KR101904506B1 - PCR Module - Google Patents
PCR Module Download PDFInfo
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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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- 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
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING 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
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING 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
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6844—Nucleic acid amplification reactions
- C12Q1/686—Polymerase chain reaction [PCR]
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01J—MEASUREMENT OF INTENSITY, VELOCITY, SPECTRAL CONTENT, POLARISATION, PHASE OR PULSE CHARACTERISTICS OF INFRARED, VISIBLE OR ULTRAVIOLET LIGHT; COLORIMETRY; RADIATION PYROMETRY
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- G01J1/42—Photometry, e.g. photographic exposure meter using electric radiation detectors
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- B—PERFORMING OPERATIONS; TRANSPORTING
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- 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
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- B—PERFORMING OPERATIONS; TRANSPORTING
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- B01L2300/161—Control and use of surface tension forces, e.g. hydrophobic, hydrophilic
- B01L2300/165—Specific details about hydrophobic, oleophobic surfaces
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
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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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- B01L2400/04—Moving fluids with specific forces or mechanical means
- B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
- B01L2400/0415—Moving fluids with specific forces or mechanical means specific forces electrical forces, e.g. electrokinetic
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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
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.
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
The
The central
The central
In this embodiment, the
The light
The excitation
In another embodiment, the
2 is a sectional view showing the PC Al module shown in FIG.
1 and 2, the
The
The
The plurality of
The
The
A
The
The
A reagent (not shown) may be disposed in the
The
The
The
The
The
When the ground voltage GND is applied to the
On the other hand, when positive potential (+) or negative potential (-) is applied to the
A specific driving method of the
The
According to the present embodiment as described above, the
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
The
The
A reagent (not shown) may be disposed in the
The
The
The
When the ground voltage GND is applied to the
On the other hand, when positive potential (+) or negative potential (-) is applied to the
The
The
According to the present embodiment as described above, the
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
(+) Or negative potential (-) is applied to the
The
A negative potential (+) or a negative potential (-) is applied to a part of the
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
Referring to FIGS. 3 to 5 and 7, a ground voltage is applied between the
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
Referring to FIGS. 3 and 9, the
3 and 10, a positive potential (+) is applied to only one
When the
3 and 11, when one side of the
Subsequently, the remaining portion of the
At this time, when the ground voltage GND is applied to the sample transporting element 441 'disposed closest to the
3 and 11, the
In the present embodiment, the
According to the present embodiment as described above, a plurality of
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
In this embodiment, not only one
14, a ground voltage GND is applied to one
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
In another embodiment, the ground voltage (GND) may be applied to only some of the sample transport elements surrounding the
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
In another embodiment, a positive voltage (+) may be applied only to some of the sample transport elements surrounding the
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
421: sample source 423: reagent
430: control interface 440: sample carrier element
445: hydrophobic film 449: hydrophilic coating
Claims (7)
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.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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KR1020160064269 | 2016-05-25 | ||
KR20160064269 | 2016-05-25 |
Publications (2)
Publication Number | Publication Date |
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KR20170133267A KR20170133267A (en) | 2017-12-05 |
KR101904506B1 true KR101904506B1 (en) | 2018-10-05 |
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Application Number | Title | Priority Date | Filing Date |
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KR1020170063196A KR101904506B1 (en) | 2016-05-25 | 2017-05-22 | PCR Module |
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KR (1) | KR101904506B1 (en) |
WO (1) | WO2017204512A1 (en) |
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FR3074267B1 (en) * | 2017-11-28 | 2020-09-25 | Osmose | AIR RENEWAL DEVICE IN A CONFINED ENCLOSURE |
KR102222511B1 (en) * | 2019-06-04 | 2021-03-03 | (주)옵토레인 | Well array for pcr |
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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 |
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2017
- 2017-05-22 KR KR1020170063196A patent/KR101904506B1/en active IP Right Grant
- 2017-05-22 WO PCT/KR2017/005298 patent/WO2017204512A1/en active Application Filing
Non-Patent Citations (1)
Title |
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An integrated CMOS quantitative-polymerasechain-reaction lab-on-chip for point-of-care diagnostics(Haig Norian, Lab on a Chip, Jan. 2012)* |
Also Published As
Publication number | Publication date |
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KR20170133267A (en) | 2017-12-05 |
WO2017204512A1 (en) | 2017-11-30 |
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