: hybridization chamber

140r: hybridization chamber cover 150, 250: micro robot

155, 255: pipette tip 160: control unit

170: pipette tip provider 172: solution provider

174: solution waste 176: pipette tip waste

178: microtube providing unit 180: light source

185 lens 190 imaging device

210a: lower substrate 210b: upper substrate

212 antibody 240r rubber cover

Claims (20)

A pretreatment unit provided in the substrate for extracting DNA from the sample; A polymerase chain reaction chamber provided in the substrate for amplifying the DNA and covered with a first rubber plate and sealed; A hybridization chamber provided in the substrate to hybridize the amplified DNA, the hybridization chamber sealed by being covered with a transparent second rubber plate; And A micro robot connected to the substrate for moving the sample or the solution containing the DNA to the pretreatment unit, the polymerase chain reaction chamber, and the hybridization chamber, The micro robot is programmed to perform a pipetting function and a dry air supply function for transferring, injecting, inhaling and discarding the solution, and The first and second rubber plates have a thickness in the range of 0.1 to 2 mm, with a restoring force close to 100% for maintaining the sealed state of the polymerase chain reaction chamber and the hybridization chamber, respectively, for the pipetting function of the microrobot. An automatic diagnostic apparatus having a. The method of claim 1, And a control unit for controlling the preprocessor and the micro robot. The method of claim 1, And a light source and an imaging device respectively provided above and below the substrate in an area provided with the hybridization chamber. The method of claim 3, wherein And the light source is a light emitting diode. The method of claim 3, wherein And the imaging device is a CMOS image sensor or a CD image sensor. The method of claim 1, And the substrate is one substrate selected from a silicon substrate, a glass substrate, and a printed circuit board. The method of claim 6, The substrate has an automatic diagnostic apparatus, characterized in that the diameter or width having a size in the range of 20 ~ 30cm. The method of claim 1, The pretreatment unit is an automatic diagnostic device characterized in that it has a vortex function and a centrifugal function at the same time. The method of claim 1, The polymerase chain reaction chamber is an automatic diagnostic device, characterized in that the form of a lab-on-a-chip. The method of claim 9, The polymerase chain reaction chamber is an automatic diagnostic device, characterized in that the chamber capable of temperature control. The method of claim 10, The polymerase chain reaction chamber is an automatic diagnostic device, characterized in that the temperature is controlled by a heating wire provided inside the substrate. delete delete The method of claim 1, And said hybridization chamber is a microarray chip. 15. The method of claim 14, The hybridization chamber is characterized in that the automatic temperature control chamber. The method of claim 15, The hybridization chamber is an automatic diagnostic device, characterized in that the temperature is controlled by the internal heating wire electrically connected to the substrate. delete delete delete delete

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