KR101904506B1 - PCR Module - Google Patents

PCR Module Download PDF

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KR101904506B1
KR101904506B1 KR1020170063196A KR20170063196A KR101904506B1 KR 101904506 B1 KR101904506 B1 KR 101904506B1 KR 1020170063196 A KR1020170063196 A KR 1020170063196A KR 20170063196 A KR20170063196 A KR 20170063196A KR 101904506 B1 KR101904506 B1 KR 101904506B1
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sample
reaction space
base substrate
potential
elements
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KR20170133267A (en
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최경학
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(주)옵토레인
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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
    • 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
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12QMEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12QMEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6844Nucleic acid amplification reactions
    • C12Q1/686Polymerase chain reaction [PCR]
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01JMEASUREMENT OF INTENSITY, VELOCITY, SPECTRAL CONTENT, POLARISATION, PHASE OR PULSE CHARACTERISTICS OF INFRARED, VISIBLE OR ULTRAVIOLET LIGHT; COLORIMETRY; RADIATION PYROMETRY
    • G01J1/00Photometry, e.g. photographic exposure meter
    • G01J1/42Photometry, e.g. photographic exposure meter using electric radiation detectors
    • 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
    • B01L2300/12Specific details about materials
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/16Surface properties and coatings
    • B01L2300/161Control and use of surface tension forces, e.g. hydrophobic, hydrophilic
    • B01L2300/165Specific details about hydrophobic, oleophobic surfaces
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/16Surface properties and coatings
    • B01L2300/168Specific optical properties, e.g. reflective coatings
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00Moving or stopping fluids
    • B01L2400/04Moving fluids with specific forces or mechanical means
    • B01L2400/0403Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0415Moving fluids with specific forces or mechanical means specific forces electrical forces, e.g. electrokinetic
    • B01L2400/0427Electrowetting

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
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  • Proteomics, Peptides & Aminoacids (AREA)
  • Engineering & Computer Science (AREA)
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  • General Health & Medical Sciences (AREA)
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  • Molecular Biology (AREA)
  • Immunology (AREA)
  • Clinical Laboratory Science (AREA)
  • Biophysics (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Engineering & Computer Science (AREA)
  • Biotechnology (AREA)
  • Genetics & Genomics (AREA)
  • Microbiology (AREA)
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  • General Physics & Mathematics (AREA)
  • Spectroscopy & Molecular Physics (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)
  • Investigating, Analyzing Materials By Fluorescence Or Luminescence (AREA)

Abstract

The PCR Module is detachably coupled to the Reader System. The PC Al module includes a base substrate, an optical sensor assembly, a barrier, a cover, sample carrying elements, a hydrophobic film, and a control circuit. The optical sensor assembly includes a plurality of optical sensors disposed in the base substrate and arrayed to generate light sensing signals by sensing emission light emitted from the sample. The partition wall protrudes on the base substrate to define a reaction space for accommodating the sample. The sample transport elements are disposed on the optical sensor assembly. The hydrophobic membrane covers the sample carrying element and defines a bottom surface of the reaction space. Wherein the control circuit is electrically connected to the optical sensor assembly and the sample transporting elements and transmits the optical sensing signal to the reader system and receives a potential control signal from the reader system, The potential potential is applied.

Description

PCR Module < RTI ID = 0.0 > {PCR Module}

The present invention relates to a PC Al module, and more particularly, to a PC Al module in which a sample is easily processed using EWOD (Electro Wetting On Dielectrics) technology and the accuracy of inspection is improved.

Gene amplification technology is an indispensable process in molecular diagnosis, and it is a technique to repeatedly replicate and amplify a specific base sequence of DNA or RNA in a sample. Among them, Polymerase chain reaction (PCR, 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 to monitor the amplification state of amplified samples in real time. It enables the quantitative analysis of DNA by measuring the intensity of fluorescence whose DNA changes depending on the amount of replication. Currently used real-time PC Al devices usually include a heat transfer block that transfers heat to a tube containing a thermoelectric element and a sample, a light source that emits excitation light to a sample inside the tube, and a light receiving unit that receives fluorescence emitted from the sample Consists of.

The PCA analysis requires a technique to rapidly increase or decrease the sample to the target temperature. However, since liquid samples have high specific heat, it takes much time to change the temperature and measurement accuracy is reduced.

Furthermore, since a sufficient amount of sample is required to be detectable in the light-receiving portion, the temperature of the sample is not easily changed.

In addition, in the process of injecting the sample into the PC Al module by manual operation, the sample is out of the predetermined position and the reagent is contaminated, causing the problem that the PC AL module is reset or discarded.

Korean Patent Application No. 10-2016-0020053 (February 19, 2016)

An object of the present invention is to provide a PC Al module which can easily process a sample using EWOD (Electro Wetting On Dielectrics) technology and improve the accuracy of inspection.

A PCR module according to an embodiment of the present invention is detachably coupled to a reader system. The PC Al module includes a base substrate, an optical sensor assembly, a barrier, a cover, sample carrying elements, a hydrophobic film, and a control circuit. The base substrate includes an insulating material. The optical sensor assembly includes a plurality of optical sensors disposed in the base substrate and arrayed to generate light sensing signals by sensing emission light emitted from the sample. The partition wall protrudes on the base substrate to define a reaction space for accommodating the sample. The cover is combined with the base substrate on which the partition is formed to maintain a constant humidity of the sample. The sample transport elements are disposed on the optical sensor assembly. The hydrophobic membrane covers the sample carrying element and defines a bottom surface of the reaction space. Wherein the control circuit is electrically connected to the optical sensor assembly and the sample transporting elements and transmits the optical sensing signal to the reader system and receives a potential control signal from the reader system, The potential potential is applied.

In one embodiment, the sample includes a droplet shape disposed on the hydrophobic film, and the height of the droplet shape and the area on a plane may be changed according to a potential potential applied to the sample transporting elements.

In one embodiment, when the PC Al module is in the observation mode, a ground potential may be applied to the sample transport element disposed under the sample.

In one embodiment, when the PC Al module is in a heating mode, positive or negative potentials may be applied to a plurality of sample transport elements disposed below the sample.

In one embodiment, the PC Al module may further include temperature control lines that include a conductive material and extend long to generate heat as the current flows.

A PCR module according to an embodiment of the present invention is detachably coupled to a reader system. The PC Al module includes a base substrate, an optical sensor assembly, a barrier, a cover, a plurality of sample delivery devices, a hydrophobic film, a hydrophilic coating, and a control circuit. The base substrate includes an insulating material. The optical sensor assembly includes a plurality of optical sensors disposed in the base substrate and arrayed to generate light sensing signals by sensing emission light emitted from the sample. The partition wall protrudes onto the base substrate. The sample transporting elements are disposed in the partition wall. The cover is combined with the base substrate on which the partition is formed to maintain a constant humidity of the sample. The hydrophobic membrane covers the sample transporting element and is formed on the upper surface of the partition wall. The hydrophilic coating is formed on the inner surface of the reaction space formed between adjacent partition walls. Wherein the control circuit is electrically connected to the optical sensor assembly and the sample transporting elements and transmits the optical sensing signal to the reader system and receives a potential control signal from the reader system, The potential potential is applied.

In one embodiment, the sample includes a droplet shape and is moved into the reaction space along the top surface of the partition in accordance with the change of the potential potential applied on the sample carrying elements.

According to the present invention, the size and area of the droplet-shaped sample can be easily changed by adjusting the potential of the substrate using the EWOD technique.

In addition, the sample transport elements and the hydrophobic membrane can be disposed on the base substrate, and the sample transport elements can be individually driven to move the sample to a desired position in the reaction space.

In addition, the sample transporting elements and the hydrophobic membrane may be disposed on the partition wall and hydrophilic coated in the reaction space, so that the sample can be easily inserted into the reaction space.

In addition, a plurality of samples may be sequentially separated from a sample source and put into a plurality of reaction spaces. Therefore, the accuracy is improved compared with the case of manually injecting the sample, and even a very small amount of sample can be injected easily.

In addition, when the contact area of the sample is reduced and the thickness is increased by adjusting the potentials of the sample transporting devices, the sensitivity of the light measured in the vertical direction is increased and the accuracy is improved.

Further, when the potential of the sample transporting elements is adjusted to increase the contact area of the sample and reduce the thickness, the temperature of the sample can be easily controlled.

Therefore, the sample is injected into the reaction space using an automated process, thereby preventing the reagent from being contaminated during the injection process.

1 is a block diagram illustrating a PC Al module installed in a reader system according to an embodiment of the present invention.
2 is a sectional view showing the PC Al module shown in FIG.
3 is a cross-sectional view illustrating a PC Al module according to another embodiment of the present invention.
4 is a plan view showing the PC Al module shown in FIG.
5 is a cross-sectional view taken along line I-I 'of FIG.
Figs. 6 and 7 are plan views showing a method of separating a sample from the sample source shown in Fig.
FIGS. 8 to 12 are cross-sectional views illustrating a method of injecting a sample into the reaction space of the PC Al module shown in FIG.
13 and 14 are cross-sectional views illustrating a method of injecting a sample into a reaction space of a PC Al module according to another embodiment of the present invention.
15 is a cross-sectional view showing that the sample shown in Fig. 14 is in a coagulated state.
16 is a cross-sectional view showing that the sample shown in Fig. 14 is unfolded.

For the embodiments of the invention disclosed herein, specific structural and functional descriptions are set forth for the purpose of describing an embodiment of the invention only, and it is to be understood that the embodiments of the invention may be practiced in various forms, The present invention should not be construed as limited to the embodiments described in Figs.

While the invention is susceptible to various modifications and alternative forms, specific embodiments thereof are shown by way of example in the drawings and are herein described in detail. It is to be understood, however, that the invention is not intended to be limited to the particular forms disclosed, but on the contrary, is intended to cover all modifications, equivalents, and alternatives falling within the spirit and scope of the invention. Similar reference numerals have been used for the components in describing each drawing.

The terms first, second, etc. may be used to describe various components, but the components should not be limited by the terms. The terms are used only for the purpose of distinguishing one component from another. For example, without departing from the scope of the present invention, the first component may be referred to as a second component, and similarly, the second component may also be referred to as a first component.

It is to be understood that when an element is referred to as being "connected" or "connected" to another element, it may be directly connected or connected to the other element, . On the other hand, when an element is referred to as being "directly connected" or "directly connected" to another element, it should be understood that there are no other elements in between. Other expressions that describe the relationship between components, such as "between" and "between" or "neighboring to" and "directly adjacent to" should be interpreted as well.

The terminology used in this application is used only to describe a specific embodiment and is not intended to limit the invention. The singular expressions include plural expressions unless the context clearly dictates otherwise. In the present application, the terms "comprises" or "having", etc., are intended to specify the presence of stated features, integers, steps, operations, components, parts, or combinations thereof, But do not preclude the presence or addition of other features, numbers, steps, operations, components, parts, or combinations thereof.

Unless defined otherwise, all terms used herein, including technical or scientific terms, have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Terms such as those defined in commonly used dictionaries are to be interpreted as having a meaning consistent with the contextual meaning of the related art and are to be interpreted as either ideal or overly formal in the sense of the present application Do not.

Hereinafter, preferred embodiments of the present invention will be described with reference to the accompanying drawings. The same reference numerals are used for the same constituent elements in the drawings and redundant explanations for the same constituent elements are omitted.

1 is a block diagram illustrating a PC Al module installed in a reader system according to an embodiment of the present invention.

Referring to FIG. 1, a PCR module 200 is detachably coupled to a reader system 100. The PC Al module 200 is driven by the reader system 100. Although FIG. 1 illustrates one PC Al module 200 coupled to the reader system 100, a person having ordinary skill in the art will recognize that a single reader system 100 may include a plurality of PC's It will be appreciated that module 200 can be modified to be coupled at the same time.

The reader system 100 includes a central information processing unit 110, a memory 120, an interface 130, and a cooling member 150.

The central information processing unit 110 reads the driving data stored in the memory 120 to drive the cooling member 150 and the PC Al module 200 and applies 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.

In this embodiment, the reader system 100 further includes a light source driver 220, a light source 230, and an excitation light source filter 233.

The light source driving unit 220 drives the light source 230 under the control of the central information processing unit 110 to apply the excitation light to the PC Al module 200.

The excitation light source filter 233 is disposed between the light source 230 and the reaction space 240 so as to filter the light generated from the light source 230 to have a uniform wavelength.

In another embodiment, the light source 230 may not be included in the reader system 100, but may be included in the PC Al module 200 as well.

2 is a sectional view showing the PC Al module shown in FIG.

1 and 2, the PC Al module 200 includes a base substrate 301, an optical sensor assembly 300, a partition 320, a cover 325, a sample 420, a control interface 430, A sample transport element 440, and a hydrophobic film 445.

The base substrate 301 includes various materials such as silicon, sapphire, silicon carbide, germanium, glass, and synthetic resin.

The optical sensor assembly 300 includes a plurality of optical sensors 310, an emission filter 313, a temperature sensor 360, and a temperature controller 370.

The plurality of optical sensors 310 are arrayed in the base substrate 301. In this embodiment, optical sensors 310 may include a plurality of photodiodes, a plurality of thin film transistors, etc. formed on a silicon substrate through a semiconductor process. For example, photodiodes can be formed by forming a P-type semiconductor layer, an N-type semiconductor layer, or the like by doping while changing the kind of impurity to a silicon substrate.

The emission filter 313 is disposed at an upper portion of the optical sensors 310 to pass only the emission light such as fluorescence and phosphorescence generated in the reaction space 240, . For example, the emissive filter 313 may comprise a cured or uncured filter with a mixture of photoresist and pigment.

The temperature sensor 360 is disposed adjacent to the reaction space 240 in the base substrate 301 or on the base substrate 301 to measure the temperature in the reaction space 240. The temperature sensing signal measured by the temperature sensor 360 is applied to the reader system 100 via the control interface 430.

A temperature controller 370 is disposed on the base substrate 301 to adjust the temperature in the reaction space 240. In this embodiment, the temperature controller 370 receives the temperature control signal from the control interface 430 and maintains or heats the temperature of the reaction space 240 constant. For example, the temperature control unit 370 may include a conductive pattern, a thermoelectric element, and the like.

The barrier ribs 320 protrude from the base substrate 301 to define a reaction space 240. The barrier ribs 320 may be formed of various materials such as plastic, PDMS, silicon, and metal.

The cover 325 is coupled with the base substrate 301 on which the partition 320 is installed to isolate the reaction space 240 from the outside and maintain the humidity in the reaction space 240. In this embodiment, oil (not shown) is covered on the surface of the sample 420 so that the sample 420 is not evaporated, and the cover 325 allows oil (not shown) to be accommodated in the reaction space 240 . Therefore, the sample 420 is prevented from drying and the electrical characteristics of the sample 420 are prevented from being changed.

A reagent (not shown) may be disposed in the reaction space 240 to react with the sample 420 to generate fluorescence or phosphorescence. In this embodiment, the reagent (not shown) that reacts with the sample 420 may include a primer, a probe, and the like. The genetic material contained in the sample 420 can be subjected to gene amplification by the primer. When excitation light is applied to the amplified dielectric material, fluorescence or phosphorescence is emitted by the probe.

The control interface 430 is connected to a temperature sensor 360, a temperature controller 370, and a plurality of sample transport elements 440.

The control interface 430 receives the temperature sensing signal from the temperature sensor 360 and transmits the temperature sensing signal to the central information processing unit 110 of the reader system 100.

The control interface 430 receives the temperature sensing signal and the temperature control signal corresponding to the PCA cycle from the central information processing unit 110 of the reader system 100 and controls the temperature controller 370.

The control interface 430 selectively controls the sample transport elements 440 to selectively apply a ground potential, a positive potential, or a negative potential to the sample transport elements 440. In the case of sample transport elements 440 to which no ground potential, positive potential or negative potential is applied, it may be in a floating state.

The sample transporting elements 440 are disposed on the base substrate 301 and are connected to the control terminal 430 by transporting the sample 420 by receiving a ground potential, a positive potential, or a negative potential from the control interface 430, Control the shape. In this embodiment, the sample transporting elements 440 include flat plate-shaped electrode pads arranged in parallel on the upper surface of the base substrate 301.

When the ground voltage GND is applied to the sample transporting element 440, the sample 420a disposed on the sample transporting element 440 maintains the aggregated state. Specifically, when the ground voltage GND is applied to the lower sample transporting element 440, the sample 420a is electrically grounded and has no electric charge, and has a droplet shape of a round shape by the hydrophobic film 445. [ When the sample 420a has a droplet shape of a round shape, the height in the longitudinal direction is increased. When the potential of the sample transport element 440 is the ground voltage (GND), the contact area between the sample 420a and the hydrophobic film 445 decreases, while the thickness in the longitudinal direction increases. As the thickness of the sample 420a in the longitudinal direction increases, the intensity of the radiation measured in the vertical direction increases, and the sensitivity and accuracy of the light measured in the vertical direction is improved.

On the other hand, when positive potential (+) or negative potential (-) is applied to the sample transporting element 440, the sample 420b disposed on the sample transporting element 440 remains unfolded. The contact area between the sample 420b and the hydrophobic film 445 increases while the thickness in the vertical direction decreases when the potential of the sample transport element 440 is positive (+) or negative (-). When the contact area between the sample 420b and the hydrophobic film 445 is increased, the heat generated in the temperature controller 370 is transmitted to the sample 420b through a large area, so that the temperature of the sample 420b can be easily Can be adjusted.

A specific driving method of the sample transporting elements 440 will be described later with reference to Figs.

The hydrophobic film 445 is disposed on the base substrate 301 and covers the upper surface of the sample transporting elements 440. When the sample 420 is placed on the sample transporting elements 440, the shape of the sample 420 can be more easily changed by the hydrophobic property of the hydrophobic film 445.

According to the present embodiment as described above, the sample transporting elements 440 and the hydrophobic film 445 are disposed on the base substrate 301 and the sample transporting elements 440 are individually driven to transport the sample 420 To a desired position in the reaction space 240.

3 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 plurality of reaction spaces and the hydrophilic coating are the same as the embodiment shown in Figs. 1 and 2, so that redundant description of the same components is omitted.

3, the PC Al module includes a base substrate 301, an optical sensor assembly 300, a partition wall 321, a cover 326, a sample 420, a control interface 431, a sample transport element 441, A hydrophobic film 446, and a hydrophilic coating 449.

The partition wall 321 defines a plurality of reaction spaces 241 protruding on the base substrate 301.

The cover 326 couples with the base substrate 301 provided with the partition 321 to isolate the reaction spaces 241 from the outside and maintain the humidity in the reaction spaces 241. In this embodiment, oil (not shown) is covered on the surface of the sample 420 so that the sample 420 is not evaporated, and the cover 326 allows oil (not shown) to be accommodated in the reaction space 241 . Therefore, the sample 420 is prevented from drying and the electrical characteristics of the sample 420 are prevented from being changed.

A reagent (not shown) may be disposed in the reaction spaces 241 to react with the sample 420 to generate fluorescence, phosphorescence, and the like. In this embodiment, different reagents (not shown) may be disposed in each of the reaction spaces 241.

The control interface 431 is connected to a temperature sensor 360, a temperature controller 370, and a plurality of sample transport elements 441.

The control interface 431 selectively controls the sample transporting elements 441 to selectively apply a ground potential, a positive potential, or a negative potential to the sample transporting elements 441.

The sample transporting elements 441 are disposed on the partition wall 321 and are adapted to transport the sample 420 by receiving the ground potential, the positive potential, or the negative potential from the control interface 431, . In this embodiment, the sample transporting elements 441 include flat electrode pads arranged in parallel on the upper surface of the partition wall 321, and there are no separate sample transport elements in the reaction space 241.

When the ground voltage GND is applied to the sample transporting element 441, the sample (420a in Fig. 2) disposed on the sample transporting element 441 remains in a coagulated state.

On the other hand, when positive potential (+) or negative potential (-) is applied to the sample transporting element 441, the sample (420b in Fig. 2) disposed on the sample transporting element 441 remains unfolded .

The hydrophobic film 446 is disposed on the upper surface of the partition wall 321 and covers the upper surface of the sample transporting elements 441. When the sample (420 in FIG. 2) is placed on the sample transporting elements 441, the hydrophobic property of the hydrophobic film 446 allows the sample (420 in FIG. 2) to move more easily on the hydrophobic film 446, Can be changed more easily.

The hydrophilic coating 449 is disposed on the inner surface of the reaction space 241 so that the sample (420 in FIG. 2) is easily accommodated. When the sample (420 in FIG. 2) moves on the hydrophobic film 446 and is disposed adjacent to the reaction space 241, the sample is inclined toward the reaction space 241 by the hydrophilic coating 449. The sample (420 in FIG. 2) inclined toward the reaction space 241 flows downward by its own weight and is inserted into the reaction space 241 by the hydrophilic coating 449.

According to the present embodiment as described above, the sample transporting elements 440 and the hydrophobic film 445 are disposed on the partition wall 321 and the hydrophilic coating 449 is placed in the reaction space 241, 420 can be easily inserted into the reaction space 241.

FIG. 4 is a plan view showing the PC Al module shown in FIG. 3, and FIG. 5 is a sectional view taken along line I-I 'of FIG.

3 to 5, a sample source 421 is disposed on one side of a base substrate 301 on which a hydrophilic coating 446 is disposed. The sample source 421 is a sample in which the samples 420 are added in the form of droplets in a capacity capable of performing a plurality of experiments.

(+) Or negative potential (-) is applied to the sample transporting elements 441 disposed at the lower portion of the sample source 421 and the sample transporting elements 441 ), A ground potential (GND) is applied so that the sample source 421 exists in a single droplet form.

The sample 420b is separated from a part of the sample source 421 and sequentially transferred to the plurality of reaction spaces 241. [ In another embodiment, different types of sample sources may be disposed on one side of the base substrate on which the hydrophilic coating is disposed, and different types of samples may be transferred into the reaction spaces 241 from the sample sources.

A negative potential (+) or a negative potential (-) is applied to a part of the sample transporting elements 441 arranged adjacent to the sample source 421, in order to separate the sample 420b from a part of the sample source 421. [ And a part of the sample source 421 is drawn out. When a part of the sample source 421 is drawn out, the ground voltage GND is applied to the sample transporting element 441 disposed between the original sample source 421 and the drawn sample 420b. The extracted sample 420b is separated from the original sample source 421 when the ground voltage GND is applied between the original sample source 421 and the drawn sample 420b.

Figs. 6 and 7 are plan views showing a method of separating a sample from the sample source shown in Fig.

3 to 6, when a positive potential (+) is applied to a part of the sample transporting elements 441 disposed adjacent to the sample source 421, a part of the sample source 421 becomes a positive potential (+) Protrudes toward the applied sample transporting elements 441.

Referring to FIGS. 3 to 5 and 7, a ground voltage is applied between the original sample source 421 and the protruding sample source. When the ground voltage is applied between the original sample source 421 and the projected sample source, the sample 420b is separated from the sample source 421. [

FIGS. 8 to 12 are cross-sectional views illustrating a method of injecting a sample into the reaction space of the PC Al module shown in FIG.

3, 7, and 8, when the potential of the sample transporting element 441 adjacent to the sample 420b sequentially changes, the sample 420b separated by the sample source 421 flows into the adjacent sample And moves along the carrier element 441. For example, when positive potential (+) is sequentially applied to the adjacent sample transport elements 441 and the ground voltage (GND) is sequentially applied to the existing sample transport element 441, As shown in FIG.

Referring to FIGS. 3 and 9, the sample carrier element 441 moves the sample 420b to a position adjacent to the reaction space 241. When the positive potential (+) is applied to the two sample transporting elements 441 adjacent to the reaction space 241, the sample 420b is in an unfolded state.

3 and 10, a positive potential (+) is applied to only one sample transport element 441 " closest to the reaction space 241 and a ground potential (" + ") is applied to the adjacent sample transport element 441 ' GND) is applied, the sample 420a is in a coagulated state.

When the sample 420a is in a coagulated state, one side of the sample 420a comes into contact with the hydrophilic coating 449 in the reaction space 241.

3 and 11, when one side of the sample 420a comes into contact with the hydrophilic coating 449 in the reaction space 241, the remaining portion of the sample 420a is also moved toward the hydrophilic coating 449.

Subsequently, the remaining portion of the sample 420a is moved toward the reaction space 241 by the self weight of the sample 420a and the attractive force of the hydrophilic coating 449.

At this time, when the ground voltage GND is applied to the sample transporting element 441 'disposed closest to the reaction space 241, it is easier for the sample 420a to move toward the reaction space 241.

3 and 11, the sample 420 is fully introduced into the reaction space 241 and brought into contact with the reagent 423.

In the present embodiment, the sample source 421 includes a sample material that can be separated into a plurality of samples 420b, and sequentially drives the sample carrier devices 441 to collect a plurality of samples 420b are sequentially separated and transferred to different reaction spaces 241. [ For example, two or more kinds of reagents (not shown) may be disposed in the plurality of reaction spaces 241.

According to the present embodiment as described above, a plurality of samples 240 can be sequentially separated from the sample source 421 and put into a plurality of reaction spaces 241. Therefore, the accuracy is improved compared with the case of manually injecting the sample, and even a very small amount of sample can be injected easily.

13 and 14 are cross-sectional views illustrating a method of injecting a sample into a reaction space of a PC Al module according to another embodiment of the present invention. In this embodiment, the remaining components except for the method of driving the sample transporting elements disposed adjacent to the reaction space are the same as the embodiment shown in Figs. 3 to 12, so that redundant description of the same components is omitted .

13, a positive potential (+) is applied to one sample transport element 441a closest to the reaction space 241 and a ground potential GND is applied to the adjacent sample transport element 441 ' The sample 420a is in a coagulated state.

In this embodiment, not only one sample transporting element 441a close to the reaction space 241 but also the other sample transporting element 441b facing each other with the reaction space 241 as a center is moved to the positive potential + Is applied. Since the positive potential (+) serves to attract the sample 420a, when the positive potential (+) is applied to the two sample transporting elements 441a and 441b facing each other, the sample 420a is more easily Can be introduced into the reaction space 421. In another embodiment, a positive potential (+) may be applied to all of the sample transport elements adjacent to the reaction space 241 as well as the two sample transport elements 441a and 441b facing each other.

14, a ground voltage GND is applied to one sample transporting element 441a disposed closest to the reaction space 241, and the other one of the sample transporting elements 441a, When the positive potential (+) is applied to the sample transporting element 441b, the sample 420a is more easily injected into the reaction space 241. [ In another embodiment, the ground voltage GND is applied to only one of the sample transporting elements 441a among all the sample transporting elements surrounding the reaction space 241, and the positive transport (+) is applied to the remaining sample transporting elements .

15 is a cross-sectional view showing that the sample shown in Fig. 14 is in a coagulated state.

Referring to FIG. 15, a ground voltage GND is applied to all sample transporting elements surrounding the reaction space 241 after the sample 420a is introduced into the reaction space 241. When the ground voltage GND is applied to all of the sample transporting elements surrounding the reaction space 241, the sample 420a is in a coagulated state. When the sample 420a is in a cohered state, the thickness of the sample increases and the sensitivity of the light measured in the vertical direction increases, thereby improving the accuracy.

In another embodiment, the ground voltage (GND) may be applied to only some of the sample transport elements surrounding the reaction space 241 and the remaining sample transport elements may be in a floating state.

According to this embodiment, when the potential of the substrate is adjusted to reduce the contact area of the sample and increase the thickness, the sensitivity of the light measured in the vertical direction increases, thereby improving the accuracy.

16 is a cross-sectional view showing that the sample shown in Fig. 14 is unfolded.

16, a positive potential (+) (or a negative potential (-)) is applied to all the sample transporting elements surrounding the reaction space 241 after the sample 420a is injected into the reaction space 241 do. When positive potential (+) is applied to all the sample transporting elements surrounding the reaction space 241, the sample 420b is in an unfolded state. When the sample 420b is unfolded, the contact area between the sample 420b and the partition wall 321 increases. When the contact area between the sample 420b and the partition 321 increases, the heat generated by the temperature controller 370 is more easily transmitted to the sample 420b.

In another embodiment, a positive voltage (+) may be applied only to some of the sample transport elements surrounding the reaction space 241 and the remaining sample transport elements may be in a floating state.

According to this embodiment, when the potential of the substrate is adjusted to increase the contact area of the sample and reduce the thickness, the temperature of the sample can be easily adjusted.

According to the embodiments of the present invention as described above, the size and area of the droplet-shaped sample can be easily changed by adjusting the potential of the substrate using the EWOD technique.

In addition, the sample transport elements and the hydrophobic membrane can be disposed on the base substrate, and the sample transport elements can be individually driven to move the sample to a desired position in the reaction space.

In addition, the sample transporting elements and the hydrophobic membrane may be disposed on the partition wall and hydrophilic coated in the reaction space, so that the sample can be easily inserted into the reaction space.

In addition, a plurality of samples may be sequentially separated from a sample source and put into a plurality of reaction spaces. Therefore, the accuracy is improved compared with the case of manually injecting the sample, and even a very small amount of sample can be injected easily.

In addition, when the contact area of the sample is reduced and the thickness is increased by adjusting the potentials of the sample transporting devices, the sensitivity of the light measured in the vertical direction is increased and the accuracy is improved.

Further, when the potential of the sample transporting elements is adjusted to increase the contact area of the sample and reduce the thickness, the temperature of the sample can be easily controlled.

Therefore, the sample is injected into the reaction space using an automated process, thereby preventing the reagent from being contaminated during the injection process.

The present invention has industrial applicability that can be used in devices for amplifying and inspecting dielectric materials.

100: Reader system 110: Central information processor
120: memory 130: interface
150: cooling member 200: PC al module
220: light source driver 230: light source
233: excitation light source filter 240: reaction space
301: base substrate 310: optical sensor array
313: Emissive filter 320:
325: cover 360: temperature sensor
370: temperature control unit 420: sample
420a: coagulated sample 420b: spread sample
421: sample source 423: reagent
430: control interface 440: sample carrier element
445: hydrophobic film 449: hydrophilic coating

Claims (7)

delete delete delete delete delete 1. A PCR module detachably coupled to a reader system,
A base substrate comprising an insulating material;
An optical sensor assembly disposed in the base substrate and arranged in an array to detect emitted light generated from the sample to generate a light sensing signal;
A partition wall protruding from the base substrate to form a reaction space;
A cover coupled to the base substrate on which the barrier rib is formed to maintain a constant humidity of the sample;
A plurality of sample carrying elements disposed in the partition wall;
A hydrophobic film covering the sample transporting device and formed on the upper surface of the barrier rib;
A hydrophilic coating formed on an inner surface of a reaction space formed between adjacent partition walls; And
The optical sensor assembly and the sample transporting elements, the optical sensing signal is transmitted to the reader system, and a potential control signal is applied from the reader system to apply different potentials to the sample transporting elements And a control circuit for controlling the control circuit.
7. The method of claim 6, wherein the sample includes a droplet shape and is inserted into the reaction space by moving along the upper surface of the partition wall in accordance with the change of the potential potential applied on the sample carrying elements. Al module.
KR1020170063196A 2016-05-25 2017-05-22 PCR Module KR101904506B1 (en)

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FR3074267B1 (en) * 2017-11-28 2020-09-25 Osmose AIR RENEWAL DEVICE IN A CONFINED ENCLOSURE
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Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7338637B2 (en) * 2003-01-31 2008-03-04 Hewlett-Packard Development Company, L.P. Microfluidic device with thin-film electronic devices
US7767439B2 (en) * 2003-12-10 2010-08-03 Samsung Electronics Co., Ltd. Real-time PCR monitoring apparatus and method
US7507575B2 (en) * 2005-04-01 2009-03-24 3M Innovative Properties Company Multiplex fluorescence detection device having removable optical modules
KR100952102B1 (en) * 2007-08-29 2010-04-13 한양대학교 산학협력단 Chip for micro polymerase chain reaction and manufacture method thereof
KR101221872B1 (en) * 2009-04-16 2013-01-15 한국전자통신연구원 Apparatus for polymerase chain reaction
KR101368463B1 (en) * 2010-04-23 2014-03-03 나노바이오시스 주식회사 Device for amplify nucleic acid comprising two heating block
KR102041205B1 (en) * 2013-03-18 2019-11-06 주식회사 미코바이오메드 Heating block for polymerase chain reaction comprising repetitively disposed patterned heater and device for polymerase chain reaction comprising the same

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
An integrated CMOS quantitative-polymerasechain-reaction lab-on-chip for point-of-care diagnostics(Haig Norian, Lab on a Chip, Jan. 2012)*

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