KR20050014797A - Bio-Disc, Bio-Driver apparatus, and Assay method using the same - Google Patents

Abstract

PURPOSE: A bio disc, a bio driver apparatus and an analysis method are provided to read a bio disc as well as a conventional optical disc and to make a remote diagnosis easy to be performed by connecting to the internet. CONSTITUTION: The bio disc(100) comprises an upper base(1), a middle base(2) and a lower base(3). The three bases(1,2,3) all form channels, allowing a fluid to flow, and chambers, storing a buffer solution. Thin film type circular column magnets(70a,70b,70c) are independently open or closed by electric magnets. The bio disc includes a preparation chamber(130) for preparing for DNA samples or serum injected by a pipette(120). A PCR(Polymer Chain Reaction) chamber(131), an analysis site(132) and a trash chamber(133) connect to the preparation chamber(130) in the bio disc(100). Other chambers(140,141,142,143) for storing buffer solutions and various enzymes needed in a hybridization process, are formed.

Description

Bio disk and bio driver device and analysis method using them {Bio-Disc, Bio-Driver apparatus, and Assay method using the same}

The present patent application is a pre- filed domestic patent application "nucleic acid hybridization method and apparatus using a cleavage method that specifically reacts to a specific sequence of complementary double bonds of nucleic acid and oligonucleotide" (2001,01,27 10-2001- 0003956) and PCT application "nucleic acid hybridization method and apparatus using a cleavage technique that specifically reacts with complementary double or single strands of nucleic acid and oligonucleotide" (2002.01.27 PCT / KR02 / 00126) and domestic patent application " Thin Film Valve Apparatus and Control Method Using Micro Beads "(2001,05,31, 10-2001-0031284) and PCT Application" Film Valve Apparatus and Control Method Using Micro Beads "(2002,05,31, PCT / KR02 / 01035).

The above-listed invention provides a nucleic acid hybrid analysis method and apparatus using a cleavage technique that specifically reacts only with complementary double strands or single strands or double strands of a specific sequence that can be used in a quantitative and qualitative analysis apparatus. In addition to providing the present invention, an object of the present invention is to provide a microvalve for controlling the flow of a fluid essential for a lab on a chip.

In addition, the pre-applicability of the present invention is that the restraint signal element or departure signal element on the analysis device is read by a detector combined with a transducer including an optical, electrochemical, capacitance, or impedance measuring device, and the read information is digitalized in computer software form. The purpose of the present invention is to provide a remote diagnosis apparatus that can be conveniently transmitted to both doctors and patients by being transmitted and received by existing communication networks such as the Internet. In addition, in the above-mentioned prior invention, an interdigitated array using an escape signal and a restraint signal is illustrated as an embodiment of a detector coupled with a transducer including an electrochemical, capacitance or impedance measuring device.

The present invention relates to an apparatus or method for optical or non-optical bio discs and biodrivers that can be used in various diagnostic analysis apparatuses, nucleic acid hybrid analysis apparatuses, and immunological verification apparatuses.

Until recently, most clinical diagnostic analytical devices for detecting small amounts of analytes in fluids have been designed for efficiency and economics by designing devices for multiple sample preparation and automated reagent addition and for analyzing large numbers of test samples in parallel or in series. Improvements were made. Often these automated reagent preparation devices and automated multiple analyzers are integrated into a single device. This type of clinical analyzer can accurately and automatically perform hundreds of assays with a small sample and reagents in less than an hour.

However, these analyzers are expensive and only centralized laboratories and hospitals can purchase them. This necessitates the transport of samples to laboratories and hospitals and often leads to the inability to quickly analyze urgent samples.

Therefore, in order to overcome these problems, there is an urgent need for an inexpensive and easy-to-use clinical analysis device. In other words, there is an urgent need for automated clinical test devices suitable for use by the patient or at the patient's home without the need for a dedicated detector.

<Optical Disc and Non-Optical Bio Disc>

A standard compact disc is formed from a 12 cm polycarbonate substrate, reflective metal layer and protective lacquer coating. The format of CDs and CD-ROMs is described by the ISO 9660 industry standard.

The polycarbonate substrate is an optical quality transparent polycarbonate. In standard printed or mass replicated CDs, the data layer is part of a polycarbonate substrate and the data is engraved in a series of pits by a stamper during the injection molding process. During this injection molding process, molten polycarbonate is injected into the mold under high pressure and then cooled so that the polycarbonate has a mirror image of a mold or "stamp" or "stamp" and a pit representing binary data on the disk substrate is produced and mastered. It is held by the polycarbonate substrate as a mirror image of the pit of the stamper generated during the mastering process. The stamping master is usually glass.

Conventional optical discs (e.g., music CDs, CD-Rs, game CDs, DVDs, etc.) read sensors detect the presence or absence of a pit by the differential reflectance of the physical pit or by the refractive index of the dye layer. It is the well-known technique of the said supplier.

In the conventional optical disk, the read method by the physical pit on the CD is that the recess of the CD is from 1/8 to the wavelength of the laser incident light. As a depth, the recess causes a destructive interference in the reflected beam, corresponding to a bit of "zero" value, and the flat area of the CD (convex) reflects the laser beam to provide a value of "1" to the corresponding bit of the detector. do.

In addition, a patent is disclosed in US Pat. No. 5,580,696 for the material of the dye layer for providing a reading method by refractive index characteristics in the optical disk. In addition, the optical disk is read by a laser scan while rotating the disk by the rotation axis.

However, such an optical disk has a disadvantage in that the optical transmitting unit and the optical receiving unit are both modular together in a conventional optical pickup device, and thus, because of the additional optical reflecting path, the optical traveling path is long and the sensitivity of the optical receiving unit is inferior. . In addition, conventional optical disks have the disadvantage of requiring optical pickup device movement to a predetermined location and disk rotation for laser scanning information reading. In addition, the bioanalytical device using the optical disk and the optical scanning method has a problem that is difficult to read with a conventional optical pickup device due to the bending of the probe.

Optical "Confocal compact scanning optical microscope based on compact disc technology" (199, Vol. 30, No, 10, Applied Optics), "Gradient-index pobjectives for CD applications" "(April, 1987, Vol 26, Issue 7, Applied Optics) and" Miniature scanning optical microscope based on compact disc technology "(Proc. Soc. Photo-opt.instrument Eng. 110, page 1139-1169, 1989) It is announced in.

In addition, US patents "Centrifugal Photometric Analyzer" (4,279,862, publication date Jul.21, 1981) and "Reaction Tube Assembly for Automatic Analyzer" (4,141,954, publication date FEB.27, 1979).

In addition, as a device for forming a fluid film on the surface of the disc using a centrifugal force, the sample injected into the inlet on the disc, the European patent "Disc for centrifuge" (GB1075800, publication date 1967.07.12) and the fluid injected into the inlet on the disc European Patent "Separating Disks for centrifuge" (3,335,946, April 12,1965) is disclosed as a device for separating a sample while moving the sample to a channel and a chamber using centrifugal force.

Also disclosed is a US patent "disc centrifuge photosedimentometer" (4,311,039, Jan. 19,1982) as a device for chemical analysis by centrifugal force and optical measurement on disc.

However, these are not suitable for LabOn a Chip configuration because they have the disadvantage of not fully automating diagnosis and analysis.

On the other hand, the reading of the bio-disc of the present invention is different from the reading method (differential reflection type) based on the refractive index characteristic of the physical layer of the conventional optical disc or the dye layer (light transmissive type); Or capacitance and impedance measurements; Alternatively, an electrochemical detection method is used, and a chamber for storing the fluid or a flow path for moving the fluid is arranged on the bio disc. In the present invention, such a bio-disc is referred to as a non-optical bio-disc in comparison with a "differential reflective optical disc" by conventional laser scanning. The optical disc is impossible to apply the optical detection technique by the transmission and non-transmission of the above light by the reflective metal layer and the dye layer.

In the context of the present invention, non-optical biodisc is a light transmission, capacitance and impedance measurement in reading an analysis site or reading an analysis site by a non-scanning method of a laser beam. Or a bio-disc using an electrochemical detection method or a method in which the disc reads an analysis site without rotation.

In the specification of the present invention, an optical bio disc means a bio disc which is read by differential reflection of laser scanning using a conventional optical pickup device.

The polycarbonate art substrate can be modified and modified by a thin film type analyzer for diagnosing and detecting a small amount of a substance in a fluid such as a bio disc, in which case a pit and dye layer on the surface of the disc during the injection molding process. Instead, a chamber may be formed that can store channels and buffer solutions through which fluid can flow. There is a need for a microvalve capable of smoothly controlling the flow and flow rate of the fluid in the flow path formed in such a thin film and electronic control for controlling them.

In addition, the present invention may be formed on the silicon wafer to form a channel (channel) for storing the fluid (flow channel) and the buffer (buffer solution) through the semiconductor process, the fluid of the flow path formed on the silicon wafer Electronic circuits for smoothly controlling the flow and flow rate of the wafers also provide highly integrated bio-discs on silicon wafers.

SUMMARY OF THE INVENTION The present invention has been made in view of the above-described problems, and an object of the present invention is to provide an apparatus and method for a bio-disc and an optical driver using optical and non-optical discs capable of remote diagnosis, sample diagnosis, nucleic acid analysis, and immunological verification. There is this.

In order to achieve this object, the bio-disc of the present invention is controlled by a control disc installed in the bio-driver. The control disc includes a control unit for supplying various control signals for controlling the bio disc, and is always connected to the bio driver device except for the integrated bio disc and the integrated bio disc. As a result, only bio-discs can be freely loaded or ejected into bio-drives.

In addition, the control disc determines whether the currently loaded disc is a normal optical disc or a bio disc such as a music CD, a CD-RW, a game CD, a DVD, and the like. It operates according to the method, and in the case of a bio disc, various control signals for Lab On a Chip on the bio disc are transmitted to the bio disc.

It is another object of the present invention to provide an integrated bio-disc device and method in which the bio-disc and the control disc are combined into a single disc.

Another aspect of the present invention is to provide an integrated bio-disc device and method having a configuration in which the integrated bio-disc and the conventional optical disc are combined into a single disc. In addition, the optical disc portion of the integrated bio-disc may not only be read by the bio driver, but also may be read and reproduced by an optical driver or a CD driver for an existing optical disc, thereby having compatibility.

In other words, the music on the optical disc surface of the integrated bio-disc can be enjoyed through a bio driver, or can be enjoyed through a conventional optical driver or a CD driver.

Another aspect of the present invention is to provide a bio-disc for PCR and a bio-disc for electrophoresis.

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a non-optical bio disc, a bio disc device including an optical or non-optical bio disc, a bio driver device, and an analysis method using the same. The present invention relates to a bio driver device including a bio disc on which a Lab On a Chip including a scientific verification device and the like is designed, and a control disc including a control unit for controlling the bio disc, and an analysis method using the same.

1A and 1B are cross-sectional views of a bio disc showing a valve device using micro beads installed in the bio disc.

FIG. 1C is an embodiment of a bio disc on which Lab On a Chip is disposed and a control disc for controlling the same.

1D is a cross-sectional view of an example showing the structure of a conductor arm.

FIG. 1E illustrates an embodiment in which the alignment of the connecting groove and the conductor arm is automatically aligned.

1F is an embodiment of a bio driver device in which a control disk is built.

FIG. 1G is another embodiment of a bio disk on which a Lab On a Chip is disposed and a control disk 200 for controlling the bio disk.

1H to 1I are one embodiment of an auxiliary substrate for supplying power to the control disk by frictional contact between the brush and the rotating electrode of FIG. 1G.

1J is yet another embodiment of a bio driver device having a built-in control disk.

2A-2B illustrate one embodiment of an integrated bio disc 700 and a bio driver.

FIG. 2C is an embodiment implemented by an electrochemical, capacitance and impedance measurement device using an interdigitated array electrode.

2D is one embodiment of an integrated biodisc.

3A is an embodiment of a bio-disc detection method.

3B is yet another embodiment of notifying the central controller that the loaded disc is a bio disc.

4A to 6D are various embodiments implemented by the optical measuring device.

7A to 7G illustrate an embodiment of an electrochemical detection device or a capacitance and impedance measurement device.

8A-8F illustrate one embodiment of a biodisc of the present invention.

Figures 9a and 9b is another embodiment of a bio-disk that can be combined with the preparation process, PCR process and electrophoresis.

10A to 10B illustrate an example of simultaneous placement on a bio-disc to simultaneously analyze an immunoassay (immunological verification device) and a nucleic acid probe reaction assay.

11A and 11B illustrate an embodiment of an appearance of a bio driver device.

Hereinafter, the configuration of the present invention with reference to the accompanying drawings in more detail.

The valve for controlling the flow or flow of the fluid of the Lab On a Chip installed on the bio-disc of the present invention is a micro-bead that moves by a magnetic force formed by an electromagnet installed on the upper and / or lower side of the bio-disc. It is provided inside the disc to open and close the flow path. This is a pre-applied domestic patent "thin film valve device and control method using micro beads" (10-2001-0031284) and PCT application "thin film valve device and control method using micro beads" (2002,05,31, PCT / KR02 / 01035).

In a preferred embodiment of the present invention, the microbeads comprise materials such as, for example, magnet balls, ferromagnetic metal particles, phase magnetic particles, semi-magnetic particles, stainless steel balls, and the like. In addition, the micro beads may be formed of solid metal, plastic, glass beads, or the like, and have a metal coating thereon. The metal sphere may also be an alloy. In addition, the micro-bead can be charged, in this case using an electrode plate disposed on the upper and lower surfaces of the bio-disc instead of the electromagnet. Charged beads open or close the pores depending on the direction of the voltage applied to the electrode plate. The microbeads have a diameter in the range of 1 μm to 1 mm, preferably 100 μm to 500 μm. As the size of the beads increases, the contact surface increases, thereby increasing the reliability of opening and closing. In addition, in the present invention, the micro bead may be spherical but thin film cylindrical permanent magnet or thin film rectangular permanent magnet is preferred.

The electromagnet may be an air core or a non-magnetic core. The diameter of the winding for the electromagnet is preferably 0.01 mm to 0.1 mm.

1A and 1B illustrate an example of a cross section of a bio disc showing a valve device using a thin film cylindrical permanent magnet installed in the bio disc 100.

The bio disc 100 is composed of an upper substrate 1, an intermediate substrate 2, and a lower substrate 3, each of which includes a channel and a buffer through which fluid can flow to the substrate surface during the injection molding process. A plurality of holes for connecting the passage and a chamber for storing a buffer solution are formed. They are closely attached to each other to form a single bio-disc 100 body.

FIG. 1A illustrates a case in which the oil hole 10 is blocked by the thin film cylindrical permanent magnet 70a and the oil passage 16a is blocked, and FIG. 1B shows that the oil hole 10 is opened to connect the oil passage 16a. In order to close the oil hole 10 to block the flow path as shown in FIG. 1A, the upper electromagnet 4a and the lower electromagnet 5a apply power in a direction in which the thin film cylindrical permanent magnet 70a is pulled downward. That is, a repulsive force is applied between the upper electromagnet 4a and the thin film cylindrical permanent magnet 70a, and a power is applied between the lower electromagnet 5a and the thin film cylindrical permanent magnet 70a so as to generate a attraction force. On the contrary, in order to connect the flow path by opening the hole 10 as shown in FIG. 1B, the upper electromagnet 4a and the lower electromagnet 5a apply power in a direction in which the thin film cylindrical permanent magnet 70a is pulled upward. That is, a power source is applied between the upper electromagnet 4a and the thin film cylindrical permanent magnet 70a to generate an attraction force, and a power source is applied between the lower electromagnet 5a and the thin film cylindrical permanent magnet 70a to generate a repulsive force.

The electromagnets 4a and 5a of the present invention are preferably air core thin film electromagnets or bobbinless coils. In addition, in the present invention, since a narrow channel 16a is formed in the disk for fluid movement, an exhaust port 12 is formed in the upper substrate 1 so that the fluid can flow smoothly without pressure. have.

1c shows a chamber for storing various buffer solutions for analysis, a chamber for carrying out various chemical processes, a flow path for moving the treated fluid and buffer solutions, and the valve devices for controlling the opening and closing of these flow paths. An embodiment of the bio-disc 100 having an included Lab On a Chip and a control disc 200 for controlling the same.

The bio-disc 100 of the present invention may be selected from various materials such as plastic, PMMA, glass, mica, silica, silicon wafer materials, and the like. However, plastics are preferred for economic reasons and ease of processing. Plastics that can be used include polypropylene, polyacrylates, polyvinyl alcohols, polyethylene, polymethylmethacrylate, and polycarbonates. Polypropylene and polycarbonate are preferred and polycarbonate is most preferred.

The bio disc 100 comprises an upper substrate 1, an intermediate substrate 2, and a lower substrate 3, each of which is a channel and a buffer through which fluid can flow on the substrate surface during the injection molding process. A plurality of holes for connecting the passage and a chamber for storing a buffer solution are formed.

They are closely attached to each other to form a body of one bio disc 100, which is

Domestic patent application "thin film valve device and control method using micro beads" (2001,05,31, 10-2001-0031284) and PCT application "thin film valve device and control method using micro beads" (2002,05,31, PCT / KR02 / 01035).

The control disk 200 may be selected from a variety of materials, such as plastic, PMMA, glass, mica, silica, silicon, the material of the printed circuit board (PCB). However, in the present invention, PCB materials and silicon wafer materials are preferred for ease of circuit design.

The bio disc 100 is formed by laminating an upper substrate 1, an intermediate substrate 2, and a lower substrate 3. The thin-film cylindrical magnets 70a, 70b and 70c are independently opened and closed controlled by the magnetic force formed by the electromagnets 4a and 5a, 4b and 5b, 4c and 5c, respectively. 120 represents a pipette or dice for injecting a sample, 121 represents a sample inlet, 170 represents a disk center void, 171a represents an interface for connecting to the control disk 200, and a control signal is supplied to the bio disk 100. A plurality of control signal connection unit 173 for and a power connection 33a for power supply. Surfaces of the connecting portions 173 and 33a are formed of connecting grooves 33 coated with a conductor.

Reference numeral 130 denotes a preparation chamber including a preparation process for preparing a DNA sample from blood or cells or a serum from blood by DNA (Reverse Transcription) from RNA. 131 is a PCR chamber for PCR (Polymer Chain Reaction) process, and 132 is a chamber for hybridization process or antigen antibody reaction, and a capture probe for analyzing and diagnosing DNA amplified by the PCR process. ) Or an immunoassay is an assay site attached to the substrate in the form of an array, and 133 is a Trash chamber for collecting debris generated by the cleaning process.

Reference numeral 140 denotes a chamber including a buffer solution containing various enzymes including polymerase and primers necessary for the PCR process, and 141, 142 and 143 denote chambers containing various enzymes necessary for the hybridization process. .

The opening and closing control of the valve at the start point and the end point of each of the processes (prep process, PCR process, hybridization process and antigen antibody reaction, washing process) are performed on electromagnets 4a and 5a provided on the upper and lower sides of the thin film cylindrical magnet. 4b and 5b, and 4c and 5c), and fluid movement is caused by centrifugal force by the rotational force of the disk.

In addition, power is supplied to the control unit 63 on the control disk 200 and the contactless interface 107 which is a wireless transmission, transmission or reception device by frictional contact between the control disk 200 and the brushes 108 and 109.

An annular electrode plate 223 for friction contact between the brushes 108 and 109 is provided on the upper plate of the control disk 200. In addition, the control signal and the power of the control unit 63 are connected to the conductor arm 13 by a pattern of a circuit connected to the interface unit 171b of the control disk 200.

Power supply and control signal transmission from the control disk 200 to the bio-disc 100 is a plurality of conductor arms 13 in close contact with the control signal connector 173 and the power connector 33a which are surface-coated with a conductor. Made by them. That is, the signal transmission is made in the form of a conductor arm 13 and the connecting groove 33, which serves as a connector between the bio-disc 100 and the control disk 200. When the conductor arm 13 starts to rotate the disk, the conductor arm 13 is engaged with the connecting groove 33 by compression bonding between the control disk 200 and the bio disk 100 to rotate simultaneously.

The power supplied by the brushes 108 and 109 is connected to the bio-disc 100 through a power connection 33b on the control disk 200 and a power connection 33a on the conductor arm 13 and the bio-disc 100. Supplied to.

In addition, the connecting grooves 33 on the bio-disc 100 connected to the conductor arm 13 are again connected to the circuit pattern on the bio-disc to supply various control signals and power necessary for each section of the bio-disc 100. .

Reference numeral 188 is a card IC, which contains protocols for Lab On a Chip, analysis algorithms, standard control values for reading and position information on analytical site, bioinformatics information, and self diagonasis. do. It can also contain biometric driver device software and patient education information for clinical analysis and can be modified. It can also include web sites and links to connect with specialists and hospitals based on the results of the diagnosis. In addition, personal encryption information can be stored so that others can not be used without permission.

The card IC 188 is preferably embedded with a RAM or ROM in the form of a smart IC card. The card IC 188 information is provided to the central control unit through wireless transmission and reception, and is utilized for remote diagnosis and analysis and personal encryption.

1D is a sectional view of an example showing the structure of the conductor arm 13.

During the start of the rotation of the disk, when the close contact between the control disk 200 and the bio disk 100, one end of the conductor arm 13 can be smoothly inserted into the connecting groove 33, the control disk 200 It is fixedly connected to the interface unit 171b of the () and the spring (13c) is built-in connection inside the conductor arm (13). Reference numerals 13a and 13b constitute a conductor arm, and an end portion of 13b is inserted into the connecting groove 33 and an end portion of 13a is fixed to the interface portion 171b. The spring 13c and the 13a and 13b of the conductor arm are interconnected by 13d to make the conductor arm 13 elastic.

FIG. 1E illustrates an example in which the connecting groove 33 of the connecting parts 173 and 33a and the conductor arm 13 are automatically aligned when the conductor arm 13 is in close contact with the connecting arm 33. Form a spiral. The conductor arms 13 are fixedly connected to the interface portion 171b of the control disk 200 at a position corresponding to the helical connecting groove 33 in one-to-one correspondence, so that these connecting grooves 33 are in close rotation. Are electrically connected).

170 of the bio disc 100 represents a disc center void, and includes a plurality of control signal connection units 173 for supplying control signals around the center gap of the bio disc 100 and a power connection unit 33a for power supply. do. Surfaces of the connection portions 173 and 33a have connection grooves 33 coated with a conductor, and the connection grooves 33 provide circuit patterns for connecting and supplying the power and control signals to the respective parts on the bio-disc 100. Have (888).

FIG. 1F illustrates an embodiment of a bio driver device in which the control disk 200 for controlling the bio disk 100 is driven.

Brushes (109, 108) for supplying power supply to the control unit (63) on the rotating control disk (200); A power supply device 110 for supplying power thereto; The 300 is the body supporting the bio driver. A circuit board 140 is jointly fastened to the bio drive body 300 at the bottom of the bio drive, and the central control unit 101 and the storage or output device 111 for controlling the bio driver on the circuit board 140. Is designed to be placed on the circuit board 140. The central control unit 101 not only controls the motor 102 to rotate or stop the disks 100 and 200, but also controls the movement of the optical pickup device 103, and controls the disk 200 when the disk starts to rotate. And the bio-disc 100 to be in close contact rotation with the connecting groove 33 by using the conductor arm 13. At this time, the lower rotor 105 is in close contact with the bottom of the bio-disc 100 rotates. The upper rotor 104 also has a plurality of connectors 143 that are fixedly connected to the control disk 200. The upper rotor 104 has a rotating groove 111 on the outside to allow free idling over the bio driver body 300.

In addition, the central controller 101 determines whether the disc currently loaded in the bio driver is a conventional optical disc (eg, a music CD, CD-R, game CD, DVD, etc.) or a bio disc. In the case of an optical disc, the content read from the disc is transferred from the optical pickup device 103 to the storage device or output device 111, or the content to be written is sent to the optical pickup device 103, and read / write (Read / Write). A normal operation for an optical disk, such as providing various control signals required for each part, and in the case of a bio-disk, various control command signals for controlling a Lab On a Chip in the non-contact interface located in the control disk 200. (106, 107) or through the card IC (188) to the control unit (63).

The control unit 63 of the control disk 200 receiving the control command supplies various control signals for controlling the Lab On a Chip on the bio-disc 100 through the conductor arm 13 or the cart IC 188. ) Supplies various control signals for controlling the Lab On a Chip on the bio-disc 100.

In addition, the control unit 63 reads the analysis site 132 obtained by the converter arm 13 through the conductor arm 13 by a transducer including an optical, non-optical, electrochemical, capacitance or impedance device on the bio disc 100. To the external central control device 101 or the storage device 111 via an infrared interface or an optical interface or a wireless interface, which are the contactless interfaces 106 and 107, or the bio-disc 100 by the card IC 188. Reading result of the analysis site 132 obtained by a transducer including an optical, electrochemical, capacitance or impedance device on the Send to).

At this time, the reading of the analysis site 132 by the transducer including the optical transmission measuring device is made by the optical analysis reading device (99a, 99b) separate from the optical pickup device (103). That is, information reading on a conventional optical disc is performed by the optical pickup device 103, and information reading of the analysis site 132 of the bio-disc, which is a non-optical disk, is performed by a separate optical analysis. Made by the reading devices 99a and 99b. 106 and 107 are receivers or transmitters or transceivers for contactless interfaces, respectively. In addition, the central control apparatus 101 may transmit a control command to the controller 63 through the contactless interface.

The non-contact interfaces 106 and 107 are made by an infrared sensor in the case of an infrared interface, and are made by a photo sensor in the case of an optical interface. The air interface is also made by stripline antennas and their demodulation device.

Reference numeral 188 denotes a card IC with a built-in memory, which is a protocol for a lab on a chip, an analysis algorithm, standard control values for reading and position information on an analysis site, bioinformatics information, and self-diagnosis (self diagonasis). ), And the relevant information. It can also contain device driver software and patient education information for clinical analysis and can be modified. It can also include web sites and links to connect with specialists and hospitals based on the results of the diagnosis. In addition, personal encryption information may be stored so that others cannot use it without permission.

The card IC 188 is preferably RAM or ROM including a smart IC card function. The card IC 188 information is provided to the central control unit 101 through wireless transmission and reception, and is utilized for remote diagnosis and analysis and personal encryption.

The output device 111 is preferably a USB (Universal Serial Bus) or IEEE1394.

1g shows a chamber for storing various buffer solutions required for analysis, a chamber for performing various chemical processes, a flow path for moving the treated fluid and buffer solutions, and the cylindrical magnets for controlling the opening and closing of these flow paths. Another embodiment of the bio-disc 100 in which the included Lab On a Chip is disposed and the control disc 200 for controlling the bio-disc 100 are included.

The bio disc 100 is formed by laminating an upper substrate 1, an intermediate substrate 2, and a lower substrate 3. Thin-film cylindrical magnets 70a, 70b, 70c are independently opened and closed controlled by magnetic forces formed by electromagnets 4a, 4b, 4c disposed on the control disk 200, respectively. 120 denotes a pipette or dice for injecting a sample, 121 denotes a sample inlet, 170 denotes a disk center pore, and 130 denotes a DNA sample from blood or cells, or DNA sample by RT (Reverse Transcription) from RNA. Or a preparation chamber including a preparation process for preparing serum from blood, 131 is a PCR chamber for a polymer chain reaction (PCR) process, and 132 is a hybridization process or an antigen. As a chamber for antibody reaction, a capture probe or immunoassay for analyzing and diagnosing DNA amplified by the PCR process is an assay site attached to a substrate in an array form, and 133 is a cleaning process. Trash chamber to collect the generated debris.

Reference numeral 140 denotes a chamber including a buffer solution containing various enzymes including polymerase and primers necessary for the PCR process, and 141, 142 and 143 denote chambers containing various enzymes necessary for the hybridization process. .

The opening and closing control of the valve at the start point and the end point of each process (prep process, PCR process, hybridization process and antigen antibody reaction, washing process) are performed on the electromagnets 4a, 4b, It is made by the power control applied to 4c), and the fluid movement is by centrifugal force by the rotational force of the disk.

Reference numeral 55 is a rotary electrode fixedly connected to the motor 102, the surface is coated with a conductive material.

Reference numeral 110 denotes a DC voltage to the power supply unit. The negative (-) terminal is connected to the motor 102 body and grounded. A prus (+) terminal is connected to the brushes 108 and 109 to supply a prus (+) voltage to the rotating electrode 55.

The frictional contact between the rotary electrode 55 and the brushes 108 and 109 supplies positive (+) power to the control unit 63 on the control disk 200 and the radio transmitting or receiving or receiving device 107, and negatively. The negative power is supplied to the control disk 200 through the motor shaft 57 and the auxiliary substrate 201 connected to the grounded motor 102.

Reference numerals 240 and 241 denote power terminals connected to the positive (+) power and the negative (-) power, respectively.

Reference numeral 181 denotes a turn table for placing the bio disc 100 or an ordinary optical disc (eg, a music CD, a CD-R, a game CD, a DVD, etc.). Is loaded into the turntable. On the other hand, the control disk 200 is fixedly coupled to the turn table 181. There is an interval 182 of about 1 mm between the control disk 200 fixedly coupled to the turn table and the bio disk loaded on the turn table.

Reference numeral 188 denotes a memory-embedded card IC, which is a protocol for a lab on a chip, an analysis algorithm, standard control values for reading and position information on an analysis site, bioinformatics information, and self diagonasis. It includes. It can also contain biometric driver device software and patient education information for clinical analysis and can be modified. It can also include web sites and links to connect with specialists and hospitals based on the results of the diagnosis. In addition, personal encryption information can be stored so that others can not be used without permission.

The card IC 188 is preferably in the form of a smart IC card. The card IC 188 information is provided to the central control unit through wireless transmission and reception, and is utilized for remote diagnosis and analysis and personal encryption.

Reference numerals 240a and 241a are surface-coated with a power connector on the bio-disc 100, respectively, and are connected to the power terminals 240 and 241 to supply power to the bio-disc 100.

1H to 1I illustrate an embodiment of an auxiliary substrate 201 for supplying power to the control disk 200 by frictional contact between the brushes 108 and 109 and the rotating electrode 55 of FIG. 1G. The auxiliary substrate in the present invention is preferably a double-sided PCB.

FIG. 1H shows the top side of the auxiliary substrate and FIG. 1I shows the bottom side of the auxiliary substrate. 91 is the ground pattern and 92 is the positive power pattern.

In FIG. 1H the motor 102 is grounded and the motor shaft 57 which is connected to the motor is also grounded as a result. In the process of inserting and fastening the motor shaft 57 into the hole 203 of the auxiliary substrate 201 (assembly process), the ground pattern 91 becomes a negative power supply by itself.

In addition, the ground pattern 91 is connected to the ground pattern 91 on the bottom surface of the auxiliary substrate 201 by a through hole (via).

1I illustrates the bottom surface of the auxiliary substrate in one embodiment for supplying positive power to the auxiliary substrate 201. The positive power supplied by the power supply unit 110 supplies a positive voltage to the rotating electrode 55 by frictional contact with the brushes 108 and 109, and the end of the rotating electrode 55 It is electrically connected to the positive power pattern 92 formed on the lower surface of the auxiliary substrate 201 to supply positive power.

The positive power of the positive power pattern 92 on the auxiliary substrate 201 and the negative power of the ground pattern 91 are electrically connected to the control disk 200 to supply power to the control disk 200.

FIG. 1J illustrates an embodiment of a bio driver device in which the control disc 200 of FIG. 1G is fixedly coupled to the turn table 181 to control the bio disc 100 of FIG. 1G.

The positive power and the negative power on the control disk 200 are connected to and supplied to the bio-disc 100 through the conductor arm 13 illustrated in FIG. 1D. One end of the positive power supply terminal 240 and the negative terminal 241 composed of the conductor arm 13 is fixedly connected to the positive power supply and the negative power supply of the control disk 200; When the other end portion is loaded with the bio-disc 100, the bio-disc 100 is closely connected to the power connectors 240a and 241a which are surface-coated with a conductor on the bio-disc 100.

Brushes 109 and 108 for supplying power to the control unit 63 on the rotating control disk 200; A power supply device 110 for supplying power thereto; The 300 is the body supporting the bio driver. A circuit board 140 is jointly fastened to the bio drive body 300 at the bottom of the bio drive, and a central control unit 101 for controlling the bio driver on the circuit board 101 and a storage device or an output device 111 are provided on the circuit board. The central control unit 101 controls not only the motor 102 for the rotation or stop of the disks 100 and 200, but also the movement of the optical pickup device 103.

In addition, the central controller 101 determines whether the disc currently loaded in the bio driver is a conventional optical disc (eg, music CD, CD-R, game CD, DVD, etc.) or the bio disc 100. In the case of a normal optical disk, the contents read from the disk are transferred from the optical pickup device 103 to the storage device or output device 111, or the contents to be written are sent to the optical pickup device 103, and the playback / recording ( Normal operation for an optical disc, such as providing various control signals required for read / write to the respective parts, and in the case of a bio disc, various control command signals for controlling a Lab On a Chip to the control disc 200. It is sent through the contactless interface 106,107 or the card IC 188 located.

The control unit 63 of the control disk 200 received the control command supplies a variety of control signals for controlling the Lab On a Chip,

In order to control the opening and closing of the valve of the bio-disc, the opening and closing of the valve is controlled by controlling the power of the electromagnets 4a, 4b, and 4c on the control disc 200. The electromagnets 4a, 4b and 4c on the control disk 200 are very close to the bio disc 100 so that the repulsive force and attractive force can be effectively exerted on the thin film cylindrical magnets 70a, 70b and 70c embedded in the bio disc. have. There is a height interval 182 of about 1 mm between the control disk 200 fixedly coupled to the turn table and the bio disk loaded on the turn table.

106 and 107 are receivers or transmitters or transceivers for contactless interfaces, respectively.

The results of reading the analysis site 132 obtained by a transducer including an optical, electrochemical, capacitance or impedance device on the bio disc 100 may be read by an infrared interface or optical interface, which is the contactless interface 1015, 107. optical or electrochemical on the bio-disc 100 by a card IC 188 embedded in the bio-disc 100 or sent to an external central controller 101 or storage 111 via an interface or a wireless interface. The result of the reading of the analysis site 132 obtained by the converter including the capacitance or the impedance device is transmitted to the external central control device 101 or the storage device or the output device 111 by the wireless transmission / reception means.

2A to 2B illustrate a case in which the control disk 200 and the bio disk 100 are combined to constitute one integrated bio disk 700. 700a represents a bio disc portion of the integrated bio disc and 700b represents a control disc portion of the integrated bio disc.

In this case, the integrated bio disc 700 is preferably a silicon wafer material.

The silicon wafer material is a monolithic integrated circuit (IC) including the controller 63, the card IC 188, the non-contact interface 107, the electrode plate or electromagnet for controlling the valve, and various circuit patterns on the silicon wafer. Not only is the integrated circuit design easy to configure, but the chamber and channel formation can be easily implemented by photolithography and etching processes.

Integrated circuit design, photolithography and general etching processes on wafers by these semiconductor processes are well known in the art.

The integrated bio-disc 700 is composed of an upper substrate (1), an intermediate substrate (2) and a lower substrate (3), and the substrates have flow channels (fluids) through which the fluid can flow by photolithography and general etching processes, and A hole for connecting the passages with the chambers 130, 131, 132, 133, 140, 141, 142 and 143 capable of storing a buffer solution is formed. Brushes 109 and 108 for supplying power supply and annular electrode plates 223 for frictional contact of the brushes 108 and 109 are provided in the control disk portion 700b of the integrated bio-disc. 170 is the disc center void. 171a and 171b are interface units, and the control unit 63 of 700b includes a plurality of control signal connection units 173 for supplying control signals to valves and electronic circuits on 700a and power connection units 33a and 33b for power supply. . In the above embodiment, the interconnections of the connecting portions 173, 33a, 33b are interconnected by vias or through holes in the interface portions 171a, 171b, but the interface portions 171a, 171b must be located near the disc center void. It can be interconnected by vias or through holes at the required location on the disk, without having to be confined to the location. Via or through hole design is a well-known technique of those skilled in the art.

Reference numeral 555 is an opening made of a transparent material (eg, glass) for reading of the assay site 132 by an optional detector comprising the optical, electrochemical, capacitance or impedance device.

2B illustrates an embodiment of a bio driver device for controlling the integrated bio disc 700. The control unit 63 reads the results of the analysis of the analysis site 132 obtained by the transducer including the optical, electrochemical, capacitance, or impedance device using an infrared interface, an optical interface, or an wireless interface, which are the contactless interfaces 106 and 107. The analysis obtained by a transducer including an optical, electrochemical, capacitance or impedance device on an integrated bio-disc 700 via an external central control device 101 or storage 111 or by means of a card IC 188 The reading result for the site 132 is transmitted to the central control unit 101 or the storage device or the output device 111 by the wireless transmission / reception means.

106 and 107 are receivers or transmitters or transceivers for contactless interfaces, respectively. In addition, the central control apparatus 101 may transmit a control command to the integrated bio-disc 700 via the non-contact interface 106 or 107 or the card IC 188 to the controller 63.

The non-contact interfaces 106 and 107 are made by an infrared sensor in the case of an infrared interface, and are made by a photo sensor in the case of an optical interface. The air interface is also made by a stripline antenna and a demodulation device.

A brush (109,108) for supplying power to the control unit (63) on the unitary bio-disc (700) which is rotating and a power supply (110) for supplying power to the brush (109,108). The 300 is the body supporting the bio driver. A circuit board 140 is jointly fastened to the drive body 300 at the bottom of the bio drive, and a central controller 101, a storage device and an output device 111 for controlling the bio driver on the circuit board are provided on the circuit board. It is designed on 140. The central controller 101 not only rotates and stops the motor 102 when the integrated bio disc 700 rotates or stops, but also controls the movement of the optical pickup device 103, and rotates the integrated bio disc 700. At the start, the upper rotor 104 and the lower rotor (turn table) 105 are controlled to rotate in close proximity to the central void 170 of the integrated biodisc 700. In addition, the central controller 101 determines whether the optical disk is a normal optical disk (eg, music CD, CD-R, game CD, DVD, etc.) or an integrated bio-disc. The optical disk to the storage device or the output device 111 from the optical pickup device 103, or to send the contents to be written to the optical pickup device 103, and provide various control signals necessary for read / write to the respective parts. In the case of the integrated bio-disc, various control command signals for controlling the Lab On a Chip are transmitted through the contactless interface 106 or 107 or the card IC 188 located in the integrated bio-disc 700. At this time, the reading of the analysis site 132 by the transducer including the optical device is performed by the optical analysis reading devices 99a and 99b separate from the optical pickup device 103. That is, information reading on a conventional optical disc is performed by the optical pickup device 103, and information reading of the analysis site of the integrated bio-disc, which is a non-optical disk, is performed by a separate optical analysis reading device. (99a, 99b).

That is, information reading on a conventional optical disc is performed by the optical pickup device 103, and information reading of the analysis site of the integrated bio-disc 700, which is a non-optical disk, is performed by a separate electrochemical detector, or Capacitance and impedance measurements are made by the device.

Reference numeral 188 denotes a card IC, which includes protocols for the Lab Oh a Chip, analysis algorithms, standard control values for reading and position information on the analysis site, bioinformatics information, and self diagonasis. do. It can also contain device driver software and patient education information for clinical analysis and can be modified. It can also include web sites and links to connect with specialists and hospitals based on the results of the diagnosis. In addition, the opening encryption information can be stored, so that others can not be used without permission.

The card IC 188 is preferably one having RAM or ROM. The card IC 188 information is provided to the central control unit 101 through a wireless transmission and reception means, and is utilized for remote diagnosis and analysis and personal encryption.

FIG. 2C illustrates an electrochemical, capacitance, and impedance measuring device using an interdigitated array to detect an analyte specific signal generated by the assay site 132 installed in the integrated bio-disc 700. Represents embodiments implemented by. This is a domestic patent application "nucleic acid hybridization method and apparatus using a cleavage technique that specifically reacts to a specific sequence of complementary double bonds of nucleic acid and oligonucleotide" (2001,01,27 10-2001-0003956) and PCT application " Nucleic acid hybridization methods and apparatus using cleavage techniques that specifically react to complementary double or single strands of nucleic acids and oligonucleotides "(2002.01.27 PCT / KR02 / 00126).

Reference numerals 371, 372, 373 and 374 denote a plurality of assay sites each having a cleavable signal element or a capture antibody having different assay specificities.

Reference numeral 271 denotes frequency generators for applying an AC signal having a certain bandwidth to the respective analysis sites. These generated alternating current signals are applied to the input terminals of the interdigitated array to measure the frequency response characteristics, thereby performing electrochemical or capacitance and impedance measurements of the respective analysis sites.

The frequency characteristics output from each analysis site are sequentially input to the control unit 63 by the multiplexer 68, and the electrochemical or capacitance and impedance of each analysis site are measured by the control unit 63. . The control of the multiplexer 68 is controlled by the selection signal 64 line.

The electrochemical, capacitance, and impedance measuring apparatus of FIG. 2C is integrated in the integrated bio-disc 700 together with the control unit 63.

When the electrochemical detector, capacitance and impedance measuring device using the interdigitated array electrode of FIG. 2C is applied to the bio-disk device illustrated in FIGS. The device 271 is designed to be placed on the bio disc 100 and integrated with the card IC 188.

2D illustrates an embodiment of the bio-disc 1000 through which the conventional optical disc 900 and the integrated bio-disc 700 are integrated. The optical disc 900 portion of the integrated bio disc 1000 includes information related to an analysis algorithm, bioinformatics information, and self diagonasis. It may also include software for storing diagnostic information at remote locations and software for device drivers. The software may include patient education information for clinical analysis and may be adapted. The software may include a web site and various links that can be connected to a specialist doctor and a hospital according to the diagnosis result. In addition, the optical disk 900 may contain contents such as a music CD, a game CD, a CD-R, a DVD, and the like. The optical disk 900 is read by the optical pick-up apparatus 103, and the reading of the analysis site 132 of the integrated bio-disc 700 part is separate from the optical pick-up apparatus 103. It is made by an analytical reading device coupled with a transducer that includes a chemistry, capacitance and impedance measurement device. That is, information reading on a conventional optical disc 900 is performed by the optical pickup device 103, and information reading of the analysis site of the integrated bio-disc 700 which is a non-optical disk is performed. It is made by a separate analysis reading device. Also in the integrated bio disc 1000 portion, the normal optical disc 900 portion may be provided as a recordable blank CD or blank DVD, such as a CD-RW or DVD-RW.

Further, in the integrated bio disc 1000, the reading of the optical disc 900 surface and the reading of the integrated bio disk 700 surface are performed by using the optical pickup device 103 and the optical, electrochemical, capacitance or impedance device. Characterized in that it can be made by using the analysis reading device by the detector included at the same time point or at different time points.

FIG. 3A illustrates the bio-disc 100 of the embodiment of FIGS. 1F and 1J, wherein the currently loaded disc is an optical disc such as a general music CD, a CD-R, a game CD, a DVD, or a non-optical disc. An embodiment of a bio-disc detection method for determining whether the control unit 63 recognizes the recognition.

The control disk uses the conductor arm 13 and the connecting groove 33 to control a constant voltage or a divided voltage (referred to as a bio-disc detection signal) generated by the resistors R1 and R2 disposed on the biodisc 100. The control part 63 of 200 makes a measurement. Since the resistors R1 and R2 are not disposed in a normal optical disk, the above constant voltage does not occur. Thereafter, the control unit 63 transmits a bio-disc detection signal to the external central control apparatus 101 by wireless transmission through the contactless interface 106 or 107 or the card IC 188 so that the currently loaded disk is a bio disc. The control device 101 can be notified.

In the case of a normal optical disc, the controller operates in a normal manner, and in the case of a bio disc, the controller 63 sends various control signals for a lab on a chip to the bio disc 100.

3B illustrates a disk in which the bio-disc 100 or the integrated bio-disc 700 and the integrated bio-disc 1000 are currently loaded into the bio driver using the contactless interface 106 or 107 or the card IC 188. Is another embodiment in which the central controller 101 is informed that is a bio disc.

The moment the controller 63 is powered on at the time of loading of the bio-disc, the bio-disc is transferred to the external central controller 101 via the contactless interface 106 or 107 or the card IC 188. By wirelessly transmitting a signal indicating that the disk is newly loaded, the central controller 101 can be notified that the currently loaded disk is a bio-disc. However, since an ordinary optical disc does not have the control part 63 mentioned above, notification is impossible.

In another embodiment, the central control apparatus 101 is notified that the disc currently loaded in the bio driver by the groove pattern or the data pattern at the specific position on the disc is the bio disc (100, 700, 1000). can do.

That is, the optical pickup device 103 reads data or groove patterns of specific positions of the currently loaded disc, so that the disc currently loaded in the bio driver can be used as a normal music CD, CD-R game CD, DVD, etc. It may be determined whether the optical compact disc or the bio disc (100, 700, 1000).

The user loads the bio-disc 100 or 700 or 1000 into the bio driver for diagnosis or analysis of the sample.

4A to 6D illustrate various embodiments of the optical analysis reading apparatuses 99a and 99b in which the detection of an analyte specific signal generated at the analysis site 132 installed in the bio-disc is performed by the optical measuring apparatus. Indicates.

4A illustrates an embodiment in which the reading of the analysis site 132 is implemented by the light transmission method of a metal sphere by a transducer including the optical device. This is distinct from the reading method by the differential reflection method of the concave and convex portions formed by the physical pits on the CD in the ordinary optical disk (different).

4A shows a case in which the signal element 557 restrained by the bio-disc 100 remains on the substrate surface, and the right figure shows that the restraint signal element 557 is largely removed and provides an escape signal element. The case is shown.

The restriction signal element and the release signal element is a pre- filed domestic patent application "nucleic acid hybridization method and apparatus using a cleavage technique that specifically reacts to a specific sequence of the complementary double bond of nucleic acid and oligonucleotide" (2001,01, 27 10-2001-0003956) and PCT application "nucleic acid hybridization method and apparatus using a cleavage technique that specifically reacts with complementary double or single strands of nucleic acid and oligonucleotide" (2002.01.27 PCT / KR02 / 00126) It is well illustrated in.

4A shows an embodiment in which the optical analysis reading apparatuses 99a and 99b are constituted by a laser beam device 99a incident on the restraint signal element and a departure signal element and an optical detector 99b which detects differential transmission signals. to be.

4B shows another embodiment in which the method of reading the analysis site is implemented in the light transmission method of the metal sphere by a transducer including the optical device.

The left figure of FIG. 4B is a case where the restraint signal element 557 remains on the substrate surface in the bio-disc, and the right figure shows a case where the restraint signal element 557 is mostly removed and provides an escape signal element.

4B illustrates the optical analysis reading apparatuses 99a and 99b implemented by the laser beam generator 99a incident on the restraint signal element and the departure signal element and the optical detector 99b for detecting differential transmission signals. Example. Reference numeral 555 denotes a transparent opening for reading the optical detector 99b.

FIG. 5A shows an embodiment in which the optical detector 99b is integrated on the substrate 1 in the light transmitting method of 4B. In this case, the optical detectors 99b are arranged in an array in a one-to-one correspondence with respect to the plurality of analysis sites. This arrangement is distinguished from the fact that in the conventional optical pickup apparatus 103, all of one optical transmitter and one optical receiver are modular together. This type of module has the disadvantage that, due to the additional light reflection path, the optical traveling path is long and the sensitivity of the light receiver is lowered.

FIG. 5B shows an embodiment of a bio-disc in which an array of the optical detectors 99b is arranged in the circumferential direction of the bio-disc. According to the rotation of the bio-disc, the optical detector 99b corresponding to the one-to-one correspondence for the plurality of analysis sites embedded in the bio-disc can be sequentially read.

FIG. 6A shows an embodiment in which both the laser beam generator 99a and the optical detector 99b are integrated in the lower substrate 3 in the light transmitting method, and FIG. 6C shows the laser beam generator 99a. Is embedded in the lower substrate 3 and the optical detector 99b is integrated in the upper substrate 1. In this case, the laser generating device 99a and the optical detector 99b are integrated and arranged in an array in one-to-one correspondence with the plurality of analysis sites. In this case, the sensitivity by the optical detector is further improved.

6A and 6C show a case where the restraint signal element 557 remains on the substrate surface in the bio-disc, and the right figure shows a case where most of the restraint signal element 557 is removed to provide an escape signal element. Indicates.

FIG. 6B illustrates an embodiment in which the array of the laser generator 99a and the optical detector 99b of FIG. 6A are integrated and arranged in the circumferential direction of the bio disc, and FIG. 6D is the laser generator of FIG. 99a) shows an embodiment in which the array of optical detectors 99b are integrated and arranged in the circumferential direction of the bio disc. One laser generator and one optical detector for one analysis site can be combined to form an optical analysis reading device for one site.

In addition, in the example of FIG. 6B, a plurality of laser generators and a plurality of optical detectors for one analysis site may be integrated to configure an optical reading device for one analysis site. This has the advantage that the analysis sites can be read with higher sensitivity.

The optical analysis reading method of FIGS. 6A-6D provides an optical analysis reading apparatus capable of directly and simultaneously reading the analysis site 132 in the bio-disc without rotating the disk. That is, as a kind of non-scanning optical transmission method, it provides a method of analyzing and reading a non-optical bio disc. Therefore, there is an advantage that the process of access to the individual analysis sites, predetermined location information, and disk rotation are not required.

This differs greatly from the optical scanning method in which a conventional optical disk moves to an optical pickup device to a predetermined location for reading information and a laser scanning method in which disk rotation is required.

7A-7G illustrate an interdigitated array disposed on a substrate 701 for detection of an analyte specific signal generated by the assay site 132 installed in the bio discs 100, 700, 1000. One embodiment of an electrochemical detection device or a capacitance and impedance measurement device implemented by a probe having a metal sphere 40 or a horseradish peroxidase (HRP) 41 attached to the electrodes 702 and 703 and the distal end of the cleavable signal element. Shows an example. In addition, an embodiment of an electrochemical detection device using an antigen-antibody reaction, or a capacitance and impedance measurement device, which is mainly used for an existing immunochromatographic reaction, is shown.

FIG. 7A shows one embodiment of an electrochemical detector or capacitance and impedance measurement device implemented by interdigitated array electrodes 702 and 703.

By applying an AC signal having a certain bandwidth from the control unit 63 to the two terminals 704 and 705 of the interdigitated array, it is possible to measure capacitance and impedance by measuring frequency response characteristics. In addition, the electrochemical detection is possible by measuring the voltage and current induced by the redox reaction (REDOX reaction) by HRP (HorseRadish Peroxidase) under H ₂ O ₂ solution. The interdigitated measuring apparatus is a pre- filed domestic patent application "nucleic acid hybridization method and apparatus using a cleavage method that specifically reacts to a specific sequence of complementary double bonds of nucleic acid and oligonucleotide" (2001,01 , 27 10-2001-0003956) and PCT application "nucleic acid hybridization method and apparatus using a cleavage technique that specifically reacts to the complementary double or single strand of nucleic acid and oligonucleotide" (2002.01.27 PCT / KR02 / 00126 Is well illustrated.

7B-7C show an interdigitated array disposed on a substrate 701 for detection of an analyte specific signal generated by the assay site 132 installed in the bio discs 100, 700, 1000. An embodiment of an electrochemical detector or a capacitance and impedance measuring device implemented by a probe having electrodes 702 and 703 and a horseradish peroxidase (HRP) 41 is shown. The electrons generated by the chain reaction of oxidation and reduction induce current and voltage at the electrodes 702 and 703 of the interdigitated array.

As the number of digits of interdigitated array electrodes 702 and 703 increases, the sensitivity of the detector increases.

The assay site 132 is a non-reactive molecule (e.g., (CH ₂ ) _n to prevent the biotin 50 labeled cleavable signal element from directly contacting the substrate surface after the surface of the substrate 701 has been amined. After forming an alkane chain monolayer on the surface, the biotin 50 labeled cleavable signal element is prepared by depositing on the surface.

Since the cleavable probes that maintain a single strand without causing hybridization after sample injection are removed after cleavage and washing by contact with nuclease enzyme, only the hybridized double strand 43 remains as a restriction signal element on the surface. Will be. Subsequently, streptavidin 51 labeled HRP is introduced to form a streptavidin-biotin bond with the biotin-labeled restriction signal element.

Subsequently, the controller 63 measures the voltage and current induced in the interdigitated array by the redox reaction by HRP (HorseRadish Peroxidase) under H ₂ O ₂ solution, thereby enabling electrochemical detection. This provides a differential electrochemical signal for the departure signal to the detection device.

7c shows the restraint signal element of the bio-disc 100, 700, and 1000 remaining on the surface of the substrate 701 so that the redox reaction occurs well under the H ₂ O ₂ solution. Most of the restraint signal elements are removed and removed after the cleaning process, and the redox reaction does not occur. They provide differential electrochemical signals to the detection device.

7D and 7E show an interdigitated array disposed on a substrate 701 for detection of an analyte specific signal generated by the assay site 132 installed in the bio discs 100, 700, 1000. ) Electrodes 702 and 703; Another embodiment of an electrochemical detector, or a capacitance and impedance measuring device, implemented by a probe attached to a mixture of a horseradish peroxidase (HRP) 41 and a metal sphere 40 is shown. Electrons generated by the chain reaction of oxidation and reduction by the HRP 41 are transferred to the metal sphere 40 to induce current and voltage to the electrodes 702 and 703 of the interdigitated array. The sensitivity of the detector can be controlled by the mixing ratio between the HRP labeled probe and the metal sphere labeled probe. The metal sphere acts as a medium for moving electrons generated by the chain reaction of oxidation and reduction, thereby increasing the sensitivity of the detection device. In the assay site 132 prepared by the biotin 50 labeled cleavable signal element, cleavable probes that maintain a single strand without causing hybridization reaction after sample injection are cleaved and cleaned by contact with a nuclease enzyme. Since it is removed after the process, only hybridized double strands 43 remain on the surface as restraint signal elements. Subsequently, the introduction of the streptavidin 51 labeled HRP and the strepavidin 51 labeled metal sphere forms the streptavidin-biotin bond with the biotin-labeled restriction signal element.

Subsequently, the controller 63 measures the voltage and current induced by redox reaction by HRP (HorseRadish Peroxidase) under H ₂ O ₂ solution, thereby enabling electrochemical detection, which is a differential signal for the deviation signal. Provide an electrochemical signal to the detection device.

7D is a conceptual diagram of the redox reaction, wherein a biotin 50 is labeled at the distal end of the cleavable signal element, and strepavidine 51 is labeled at each of the HRP 41 and the metal sphere 40. Thus, streptavidin-biotin binding occurs due to the contact between the restraint signal element and the HRP 41 or the contact between the restraint signal element and the metal sphere 40.

The figure on the left of Figure 7e is that the bio-disc (100,700,1000) for HRP (41) and the metal fitting 40 covers the confined signal element substrate 701 remaining on the surface of the redox reaction in the H ₂ O ₂ solution in This is a case where it occurs well, and the figure on the right shows a case where the restraint signal element is removed from the internal dust after the cutting and cleaning process, and thus the redox reaction does not occur. They provide differential electrochemical signals to the detector.

FIG. 7F illustrates an interdigitated array electrode disposed on a substrate 701 for detection of an analyte specific signal generated by the assay site 132 installed in the bio discs 100, 700, and 1000. 702,703); a conjugate of conjugate-antigen by binding between a conjugate antibody (471) and a sample (antigen or analyte) 472 to be analyzed; A capture antibody 473 immobilized on a substrate 701 in the assay site 132; An embodiment of an electrochemical detection device or a capacitance and impedance measuring device implemented by an antigen-antibody reaction between the conjugate-antigen conjugate and the capture antibody is shown.

In the present invention, the conjugate antibody is generally preferred to gold or latex (latex) as the particles for color development (474).

After formation of the conjugate of the conjugate-antigen, an antigen-antibody reaction has taken place providing a restriction signal element; After conjugate-antigen conjugates, if no antigen-antibody reactions occur, the escape signal element is activated. By measuring the frequency response characteristics for these, it is possible to measure capacitance and impedance for each analysis site.

7G shows a case in which the binding signal element (gold or latex) remains on the surface of the substrate 701 by the antigen-antibody reaction to the biodiscs 100, 700, and 1000 after the washing process. Most cases were removed after the procedure. They provide differential capacitance and impedance signals to the detection device.

8A to 8F illustrate one embodiment of the biodisc of the present invention.

8A and 8C illustrate an embodiment in which a lab on a chip is disposed on bio discs 100, 700, and 1000.

Reference numeral 170 denotes a central void of the disk, and 171 provides a connection for interfacing with the control disk 200.

Reference numeral 130 is a preparation chamber including a preparation process for preparing a DNA sample or serum from blood or cells or RNA, and 131 and 131a are PCR for a polymer chain reaction (PCR) process. The chamber is a chamber that stores a buffer solution containing various enzymes including polymerase, primer, etc. necessary for the PCR process, and 132 is a DNA for amplification into a chamber for hybridization process or antigen-antibody reaction. A biotin-labeled capture probe or immunoassay for analysis and diagnosis is an assay site attached to a substrate in the form of an array, and 133 is a Trash chamber for collecting debris generated by the cleaning process. chamber).

The main processes (prep process, PCR process, hybridization process or antigen-antibody reaction, washing process) are arranged in a spiral connection on the bio disc. This facilitates the movement of the fluids required for each of these processes by centrifugal force. In addition, chambers with reagents to support the main process are arranged in a circumferential manner.

Reference numeral 129 denotes a chamber containing a washing buffer, and 129a denotes a chamber containing distilled water. 144 is a chamber for storing a hybridization buffer, and 136 is a chamber containing a DNAse for a fragmentation process to cut DNA into an appropriate size. 141, 142 and 143 are chambers containing various enzymes required for hybridization.

141 is a chamber for storing nuclease enzymes for cleaving single strands, and 142 is a chamber for storing strepavidin labeled metal microspheres. 143 is a chamber for storing Phosphate Buffered Saline (PBS) solution.

Reference numerals 150,151,152,153,154,155,156,157,158160,161,162 are valves.

Fluid movement on these bio discs (100, 700, 1000) is due to the centrifugal force and valve opening and closing by the disk rotation.

Reference numeral 177 may be operated by placing on or below the preparation chamber 130, instead of embedded with an electromagnet embedded in the bio-disc (100, 700, 1000).

Valve opening and closing control at the start and end of the main process (prep process, PCR process, hybridization process and antigen-antibody reaction, washing process) is performed on the electromagnets installed on the upper and lower sides of the thin film cylindrical magnet in the bio-disc. By the control unit 63 for controlling the off. Reference numeral 128 denotes a chamber containing distilled water, and 135 denotes a trech chamber.

FIG. 8A illustrates an embodiment of a bio disc in which a Lab On a Chip having one PCR chamber is disposed, and FIG. 8B illustrates an embodiment of a bio disc in which a plurality of PCR chambers are configured.

In FIG. 8B, each of the plurality of PCR chambers 131a may include primers of different kinds or primers of the same type. Alternatively, a plurality of primers may enter each of the plurality of PCR chambers.

DNAs amplified from each of the plurality of PCR chambers are combined in chamber 131b.

Figure 8c is an embodiment of a bio-disc disposed Lab On a Chip implemented by the antigen-antibody reaction on the bio-disc (100, 700, 1000).

Reference numeral 130 is a preparation chamber including a preparation process for preparing serum from blood injected through the inlet, and 132 is a chamber for antigen-antibody reaction. ) Is an assay site attached to a substrate in an array form. The capture antibody is immobilized on the assay site. 133 is a Trash chamber for collecting the debris generated by the cleaning process.

The main processes (prep process, antigen-antibody reaction, washing process) are arranged in a spiral connection on the bio-disc. This facilitates the movement of the fluids required for each of these processes by centrifugal force. In addition, chambers with reagents to support the main process are arranged in a circumferential manner.

Reference numeral 129 denotes a chamber containing a washing buffer.

142a is a conjugate chamber for storing conjugate antibodies. In general, conjugate antibodies have gold or latex as particles for color development. Reference numerals 150, 152, 153 and 156 denote valves.

Fluid movement on these bio discs (100, 700, 1000) is due to the centrifugal force and valve opening and closing by the disk rotation.

Reference numeral 177a extracts serum from blood with a filtration filter embedded in the bio discs 100, 700, and 1000.

8D and 8E are cross-sectional views of the bio disc for the chamber according to the main process of FIGS. 8A, 8B and 8C.

The thin-walled cylindrical magnets 150, 151, 153 and 156 for the valves of the main process are independently opened and closed by magnetic forces formed by the electromagnets 4d and 5d, 4a and 5a, 4b and 5b, 4c and 5c, respectively. 121 is a sample inlet.

Reference numeral 130 is a preparation chamber including a preparation process for preparing a DNA sample or serum from blood or cells or RNA. The prep chamber contains ferromagnetic beads that have affinity with DNA for DNA extraction and Lysis buffer solution to break cells.

131 is a PCR chamber for a PCR (Polymer Chain Reaction) process, and a chamber for storing a buffer solution containing various enzymes such as polymerase, dNTP, primer, etc. necessary for the PCR process, and 132 is a hybridization ( As a chamber for a hybridization process or an antigen-antibody reaction, a capture probe or an immunoassay for analyzing and diagnosing DNA amplified by the PCR process is attached to a substrate in an array form. 133 is a Trash chamber for collecting the debris generated by the cleaning process. A filtration filter 177a is used in the preparation chamber 130 to prepare serum from the blood.

An embodiment of a main process for the Lab On a Chip of FIGS. 8A and 8B is as follows.

<Prep process>

An embodiment of the preparation process is a chamber for extracting DNA from a sample in the preparation chamber 130 as follows.

1) 10 μl of blood (EDTA, ACD Tube) or 5 μl (Heparin Tube) is injected through the sample inlet 121 installed in the preparation chamber 130. The preparation chamber 130 contains a Lysis buffer solution for breaking DNA and extracting DNA, and a ferromagnetic bead having affinity with the extracted DNA.

2) After incubation for 5 minutes, DNA is extracted from the cell and adhered to the ferromagnetic beads having affinity with DNA.

3) After the electromagnet 177 of FIG. 8a is turned on to allow the ferromagnetic beads to stand, the air is waited for 1 to 3 minutes.

4) While slowly rotating the bio-disc, valve 161 is opened to wash debris from the cell destruction into the trash chamber 135. Close valve 161 and stop bio disc rotation.

5) The electromagnet 177 is turned off.

6) While opening the valve 150 and slowly rotating the bio-disc. The washing buffer of the chamber 129 is introduced into the preparation chamber 130.

7) Repeat the above 3) ~ 6) two times, and finally

While slowly rotating the bio-disc, the valve 161 is opened and flushed to the trash chamber 135. Close valve 161 and stop bio disc rotation.

8) After the electromagnet 177 is turned off, the valve 151 is opened while the disk is slowly rotated so that distilled water of the chamber 129a is introduced into the preparation chamber 130.

9) Either the DNA is attached to the ferromagnetic beads by using a heater 960 embedded in the prep chamber 130 to be detached or resuspensioned using a resuspension buffer.

<PCR step>

The PCR chamber 131 or 131a is a chamber for amplifying DNA.

1) While slowly rotating the bio-disc, valve 152 is opened to move DNA released from the ferromagnetic beads in the preparation chamber 130 to the PCR chamber 131 by the preparation process.

2) After completion of DNA transfer to the PCR chamber, the valve 152 is closed and the bio disc is stopped.

3) Amplify DNA by repeating the PCR cycle about 30 times using the heater 961 and the temperature sensor 520 embedded in the PCR chamber 131.

4) Cool for 1 ~ 2 minutes.

In the case of FIG. 8B, the DNA amplified in the plurality of PCR chambers 131a is then moved to the chamber 131b by opening the valve 152a while slowly rotating the disk.

<Fragmentation Process>

The fragmentation process is an optional step for cutting the DNA amplified in the PCR process to a size suitable for hybridization.

1) While slowly rotating the bio disc, the valve 158 is opened to introduce DNAse in the chamber 136 into the PCR chambers 131 and 131b to fragment the DNA.

2) Close the valve 158 and stop the bio disc.

3) After incubation for 1 to 2 minutes, the heater 961 is heated to a high temperature to stop the function of DNAse, thereby stopping the fragmentation reaction. In addition, at high temperature, DNA denatures to form a single strand.

DNA length control by the fragmentation is controlled by the incubation time of step (3). In the case of Fig. 8B, fragmentation of DNA having different lengths is possible by fragmentation by using a plurality of chambers 131b corresponding to a plurality of PCR chambers, and placing a separate heater (independent incubation time) for each of the plurality of chambers 131b.

<Hybridization process>

In the hybridization process, a single-stranded fragmented DNA or a single-stranded DNA by high temperature treatment after a PCR process is used to generate a hybridization reaction with a biotin-labeled capture probe prepared in advance on the assay site 132. One embodiment of the process is as follows.

1) Open valve 153 while slowly rotating the bio disc to move the single stranded DNA into assay site 132.

2) After the DNA is evenly spread on the bio disc analysis site, close the valve 153, stop the disc rotation, and incubate the bio disc for 3 to 5 minutes at room temperature. In addition, the hybrid reaction is controlled by electric field control using the external electrode pattern 962 and the electrode plate 963 or heat control by the heater 962. (Hybrid reaction).

The electrode pattern 962 alone acts as a heater. In combination with the electrode plate 963, it also serves as an electrode plate for generating an electric field in the vertical direction.

3) While the bio disc is rotating, the valve 157 is opened to inject the hybridization buffer into the analysis site 132, and is cleaned by addition or washing by applying an external electric field distributed up and down of the disc (first). Cleaning process). Then close valve 157. Valve 156 is opened during the cleaning process. After cleaning, close valve 156 again.

4) Thereafter, while slowly rotating the disk, valve 154 is opened to introduce the nuclease enzyme solution for cutting the single strand into the assay site 132 to be dispersed by rotating the disk. After closing valve 154, the disc is incubated for 1-2 minutes (cutting process).

5) Then, while slowly rotating the disk, open the valve 160 to clean the PBS solution under the temperature of 80 ° C. Alternatively, close the valve 160 after the disk rotation and the cleaning by the external electric field.

6) Open valve 155 to introduce a streptavidin-labeled metal microsphere suspension on the disk and gently rotate it to distribute the metal particles evenly (“binding probe-label” formation). At this time, a biotin-strepavidin binding structure is made between the biotin-labeled capture probe and the streptavidin-labeled metal microspheres 40. The valve 155 is then closed.

The temperature and the electric field are generated using the external electrode pattern 962 and the electrode plate 963. The electrode pattern 962 alone acts as a heater but in combination with the electrode plate 963 also serves as an electrode plate for generating an electric field in the vertical direction.

7) Then, while the disk is rotating strongly, valve 162 is opened to clean by adding distilled water from chamber 128, or by applying electric field (second cleaning process).

Open valve 156 during the cleaning process.

<Detection process>

The reading is then immediately made by a detector coupled with a transducer comprising the optical, electrochemical, capacitance or impedance device, programmed to inspect a predetermined site where the cleavable signal element is deposited.

Thereafter, the diagnosis result and the prescription according to the reading result are displayed on the computer monitor, automatically or manually remotely connected through the corresponding doctor and the Internet network, and the diagnosis data and the result are remotely transmitted to the specialist when necessary. The patient then waits for a prescription from a specialist.

The cleavage process, the first washing process, the second washing process, and the remote diagnosis process are performed by nucleic acid hybridization analysis using a cleavage technique that specifically reacts to a specific sequence of complementary double bonds of the domestic patent application "nucleic acid and oligonucleotide". Methods and Apparatus "(2001,01,27 10-2001-0003956) and PCT Application" Methods and Apparatus for Nucleic Acid Hybridization Using Cleavage Techniques that Respond Specificly to Complementary Double or Single Strands of Nucleic Acids and Oligomers "( 2002.01.27 PCT / KR02 / 00126).

FIG. 8D is an embodiment in which an electrochemical detection or capacitance and impedance measurement device using the interdigitated array 701 is embedded in the analysis site 132, and FIG. 8E is coupled with a transducer including the optical device. Optical analysis detection devices 99a and 99b are an embodiment in which the semiconductor process is integrated by a semiconductor process.

The optical detectors of FIGS. 5A, 5B, 6A, and 6B may be variously modified and applied to the optical analysis detecting apparatus of FIG. 8E.

An embodiment of a main process for the Lab On a Chip of FIG. 8C is as follows.

<Prep process>

An embodiment of the preparation process is a chamber for extracting serum from blood in the preparation chamber 130 as follows.

1) 10 μl of blood (EDTA, ACD Tube) is injected through the sample inlet 121 installed in the preparation chamber 130. The outlet side of the prep chamber 130 contains a filtration filter 177a.

2) While opening the valve 152 and slowly rotating the bio-disc. The blood of the chamber 130 passes through the filtration filter 177a and flows into the conjugate chamber 142a.

3) Finally, close the valve 152 after stopping the disk rotation.

<Antigen-antibody reaction>

In the conjugate chamber 142a of FIG. 8C, a conjugated antibody labeled with gold or latex is stored as a particle for color development, and a capture antibody is immobilized on a substrate in the assay site 132.

In this step, the antigen in the serum extracted in the preparation process binds to the conjugate antibody in the conjugate chamber 142a to form a "conjugat-antigen conjugate", and then the conjugate-antigen conjugate in the assay site 132. Antibodies-antibody reaction between the capture antibody and one embodiment as follows.

1) Incubate for 1-2 minutes to form a "conjugate-antigen conjugate" between the antigen introduced into the conjugate chamber 142a and the conjugate antibody.

2) Open valve 153 and slowly rotate the bio disc to move the "conjugate-antigen combination" in chamber 142a into the assay art 132.

3) Close the valve 153 after stopping disk rotation.

4) Incubate the biodisc for 3-5 minutes at room temperature and allow the antigen-antibody reaction to occur between the "conjugate-antigen conjugate" and the capture antibody.

5) Then, while the disk is rotating, valves 150, 153 and 156 are opened to clean the assay site 132 by adding the washing buffer in chamber 129.

<Detection process>

The analysis site 132 is then read by a detector coupled with a transducer comprising the optical, electrochemical, capacitance or impedance device, which is then programmed to examine the predetermined site where the restraint or departure signal component is deposited. .

Thereafter, the diagnosis result and the prescription according to the reading result are displayed on the computer monitor, automatically or manually remotely connected through the corresponding doctor and the Internet network, and the diagnosis data and the result are remotely transmitted to the specialist when necessary. The patient then waits for a prescription from a specialist.

Figure 8f is an embodiment of the heater and the electric field generating device required for the preparation process, PCR process and hybridization process. Reference numerals 960,961 and 962 of FIGS. 8D and 8E denote heaters formed of electrode patterns.

The electrode pattern 962 alone acts as a heater but also serves as an electrode plate for generating an electric field in the vertical direction in combination with the electrode plate 963.

The temperature control and the electric field control are controlled by the controller 63. 962 is an electrode pattern for a heater, by applying a voltage to the input terminals 962a and 962b so that a current flows in the electrode pattern 962 so that the electrode pattern 962 acts as a resistance line or a heating line.

The controller 63 supplies a current to the input terminals 962a and 962b of the electrode pattern 962 and measures the temperature generated by the current electrode pattern 962 by the temperature sensor 520 to control the current amount. Make adjustments. In addition, in order to generate an electric field by combining the electrode pattern 962 with the electrode plate 963, the same voltage is applied to two input terminals 962a and 962b of the electrode pattern 962 and treated as one input terminal. This can be done by treating the electrode plate 963 as another voltage application terminal. In other words, an AC voltage is applied between the electrode pattern 962 and the electrode plate 963 to generate an AC electric field. Since DNA has a negative charge, an alternating voltage applied between the electrode plate 963 and the electrode pattern 962 by the controller 63 is alternating between the electrode pattern 962 and the electrode plate 963. By generating an electric field, not only DNA stringency control can be performed, but also SNP (Single Nucleotide Polymorphism) detection ability is improved.

Regarding SNP detection, a pre- filed domestic patent application "nucleic acid hybridization method and apparatus using cleavage techniques that specifically react to specific sequences of complementary double bonds of nucleic acids and oligonucleotides" (2001,01,27 10-2001- 0003956) and PCT Application "Nucleic Acid Hybridization Methods and Apparatus Using Cleavage Techniques That Respond Specificly to Complementary Double or Single Strands of Nucleic Acids and Oligonucleotides" (2002.01.27 PCT / KR02 / 00126) .

8d and 8e, the temperature sensor 520 is used only for a PCR process requiring precise temperature control, but may be used for all processes requiring temperature sensing.

When the bio disc is loaded into the bio drive, the analysis starts automatically.

However, when the sample is loaded without being injected into the sample inlet, eject and / or a warning message is sent back to the user.

The sample injection can be confirmed by further comprising an impedance measuring device in the preparation chamber 130. That is, when the sample is injected or not, the impedance characteristics are different, so whether the sample is injected can be known.

One embodiment of this is the impedance measurement device by the interdigitated array used in the analysis site 132.

If during the diagnosis or analysis of the sample by the bio-disc, when the bio-disc ejects (un-loading) or stops the bio-disc from the user, the bio-driver ignores the bio-driver and continues the analysis and diagnosis. At this time, a warning message is notified to the user or a password is required.

If the password is correct, accept the user's eject (un-loading) or stop request.

Upon completion of diagnostics and analysis, it accepts the user's eject request so that the bio-disk can be ejected from the bio driver.

In addition, the memory of the card IC 188 stores information on how many times the disk has been used, information on expiration date, and the type of disease to be diagnosed.

In other words, when the disposable bio-disc is ejected during use or completion, the history of the bio-disc is recorded in the memory of the card IC 188, and the bio-disc can not be diagnosed when it is reloaded later. Inform

It also informs the user that the bio disc is not available for diagnosis even after the expiration date.

Figures 9a and 9b is another embodiment of a bio-disk that can be combined with the preparation process, PCR process and electrophoresis.

9A shows a bio disk for PCR including a preparation process and a PCR process.

Reference numeral 170 denotes a central void of the disk, and 171 provides an interface for connecting to the control disk 200.

Reference numeral 130 is a preparation chamber including a preparation process for preparing a DNA sample from blood or cells or RNA, and 131a is a PCR chamber for a polymer chain reaction (PCR) process. It is a chamber that stores a buffer solution containing various enzymes, including enzymes and primers, and 88a is an out chamber which outputs a PCR product.

Reference numeral 129 denotes a chamber containing a washing buffer, and 129a denotes a chamber containing distilled water. 144a is a chamber for storing the ladder marker, and 141a is a chamber containing positive or negative control. There are output chambers 88b and 88c for each of these.

142a and 143a are chambers containing various solutions for electrophoresis, including staining. There are output chambers 88d and 88e for each of these.

Reference numerals 150,151,152,153,154a, 155a, 156a, 157a denote valves.

The output chamber 88a may have an outlet for allowing electrophoresis by manual operation by collecting a PCR product by a picket or a die.

Figure 9b shows one embodiment of an electrophoretic disk including electrophoresis.

The electrophoresis disk is combined with the PCR biodisc to provide a biodisc device capable of automated electrophoresis.

The electrophoresis disk is located on the bottom of the PCR bio disk.

The electrophoresis disk is provided with electrodes 555a and 555b for applying a voltage to a gel plate 555c composed of agarosdegel and / or polyacrylamide gel. have.

The output chambers 88a, 88b, 88c, 88d and 88e of the PCR product, ladder marker, positive / negative controls and stains are connected to the input chambers 99a, 99b, 99c, 99d and 99e of the electrophoresis disk. When the valves 152a, 157a, 154a, 155a, and 156a are opened, the contents of the output chamber flow into the input chamber of the electrophoretic disk and a voltage is applied to the electrodes. Proceed.

The applied voltage is removed to stop electrophoresis after a certain time.

The voltage control and valve control are by the control unit 63.

The control disk 200 is connected to the PCR disk and the electrophoretic disk by the interface unit 171.

In addition, the bio-disc device having the electrophoretic disk may further include a UV (Ultra Violet) irradiation device and a camera to measure, store, and transmit the band generated in the gel plate 555c.

In addition, the analysis apparatus of FIGS. 10A to 10B of the present invention may be co-located on a bio-disc to simultaneously analyze the immunoassay (immunological verification apparatus) and nucleic acid probe (analysis probe reaction) assay. 170 is the central void of the disc

FIG. 10A shows that an immunoassay sector for antigen antibody reaction in an angular direction and an assay sector for response analysis of a nucleic acid probe are separated, and FIG. 10B shows an immuno antibody for antigen antibody response in a radial direction. Indicates that the analysis sector for the reaction analysis of the analysis sector and the nucleic acid probe is separated.

By simultaneously testing the immunoassay (immunological verification device) and nucleic acid probe (analysis of probe reaction) analysis simultaneously, the reliability of disease analysis can be doubled and the number of assay sites can be reduced by appropriate combination.

11A and 11B illustrate an appearance of a bio driver device, in which 751 is a case of the bio driver device and 750 is a tray for loading the bio discs 100, 700, and 1000. In addition, the bio-disc driver device of the present invention has a play and seek button 745 and a stop button 746 for normal optical disc reproduction.

11A illustrates an embodiment in which a progress state of a bio driver device is displayed using a light emitting diode.

A light emitting diode 741 is provided to indicate that the currently loaded disk is a bio disk, and a progress display light emitting diode 742 is displayed to display the progress of the current analysis. Reference numeral 743 denotes a light emitting diode for indicating that a conventional optical disk is loaded. As the light emitting diode, another display device may be used.

FIG. 11B illustrates an embodiment in which the liquid crystal display device 760 displays the progress state of the bio driver device.

Progress according to the main process (prep process, PCR process, hybridization process and antigen-antibody reaction) can be displayed in the form of percentage (%) or bar graph (bar graph).

Alternatively, you can use a computer monitor to display the progress of the bio driver device. Progress according to the main process (prep process, PCR process, hybridization process and antigen-antibody reaction) can be displayed in the form of percentage (%), bar graph (pie graph), pie graph (pie graph).

Although the present invention has been described in terms of embodiments and examples, it is not intended to limit the invention thereto. In addition, those skilled in the art will recognize that various modifications and variations are possible in addition to those described herein. Such modifications also fall within the scope of the appended claims.

In order to achieve the object of the present invention, the present invention is a flow channel (channel) for the flow of fluid on the surface of the substrate (chamber) for storing the buffer solution, an analysis site in which the pores and biomaterials are connected to connect the flow path a solid substrate comprising an assay site and a valve for opening and closing the hole, the assay site comprising a transducer coupled detection comprising a light transmission measuring device or an electrochemical or capacitance and impedance measuring device. A non-optical bio disc is provided which is read by a detector.

In the context of the present invention, the assay site is used interchangeably with the hybridization chamber or the antigen-antibody reaction chamber, meaning that the hybrid material or the hybridization or antigen-antibody reaction occurs.

In the bio-disc of the present invention, preferably, the biomaterial is at least one selected from DNA, RNA, PNA or protein.

In the bio-disc of the present invention, preferably, the chamber comprises at least one preparation chamber for preparing DNA samples from blood or cells or RNA and / or; At least one PCR chamber for PCR amplification of the prepared DNA sample and / or; At least one hybridization chamber to which analytical and diagnostic probes for hybridizing with DNA amplified by the PCR process are attached to the substrate in the form of an array; It is characterized by consisting of a Trash chamber (Trash chamber) for collecting the debris generated by the cleaning process.

In the bio-disc of the present invention, preferably, the preparation chamber includes a Lysis buffer solution for extracting DNA by breaking a cell; It is characterized in that the ferromagnetic beads (afad) having affinity (affinity) with the extracted DNA is contained.

In the bio-disc of the present invention, preferably, the PCR chamber is composed of a plurality of primers, and different primers are put into each of the plurality of PCR chambers; Or primers of the same type; Alternatively, a plurality of primers may be inserted into each of the plurality of PCR chambers.

In the bio-disc of the present invention, preferably, the chamber comprises at least one preparation chamber for preparing serum samples or antigens to antibodies from blood or cells; At least one antigen-antibody reaction chamber (Ag-Ab reaction chamber) in which an immunoprobe for antigen-antibody reaction with the prepared antigen to antibody is attached to a substrate in an array form; It is characterized by consisting of a Trash chamber (Trash chamber) for collecting the debris generated by the cleaning process.

In the bio-disc of the present invention, the chamber is preferably characterized by further comprising a conjugate chamber and a filtration filter for storing the conjugate antibody. Herein, the conjugate antibody is characterized in that it has gold or latex (latex) as particles for color development.

In the bio-disc of the present invention, preferably, the valve is a micro bead located in the hole; It is characterized by consisting of an electromagnet by an air core or a non-magnetic core. Here, the micro-bead is characterized in that the thin film cylindrical magnet.

In the bio-disc of the present invention, preferably, the optical transmission measuring device detects a differential beam transmission signal between the laser beam device and the signal elements in which the laser beam is incident on the restraint signal element and the departure signal element in the analysis site. It is characterized by consisting of an optical detector.

In the bio-disc of the present invention, preferably, the at least one or more optical detectors are arranged in an array in the circumferential direction on the bio-disc in one-to-one correspondence with the plurality of analysis sites, or with the at least one or more laser generating devices. All of the one or more optical detectors are integrally arranged in an array form in the circumferential direction on the bio disc in a one-to-one correspondence with the plurality of analysis sites. In the former case, the sensitivity is good because the optical detector is closer to the analysis site. In the latter case, the assay site is read in a non-scanning manner without disc rotation.

In the bio-disc of the present invention, preferably, the electrochemical detection device, or the capacitance and impedance measurement device, is disposed at the distal end of the interdigitated array electrode and the restraint signal element disposed on the substrate of the analysis site. It is characterized by consisting of a HRP (Horse Radish Peroxidase) and / or metal sphere attached probe.

In the bio-disc of the present invention, it is preferable that the electrochemical detector, capacitance and impedance measuring device using the interdigitated array electrode be implemented by a multiplexer and a frequency generator. It features.

In the bio-disc of the present invention, preferably, the bio-disc is a protocol, an analysis algorithm, standard control values for reading or position information on an analysis site, bioinformatics information, self-diagnosis (self diagonasis). Additional information or device driver software, patient education information for clinical analysis, web sites that can be remotely connected to specialist doctors and hospitals based on diagnostic results, and memory or card ICs for storing various links or encrypted personal information. Characterized in that provided.

In order to achieve another object of the present invention, the present invention provides a non-optical or optical bio-disc according to the present invention; A control disk having a control unit for supplying a power or control signal necessary for the bio-disc; And an interface unit for connecting the bio-disc and the control disc.

In the bio-disc device of the present invention, preferably, the interface unit includes a plurality of control signal connection units for supplying a control signal and / or a power connection unit for power supply, and is electrically connected to the bio-disc.

In the bio-disc device of the present invention, preferably, the interface unit is formed by connecting conductor grooves on a control disc and conductor grooves coated with conductors on a spiral-shaped bio disc.

In the bio-disc device of the present invention, the power supply to the control disk is preferably made by frictional contact between a brush connected to an external power supply device and the annular electrode plate on the control disk.

In the bio-disc device of the present invention, preferably, the control disc is composed of a printed circuit board (PCB) or a circuit integrated on a silicon wafer.

In the bio-disc device of the present invention, preferably, the fluid movement is caused by the centrifugal force induced by the bio-disc simultaneously rotating and mechanically connected to the control disc and the valve opening and closing.

In the bio-disc device of the present invention, the control disc preferably transmits the reading of the analysis site obtained by the detection device to an external central control device or storage device or output device through an infrared, optical or wireless interface. It further comprises a contactless interface for.

In the bio-disc device of the present invention, preferably, the bio-disc and the control disc are combined to constitute one integrated bio-disc.

In the bio-disc device of the present invention, preferably, the integrated bio-disc comprises an electronic circuit including the control unit, a card IC, a non-contact interface, an electrode plate or an electromagnet for controlling the valve, and various circuit patterns using a silicon wafer material. The chambers and channels are designed as monolithic integrated circuits by photolithography and etching on silicon wafers.

In the bio-disc device of the present invention, preferably, the integrated bio-disc is composed of an integrated bio-disc combined with a conventional optical disc (CD-RW, DVD-RW, CD or DVD).

In order to achieve another object of the present invention, the present invention provides a control disk having a control unit for supplying a power or control signal required for the non-optical or optical bio-disc according to the present invention; A motor for rotating the disk; A brush for supplying power to the control unit on the control disk; An interface unit for supplying a control signal and / or a power signal of the controller to the bio disc; And a body supporting the bio driver.

The bio driver device of the present invention is preferably characterized by further comprising a transducer coupled detection device comprising a light transmission measuring device for reading the analysis site.

In the bio driver device of the present invention, preferably, the apparatus further comprises contactless interface means for sending a read result of the analysis site to an external central control device or storage or output device or to receive a command from the central control device. It is characterized by.

In the bio driver device of the present invention, preferably, a circuit board on which a central control device and a storage or output device are designed is jointly fastened to the bio drive body, and the central control device rotates the bio disc and the control disc. Alternatively, in addition to stopping the motor when the motor is stopped, the control disk and the bio-disc are mechanically and / or electrically connected to each other by the interface unit when the disk starts to rotate.

In the bio driver device of the present invention, preferably, the output device has a communication standard of USB (Universal Serial Bus) or IEEE1394.

In order to achieve another object of the present invention, the present invention provides a non-optical or optical bio-disc according to the present invention; A turn table for placing the bite disk or a conventional optical disk; And a control disc having a control unit for supplying a power or control signal to the bio disc, wherein the control disc is fixedly coupled to the turn table to control the bio disc loaded on the turn table. Provide the device.

In the bio-disc device of the present invention, preferably, the control disc further includes an electromagnet for controlling the thin-film magnet embedded in the bio-disc.

In the bio-disc device of the present invention, preferably, there is a height interval of 0.1-5 mm between the control disk fixedly coupled to the turn table and the bio-disc loaded on the turn table, more preferably about 1 mm. It has a height gap.

In the bio-disc device of the present invention, preferably, the control disc is supplied with power from the outside by frictional contact between the rotating electrode and the brush to supply power to the bio-disc.

In the bio-disc device of the present invention, preferably, the control disc is composed of a printed circuit board (PCB) or a circuit integrated on a silicon wafer.

In the bio-disc device of the present invention, the control disc preferably transmits the reading of the analysis site obtained by the detection device to an external central control device or storage device or output device through an infrared, optical or wireless interface. It further comprises a contactless interface for.

In order to achieve another object of the present invention, the present invention provides a non-optical or optical bio-disc according to the present invention or a turn table for mounting a conventional optical disk; A control disk fixedly coupled to the turntable, for supplying power to the bio disk, and having a control unit and an electromagnet for controlling a valve embedded in the bio disk; A motor for rotating the disk; Power supply means for supplying a power supply to a control unit on the control disk; And a body supporting the bio driver.

In the bio driver device of the present invention, preferably, the power supply means supplies positive power by frictional contact between the rotating electrode and the brush, and the negative power supply is a grounded motor or a grounded motor shaft. It is characterized in that the supply to the control disk through the electrical connection with.

The bio driver device of the present invention is preferably characterized by further comprising a transducer coupled detection device comprising a light transmission measuring device for reading the assay site.

In the bio driver device of the present invention, preferably, the apparatus further comprises contactless interface means for sending a read result of the analysis site to an external central control device or storage or output device or to receive a command from the central control device. It is characterized by.

In the bio driver device of the present invention, a circuit board on which the central control device and the storage means or the output device are designed is jointly fastened to the bio driver body, and the central control device is a When the rotation or stop the motor is characterized in that to stop the rotation.

The bio driver device of the present invention is preferably characterized by further comprising an optical pickup device for reading an ordinary optical disk (e.g., music CD, CD-R, game CD, or DVD).

In the bio driver device of the present invention, preferably, the control unit determines whether the disc loaded in the bio driver device is an optical disc such as a general music CD, a CD-R, a game CD, a DVD, or a bio disc. It further comprises a bio-disc detection means for determining.

In the bio driver apparatus of the present invention, preferably, the bio-disc detection means measures the constant voltage generated by the voltage dividing means disposed on the bio disc by the control unit of the control disc. The controller transmits a bio-disc detection signal to the central control unit via a non-contact interface to wirelessly notify the central control unit that the currently loaded disk is a bio-disc.

In the bio driver apparatus of the present invention, preferably, the optical pickup apparatus reads a groove pattern or a data pattern at a specific position on the bio disc so that the disc currently loaded in the bio driver is a bio disc. Characterized in that the central control unit recognizes.

In the bio driver device of the present invention, preferably, the central controller is a normal optical disc by judging whether it is a normal optical disc (eg, music CD, CD-R, game CD, DVD, etc.) or a bio disc. In this case, the optical disc may be transferred from the optical pickup device to the storage device or output device, or the content may be sent to the optical pickup device, and various control signals required for read / write may be provided to the respective parts. Normal operation for, and in the case of a bio-disc characterized in that it transmits various control command signals for the control of the bio-disc through a contactless interface.

In the bio driver device of the present invention, preferably, the bio driver device is a bio disc protocol, an analysis algorithm, standard control values for reading or position information on an analysis site, bioinformatics information, self diagnosis (self). diagonasis) or device driver software and patient education information for clinical analysis, web sites that can be remotely connected to specialist doctors and hospitals according to the diagnosis results, and memory or storage means for storing various links or personal encryption information. Or further comprising a card IC.

In the bio driver device of the present invention, it is preferable that the bio disc is newly loaded in the central controller by wirelessly transmitting the bio disc to the central controller through a contactless interface or a card IC on the bio disc at the time of loading the bio disc. The central controller may recognize that the disc loaded in the driver is a bio disc.

In order to achieve another object of the present invention, the present invention provides a solid substrate including a channel through which a fluid can flow on a substrate surface, a chamber for storing a buffer solution, and a hole connecting the channel. A valve for opening and closing the pores, wherein the chamber comprises at least one preparation chamber for preparing DNA samples from blood or cells or RNA; At least one PCR chamber for storing a buffer solution containing various enzymes including polymerase, primer, and the like necessary for PCR amplifying the prepared DNA sample; And a plurality of out chambers connected to the solid substrate to collect PCR products obtained by the PCR process.

In the PCR bio disc apparatus of the present invention, preferably, the output chamber is provided with an outlet for collecting the PCR product by pipette or dice.

In the PCR bio disc apparatus of the present invention, preferably, the solid substrate comprises: a ladder chamber for storing a ladder marker; and a control chamber and a stain chamber for storing positive control and negative control samples.

In the PCR bio-disc device of the present invention, preferably, the PCR bio-disc is integrated with the disk for electrophoresis.

In the PCR biodisk apparatus of the present invention, preferably, the electrophoresis disk is applied with a voltage to a gel plate composed of an agarosdegel and / or an acrylamide gel. It characterized by comprising an electrode for.

In the PCR biodisk apparatus of the present invention, preferably, the PCR biodisk apparatus further includes a UV (ultra violet) irradiation apparatus and a camera to measure, store, and transmit a band.

In order to achieve another object of the present invention, the present invention comprises a preparation process step for preparing a DNA sample from blood or cells or RNA; PCR process for amplifying the prepared DNA; Collecting the PCR products obtained by the PCR process in an out chamber; Moving the contents of the output chamber to an electrophoretic disk; Incubating while applying voltage to the electrophoretic electrode (gel running step); And it provides a nucleic acid analysis method using a PCR bio-disc device according to claim 53, comprising the step of measuring, storing or transmitting a band (band).

In order to achieve another object of the present invention, the present invention comprises a preparation process step for preparing a DNA sample from blood or cells or RNA; PCR process for amplifying the prepared DNA sample; A hybridization process step of hybridizing the DNA obtained by the PCR process with an analytical and diagnostic probe arrayed at an assay site; And reading the cleavable signal element in the assay site by means of a transducer coupled detector comprising a light transmission measuring device, an electrochemical, capacitance or impedance measuring device. To provide.

In the nucleic acid analysis method of the present invention, preferably, the preparation process comprises the steps of injecting blood through a sample inlet installed in the preparation chamber; an incubation step for attaching the DNA extracted from the cell to the ferromagnetic beads; After the ferromagnetic beads are left standing, washing and flowing debris from the cell break down into the trech chamber while slowly rotating the bio disc; And, characterized in that it comprises the step of leaving or resuspension the DNA attached to the ferromagnetic beads (bead).

In the nucleic acid analysis method of the present invention, preferably, the PCR process comprises the steps of moving the DNA obtained by the preparation process to the PCR chamber while slowly rotating the bio-disc; And amplifying the DNA by repeating the PCR cycle several times using a heater and a temperature sensor embedded in the PCR chamber after completion of DNA transfer to the PCR chamber.

In the nucleic acid analysis method of the present invention, preferably, after the PCR process, the step of introducing the DNAse into the PCR chamber while slowly rotating the bio-disc; It is characterized in that it further comprises a fragmentation process comprising heating to a high temperature to stop the function of DNAse (stop incubation) and to make a single strand of DNA (denaturing step).

In the nucleic acid analysis method of the present invention, it is preferable that fragmentation of DNA having different lengths is possible by fragmentation by providing one-to-one independent heaters (independent incubation time) for each of the plurality of PCR chambers.

In order to achieve another object of the present invention, the step of separating the serum to the antigen from the blood through the filter for filtration; Rotating the bio-disc to introduce the antigen into the conjugate chamber, and incubating for 1-2 minutes to form a "conjugate-antigen conjugate" between the antigen and the conjugate antibody; Moving the “conjugate-antigen conjugate” into the assay site while slowly rotating the bio disc; Culturing the bio disc in a stationary state and culturing the antigen-antibody reaction between the “conjugate-antigen conjugate” and the capture antibody (immuno probe); A method of immunoassay using a bio-disc according to claim 6, comprising the step of washing the assay site by adding a washing buffer while the disc is rotating.

In the bio-disc of the present invention, preferably, the assay site is an immunoassay in an angular direction or a radial direction in order to simultaneously analyze an immunoassay and a nucleic acid probe assay. The sector and the nucleic acid probe analysis sector are separated.

In the bio driver device of the present invention, preferably, when the bio disc is loaded while the sample is not injected into the preparation chamber, the bio driver is ejected or a warning message is sent to the user.

In the bio-disc of the present invention, preferably, an impedance measuring device is further provided in the preparation chamber to determine whether the sample is injected. Here, the impedance measuring device is characterized by an interdigitated array.

In the bio driver device of the present invention, preferably during the diagnosis or analysis of the sample, when ejecting (un-loading) or stopping the bio disk from the bio driver by the user, the bio driver is ignored and the analysis and diagnosis are continued. Optionally, a warning message (warning message) is notified to the user or a password is requested, and the user's eject (un-loading) or stop request is accepted only if the password is correct.

In the bio driver device of the present invention, the bio disk device further includes a memory means for storing information on how many times the bio disk device has been used, expiration date information, and a type of disease to be diagnosed. Each time the user can be diagnosed or not, and the information can be provided.

In the bio driver apparatus of the present invention, preferably, the bio driver apparatus comprises: a play and seek button, a stop button for normal optical disc playback; And a light emitting diode indicating that the currently loaded disk is a bio-disc.

In the bio driver device of the present invention, preferably, the bio driver device includes a liquid crystal display device, and the progress rate according to the main process (prep process, PCR process, hybridization reaction process) of the bio driver device (bar) or bar is used. It is characterized by displaying in the form of bar graph.

In the bio driver device of the present invention, preferably, the bio driver device includes a monitor display device to determine a progress rate of the bio driver device according to the main process (prep process, PCR process, hybridization reaction process) as a percentage ( %) Or a bar graph or pie graph.

In the bio driver apparatus of the present invention, preferably, the bio driver apparatus comprises: a play and seek button, a stop button for normal optical disc playback; And a display device for indicating that the currently loaded disk is a bio disk.

As described above, the apparatus and method of the bio-disc and the bio driver using the optical or non-optical disc of the present invention is suitable for the configuration of a Lab On a Chip including various diagnostic analysis apparatuses, nucleic acid hybrid analysis apparatuses, and immunological verification. In particular, the biodriver device and method are compatible with optical disc devices such as the conventional CD-ROM and DVD reader as well as the bio-disc readout, so that the conventional optical CD such as music CD, CD-R, game CD, DVD, etc. It also functions as a read / play function of the Disc, which provides much convenience in use as well as price competition. In addition, the bio driver device is connected to a computer to facilitate remote diagnosis using the existing Internet network.

Claims (72)

A solid substrate including a channel through which a fluid can flow on a surface of a substrate, a chamber for storing a buffer solution, an assay site in which holes and biomaterials are connected to connect the channel, and A valve for opening and closing the hole, wherein the analysis site is read by a transducer coupled detector including a light transmission measuring device or an electrochemical or capacitance and impedance measuring device. Non-optical bio-disc. The bio-disc according to claim 1, wherein the biomaterial is at least one selected from DNA, RNA, PNA or protein. The method of claim 1, wherein the chamber comprises at least one preparation chamber for preparing DNA samples from blood or cells or RNA; At least one PCR chamber for PCR amplification of the prepared DNA sample and / or; At least one hybridization chamber to which analytical and diagnostic probes for hybridizing with DNA amplified by the PCR process are attached to the substrate in the form of an array; Bio disk, characterized in that consisting of a Trash chamber (Trash chamber) for collecting the debris generated by the cleaning process. 4. The preparation chamber of claim 3, further comprising: a Lysis buffer solution for extracting DNA by breaking a cell; A bio-disc comprising ferromagnetic beads having affinity with the extracted DNA. The method of claim 3, wherein the PCR chamber is composed of a plurality of different types of primers into each of the plurality of PCR chambers; Or primers of the same type; Or a plurality of primers enter each of the plurality of PCR chambers. The method of claim 1, wherein the chamber comprises at least one preparation chamber for preparing serum samples or antigens or antibodies from blood or cells; At least one antigen-antibody reaction chamber (Ag-Ab reaction chamber) in which an immunoprobe for antigen-antibody reaction with the prepared antigen to antibody is attached to a substrate in an array form; Bio disk, characterized in that consisting of a Trash chamber (Trash chamber) for collecting the debris generated by the cleaning process. The bio-disc according to claim 6, wherein the chamber further comprises a conjugate chamber for storing the conjugated antibody and a filter for filtration. The bio-disc device according to claim 7, wherein the conjugate antibody has gold or latex as particles for color development. The valve of claim 1, wherein the valve comprises: a micro bead located in the hole; A bio-disc comprising an electromagnet by an air core, a non-magnetic core, or a bobbinless coil. 10. The bio-disc according to claim 9, wherein the micro bead is a thin film cylindrical magnet. The apparatus of claim 1, wherein the optical transmission measuring device comprises a laser beam device that enters a laser beam into a restraint signal element and an escape signal element in an analysis site, and an optical detector for detecting a differential light transmission signal between the signal elements. Bio disk, characterized in that. 12. The bio-disc according to claim 11, wherein the at least one or more optical detectors are arranged in an array in a circumferential direction on the bio-disc in a one-to-one correspondence with the plurality of analysis sites. 12. The bio-disc according to claim 11, wherein both the at least one or more laser generating devices and the one or more optical detectors are arranged in an array in a circumferential direction on the bio-disc in a one-to-one correspondence with the plurality of analysis sites. The bio-disc according to claim 1, wherein the assay site is read in a non-scanning manner without disc rotation. The method of claim 1, wherein the electrochemical detection device, or the capacitance and impedance measuring device is a HR (HorseRadish Peroxidase) at the distal end of the interdigitated array electrode and the restraint signal element disposed on the substrate of the analysis site And / or a probe having a metal sphere attached thereto. 16. The bio-disc according to claim 15, wherein the electrochemical detector, capacitance and impedance measuring device using the interdigitated array electrode is implemented by a multiplexer or / and a frequency generator. According to claim 1, wherein the bio-disc is information or apparatus related to the protocol, analysis algorithm, standard control value for reading or location information on the analysis site, bioinformatics information, self-diagnosis (self-diagonasis) It is equipped with driver software and patient education information for clinical analysis, a web site that can be remotely connected to specialist doctors and hospitals according to the diagnosis result, and memory or storage means or card IC for storing various links or personal encrypted information. Bio disk, characterized in that. Non-optical or optical bio-disc according to any one of claims 1 to 17; A control disk having a control unit for supplying a power or control signal necessary for the bio-disc; And an interface unit for connecting the bio disc and the control disc. 19. The bio-disc device of claim 18, wherein the interface unit is electrically connected to the bio-disc including a plurality of control signal connection units for supplying control signals and / or power connection units for power supply. 20. The bio-disc device according to claim 19, wherein the interface unit is formed by connecting connection grooves coated with a conductor on the bio-disc and conductor arms on the control disc to each other. 19. The bio-disc device according to claim 18, wherein the power supply to the control disc is made by frictional contact between a brush connected to an external power supply and an annular electrode plate on the control disc. 19. The bio-disc device according to claim 18, wherein the control disk is formed by a printed circuit board (PCB) or a circuit integrated on a silicon wafer. 19. The bio-disc device according to claim 18, wherein the fluid movement is caused by the centrifugal force induced by the bio-disc simultaneously rotating and mechanically coupled to the control disc and opening and closing the valve. 19. The apparatus of claim 18, wherein the control disk further comprises a contactless interface for sending readings of the assay site obtained by the detection device to an external central control device, storage device or output device via an infrared, optical or wireless interface. The bio-disc device characterized in that. 19. The bio-disc device according to claim 18, wherein the bio-disc and the control disc are combined into one integrated bio-disc. 26. The silicon wafer of claim 25, wherein the integrated bio-disc comprises a silicon wafer material, a silicon wafer containing the control circuit, a card IC, a non-contact interface, an electrode plate or electromagnet for controlling the valve, and various circuit patterns. A bio-disc device, which is designed as a monolithic integrated circuit by photolithography and etching processes. 26. The bio-disc device according to claim 25, wherein the integrated bio-disc is composed of an integrated bio-disc combined with a conventional optical disc (CD-RW, DVD-RW, CD or DVD). 18. A control disk comprising: a control unit for supplying power or control signals required for a non-optical or optical bio-disc according to any one of claims 1 to 17; A motor for rotating the disk; Power supply means for supplying power to a control unit on the control disk; An interface unit for supplying a control signal and / or a power signal of the controller to the bio disc; And a body supporting the bio driver. 29. The bio driver device of claim 28, further comprising a transducer coupled detector comprising a light transmissive measurement device for reading the assay site. 29. The bio driver according to claim 28, further comprising a non-contact interface means for sending a read result of the analysis site to an external central control device or storage or output device or to receive a command from the central control device. Device. 29. The circuit board according to claim 28, wherein a circuit board on which a central control device and a storage or output device are designed is jointly fastened to the bio drive body, and the central control device rotates a motor when the bio disc and the control disc are rotated or stopped. A bio driver apparatus for not only stopping, but also simultaneously rotating the control disk and the bio disk by mechanically and / or electrically connecting the control disk and the bio disk when the disk starts to rotate. 32. The bio driver apparatus according to claim 31, wherein the output device has a communication standard of USB (Universal Serial Bus) or IEEE1394. Non-optical or optical bio-disc according to any one of claims 1 to 17; A turn table for placing the bio-disc or ordinary optical disc; And a control disc having a control unit for supplying a power or control signal to the bio disc, wherein the control disc is fixedly coupled to the turn table to control the bio disc loaded on the turn table. Device. 34. The bio-disc device according to claim 33, wherein the control disc further comprises an electromagnet for controlling a thin film magnet embedded in the bio-disc. The bio-disc device of claim 33, wherein there is a height interval of 0.1-5 mm between the control disk fixedly coupled to the turn table and the bio-disc loaded on the turn table. The bio-disc device according to claim 33, wherein the control disc receives power from the outside by frictional contact between the rotating electrode and the brush to supply power to the bio-disc. The bio-disc device according to claim 33, wherein the control disk is formed by a printed circuit board (PCB) or a circuit integrated on a silicon wafer. 34. The apparatus of claim 33, wherein the control disk further comprises a contactless interface for sending readings of the analysis site obtained by the detection device to an external central control device, storage device or output device via an infrared, optical or wireless interface. The bio-disc device characterized in that. A turntable for placing a non-optical or optical bio-disc according to any one of claims 1 to 17 or a conventional optical disc; A control disk fixedly coupled to the turntable, for supplying power to the bio disk, and having a control unit and an electromagnet for controlling a valve embedded in the bio disk; A motor for rotating the disk; Power supply means for supplying a power supply to a control unit on the control disk; And a body supporting the bio driver. 40. The apparatus of claim 39, wherein the power supply means supplies positive power by frictional contact between the rotating electrode and the brush, and negative power supplies electrical power to a grounded motor or a grounded motor shaft. A bio driver apparatus, which is supplied to a control disk. 40. The bio driver device according to claim 39, further comprising a transducer coupled detection device comprising a light transmission measuring device for reading the analysis site. 40. The bio driver according to claim 39, further comprising a non-contact interface means for sending a read result of the analysis site to an external central control device or storage or output device or to receive a command from the central control device. Device. 40. The circuit board according to claim 39, wherein a circuit board on which the central control device and the storage means or the output device are designed is jointly fastened to the bio drive body, wherein the central control device stops the motor when the bio disc and the control disc rotate or stop. A bio driver device for rotating stop. 40. The bio driver apparatus according to claim 28 or 39, further comprising an optical pickup device for reading a conventional optical disc (e.g., music CD, CD-R, game CD, or DVD). The bio disc according to claim 44, wherein the controller determines whether the disc loaded in the bio driver device is an optical disc such as a general music CD, a CD-R, a game CD, a DVD, or a bio disc. And a bio-disc detection means. The bio-disc detection unit of claim 45, wherein the bio-disc detection unit measures the constant voltage generated by the voltage dividing unit disposed on the bio-disc by the control unit of the control disc. And (Bio-disc detection signal) to be wirelessly transmitted to the central control device via a non-contact interface, to notify the central control device that the currently loaded disk is a bio-disc. 46. The apparatus of claim 45, wherein the optical pickup device reads a groove pattern or a data pattern at a specific position on the bio disc so that the central controller recognizes that the disc currently loaded in the bio driver is a bio disc. Bio driver device, characterized in that. The apparatus of claim 45, wherein the central controller determines whether the optical disc is a normal optical disc (e.g., music CD, CD-R, game CD, DVD, etc.) or a bio disc. Normal operation for an optical disc such as transferring contents from the optical pickup device to a storage device or an output device, sending contents to be written to the optical pickup device, and providing various control signals necessary for read / write to the respective parts; And a bio-disc, wherein the bio driver apparatus transmits various control command signals for controlling the bio-disc through a non-contact interface. 46. The method of claim 45, wherein at the time of loading of the bio-disc via wireless contactless interface or card IC on the bio-disc, the wireless control unit transmits the newly loaded bio-disc to the central controller, thereby loading the current bio-driver. And causing the central controller to recognize that the disc is a bio disc. A channel through which fluid flows on the surface of the substrate, a chamber for storing a buffer solution, a solid substrate including a hole connecting the channel, and a valve for opening and closing the hole; At least one preparation chamber for preparing DNA samples from blood or cells or RNA; At least one PCR chamber for storing a buffer solution containing various enzymes including polymerase and primers necessary for PCR amplifying the prepared DNA sample; And a plurality of out chambers connected to the solid substrate to collect PCR products obtained by the PCR process. 51. The PCR bio disc apparatus according to claim 50, wherein the output chamber provides an outlet for collecting a PCR product by pipette or dice. 51. The apparatus of claim 50, wherein the solid substrate comprises: a ladder chamber for storing a ladder marker; PCR bio disc apparatus further comprising a control chamber and a stain chamber for storing positive control and negative control samples. 51. The PCR bio disc apparatus according to claim 50, wherein the PCR bio disc is integrated with the disc for electrophoresis. 51. The disk of claim 50, wherein the disk for electrophoresis further comprises an electrode for applying a voltage to a gel plate consisting of agarosdegel and / or polyacrylamide gel. PCR bio-disc device, characterized in that. 51. The PCR biodisk apparatus according to claim 50, wherein the PCR biodisk apparatus further comprises a UV (ultraviolet) irradiation apparatus and a camera to measure, store, and transmit a band. A preparation process step for preparing DNA samples from blood or cells or RNA; PCR process for amplifying the prepared DNA; Collecting the PCR products obtained by the PCR process in an out chamber; Moving the contents of the output chamber to an electrophoretic disk; Incubating while applying voltage to the electrophoretic electrode (gel running step); And measuring, storing, or transmitting a band, wherein the nucleic acid analysis method using the PCR bio-disc device according to claim 53. A preparation process step for preparing DNA samples from blood or cells or RNA; PCR process for amplifying the prepared DNA sample; A hybridization process step of hybridizing the DNA obtained by the PCR process with an analytical and diagnostic probe arrayed at an assay site; And reading the cleavable signal element in the assay site by means of a transducer coupled detector comprising a light transmission measuring device, an electrochemical, capacitance or impedance measuring device. Way. The method of claim 56 or 57, wherein the preparation process comprises the steps of injecting blood through a sample inlet installed in the preparation chamber; an incubation step for attaching the DNA extracted from the cell to the ferromagnetic beads; After the ferromagnetic beads are left standing, washing and flowing debris from the cell break down into the trech chamber while slowly rotating the bio disc; And, nucleic acid analysis method comprising the step of leaving or resuspension the DNA attached to the ferromagnetic beads (bead). 58. The method of claim 56 or 57, wherein the PCR process comprises: moving the DNA obtained by the preparation process to the PCR chamber while slowly rotating the bio disc; And amplifying the DNA by repeating the PCR cycle several times using a heater and a temperature sensor embedded in the PCR chamber after completion of DNA transfer to the PCR chamber. 60. The method of claim 59, further comprising: introducing DNAse into the PCR chamber while slowly rotating the bio-disc after the PCR process; A nucleic acid analysis method further comprising a fragmentation process comprising heating to a high temperature to stop the function of DNAse (stop incubation) and to make a single strand of DNA (denaturing step). 61. The nucleic acid analysis method according to claim 60, wherein fragmentation of DNA having different lengths is possible by fragmentation by providing an independent heater (independent incubation time) corresponding to each of the plurality of PCR chambers. Separating serum and antigen from blood through the filtration filter while slowly rotating the bio-disc; Rotating the bio-disc to introduce the antigen into the conjugate chamber, and incubating for 1-2 minutes to form a "conjugate-antigen conjugate" between the antigen and the conjugate antibody; Moving the “conjugate-antigen conjugate” into the assay site while slowly rotating the bio disc; Culturing the bio disc in a stationary state and culturing the antigen-antibody reaction between the “conjugate-antigen conjugate” and the capture antibody; A method of immunoassay using a bio-disc according to claim 6, comprising the step of washing the assay site by adding a washing buffer while the disc is rotating. 18. The method according to any one of claims 1 to 17, wherein the assay site is angular or radial in order to simultaneously analyze the immunoassay and nucleic acid probe assay. The bio-disc characterized by separating the immunoassay sector and the nucleic acid probe analysis sector. 40. The bio driver apparatus according to claim 28 or 39, wherein the bio disc is ejected or a warning message is sent to the user when the bio disc is loaded while the sample is not injected into the preparation chamber. The bio-disc according to any one of claims 1 to 17, further comprising an impedance measuring device in the preparation chamber to determine whether a sample is injected. 66. The bio-disc according to claim 65, wherein the impedance measuring device is an interdigitated array. 40. The method according to claim 28 or 39, wherein during the diagnosis or analysis of the sample, upon ejecting (un-loading) or stopping of the bio disc from the bio driver by the user, the bio driver is ignored and the analysis and diagnosis are continued. Optionally, a warning message (warning message) to inform the user or a bio-driver device characterized in that accepting the user's eject (un-loading) or stop request only if the password is correct. 40. The biodisc according to claim 28 or 39, further comprising a memory means for storing information on how many times the biodisc device has been used, expiration date information, and a type of disease to be diagnosed. The bio driver apparatus, characterized in that for each user can be provided with the diagnosis and whether the information is provided. The bio driver apparatus according to claim 28 or 39, wherein the bio driver apparatus comprises: a play and seek button, a stop button for normal optical disc playback; And a light emitting diode (LED) indicating that the currently loaded disk is a bio disk. 40. The bio driver device according to claim 28 or 39, wherein the bio driver device comprises a liquid crystal display device to determine a progress rate according to a main process (prep process, PCR process, hybridization process or antigen-antibody reaction) of the bio driver device. Or a bar graph format. 40. The bio driver apparatus according to claim 28 or 39, wherein the bio driver apparatus comprises a monitor display device to determine the progress of the bio driver apparatus according to the main process (prep process, PCR process, hybridization process or antigen-antibody reaction). The bio driver device, characterized by displaying in percentage (%), bar graph (pie graph), pie graph (pie graph) format. The bio driver apparatus according to claim 28 or 39, wherein the bio driver apparatus comprises: a play and seek button, a stop button for normal optical disc playback; And a display device for indicating that the currently loaded disk is a bio disk.