KR101803497B1 - Pcr module, pcr system having the same, and method of testing using the same - Google Patents

Pcr module, pcr system having the same, and method of testing using the same Download PDF

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KR101803497B1
KR101803497B1 KR1020160020053A KR20160020053A KR101803497B1 KR 101803497 B1 KR101803497 B1 KR 101803497B1 KR 1020160020053 A KR1020160020053 A KR 1020160020053A KR 20160020053 A KR20160020053 A KR 20160020053A KR 101803497 B1 KR101803497 B1 KR 101803497B1
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module
temperature
optical sensor
sensor assembly
signal
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KR1020160020053A
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KR20160112941A (en
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이도영
전인균
최안식
최경학
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(주)옵토레인
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Priority to US15/064,816 priority Critical patent/US10279352B2/en
Priority to CN201610209959.5A priority patent/CN105985905B/en
Priority to ES16160789T priority patent/ES2734281T3/en
Priority to EP16160789.0A priority patent/EP3069791B1/en
Publication of KR20160112941A publication Critical patent/KR20160112941A/en
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Publication of KR101803497B1 publication Critical patent/KR101803497B1/en
Priority to US16/361,594 priority patent/US10710084B2/en

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    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L7/00Heating or cooling apparatus; Heat insulating devices
    • B01L7/52Heating or cooling apparatus; Heat insulating devices with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/14Process control and prevention of errors
    • B01L2200/141Preventing contamination, tampering
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/14Process control and prevention of errors
    • B01L2200/143Quality control, feedback systems
    • B01L2200/147Employing temperature sensors
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/02Identification, exchange or storage of information
    • B01L2300/023Sending and receiving of information, e.g. using bluetooth
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/06Auxiliary integrated devices, integrated components
    • B01L2300/0627Sensor or part of a sensor is integrated
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/18Means for temperature control

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  • Chemical & Material Sciences (AREA)
  • Biochemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)
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  • Analytical Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Physics & Mathematics (AREA)
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Abstract

The PC Al module is detachably coupled to the reader system. The reader system includes a central information processing unit for receiving a light sensing signal to calculate a gene amplification amount in real time, and generating a temperature control signal using temperature signal and temperature control information. The PC Al module includes an optical sensor assembly, a partition, and an interface module. The optical sensor assembly includes a plurality of optical sensors arranged in an array to generate a light sensing signal by sensing emission light emitted from the sample, and a temperature sensor for sensing a temperature and outputting a temperature signal. The partition wall protrudes on the optical sensor assembly to define a reaction space for accommodating the sample. The interface module is electrically connected to the optical sensor assembly to transmit the light sensing signal and the temperature signal to the reader system.

Description

TECHNICAL FIELD [0001] The present invention relates to a PCR module, a PCR method using the PCR module, and a PCR method using the PCR module.

The present invention relates to a PC Al module, a PC Al system including the PC Al module, and a method of inspecting the PC Al module. More particularly, the present invention relates to a PC Al module to be detachably attached to a reader system capable of real- And a real time inspection method using the same.

Gene amplification technology is an indispensable process in molecular diagnostics and it is a technique to repeatedly replicate and amplify a specific base sequence of deoxyribonucleic acid (DNA) or ribonucleic acid (RNA) in a sample. Among them, Polymerase chain reaction (PCR) is a typical gene amplification technique consisting of DNA denaturation, primer annealing and DNA replication. Since the step depends on the temperature of the sample, DNA can be amplified by changing the temperature of the sample repeatedly.

Real-time PCR (real-time PCR) is a method for real-time monitoring of the amplification state of a sample in an amplification process. It enables the quantitative analysis of DNA by measuring the intensity of fluorescence whose DNA varies depending on the replication amount. Conventional real-time PC Al devices usually include a heat transfer block that transfers heat to a thermoelectric element and a tube containing the sample, a light source that irradiates the excitation light to the sample inside the tube, and a light receiving unit that receives fluorescence emitted from the sample .

At present, a table top type real time PC Al device is occupied by an optical part for detecting the fluorescence of the sample in about 80% of the total volume. Because of this, there is almost no mobility, so on-site diagnosis is almost impossible and the equipment price is very expensive. In addition, it takes a lot of time to rearrange and correct the error due to moving process due to relocation, device relocation, and the like.

It also takes a lot of time to set up various reagents and the possibility of contamination is high. Furthermore, since the size of the system is so large, most of them are constituted by independent systems and it is difficult to exchange information with the outside.

An object of the present invention is to provide a PC Al module which is detachably coupled to a reader system capable of real-time inspection.

It is an object of the present invention to provide a PCA system including the PCAl module.

An object of the present invention is to provide a real-time inspection method using a PC al system including the PC Al module.

In order to achieve the above object, the PC Al module is detachably coupled to a reader system. The reader system includes a central information processing unit which receives a photodetection signal and calculates a gene amplification amount in real time and generates a temperature regulation signal by using a temperature signal and temperature control information; A memory for storing control information; and an interface connected to the central information processing unit for transmitting the amplified amount of the gene, which is received from the central information processing unit in real time, to the outside or for applying an external input signal to the central information processing unit. The PC Al module includes an optical sensor assembly, a partition, and an interface module. The optical sensor assembly includes a plurality of optical sensors arranged in an array to generate a light sensing signal by sensing emission light emitted from the sample, and a temperature sensor for sensing a temperature and outputting a temperature signal. The partition wall protrudes on the optical sensor assembly to define a reaction space for accommodating the sample. The interface module is electrically connected to the optical sensor assembly to transmit the light sensing signal and the temperature signal to the reader system.

In one embodiment, the PC Al module includes a light source for supplying light to the reaction space, an optical filter disposed on an upper surface of the optical sensor assembly for transmitting the emitted light, and an opaque material The cover may further include a cover.

In one embodiment, the reader system further includes a light source for supplying light to the reaction space, and the PC Al module may further include a cover defining an upper portion of the reaction space and including a transparent material.

In one embodiment, the reader system may further include a temperature control module that receives the temperature control signal and adjusts the temperature of the reaction space.

In one embodiment, the PC Al module further includes a temperature controller for receiving the temperature control signal and adjusting the temperature of the reaction space. The interface module may receive the temperature control signal and apply the temperature control signal to the temperature controller. have.

In one embodiment, the reader system may further comprise a thermal conductor surrounding the PC Al module, and a temperature-maintaining member held at a constant temperature and exchanging heat with the thermal conductor.

In one embodiment, the PC Al module may further include a thermal conductor for receiving the temperature control signal and transferring the heat of the reaction space to the outside.

In one embodiment, the PC Al module may further include a heating unit that receives the temperature control signal to increase the temperature of the reaction space.

In one embodiment, the photosensor may have a plurality of photosensor units connected to one output electrode.

In one embodiment, the optical sensor assembly may further include an optical sensor array including a plurality of optical sensors including a different number of optical sensor units.

In one embodiment, the reader system may be detachably coupled to a plurality of PC Al modules.

In one embodiment, the PC Al module comprises a hydrophilic material disposed on the optical sensor assembly and dissolved or not dissolved when mixed with water, wherein the polymer chains or polymer chains are crosslinked to maintain a three-dimensional structure, Small DNA attached near the sequence may include a 3D organic pad containing a primer that is a starting point when the polymerase amplifies the DNA.

In one embodiment, the 3D organic pad may include a hydrogel pad or a spin on glass (SOG) pad.

In one embodiment, the optical sensor assembly and the interface module may be electrically connected using wire bonding.

In one embodiment, the optical sensor assembly and the interface module may be electrically connected using a silicon through electrode.

In order to achieve the above object, the PC Al system includes a reader system and a PC Al module. The reader system includes a central information processing unit, a memory, and an interface. The central information processing unit receives the photodetection signal, calculates the amplification amount of the gene in real time, and generates a temperature regulation signal using the temperature signal and the temperature control information. The memory is connected to the central information processing unit to store the gene amplification amount and the temperature control information. The interface is connected to the central information processing unit and transmits the amplified amount of gene amplified in real time from the central information processing unit to the outside or applies an external input signal to the central information processing unit. The PC Al module includes an optical sensor assembly, a partition, and an interface module. The optical sensor assembly includes a plurality of optical sensors arranged in an array to generate a light sensing signal by sensing emission light emitted from the sample, and a temperature sensor for sensing a temperature and outputting a temperature signal. The partition wall protrudes on the optical sensor assembly to define a reaction space for accommodating the sample. The interface module is electrically connected to the optical sensor assembly to transmit the light sensing signal and the temperature signal to the reader system. The PC Al module is detachably coupled to the reader system.

In one embodiment, the reader system further includes a second temperature control module for decreasing the temperature of the PC Al module using the temperature control signal, wherein the PC Al module controls the temperature of the reaction space The temperature control unit may further include a first temperature control unit for increasing the temperature of the first temperature control unit.

In order to achieve the above object, the present invention provides a method of inspecting a PC system using a PC system, the PC system including a PC module and a reader system. The reader system includes a central information processing unit, a memory, and an interface. The central information processing unit receives the photodetection signal, calculates the amplification amount of the gene in real time, and generates a temperature regulation signal using the temperature signal and the temperature control information. The memory is connected to the central information processing unit to store the gene amplification amount and the temperature control information. The interface is connected to the central information processing unit and transmits the amplified amount of gene amplified in real time from the central information processing unit to the outside or applies an external input signal to the central information processing unit. The PC Al module is detachably coupled to the reader system. The PC Al module includes an optical sensor assembly, a partition, and an interface module. The optical sensor assembly includes a plurality of optical sensors arranged in an array to generate a light sensing signal by sensing emission light emitted from the sample. The partition wall protrudes on the optical sensor assembly to define a reaction space for accommodating the sample. The interface module is electrically connected to the optical sensor assembly to transmit the light sensing signal and the temperature signal to the reader system. In the inspection method using the PC Al system, sample information is input first. Subsequently, the sample information is matched with the reagent information. Thereafter, the PC Al module in which the reagent matched to the reagent information is embedded is manufactured. Subsequently, the sample is injected into the PC Al module, and the sample is analyzed by mounting the sample in the reader system.

In one embodiment, the step of matching the sample information with the reagent information may include checking whether there is a reagent matching the sample information among the previously stored reagent information.

In one embodiment, when there is no reagent matching the sample information among the previously stored reagent information, transmitting the reagent information to a plurality of reagent developer terminals, and transmitting the reagent information to the reagent developer terminal And selecting the developer of the reagent to develop the reagent.

In order to achieve the above object, the PCA system includes a PCA module and a reader system. The PC Al module includes an optical sensor assembly, a 3D organic pad, and a reaction vessel. The optical sensor assembly includes a plurality of optical sensors arrayed in an array. Wherein the 3D organic pad is disposed on the optical sensor assembly and is not dissolved or dissolved when mixed with water, the polymer chain or the polymer chain is crosslinked to maintain a three-dimensional structure, and a small As a DNA, a polymerase includes a primer that is a starting point when DNA is amplified. The reaction vessel is disposed on the optical sensor assembly and houses the 3D organic pad. The reader system includes a central information processing unit, a memory, and an interface. The central information processing unit receives the light sensing signal from the PC Al module and calculates the amplification amount of the gene in real time, receives the temperature signal corresponding to the temperature of the reaction container in real time, and compares it with the temperature control signal to generate the temperature control signal . The memory is connected to the central information processing unit to store the gene amplification amount and the temperature control information. The interface is connected to the central information processing unit and transmits the amplified amount of gene amplified in real time from the central information processing unit to the outside or applies an external input signal to the central information processing unit.

According to another aspect of the present invention, there is provided a method of manufacturing a PSA module, the PSA module including: an optical sensor assembly including a plurality of optical sensors arranged in an array; A hydrophilic substance which is not dissolved or dissolved when mixed with water and which has a polymer chain or a polymer chain crosslinked to maintain a three-dimensional structure, and a polymerase that amplifies the DNA as a small DNA attached near the genetic sequence to be amplified And a reaction vessel disposed on the optical sensor assembly and containing the 3D organic pads. The PC Al module is applied to a PC Al system including a reader system that receives a photodetection signal to calculate a gene amplification amount in real time and adjusts the temperature to the reaction container. In the method of manufacturing the PC Al module, the optical sensors are first formed on a substrate using a semiconductor process. Next, the 3D organic pads are formed on the substrate on which the optical sensors are formed.

In order to accomplish the object of the present invention, a method for inspecting an object of the present invention comprises disposing a reaction vessel and a PCR module having an optical sensor for detecting fluorescence emitted from the reaction vessel, (Reader System) which drives the reader. The reader system receives a light sensing signal from the PC Al module and calculates a genetic amplification amount in real time and receives a temperature signal corresponding to the temperature of the reaction container in real time to generate a temperature control signal by comparing with a temperature control signal A memory for storing the gene amplification amount and the temperature control information in association with the central information processing unit; a temperature control module for controlling the temperature of the PC Al module in response to the temperature control signal; And an interface connected to the information processing unit to transmit the amplified amount of the gene that is received in real time from the central information processing unit to the outside or to apply an external input signal to the central information processing unit. In the above inspection method, first, sample information is input. Subsequently, the sample information is matched with the reagent information. Thereafter, the PC Al module in which the reagent matched to the reagent information is embedded is manufactured. Subsequently, a sample is injected into the PC Al module, and the sample is analyzed by mounting the sample in the reader system.

According to the present invention, the optical part is embedded in the PC Al module, and the PC Al module is formed in a detachable module form, thereby greatly reducing the size of the reader system. In addition, the size of PC Al module and reader system is drastically reduced and manufacturing costs are reduced.

In addition, even if the reader system is moved, since reordering due to device rearrangement and correction are unnecessary, the mobility can be remarkably improved and the field inspection can be performed. Especially, in case of an emergency such as infectious disease inspection, identification of the disaster scene, it is possible to input immediately, which can contribute to reduce the damage.

In addition, since the reagent is introduced in the PC Al module, there is no need for a separate procedure for setting the reagent, so that the possibility of contamination is drastically reduced and a separate procedure for preparation of the test is not necessary.

In addition, since it is possible to exchange information with the outside through the Internet, various customers and a large number of reagent developers can establish a system such as an app store or market through a central processing server to exchange reagents and information.

In addition, the PCAl module includes a plurality of hydrogel pads, and each hydrogel pad is provided with a different primer to detect multiple genotypes.

In addition, since a general multi-detection method uses a method of changing the fluorescence wavelength, there is a problem that the structure of the optical part is complicated. However, in this embodiment, the arrangement of the different primers in the respective hydrogel pads enables the multi-detection even if a single fluorescent material is used, so that the structure of the optical sensor assembly is simplified.

By alternately arranging the samples and the buffer in the sample injecting unit, the samples can be injected into the plurality of hydrogel pads sequentially by a simple operation of applying pressure to one side of the sample injecting unit.

In addition, in the conventional array method, the gene amplification rate is very slow because the dielectric material is disposed only on the surface. However, the hydrogel pad has a very fast gene amplification rate because gene amplification occurs not only on the surface but also inside the hydrogel pad due to the three-dimensional structure of the polymer chain. Therefore, it is possible to real-time gene amplification by position by forming an array with hydrogel pads. In addition, since the fluorescence is emitted only from the hydrogel pad, the intensity of the detected signal is increased due to an increase in the amount of light, and more sensitive experiments are possible.

In addition, the PC Al module can include a thermal conductor and a heating part to easily adjust the temperature of the reaction space.

In addition, by using a plurality of optical sensors including different numbers of optical sensor units, optimized detection can be performed according to the size of input light, and accuracy is improved by using signals output from the plurality of optical sensors.

Also, since the optical sensor assembly includes the light source driving unit or the driving circuit unit, the size of the PC Al system can be further reduced.

1 is a block diagram illustrating a reader system for a PC Al module according to an embodiment of the present invention.
FIG. 2 is a perspective view showing the reader system for the PC Al module shown in FIG. 1. FIG.
3 is a graph showing temperature control data of the reader system for the PC Al module shown in FIG.
4 is a graph showing the temperature of the reaction vessel of the PC Al module according to the control of the reader system for the PC Al module shown in FIG.
5 is a graph showing a temperature control signal of the reader system for the PC Al module shown in FIG.
6 is a block diagram showing the second temperature control unit shown in Fig.
7 is a block diagram illustrating a reader system for a PC Al module according to another embodiment of the present invention.
8 is a block diagram illustrating an inspection method according to an embodiment of the present invention.
Fig. 9 is a flowchart showing the inspection method shown in Fig.
10 is a perspective view illustrating a PC Al module according to an embodiment of the present invention.
11 is a cross-sectional view taken along line I-I 'of FIG.
12 to 15 are sectional views showing a method of manufacturing the PC Al module shown in FIG.
16 is a cross-sectional view illustrating a PC Al module according to another embodiment of the present invention.
17 to 22 are sectional views showing a method of manufacturing the PC Al module shown in FIG.
23 is a cross-sectional view illustrating an inspection method using a PC Al module according to another embodiment of the present invention.
24 is an enlarged sectional view showing a hydrogel pad used in a method of inspecting using a PC Al module according to an embodiment of the present invention.
25 is a cross-sectional view illustrating a PC Al module according to another embodiment of the present invention.
26 is a cross-sectional view illustrating a PC Al module according to another embodiment of the present invention.
27 is a cross-sectional view illustrating a PC Al module according to another embodiment of the present invention.
28 is a cross-sectional view illustrating a PC Al module according to another embodiment of the present invention.
29 is a cross-sectional view illustrating a PC Al module according to another embodiment of the present invention.
30 is a plan view showing a constant temperature member according to an embodiment of the present invention.
31 is a cross-sectional view taken along the line T-T 'in FIG.
32 is a cross-sectional view illustrating a PC Al module according to another embodiment of the present invention.
33 is a cross-sectional view illustrating a PC Al module according to another embodiment of the present invention.
34 is a cross-sectional view illustrating a PCA module according to another embodiment of the present invention.
35 is a cross-sectional view illustrating a PC Al module according to another embodiment of the present invention.
36 is a plan view showing an optical sensor according to an embodiment of the present invention.
37 is a plan view showing an optical sensor according to another embodiment of the present invention.
38 is a plan view showing an optical sensor according to another embodiment of the present invention.
39 is a plan view showing an optical sensor according to another embodiment of the present invention.
40 is a plan view showing an optical sensor array manufactured by combining Figs. 36 to 39. Fig.
41 is a graph showing an output signal of the photosensor array shown in Fig.
42 is a sectional view showing an optical sensor assembly according to an embodiment of the present invention.
43 is a cross-sectional view showing an optical sensor assembly according to another embodiment of the present invention.

Hereinafter, a reader system for a PC Al module according to the present invention and an inspection method using the same will be described in detail with reference to the accompanying drawings.

FIG. 1 is a block diagram showing a reader system for a PC Al module according to an embodiment of the present invention, and FIG. 2 is a perspective view illustrating a reader system for a PC Al module shown in FIG. 1.

Referring to FIGS. 1 and 2, a reader system 100 for a PC Al module is detachably coupled to a PC Al module (PCR module 200) to drive the PC Al module 200. 2, one PC Al module 200 is shown coupled to the reader system 100, but one skilled in the art will appreciate that a plurality of PC Al modules 200 can be coupled to one reader system 100 at a time It will be understood that modifications may be made.

The reader system 100 includes a central information processing unit 110, a memory 120, an interface 130, a second temperature controller 150, a light source 230, a light source filter 233, and a light source driver 220 do.

The central information processing unit 110 reads the driving data stored in the memory 120 to drive the second temperature control unit 150 and the PC Al module 200 and outputs optical sensing information and temperature information from the PC Al module 200 And stores it in the memory 120 in real time. The central information processing unit 110 generates the gene amplification amount information by calculating the amplification amount of the gene in real time using the optical sensing information and the temperature information received from the PC Al module 200 in real time. The central information processing unit 110 stores the gene amplification amount information in the memory 120 in real time and transmits the information to the interface 130.

The light source driving unit 220 drives the light source 230 using the light source driving signal received from the central information processing unit 110.

The light source 230 generates an excitation light using the light source driving signal.

The light source filter 233 is disposed under the light source 230 to filter the excitation light generated by the light source 230. For example, the light source filter 233 may filter the excitation light to transmit light having a wavelength of a specific band.

A sample in the reaction vessel 240 is inspected using light that has passed through the light source filter 233. The reason for disposing the light source filter 233 in this embodiment is to minimize the noise due to the external light to reduce the error of the optical sensor 250 due to the change in the brightness of the external light.

3 is a graph showing temperature control data of the reader system for the PC Al module shown in FIG.

1 to 3, the temperature control data represents a temperature corresponding to the point of time at which the PC Al module 200 is driven. For example, the temperature control data may include data for one cycle in which the temperature is sequentially changed with time at 95 ° C, 55 ° C, 25 ° C, 55 ° C, 95 ° C, 64 ° C and 72 ° C.

1 to 5, the temperature control signal includes a signal for controlling the temperature so that the temperature of the reaction container 240 in the PC Al module 200 corresponds to the temperature control data. For example, the temperature of the sample includes a constant section PU, a section P3, P4, P6, P7 where the temperature rises, a section P1, P2, P5 where the temperature falls, and the like.

The section PU in which the temperature is maintained is a section where the temperature is maintained without changing the temperature in the reaction vessel 240. The reaction vessel 240 has a thermal / The central information processing unit 110 compares the current temperature of the temperature control data with the current temperature of the reaction container 240 to generate a temperature control signal for slightly heating / cooling the temperature of the reaction container 240, 1 temperature controller 270 and the second temperature controller 150, respectively.

The temperature rise sections P3, P4, P6 and P7 are sections in which the temperature in the reaction vessel 240 rises sharply and rapidly raise the temperature of the reaction vessel 240 by heating the PC Al module 200 rapidly. In the present embodiment, a temperature control signal corresponding to a temperature higher than the target temperature to be raised is generated at the initial stage P1 of the temperature raising period to rapidly heat the reaction vessel 240, And generates a convergent temperature control signal. For example, the temperature control signal is boosted (B1) at an initial stage of the boosting period P1 corresponding to a period in which the temperature is changed. The boosted magnitude B1 has a magnitude of 1/5 to 1/2 of the temperature change value D1. When the boosted size B1 is smaller than 1/5 of the temperature change value D1, the boosting effect is small and the time for the temperature to change to the target temperature increases. If the boosted magnitude B1 is larger than 1/2 of the temperature change value D1, the boosted temperature is too high and a part of the sample may be deformed.

The intervals P1, P2, and P5 where the temperature falls are drastically lowered in the reaction vessel 240, and the temperature of the reaction vessel 240 is lowered by rapidly cooling the PC Al module 200. In the present embodiment, a temperature control signal corresponding to a temperature lower than the target temperature to be lowered is generated at the beginning of the temperature lowering unit so as to rapidly cool the reaction vessel 240 and to converge to a temperature to be gradually lowered And generates an adjustment signal.

In this embodiment, the temperature of the reaction vessel 240 is rapidly boosted by boosting the temperature of the reaction vessel 240 to prevent deterioration of the sample in the reaction vessel 240 and to improve the reliability of the experiment .

The memory 120 is connected to the central information processing unit 110 to drive the second temperature control unit 150 and the PC Al module 200 using the previously stored drive data and to display the optical sensing information, . The drive data includes temperature control data, light control data, and the like, and may be stored in the form of data in the memory 120 or may be input from outside via an input device (not shown) and stored. For example, the memory 120 may include various storage devices such as DDR3, SRAM (Frame), SSD (FLASH), and the like.

The interface 130 is connected to the central information processing unit 110 and transmits the amplified amount of gene amplification information received from the central information processing unit 110 to the outside or the input signal of the upper part to the central information processing unit 110. In this embodiment, the interface 130 includes a communication system (not shown) such as a wireless LAN (WLAN), a WiFi, a Bluetooth, etc., a universal serial bus (USB) (I 2 C), a Universal Asynchronous Receiver / Transmitter (UART), a Pulse Width Modulation (PWM), a Low Voltage Differential Signaling (LVDS), a Mobile I / (LCD), an organic light emitting display (OLED), a cathode ray tube (CRT), and a cathode ray tube An output device (not shown) such as a display device (not shown) such as a mouse, a keyboard, an input device (not shown), a printer, or a fax machine.

The second temperature control unit 150 is connected to the central information processing unit 110 and controls the temperature of the PC Al module 200 using the temperature control data supplied from the central information processing unit 110.

6 is a block diagram showing the second temperature control unit shown in Fig.

1 to 6, the second temperature control unit 150 includes an auxiliary information processing unit 152 and a thermal control unit 154.

The auxiliary information processing unit 152 applies the temperature control signal applied from the central information processing unit 110 to the thermal control unit 154. [

The thermal controller 154 adjusts the temperature of the PC Al module 200 according to the temperature control signal applied from the auxiliary information processor 152. In this embodiment,

The thermal control unit 154 includes a temperature sensor 154a and an air-cooled fan (Fan, 154b). The temperature sensor 154a measures the temperature of the PC Al module 200 and transmits the measured temperature to the auxiliary information processor 152. [ The fan 154b heats or cools the PC Al module 200 according to the temperature control signal.

In another embodiment, the thermal control 154 does not include the temperature sensor 154a and the air-cooled fan 154b, and may include a thermoelectric element (not shown). In another embodiment, the thermal control 154 may include a water cooled cooling unit (not shown).

In accordance with the control of the reader system 100, the PC Al module 200 amplifies the dielectric material contained in the sample and monitors the amount of the amplified dielectric material in real time to transmit the optical sensing signal to the reader system 100. In this embodiment, the PC Al module 200 also transmits a temperature signal to the reader system 100.

In this embodiment, the PC Al module 200 includes a control interface 210, a reaction container 240, an optical sensor 250, a temperature sensor 260, and a first temperature controller 270. For example, the PC Al module 200 is an interchangeable module having a unique sample, which can be used after being used for one time and discarded. In another embodiment, the PC Al module 200 may include a light source driver 220 and a light source 230.

In one embodiment, the control interface 210 receives the temperature control signal from the reader system 100 and transmits it to the first temperature controller 270. The control interface 210 receives the optical sensing signal generated by the optical sensor 250 and the temperature signal generated by the temperature sensor 260 and transmits the received optical sensing signal to the reader system 100.

The reaction vessel 240 houses the sample and amplifies the dielectric material contained in the sample. In this embodiment, the reaction vessel 240 may include only one storage space or may include two or more storage spaces. When the reaction vessel 240 includes two or more receiving spaces, it is possible to simultaneously test one sample or a plurality of samples.

The reaction vessel 240 may include various materials such as silicon, plastic, and the like.

The light sensor 250 is disposed adjacent to the reaction vessel 240 and is configured to emit light emitted from the sample placed in the reaction vessel 240 using the light generated by the light source 230 and passed through the light source filter 233, And the luminance of the light is measured. For example, emitted light may include fluorescence, phosphorescence, and the like. The brightness of the emitted light measured by the optical sensor 250 is changed to a light sensing signal and applied to the control interface 210. [

The temperature sensor 260 is disposed adjacent to the reaction vessel 240 to represent the temperature of the sample placed in the reaction vessel 240. The temperature measured by the temperature sensor 260 is changed to a temperature signal and applied to the control interface 210.

The first temperature control unit 270 is disposed in contact with the reaction vessel 240 to adjust the temperature of the reaction vessel 240. In this embodiment, the first temperature control unit 270 receives the temperature control signal from the control interface 210, and maintains the temperature of the reaction container 240 at a specific temperature, or heats or cools it. For example, the first temperature controller 270 may include a heater, a thermoelectric element, a cooler, or a combination thereof.

In this embodiment, the first temperature controller 270 raises the temperature of the reaction container 240, and the second temperature controller 150 can lower the temperature of the counter container 240. In another embodiment, the first temperature controller 270 and the second temperature controller 150 may be integrally formed.

In this embodiment, a substance having high thermal conductivity is disposed between the temperature sensor 260 and the reaction container 240 and between the first temperature control unit 270 and the reaction container 240 to allow heat to be conducted smoothly . For example, a variety of materials such as silicon, glass, metal, metal compound, synthetic resin, etc. may be formed between the temperature sensor 260 and the reaction container 240 and between the first temperature control unit 270 and the reaction container 240 .

In this embodiment, the arrangement of the light source 230, the optical sensor 250, the temperature sensor 260, the first temperature controller 270, and the reaction vessel 240 may have various combinations. For example, the light source 230 may be disposed on one side of the reaction vessel 240, and the light sensor 250 may be disposed on the other side thereof. The light source 230 and the light sensor 250 are disposed on the same side so that the brightness of the light source 230 may be measured instead of the actual brightness of the reaction container 240. Therefore, Are disposed on different sides.

The first temperature controller 270 may be disposed on the same plane as the optical sensor 250. When the temperature sensor 260 and the first temperature controller 270 are disposed on the same side surface, the temperature of the first temperature controller 270 may be measured instead of the actual temperature of the reaction vessel 240. Therefore, And the first temperature controller 270 are disposed on different sides.

In the present embodiment, a temperature sensor may employ a combined temperature sensor system including a temperature sensor 260 of the PC Al module 200 and a temperature sensor 154a of the reader system 100. [ In another embodiment, it may include only the temperature sensor 260 of the PC Al module 200 that is formed integrally with the optical sensor 250. In another embodiment, a photosensor (not shown) may be integrally formed with the second temperature controller 150.

7 is a block diagram illustrating a reader system for a PC Al module according to another embodiment of the present invention. In the present embodiment, the remaining components except for the light source and the light source driving unit are the same as those in FIG. 1 to FIG. 6, so that duplicated description of the same components will be omitted.

Referring to FIG. 7, the reader system 100 for a PC Al module is detachably coupled to a PC Al module (PCR module 200) to drive the PC Al module 200.

The reader system 100 includes a central information processing unit 110, a memory 120, an interface 130, and a second temperature control unit 159.

The PC Al module 200 includes a control interface 210, a light source 230, a light source filter 233, a reaction container 240, an optical sensor 250, a temperature sensor 260, a first temperature controller 270, . The PC Al module 200 is an interchangeable module having a unique sample, which can be used after being used in a single use and discarded.

FIG. 8 is a block diagram showing an inspection method according to an embodiment of the present invention, and FIG. 9 is a flowchart illustrating an inspection method shown in FIG. In the present embodiment, the reader system and the PC al module are the same as the embodiment shown in Figs. 1 to 7, so that redundant description of the same components will be omitted.

Referring to FIGS. 2, 8, and 9, first, sample information is input through the customer terminal 1200 (step S110). The sample information input to the customer terminal 1200 is transmitted to the central processing server 1000 through a communication network such as the Internet. For example, the customer terminal 1200 includes various types of terminals capable of wired / wireless communication such as a smart phone, a personal computer, and the like.

Then, the central processing server 1000 matches the sample information inputted through the customer terminal 1200 with the previously stored reagent information (step S120).

Thereafter, it is checked whether there is a reagent matching the inputted sample information from the previously stored reagent information (step S130).

If there is a reagent matching the sample information inputted from the previously stored reagent information, information for purchasing the reagent is transmitted to the reagent developer terminal 1100 (step S140).

If there is no reagent matching the sample information inputted from the previously stored reagent information, the information about the developer selection is transmitted to the plurality of reagent developer terminals 1100, and the information transmitted from the reagent developer terminal 1100 The developer of the reagent is selected (step S150) and the reagent is developed (step S160).

Next, the sample is analyzed using the reader system 100 and the PC Al module 200 shown in FIGS. 1 to 7 (step S170). In this embodiment, the PC Al module 200 is provided with a built-in reagent provided by the reagent developer. After the sample supplied by the customer is injected into the PC Al module 200 containing the reagent, the sample is loaded into the reader system 100 and analyzed. In this embodiment, since the reader system 100 can be downsized, it can be formed integrally with the customer terminal 1200.

Thereafter, the analyzed result is transmitted to the central processing server 1000 and / or the customer terminal 1200 (step S180).

FIG. 10 is a perspective view showing a PC Al module according to an embodiment of the present invention, and FIG. 11 is a sectional view taken along line I-I 'of FIG. In this embodiment, the remaining components except for the hydrogel pad are the same as those in the embodiment shown in Figs. 1 to 9, so that redundant description of the same components will be omitted. For convenience of explanation, the partition wall and the cover are omitted in Fig.

10 and 11, the PC Al module includes an optical sensor assembly 300, a 3D organic pad, a partition 320, and a cover 350. In this embodiment, the 3D organic pad includes a hydrogel pad 400, a spin on glass (SOG) pad, etc. as a pad capable of three-dimensionally amplifying a sample containing a dielectric material.

The optical sensor assembly 300 includes an optical sensor array 310, a fluorescence filter 313, a first temperature controller 370, and a temperature sensor 360. The optical sensor array 310 includes a plurality of optical sensors arrayed in an array. For example, the photosensor array 310 may include a plurality of photodiodes, a plurality of thin film transistors, and the like.

The fluorescence filter 313 is disposed on the optical sensor array 310 to filter out noises of external light, light generated from a light source, and the like, and transmit only fluorescence generated in the sample.

The hydrogel pad 400 is disposed on the optical sensor assembly 300 and includes a hydrogel. A hydrogel is a hydrophilic material that, when mixed with water, is not dissolved or dissolved and the polymer chains or polymer chains are crosslinked to maintain a three-dimensional structure, including polymer chains that form multiple cross links. For example, the hydrogel may be selected from the group consisting of polyethylene diacrylate (PEGDA) hydrogel, PMA hydrogel, polydimethylamino acrylamide (PDGPA) hydrogel, polyethyloxazoline, silicone hydrogel, And various types of hydrogels. In this embodiment, the hydrogel pad 400 may comprise a PEGDA hydrogel.

In another embodiment, a pad (not shown) may be formed using Spin On Glass (SOG) instead of the hydrogel pad 400.

The hydrogel pads 400 may be formed in a circular disc shape, a square disc shape, a hexagonal disc shape, a hexahedron shape, a bowl shape, a pillar shape with a groove at the center, a concave lens shape, a convex lens shape, And can have various shapes.

In this embodiment, the hydrogel pads 400 can be formed by photo-patterning using an optical mask and ultraviolet rays. In another embodiment, a raw hydrogel pad (not shown) may be formed using an external photoprocessing process and then placed on the optical sensor assembly 300 to join the hydrogel pad 400. For example, the hydrogel pads 400 may be sequentially dripped by flowing a raw hydrogel pad (not shown) along with the fluid on the optical sensor assembly 300. Alternatively, various methods such as printing, sticking, etc. may be used.

The hydrogel pad 400 includes a primer and a DNA probe. A primer is a small DNA attached near the genomic sequence to be amplified, and is a starting point when polymerase amplifies DAN. A DNA probe refers to a DNA fragment of short length that is bound to the specific DNA for detection of a specific DNA. In another embodiment, a DNA chip may be used in place of the hydrogel pad 400.

In this embodiment, the PC Al module includes a plurality of hydrogel pads 400, and each of the hydrogel pads 400 is provided with another primer to detect multiple genotypes. In one embodiment, if the same primers are arranged along the same column and different primers are arranged when the columns are different, a plurality of data detected in the same column are compared to secure the reliability of the test results It is possible.

In addition, since a general multi-detection method uses a method of changing the fluorescence wavelength, there is a problem that the structure of the optical part is complicated. However, in the present embodiment, by arranging different primers in each of the hydrogel pads 400, even if a single fluorescent material is used, multiple detection can be performed, so that the structure of the optical sensor assembly 300 is simplified.

In addition, in the conventional array method, the gene amplification rate is very slow because the dielectric material is disposed only on the surface. However, since the hydrogel pad 400 has a three-dimensional structure of the polymer chain, the gene amplification is performed not only on the surface but also inside the hydrogel pad 400, so that the gene amplification rate is very fast. Accordingly, an array is formed by the hydrogel pads 400, and real-time gene amplification is possible by position. Since the fluorescence is emitted only from the hydrogel pad 400, the intensity of the detected signal is increased due to an increase in the amount of light, and more sensitive experiments are possible.

The partition 320 extends from the edge of the optical sensor assembly 300 to form a reaction vessel 340. The barrier ribs 320 may be formed of various materials such as plastic, PDMS, silicon, and metal.

The cover 350 covers the top of the partition 320 and is formed with an inlet 352 and an outlet 354. A sample (not shown) is injected into the reaction vessel 340 via an inlet 352 and the reaction sample (not shown) is discharged to the outside through an outlet 354.

12 to 15 are sectional views showing a method of manufacturing the PC Al module shown in FIG.

Referring to FIG. 12, first, the optical sensor assembly 300 is formed. In this embodiment, a photosensor array 310, a temperature sensor 360, and a first temperature controller 370 are formed on a base substrate, and a fluorescent filter 313 is formed thereon. For example, the optical sensor array 310, the temperature sensor 360, and the first temperature controller 370 may be formed through a semiconductor process.

Referring to FIG. 13, hydrogels 400a and 400b are coated on the optical sensor assembly 300. FIG. A portion 400a of the coated hydrogels 400a and 400b is exposed through a mask 407. [

Referring to FIG. 14, the coated hydrogels 400a and 400b are developed to form the hydrogel pads 400.

Referring to FIG. 15, a partition 320 and a cover 350 are formed on an optical sensor assembly 300 on which a hydrogel pad 400 is formed.

16 is a cross-sectional view illustrating a PC Al module according to another embodiment of the present invention. In this embodiment, the remaining components except for the banks are the same as those in the embodiment shown in Figs. 10 and 11, so duplicate descriptions of the same components will be omitted.

Referring to FIG. 16, the PC Al module includes an optical sensor assembly 300, a hydrogel pad 401, a partition 320, a bank 325, and a cover 350.

The banks 325 are disposed on the photosensor assembly 300 and form spaces partitioned into an array. The banks 325 may include a variety of materials such as inorganic insulating materials, photoresists, plastics, silicon, metals, and the like.

The hydrogel pad 401 is disposed in a space defined by the adjacent banks 325 on the optical sensor assembly 300 and includes a hydrogel.

The barrier ribs 320 extend from the edges of the optical sensor assemblies 300 on which the banks 325 are formed to form reaction vessels 340. The barrier ribs 320 may include various materials such as silicon, plastic, rubber, polymer, metal, ceramic, PDMS, carbon based materials, and the like.

17 to 22 are sectional views showing a method of manufacturing the PC Al module shown in FIG.

Referring to FIG. 17, first, the optical sensor assembly 300 is formed.

Referring to FIG. 18, a bank 325 is formed on the optical sensor assembly 300. In this embodiment, the banks 325 may be formed by various methods such as a photolithography process, a fining process, and a nano-fabrication process.

Referring to FIG. 19, a hydrogel liquid droplet 401a is dripped into a space formed by the adjacent banks 325. In this embodiment, the dripped hydrogel droplet 401 'may have fluidity without curing.

Referring to FIGS. 20 and 21, ultraviolet rays (UV) are irradiated (490) on the hydrogel droplet 401 'to be subsequently dropped to form a hydrogel pad 401.

22, the barrier 320 and the cover 350 are formed on the optical sensor assembly 300 on which the hydrogel pads 401 are formed.

23 is a cross-sectional view illustrating an inspection method using a PC Al module according to another embodiment of the present invention. In this embodiment, the remaining components except for the sample injecting portion, the bank, the bank, and the cover are the same as the embodiment shown in FIG. 16, so that a duplicated description of the same components will be omitted.

Referring to FIG. 23, the PC Al module includes an optical sensor assembly 300, a hydrogel pad 400, a partition wall 322, a bank 321, a sample injection portion 326, and a cover 352.

In this embodiment, the bank 321 protrudes higher than the hydrogel pad 400, and the hydrogel pad 400 is accommodated in the space defined by the adjacent banks 321.

The barrier rib 322 protrudes from the edge of the optical sensor assembly 300 and is opened at one side and connected to the sample injection unit 326.

The cover 352 is connected to the upper surface of the partition 322. In this embodiment, the partition 322 protrudes from the bank 321, and the sample 52a, 52b, 52c, 52d and the buffer agent 54 pass between the lower surface of the partition 322 and the upper surface of the bank 321 A passageway is formed.

Buffer 54 includes fluids that are less reactive with samples 52a, 52b, 52c, and 52d. For example, buffer 54 may comprise oil, gel, pure water, and the like. The buffer 54 separates adjacent samples 52a, 52b, 52c, 52d so that they do not mix with each other.

A method of injecting the samples 52a, 52b, 52c, and 52d into the PC Al module using the sample injection unit 326 is as follows.

First, the samples 52a, 52b, 52c, 52d and the buffer 54 are alternately arranged in the sample injecting section 326.

Subsequently, when pressure is applied to one side of the sample injecting section 326, the first sample 52a disposed in the sample injecting section 326 is moved toward the partition wall 322. [

Thereafter, when pressure is applied to one side of the sample injecting section 326, the first sample 52a in the sample injecting section 326 passes through the partition wall 322. The first sample 52a that has passed through the partition 322 flows downward due to its own weight and is dropped into a space formed between the bank 321 and the partition 322 to cover the hydrogel pad 400. [

Subsequently, when a pressure is applied to one side of the sample injecting section 326, the buffer material 54 disposed between the first sample 52a and the second sample 52b separates the space between the bank 321 and the partition wall 322 Fill it.

Thereafter, when a pressure is applied to one side of the sample injecting section 326, the second sample 52b passes through the space between the partition 322, the partition 322 and the bank 321, and the space between the partition 322 and the bank 321, (321).

Subsequently, when a pressure is applied to one side of the sample injecting section 326, the second sample 52b is dropped into a space between the adjacent banks 321 to cover the second hydrogel pad 400. [

The second sample 52b, the buffer 54, the third sample 52c, the buffer 54, and the fourth sample 52d are sequentially adjacent to each other in the same manner by applying pressure to one side of the sample injection unit 326 Filling the spaces formed by the banks 321.

According to the present embodiment as described above, the samples 52a, 52b, 52c, and 52d and the buffer 54 are alternately disposed in the sample injecting section 326 to apply pressure to one side of the sample injecting section 326 The samples 52a, 52b, 52c, and 52d can be sequentially injected into the plurality of hydrogel pads 400 by a simple operation.

24 is an enlarged sectional view showing a hydrogel pad used in a method of inspecting using a PC Al module according to an embodiment of the present invention.

Referring to FIGS. 10 and 24, a dielectric material 421 to be inspected is dripped onto the hydrogel pad 400. The dripped dielectric material 421 is uniformly distributed in three dimensions in the hydrogel pads 400.

The gene in the genetic material 421 is amplified 420 by a primer in each hydrogel pad 400.

In this embodiment, the dielectric materials 421 are evenly imbedded by the polymer chains 410 of the hydrogel pad 400. The gene of the genetic material 421 impregnated into the hydrogel pad 400 is amplified 420 by a primer. In this embodiment, the temperature controller adjusts the temperature of the hydrogel pad 400 for gene amplification.

When the light generated in the light source is irradiated to the fluorescent substance attached to the amplified gene, fluorescence of a specific wavelength is emitted from the fluorescent substance.

The photosensor array detects the fluorescence emitted from the fluorescent material and checks for the presence of the gene.

25 is a cross-sectional view illustrating a PC Al module according to another embodiment of the present invention. In the present embodiment, the remaining components except for the wires 311 and 371, the bonding portions 311a and 371a, the light source 331, the light shielding pattern 332, the sample injecting portion 353, and the interface member 390, 23, so that duplicate descriptions of the same components will be omitted.

25, the PC Al module includes an optical sensor assembly 301, barrier ribs 321 and 322, wires 311 and 371, bonding 311a and 371a, an optical filter 315, a light source 331, A pattern 332, a sample injection section 353, a cover 350, a first temperature control section 370, and an interface member 390. [

The optical sensor assembly 301 includes an optical sensor, a temperature sensor, a drive circuit, and the like. In this embodiment, the optical sensor assembly 301 may include a first temperature control unit.

The barrier ribs 321 and 322 protrude from the optical sensor assembly 301 in a vertical direction to form a reaction space 241. The barrier ribs 321 and 322 may include a barrier rib 322 disposed at an edge of the optical sensor assembly 301 and a barrier rib 321 disposed at a central portion of the optical sensor assembly 301. In this embodiment, For example, the height of the partition wall 322 disposed at the edge of the optical sensor assembly 301 may be higher than the height of the partition wall 321 disposed at the center of the optical sensor assembly 301. When the height of the partition 322 disposed at the edge of the optical sensor assembly 301 is higher than the height of the partition 321 disposed at the center of the optical sensor assembly 301, .

The optical filter 315 is disposed between the partition walls 321 and 322 and the optical sensor assembly 301 to remove noise and transmit only fluorescence (or phosphorescence) generated in the sample.

The light source 321 irradiates light to the sample placed in the reaction space 241. The material disposed in the sample generates fluorescence or phosphorescence using light generated from the light source 321. The fluorescence or phosphorescence is applied to the optical sensor assembly 301 through the optical filter 315.

In this embodiment, the light source 321 is disposed at the lower portion of the partition 320. For example, the light shielding pattern 332 may be disposed under the light source 321 to prevent the light generated from the light source 321 from being directly applied to the optical filter 315.

The sample injecting section 353 opens one side of the reaction space 241 and injects the sample.

In this embodiment, the first temperature control unit 370 is formed at the lower portion of the optical sensor assembly 301. In another embodiment, the first temperature controller 370 may be disposed at various positions, such as the top of the optical sensor assembly 301, the top of the cover 350, the side of the partitions 321 and 322, and the like.

The interface member 390 is disposed below the optical sensor assembly 301 and controls the optical sensor assembly 301, the light source 321, the first temperature controller 370, and the like.

The wires 311 and 371 electrically connect the interface member 380 to the optical sensor assembly 301, the first temperature controller 370 and the like. The bonding portions 311a and 371a are disposed at the ends of the wires 311 and 317 to attach the wires 311 and 317 to the interface member 380 and the optical sensor assembly 301 and the like. For example, the bonding 311, 371a may include soldering.

The cover 350 defines the upper part of the reaction space 241 and may include plastic, polydimethylsiloxane (PDMS), glass, silicon, carbon-based materials, diamond, metal,

26 is a cross-sectional view illustrating a PC Al module according to another embodiment of the present invention. In this embodiment, the remaining components except for the silicon penetrating electrode 312 and the connecting portions 312a and 372a are the same as those in the embodiment shown in FIG. 25, so that duplicate descriptions of the same components will be omitted.

26, the PC Al module includes an optical sensor assembly 301, partition walls 321 and 322, a through silicon via (TSV) 312, connection portions 312a and 372a, an optical filter 315, A light source 331, a light shielding pattern 332, a sample injection unit 353, a cover 350, a first temperature control unit 370, and an interface member 390.

The silicon penetrating electrode 312 is electrically connected to an electrode disposed inside the optical sensor assembly 301 through the optical sensor assembly 301.

The optical sensor assembly 301 is electrically connected to the interface member 390 using the silicon penetrating electrode 312 and the connecting portions 312a and 372a. For example, an electrode disposed inside the optical sensor assembly 301 is electrically connected to the interface member 390 through the silicon penetrating electrode 312 and the connection portion 312a, and the first temperature control portion 370 is electrically connected to the connection member And may be electrically connected to the interface member 390 through the connection member 372a.

In this embodiment, a method of coupling the interface member 390 to the optical sensor assembly 301 is as follows.

First, an optical sensor assembly 301 including an electrode disposed therein is prepared.

Then, a via hole is formed from the bottom of the optical sensor assembly 301 to expose a part of the electrodes disposed therein.

Thereafter, the via hole is filled with a conductive material to form the silicon through electrode 312.

Subsequently, the connection portions 312a and 372a are disposed at the lower portion of the optical sensor assembly 301. For example, the connection portions 312a and 372a may include an anisotropic conductive film, a ball and a pad.

Then, the interface member 390 is coupled from the bottom of the optical sensor assembly 301.

According to the present embodiment as described above, there is no need for separate wires or soldering for joining the optical sensor assembly 301 and the interface member 390, thereby reducing defects and enhancing the strength against external impact.

27 is a cross-sectional view illustrating a PC Al module according to another embodiment of the present invention. In this embodiment, the remaining components except for the light source 331s and the light shielding pattern are the same as those in the embodiment shown in Fig. 25, so duplicate descriptions of the same components will be omitted.

Referring to FIG. 27, the light source 331s is disposed in the middle of the partition walls 321 and 322 to supply light into the reaction space 241. In this embodiment, the light shielding pattern (332 in Fig. 25) can be omitted.

28 is a cross-sectional view illustrating a PC Al module according to another embodiment of the present invention. In this embodiment, the remaining components except for the light source 331t and the light-shielding pattern are the same as those in the embodiment shown in Fig. 25, so that duplicated description of the same components will be omitted.

28, the light source 331t is disposed in the cover 350 to supply light into the reaction space 241. [ In this embodiment, the light shielding pattern (332 in Fig. 25) can be omitted.

29 is a cross-sectional view illustrating a PC Al module according to another embodiment of the present invention. In the present embodiment, the remaining components except for the light source 331u are the same as the embodiment shown in Fig. 25, so that a duplicated description of the same components will be omitted.

Referring to FIG. 29, a light source 331u is disposed on the optical film assembly 301 to supply light into the reaction space 241. For example, the light source 331u may be disposed on the upper surface of the optical filter 315. [

The light shielding pattern 332u is disposed under the light source 331u. For example, the light shielding pattern 332u may be disposed between the lower surface of the light source 331u and the upper surface of the optical filter 315. [

FIG. 30 is a plan view showing a constant temperature member according to an embodiment of the present invention, and FIG. 31 is a sectional view taken along line T-T 'of FIG. In this embodiment, the PC Al module is the same as the embodiment shown in FIGS. 1 to 29, so that duplicate description of the same components will be omitted.

Referring to FIGS. 30 and 31, the leader system includes a plurality of constant temperature members 510, 520, 530, and 540 and a plurality of heat insulating members 505.

The plurality of constant temperature members 510, 520, 530, and 540 are arranged in a line and maintain the temperatures corresponding to each step of the PCR cycle. For example, the constant temperature members 510, 520, 530, and 540 may be arranged in various directions such as a linear direction, a lattice direction, a curved direction, and a circumferential direction.

In this embodiment, the first thermostatic member 510 corresponds to a denaturation stage in the PCA cycle and maintains 92 ° C to 95 ° C. The second constant temperature member 520 corresponds to the extension stage in the PCA cycle and maintains 72 ° C to 75 ° C. The third constant temperature member 530 corresponds to an annealing stage and maintains 52 ° C to 55 ° C. The fourth thermostat member 540 corresponds to the cooling and test stage and maintains a temperature of from 10 캜 to 15 캜.

The heat insulating members 505 are disposed between the adjacent constant temperature members 510, 520, 530, 540 to prevent heat exchange between adjacent constant temperature members 510, 520, 530, 540.

In this embodiment, each constant temperature member 510 includes a plurality of constant temperature portions 512, 524. For example, the first constant temperature member 510 includes a first constant temperature portion 512 disposed at a lower portion of the PC Al module 200 and a second constant temperature portion 514 disposed at an upper portion of the PC Al module 200 .

The PC Al module 200 is surrounded by the first heat conduction part 502 and the second heat conduction part 504 and exchanges heat with the respective constant temperature parts 510, 520, 530, and 540. For example, the lower portion of the PC Al module 200 may be surrounded by the first heat conduction portion 502 and the upper portion may be surrounded by the second heat conduction portion 504.

The PC Al module 200 surrounded by the first heat conduction part 502 and the second heat conduction part 504 moves between the constant temperature members 510, 520, 530, 540 corresponding to the respective phases of the PC cycle The PCA cycle is performed.

The flexible printed circuit board 395 may be disposed in a space between the first thermal conductive part 502 and the second thermal conductive part 504 and the driving signal of the PC Al module 200 may be transmitted through the flexible printed circuit board 395, A light sensing signal, a temperature signal, etc. may be transmitted.

In this embodiment, a method using the constant temperature members 510, 520, 530, and 540 that maintain different temperatures is used, but this is an exemplified one, and various methods can be used. In another embodiment, instead of the constant temperature members, an air cooling system such as a fan (FAN), an air compressor or the like may be used, or a system of cooling or heating using a fluid such as water or oil may be used, , A method in which a liquid such as alcohol is easily evaporated is cooled by spraying, or a thermoelectric element such as Peltier is used.

32 is a cross-sectional view illustrating a PC Al module according to another embodiment of the present invention. In this embodiment, the remaining components except for the first heat conductor 502a, the second heat conductor 504a, and the internal heat conductor 503a are the same as the embodiment shown in Fig. 25, And the description thereof will be omitted.

Referring to FIG. 32, the PC Al module further includes a first thermal conductor 502a, a second thermal conductor 504a, and an inner thermal conductor 503a. The first heat conductor 502a, the second heat conductor 504a, and the inner heat conductor 503a regulate the temperature of the PC Al module by supplying heat to the PC Al module or radiating the heat of the PC Al module to the outside.

In this embodiment, the first heat conductor 502a is disposed on the cover 350 to control the temperature of the top of the PC Al module. The second heat conductor 504a is disposed below the optical sensor assembly 301 to control the temperature of the bottom of the PC Al module. The inner heat conductor 503a is disposed on the outer surface of the partition 322 to control the temperature of the central portion of the PC Al module.

In another embodiment, the PC Al module may include only one or two of the first thermal conductor 502a, the second thermal conductor 504a, and the thermal conductor 503a.

33 is a cross-sectional view illustrating a PC Al module according to another embodiment of the present invention. In this embodiment, the remaining components except for the inner heat conductor 503b are the same as the embodiment shown in Fig. 32, so duplicate descriptions of the same components are omitted.

33, a part of the internal heat conductor 503b is disposed inside the reaction space 241 and the remaining part is protruded outside the reaction space 241. [ For example, a part of the inner heat conductor 503b is disposed on the inner surface of the partition 322, and the other part is protruded outside the reaction space 241 through the partition 322. [

The inner heat conductor 503b may include a metal, a diamond, a metal oxide, or the like. For example, a transparent metal oxide such as a metal coating, indium tin oxide (ITO), or the like may be included.

In another embodiment, the inner heat conductor 503b may be disposed on the partition wall 321 inside the reaction space 241. [

34 is a cross-sectional view illustrating a PCA module according to another embodiment of the present invention. In this embodiment, the remaining components except for the heat transfer fluid 506 are the same as the embodiment shown in FIG. 32, so duplicate descriptions of the same components are omitted.

Referring to FIG. 34, heat transfer fluid 506 is disposed on the outer surface of partition wall 322. The heat transfer fluid 506 controls the temperature of the reaction space 241 by cooling or heating the outer surface of the partition wall 322. For example, heat transfer fluid 506 may be circulated through a pump (not shown).

35 is a cross-sectional view illustrating a PC Al module according to another embodiment of the present invention. In the present embodiment, the remaining components except for the heat conductor 503b and the heating portion 375 are the same as those in the embodiment shown in Fig. 32, so that a duplicate description of the same components will be omitted.

35, the inner heat conductor 503b is disposed in the middle portion of the PC Al module and protrudes out of the reaction space 241. The first heat conductor 502a, the second heat conductor 504a, and the inner heat conductor 503b dissipate the heat of the PC Al module to the outside to reduce the temperature of the reaction space 241.

The heating unit 375 is disposed inside the reaction space 241 to raise the temperature of the reaction space 241. In another embodiment, the heating portion 375 may be disposed on the upper surface of the cover 350, the lower surface of the optical sensor assembly 301, and the like.

According to the present embodiment as described above, the PC Al module can easily adjust the temperature of the reaction space 241 by including the heat conductors 502a, 503b and 504a and the heating part 375.

36 is a plan view showing an optical sensor according to an embodiment of the present invention. In this embodiment, the remaining components except for the optical sensor are the same as those in the embodiment shown in Fig. 25, so that redundant description of the same components will be omitted.

Referring to FIG. 36, the optical sensor includes one optical sensor unit 307 and one output electrode 307a. In this embodiment, one output electrode 307a corresponds to one optical sensor unit 307, and an optical sensor signal applied to one optical sensor unit 307 is output through one output electrode 307a do.

37 is a plan view showing an optical sensor according to another embodiment of the present invention. In this embodiment, the remaining components except for the optical sensor are the same as those in the embodiment shown in FIG. 36, so that redundant description of the same components will be omitted.

Referring to FIG. 37, the optical sensor includes two optical sensor units 307 and one output electrode 307a. In this embodiment, one output electrode 307a corresponds to two photosensor units 307, and photosensor signals applied to the two photosensor units 307 are summed to form one output electrode 307a .

Therefore, the sensitivity for the same amount of light is doubled as compared with the photosensor shown in Fig.

38 is a plan view showing an optical sensor according to another embodiment of the present invention. In this embodiment, the remaining components except for the optical sensor are the same as those in the embodiment shown in FIG. 36, so that redundant description of the same components will be omitted.

Referring to Fig. 38, the optical sensor includes four optical sensor units 307 and one output electrode 307a. In this embodiment, one output electrode 307a corresponds to four photosensor units 307, so that photosensor signals applied to the four photosensor units 307 are summed to form one output electrode 307a .

Therefore, the sensitivity for the same amount of light is increased four times as compared with the photosensor shown in Fig.

39 is a plan view showing an optical sensor according to another embodiment of the present invention. In this embodiment, the remaining components except for the optical sensor are the same as those in the embodiment shown in FIG. 36, so that redundant description of the same components will be omitted.

39, the optical sensor includes eight optical sensor units 307, two output electrodes 307a and 307b, and one connection line 307c. The total output signal corresponds to eight photosensor units 307 through one connection line 307c and two output electrodes 307a and 307b so that eight photosensor units 307 Is summed and output as a single output signal.

Therefore, the sensing sensitivity for the same amount of light increases by eight times that of the optical sensor shown in Fig.

FIG. 40 is a plan view showing an optical sensor array manufactured by combining FIGS. 36 to 39, and FIG. 41 is a graph showing output signals of the optical sensor array shown in FIG.

40 and 41, the optical sensor array includes two first optical sensors 307_1, a second optical sensor 307_2, a third optical sensor 307_4, and a fourth optical sensor 307_8 do.

In this embodiment, the first photosensor 307_1 is the same as the photosensor shown in Fig. 36, the second photosensor 307_2 is the same as the photosensor shown in Fig. 37, the third photosensor 307_4 is the same as the photosensor shown in Fig. Is the same as the optical sensor shown in Fig. 38, and the fourth optical sensor 307_8 is the same as the optical sensor shown in Fig.

The signals output from the first through fourth optical sensors 307_1, 307_2, 307_4, and 307_8 have output signals of different sizes, even if the same light is applied. As the number of the optical sensor units included in one optical sensor 307_1, 307_2, 307_4, and 307_8 increases, the sensitivity of the optical sensor increases.

However, if the sensitivity of the optical sensor is excessively increased, the detection capability of the optical sensor is easily saturated.

In the exemplary embodiment of the present invention, optimal sensing can be performed according to the size of light input using a plurality of optical sensors 307_1, 307_2, 307_4, and 307_8 including different numbers of optical sensor units, The accuracy is improved by using the signals output from the signal amplifiers 307_1, 307_2, 307_4, and 307_8.

42 is a sectional view showing an optical sensor assembly according to an embodiment of the present invention. In the present embodiment, the remaining components except for the light source driving circuit are the same as those in the embodiment shown in FIGS. 10 to 40, so that duplicated description of the same components will be omitted.

10 and 42, the optical sensor assembly includes an optical sensor array 310, a fluorescence filter 313, a first temperature controller 370, a temperature sensor 360, and a light source driver circuit 335 .

The light source driving circuit 335 applies driving power to the light source (331 in Fig. 25) under the control of the reader system 100 or the interface member (390 in Fig. 25).

43 is a cross-sectional view showing an optical sensor assembly according to another embodiment of the present invention. In the present embodiment, the remaining components except for the driving circuit are the same as the embodiment shown in FIG. 42, so that duplicated description of the same components will be omitted.

10 and 43, the optical sensor assembly includes an optical sensor array 310, a fluorescence filter 313, a first temperature control unit 370, a temperature sensor 360, and a driving circuit unit 337.

The driving circuit unit 337 applies driving power to the light source (331 in FIG. 25) or controls signal input / output of the optical sensor assembly under the control of the reader system 100 or the interface member (390 in FIG. 25).

According to the present invention, the optical part is embedded in the PC Al module, and the PC Al module is formed in a detachable module form, thereby greatly reducing the size of the reader system. In addition, the size of PC Al module and reader system is drastically reduced and manufacturing costs are reduced.

In addition, even if the reader system is moved, since reordering due to device rearrangement and correction are unnecessary, the mobility can be remarkably improved and the field inspection can be performed. Especially, in case of an emergency such as infectious disease inspection, identification of the disaster scene, it is possible to input immediately, which can contribute to reduce the damage.

In addition, since the reagent is introduced in the PC Al module, there is no need for a separate procedure for setting the reagent, so that the possibility of contamination is drastically reduced and a separate procedure for preparation of the test is not necessary.

In addition, since it is possible to exchange information with the outside through the Internet, various customers and a large number of reagent developers can establish a system such as an app store or market through a central processing server to exchange reagents and information.

In addition, the PCAl module includes a plurality of hydrogel pads, and each hydrogel pad is provided with a different primer to detect multiple genotypes.

In addition, since a general multi-detection method uses a method of changing the fluorescence wavelength, there is a problem that the structure of the optical part is complicated. However, in this embodiment, the arrangement of the different primers in the respective hydrogel pads enables the multi-detection even if a single fluorescent material is used, so that the structure of the optical sensor assembly is simplified.

By alternately arranging the samples and the buffer in the sample injecting unit, the samples can be injected into the plurality of hydrogel pads sequentially by a simple operation of applying pressure to one side of the sample injecting unit.

In addition, in the conventional array method, the gene amplification rate is very slow because the dielectric material is disposed only on the surface. However, the hydrogel pad has a very fast gene amplification rate because gene amplification occurs not only on the surface but also inside the hydrogel pad due to the three-dimensional structure of the polymer chain. Therefore, it is possible to real-time gene amplification by position by forming an array with hydrogel pads. In addition, since the fluorescence is emitted only from the hydrogel pad, the intensity of the detected signal is increased due to an increase in the amount of light, and more sensitive experiments are possible.

In addition, the PC Al module can include a thermal conductor and a heating part to easily adjust the temperature of the reaction space.

In addition, by using a plurality of optical sensors including different numbers of optical sensor units, optimized detection can be performed according to the size of input light, and accuracy is improved by using signals output from the plurality of optical sensors.

Also, since the optical sensor assembly includes the light source driving unit or the driving circuit unit, the size of the PC Al system can be further reduced.

INDUSTRIAL APPLICABILITY The present invention has industrial applicability that can be used for research, disaster prevention, medical use, animal husbandry, and pet treatment apparatus for amplifying and inspecting genetic material.

52a, 52b, 52c, 52d: Sample 54: Buffer
100: Reader system 110: Central information processor
120: memory, drive data 130: interface
150, 159: second temperature control module 152: auxiliary information processor
154: Thermal controller 154a: Temperature sensor
154b: thermoelectric element 200: PC Al module (PCR Module)
210: control interface 220: light source driver
230, 330, 331: Light source 332: Shading pattern
335: light source driving circuit 337: driving circuit part
233: excitation light source filter 240, 340: reaction vessel
250: optical sensor 253, 313: fluorescent filter
315: Optical filter 260, 360: Temperature sensor
270, 370: first temperature control unit 300, 301: optical sensor assembly
310: optical sensor array 320:
321, 325: bank 326: sample injection unit
350: Cover 352: Inlet
353: Sample injection part 354: Outlet
307: photodiode 307a: output electrode
311, 371: wire 372: silicon penetrating electrode
311a, 371a: bonding 312a, 372a:
375: heating section 390: interface member
395: Flexible circuit board 400, 405: Hydrogel pad
400a: hydrogel droplet 410: polymer chain
420: sample 421: dielectric material
490: UV irradiation 502, 502a: first thermoconductor
503a, 503b: an inner heat conductor 504, 504a: a second heat conductor
505: Heat insulating member 506: Heat transfer fluid
510, 520, 530, 540: constant temperature member 512: first constant temperature unit
514: Second Constant Temperature Unit 1000: Central Processing Server
1100: reagent developer terminal 1200: customer terminal

Claims (20)

A central information processing unit for receiving a light sensing signal to calculate a gene amplification amount in real time and generating a temperature control signal using temperature signal and temperature control information, and a control unit connected to the central information processing unit to store the gene amplification amount and the temperature control information And an interface that is connected to the central information processing unit and transmits the gene amplification amount received in real time from the central information processing unit to the outside or applies an external input signal to the central information processing unit In the PC Al module to be combined,
An optical sensor assembly including a plurality of optical sensors arranged in an array and generating emission light from the sample to generate the light sensing signal, and a temperature sensor for sensing a temperature and outputting a temperature signal;
A barrier wall protruding on the optical sensor assembly to define a plurality of reaction spaces for accommodating the sample; And
And an interface module electrically connected to the optical sensor assembly to transmit the optical sensing signal and the temperature signal to the reader system,
A plurality of optical sensors correspond to each reaction space,
Wherein the optical sensor assembly includes a first photosensor and a second photosensor having different sensed sensitivities to the emitted light even when the same emitted light is applied, and the first photosensor and the second photosensor have different sizes And outputs the output signals.
The apparatus of claim 1, further comprising: a light source for supplying light to the reaction space;
An optical filter disposed on an upper surface of the optical sensor assembly to transmit the emitted light; And
Further comprising a cover defining an upper portion of the reaction space and comprising an opaque material.
The method of claim 1, wherein the reader system further comprises a light source for supplying light to the reaction space, and the PC Al module further comprises a cover defining an upper portion of the reaction space and including a transparent material The PC Al module. The PC Al module according to claim 1, wherein the reader system further comprises a temperature control module for receiving the temperature control signal and adjusting a temperature of the reaction space. The apparatus according to claim 1, further comprising a temperature controller for receiving the temperature control signal and adjusting a temperature of the reaction space, wherein the interface module receives the temperature control signal and applies the temperature control signal to the temperature controller. Al module. 6. The PC Al module according to claim 5, wherein the reader system further comprises a heat conductor surrounding the PC Al module, and a constant temperature member held at a constant temperature and exchanging heat with the heat conductor. 6. The PC Al module according to claim 5, wherein the PC Al module further comprises a thermally conductive material for receiving the temperature control signal and transferring the heat of the reaction space to the outside. [6] The PC Al module according to claim 5, wherein the PC Al module further comprises a heating unit for receiving the temperature control signal to increase the temperature of the reaction space. 2. The PC Al module according to claim 1, wherein a plurality of optical sensor units are connected to one output electrode of the optical sensor. 10. The PC Al module of claim 9, wherein the optical sensor assembly further comprises a photosensor array comprising a plurality of photosensors comprising a different number of photosensor units. The PC Al module of claim 1, wherein the reader system is detachably coupled to a plurality of PC Al modules. The method of claim 1, further comprising the steps of: providing a hydrophilic material disposed on the optical sensor assembly and not dissolved or released when mixed with water, wherein the polymer chains or polymer chains are crosslinked to maintain a three-dimensional structure, As a small DNA, a polymerase includes a plurality of 3D organic pads including a primer that is a starting point when amplifying DNA,
Wherein the 3D organic pads correspond to respective reaction spaces.
13. The PC Al module of claim 12, wherein the 3D organic pad comprises a hydrogel pad or a spin on glass (SOG) pad. The PC Al module according to claim 1, wherein the optical sensor assembly and the interface module are electrically connected by wire bonding. The PC Al module according to claim 1, wherein the optical sensor assembly and the interface module are electrically connected using a silicon through electrode. A central information processing unit for receiving a light sensing signal to calculate a gene amplification amount in real time and generating a temperature control signal using temperature signal and temperature control information, and a control unit connected to the central information processing unit to store the gene amplification amount and the temperature control information And an interface connected to the central information processing unit to transmit the amplified amount of gene amplified in real time from the central information processing unit to the outside or to apply an external input signal to the central information processing unit; And
An optical sensor assembly including a plurality of optical sensors arranged in an array and configured to detect emitted light generated from the sample to generate the optical sensing signal and a temperature sensor for sensing temperature and outputting a temperature signal; And an interface module electrically connected to the optical sensor assembly for transmitting the optical sensing signal and the temperature signal to the reader system, wherein the reader module includes a plurality of reaction chambers protruding on the assembly to define a plurality of reaction spaces, And a PC Al module detachably coupled to the system,
A plurality of optical sensors correspond to each reaction space,
Wherein the optical sensor assembly includes a first photosensor and a second photosensor having different sensed sensitivities to the emitted light even when the same emitted light is applied, and the first photosensor and the second photosensor have different sizes And outputs the output signals.
17. The method of claim 16, wherein the reader system further comprises a second temperature control module for reducing the temperature of the PC Al module using the temperature control signal, Further comprising a first temperature controller for increasing the temperature of the space. A central information processing unit for receiving a light sensing signal to calculate a gene amplification amount in real time and generating a temperature control signal using temperature signal and temperature control information, and a central information processing unit connected to the central information processing unit to store the gene amplification amount and the temperature control information A memory, and an interface connected to the central information processing unit and transmitting an external input signal to the central information processing unit, the interface signal being detachably coupled to the reader system. An optical sensor assembly arranged on the optical sensor assembly and arranged in an array shape to detect the emitted light generated from the sample to generate the optical sensing signal, a plurality of optical sensor assemblies protruding on the optical sensor assembly, A partition wall defining reaction spaces, A testing methodology is sensor assembly and electrically connected to the PC using Al system including a PC Al module including the light sensing signal and the interface module for transmitting the temperature signal to the reader system,
Inputting sample information;
Matching the sample information with reagent information;
Preparing a PC Al module in which a reagent matched with the reagent information is embedded; And
Injecting the sample into the PC Al module and analyzing the sample by mounting the sample in the reader system,
A plurality of optical sensors correspond to each reaction space,
Wherein the optical sensor assembly includes a first photosensor and a second photosensor having different sensed sensitivities to the emitted light even when the same emitted light is applied, and the first photosensor and the second photosensor have different sizes And outputting the output signals.
19. The method according to claim 18, wherein the step of matching the sample information with the reagent information includes checking whether there is a reagent matching the sample information among the previously stored reagent information. Way. 20. The method of claim 19, further comprising: transmitting the reagent information to a plurality of reagent developer terminals when no reagent matching the sample information exists among the previously stored reagent information; And
And developing the reagent by selecting a developer of the reagent through the response information from the reagent developer terminal.
KR1020160020053A 2015-03-18 2016-02-19 Pcr module, pcr system having the same, and method of testing using the same KR101803497B1 (en)

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US15/064,816 US10279352B2 (en) 2015-03-18 2016-03-09 PCR module, PCR system having the same, and method of inspecting using the same
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ES16160789T ES2734281T3 (en) 2015-03-18 2016-03-17 PCR module, PCR system that has the same and inspection method that uses the same
EP16160789.0A EP3069791B1 (en) 2015-03-18 2016-03-17 Pcr module, pcr system having the same, and method of inspecting using the same
US16/361,594 US10710084B2 (en) 2015-03-18 2019-03-22 PCR module, PCR system having the same, and method of inspecting using the same

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