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 PDFInfo
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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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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L7/00—Heating or cooling apparatus; Heat insulating devices
- B01L7/52—Heating 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
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
- G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/14—Process control and prevention of errors
- B01L2200/141—Preventing contamination, tampering
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- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/14—Process control and prevention of errors
- B01L2200/143—Quality control, feedback systems
- B01L2200/147—Employing temperature sensors
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- B01L2300/00—Additional constructional details
- B01L2300/02—Identification, exchange or storage of information
- B01L2300/023—Sending and receiving of information, e.g. using bluetooth
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/06—Auxiliary integrated devices, integrated components
- B01L2300/0627—Sensor or part of a sensor is integrated
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
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- B01L2300/18—Means for temperature control
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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
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
The
The central
The light
The
The
A sample in the
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
1 to 5, the temperature control signal includes a signal for controlling the temperature so that the temperature of the
The section PU in which the temperature is maintained is a section where the temperature is maintained without changing the temperature in the
The temperature rise sections P3, P4, P6 and P7 are sections in which the temperature in the
The intervals P1, P2, and P5 where the temperature falls are drastically lowered in the
In this embodiment, the temperature of the
The
The
The second
6 is a block diagram showing the second temperature control unit shown in Fig.
1 to 6, the second
The auxiliary
The
The
In another embodiment, the
In accordance with the control of the
In this embodiment, the
In one embodiment, the
The
The
The
The
The first
In this embodiment, the
In this embodiment, a substance having high thermal conductivity is disposed between the
In this embodiment, the arrangement of the
The
In the present embodiment, a temperature sensor may employ a combined temperature sensor system including a
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
The
The
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
Next, the sample is analyzed using the
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
The
The
The
In another embodiment, a pad (not shown) may be formed using Spin On Glass (SOG) instead of the
The
In this embodiment, the
The
In this embodiment, the PC Al module includes a plurality of
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
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
The
The
12 to 15 are sectional views showing a method of manufacturing the PC Al module shown in FIG.
Referring to FIG. 12, first, the
Referring to FIG. 13,
Referring to FIG. 14, the
Referring to FIG. 15, a
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
The
The
The
17 to 22 are sectional views showing a method of manufacturing the PC Al module shown in FIG.
Referring to FIG. 17, first, the
Referring to FIG. 18, a
Referring to FIG. 19, a
Referring to FIGS. 20 and 21, ultraviolet rays (UV) are irradiated (490) on the hydrogel droplet 401 'to be subsequently dropped to form a
22, the
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
In this embodiment, the
The
The
A method of injecting the samples 52a, 52b, 52c, and 52d into the PC Al module using the
First, the samples 52a, 52b, 52c, 52d and the
Subsequently, when pressure is applied to one side of the
Thereafter, when pressure is applied to one side of the
Subsequently, when a pressure is applied to one side of the
Thereafter, when a pressure is applied to one side of the
Subsequently, when a pressure is applied to one side of the
The second sample 52b, the
According to the present embodiment as described above, the samples 52a, 52b, 52c, and 52d and the
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
The gene in the
In this embodiment, the
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
25, the PC Al module includes an
The
The
The
The
In this embodiment, the
The
In this embodiment, the first
The
The
The
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
26, the PC Al module includes an
The silicon penetrating electrode 312 is electrically connected to an electrode disposed inside the
The
In this embodiment, a method of coupling the
First, an
Then, a via hole is formed from the bottom of the
Thereafter, the via hole is filled with a conductive material to form the silicon through electrode 312.
Subsequently, the
Then, the
According to the present embodiment as described above, there is no need for separate wires or soldering for joining the
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
Referring to FIG. 27, the
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
28, the
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
Referring to FIG. 29, a
The
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
The plurality of
In this embodiment, the first
The
In this embodiment, each
The
The
The flexible printed
In this embodiment, a method using the
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
Referring to FIG. 32, the PC Al module further includes a first
In this embodiment, the
In another embodiment, the PC Al module may include only one or two of the first
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
33, a part of the
The
In another embodiment, the
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
Referring to FIG. 34,
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
35, the
The
According to the present embodiment as described above, the PC Al module can easily adjust the temperature of the
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
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
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
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
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
The light
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
The driving
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:
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
250:
315:
270, 370: first
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:
400a: hydrogel droplet 410: polymer chain
420: sample 421: dielectric material
490:
503a, 503b: an
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)
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.
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.
Wherein the 3D organic pads correspond to respective reaction spaces.
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.
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.
And developing the reagent by selecting a developer of the reagent through the response information from the reagent developer terminal.
Priority Applications (5)
Application Number | Priority Date | Filing Date | Title |
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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 |
CN201610209959.5A CN105985905B (en) | 2015-03-18 | 2016-03-16 | PCR module, PCR system having the same, and detection method using the same |
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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KR1020150037725 | 2015-03-18 | ||
KR20150037725 | 2015-03-18 |
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KR1020170060203A Division KR20170098193A (en) | 2017-05-15 | 2017-05-15 | Pcr module, pcr system having the same, and method of testing using the same |
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KR20160112941A KR20160112941A (en) | 2016-09-28 |
KR101803497B1 true KR101803497B1 (en) | 2017-12-28 |
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KR101882239B1 (en) * | 2016-12-06 | 2018-07-26 | (주)옵토레인 | Pcr module capable of multi-temperature setting, pcr system including the same, and pcr testing method |
KR102198870B1 (en) * | 2019-06-04 | 2021-01-05 | (주)옵토레인 | Polymerase chain reaction device |
CN111443213B (en) * | 2020-04-09 | 2023-07-18 | 星源智(珠海)生物科技有限公司 | Multi-variable reaction dynamics real-time detector device and detection method |
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KR100668320B1 (en) * | 2003-12-10 | 2007-01-12 | 삼성전자주식회사 | Module for polymerase chain reaction and multiple polymerase chain reaction system |
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KR100668320B1 (en) * | 2003-12-10 | 2007-01-12 | 삼성전자주식회사 | Module for polymerase chain reaction and multiple polymerase chain reaction system |
Non-Patent Citations (3)
Title |
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A lab-on-chip for malaria diagnosis and surveillance(Brian J Taylor, Malaria Journal, 2014)* |
An integrated CMOS quantitative-polymerasechain-reaction lab-on-chip for point-of-care diagnostics(Haig Norian, Lap on a Chip, 2014)* |
CMOS Time-Resolved, Contact, and Multispectral Fluorescence Imaging for DNA Molecular Diagnostics(Nan Guo, Sensors, 2014)* |
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