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WO2023128298A1 - Point-of-care molecular diagnostic device - Google Patents

Point-of-care molecular diagnostic device Download PDF

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Publication number
WO2023128298A1
WO2023128298A1 PCT/KR2022/018756 KR2022018756W WO2023128298A1 WO 2023128298 A1 WO2023128298 A1 WO 2023128298A1 KR 2022018756 W KR2022018756 W KR 2022018756W WO 2023128298 A1 WO2023128298 A1 WO 2023128298A1
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WO
WIPO (PCT)
Prior art keywords
sample
unit
passage
reaction
light
Prior art date
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Ceased
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PCT/KR2022/018756
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French (fr)
Korean (ko)
Inventor
천진우
이재현
정지용
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Institute for Basic Science
University Industry Foundation UIF of Yonsei University
Original Assignee
Institute for Basic Science
University Industry Foundation UIF of Yonsei University
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Priority claimed from KR1020220155402A external-priority patent/KR102887985B1/en
Application filed by Institute for Basic Science, University Industry Foundation UIF of Yonsei University filed Critical Institute for Basic Science
Publication of WO2023128298A1 publication Critical patent/WO2023128298A1/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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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
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • 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
    • C12Q1/70—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving virus or bacteriophage
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor

Definitions

  • the present invention relates to a field-oriented molecular diagnosis device, and more particularly, to a field-oriented molecular diagnosis device capable of performing amplification of a target nucleic acid through PCR (Polymerase Chain Reaction) in a medical field.
  • PCR Polymerase Chain Reaction
  • a large-scale diagnosis is required in the context of the pandemic of the coronavirus infection (COVID-19).
  • COVID-19 coronavirus infection
  • PCR polymerase chain reaction
  • NAAT nucleic acid amplification test
  • RT-PCR reverse transcription PCR
  • the present invention is to solve the above problems, and an object of the present invention is to provide an in-situ molecular diagnostic device capable of quickly and effectively detecting nucleic acids through PCR.
  • Another object of the present invention is to provide an on-site molecular diagnosis device that continuously performs sample input, sample pretreatment, PCR, and target nucleic acid detection.
  • the reaction unit is a reaction in which the sample flows or stays mixed with a pyrogen generating heat when irradiated with first light, a primer, and a polymerase.
  • a first light source for radiating the first
  • the on-site molecular diagnosis device includes an enrichment unit disposed between the input unit and the reaction unit, collecting the transferred sample, removing impurities present in the sample, and concentrating nucleic acids present in the sample. can include more.
  • the enrichment unit the collection body for collecting the sample; a collecting chamber in which the collecting body is disposed; a washing solution storage chamber storing one or more washing solutions for washing impurities present in the sample; It may include; a cleaning solution supply passage connecting the cleaning solution storage chamber and the collection chamber.
  • the enrichment unit may include a washing solution discharge channel for discharging the washing solution discharged from the collecting body; and a discharge chamber for collecting the cleaning solution discharged through the cleaning solution discharge passage.
  • the in-situ molecular diagnosis device may further include a mixing unit disposed between the enrichment unit and the reaction unit and mixing the pyrogen, the primer, and the polymerase with the sample transferred from the enrichment unit. there is.
  • the mixing unit may include a separation solution storage chamber for storing a separation solution for separating a sample in which impurities are removed from the collection body; a separation solution supply passage connecting the separation solution storage chamber and the collecting chamber; a sample discharge passage through which the sample discharged together with the separation solution from the collection chamber is discharged; and a mixing chamber configured to store a mixed solution including the exothermic material, the primer, and the polymerase, and mix the sample introduced through the sample discharge channel with the mixed solution.
  • the in-situ molecular diagnosis device may further include a first heating unit disposed between the input unit and the enrichment unit and heating the sample transferred to the enrichment unit to a first temperature so that nucleic acid is extracted from the sample.
  • the first heating unit may include a first heating passage connecting the input unit and the enrichment unit and through which the sample flows; and a first heater disposed to heat the first heating passage to a first temperature.
  • the in-situ molecular diagnosis device is disposed between the mixing unit and the reaction unit, and heats the sample transferred to the reaction unit to a second temperature so that reverse transcription of RNA included in the sample occurs. Wealth may be further included.
  • the second heating unit may include a second heating passage connecting the mixing unit and the reaction unit and through which the sample flows; and a second heater disposed to heat the second heating passage to a second temperature.
  • the exothermic material has magnetism
  • the on-site molecular diagnosis device may further include a separation unit that separates the exothermic material from the sample transferred from the reaction unit by fixing the exothermic material by magnetic force.
  • the separator may include a separation passage through which the sample transferred from the reaction unit stays or flows; and a magnet providing magnetic force to the separation passage to fix the exothermic material to the inside of the separation passage.
  • the in-situ molecular diagnosis device may further include a detection unit for detecting target nucleic acid present in the sample transferred from the reaction unit.
  • the detection unit a detection passage through which the sample transferred from the reaction unit stays or flows; a second light source radiating a second light for detecting the target nucleic acid to the detection channel; and a detector for detecting the second light passing through the detection passage.
  • the reaction channel may include an irradiated area irradiated with the first light and a non-irradiated area not irradiated with the first light, and the first light source may radiate the first light to the irradiated area.
  • the first light may be irradiated to the reaction channel as a whole, and the first light source may intermittently irradiate the first light to the reaction channel.
  • the in-situ molecular diagnosis device enables PCR to be performed quickly and efficiently by repeatedly heating and cooling a sample mixed with a pyrogen in a reactor.
  • the on-site molecular diagnostic device enables sample pre-processing, PCR, and target nucleic acid detection to be sequentially performed inside a continuous flow path, thereby increasing the efficiency and accuracy of pathogen testing. raises
  • FIG. 1 is a block diagram of an on-site molecular diagnosis device according to an embodiment of the present invention.
  • FIG. 2 is a diagram showing the configuration of a first heating unit of an on-site molecular diagnostic device according to an embodiment of the present invention.
  • FIG. 3 is a diagram showing the configuration of an enrichment unit of an on-site molecular diagnostic device according to an embodiment of the present invention.
  • FIG. 4 is a diagram showing the configuration of a mixing unit of an on-site molecular diagnosis device according to an embodiment of the present invention.
  • FIG. 5 is a diagram showing the configuration of a second heating unit of an on-site molecular diagnosis device according to an embodiment of the present invention.
  • FIG. 6 is a diagram showing the configuration of a reaction unit of an on-site molecular diagnostic device according to an embodiment of the present invention.
  • FIG. 7 is a graph showing temperature changes of samples repeating PCR cycles in a reaction unit of an on-site molecular diagnosis device according to an embodiment of the present invention.
  • FIG. 8 is a view showing the configuration of a modified example of a reaction unit of an on-site molecular diagnostic device according to an embodiment of the present invention.
  • MPN magneto-plasmonic nanoparticle
  • FIG. 10 is a diagram showing the configuration of a separation unit of an on-site molecular diagnosis device according to an embodiment of the present invention.
  • FIG. 11 is a diagram showing the configuration of a detection unit of an on-site molecular diagnosis device according to an embodiment of the present invention.
  • Words and terms used in this specification and claims are not construed as limited in their ordinary or dictionary meanings, but in accordance with the principle that the inventors can define terms and concepts in order to best describe their inventions. It should be interpreted as a meaning and concept that corresponds to the technical idea.
  • a component being in the "front”, “rear”, “above” or “below” of another component means that it is in direct contact with another component, unless there are special circumstances, and is “in front”, “rear”, “above” or “below”. It includes not only those disposed at the lower part, but also cases in which another component is disposed in the middle.
  • the fact that certain components are “connected” to other components includes cases where they are not only directly connected to each other but also indirectly connected to each other unless there are special circumstances.
  • FIG. 1 is a block diagram of an on-site molecular diagnosis device according to an embodiment of the present invention.
  • the in-situ molecular diagnosis device 1 enables PCR (Polymerase Chain Reaction) to be performed quickly and efficiently by repeating heating and cooling of a heating material mixed in a sample.
  • the on-site molecular diagnosis device 1 includes an inlet unit 100, a first heating unit 200, an enrichment unit 300, a mixing unit 400, It may include a second heating unit 500, a reaction unit 600, a separation unit 700, a detection unit 800, and a pressure supply unit 900.
  • a sample for PCR is introduced through the input unit 100.
  • the sample may be taken from the oral cavity or nasal cavity of the subject.
  • the input unit 100 may be formed as an input passage having an input port into which a sample is input.
  • the sample is subject to nucleic acid detection through PCR, and may be prepared by purifying RNA or DNA from saliva of a subject.
  • the nucleic acid to be detected may be the N1 and N2 genes for detecting the SARS-CoV-2 virus and the human RPP30 gene for confirming that the sample is a human sample.
  • the nucleic acid to be detected may vary depending on the type of infection to be diagnosed.
  • the first heating unit 200 is disposed between the input unit 100 and the enrichment unit 300 and heats the sample transferred to the enrichment unit 300 to a first temperature so that nucleic acids are extracted from the sample.
  • the first temperature may be selected from 90 ⁇ 100 °C.
  • the first heating unit 200 may heat the sample to 95°C.
  • viruses may be lysed and RNA may be extracted from the sample.
  • the first heating unit 200 may include a first heating passage 210 and a first heater 220 .
  • the first heating passage 210 connects the input unit 100 and the enrichment unit 300 and is arranged so that the sample flows.
  • the first heating passage 210 may be microtubules.
  • the first heating passage 210 may be provided as a tube having a diameter of several millimeters (eg, 1 mm to 5 mm).
  • the first heater 220 is disposed to heat the first heating passage 210 to a first temperature.
  • the first heater 220 may be a heater block disposed adjacent to the first heating passage 210 .
  • the enrichment unit 300 is disposed between the first heating unit 200 and the mixing unit 400 .
  • the enrichment unit 300 collects the sample transported through the first heating unit 200, removes impurities present in the sample, and concentrates nucleic acids present in the sample.
  • the enrichment unit 300 includes a collecting body 310, a collecting chamber 320, a cleaning solution storage chamber 330, a cleaning solution supply channel 340, a cleaning solution discharge channel 350, and a discharge chamber. (360).
  • Collecting body 310 collects the sample.
  • the collection body 310 may be made of resin.
  • the collector 310 may have a cylindrical shape.
  • the collecting chamber 320 has a collecting body 310 disposed therein.
  • the collection chamber 320 may be connected to the first heating passage 210 so that the sample in which the virus is dissolved and the RNA is extracted is transported through the first heating passage 210 .
  • the cleaning solution storage chamber 330 stores one or more cleaning solutions for cleaning impurities present in the sample.
  • the washing solution storage chamber 330 includes a first sub-storage chamber 331 storing ethanol, a second sub-storage chamber 332 storing a wash buffer, A third sub storage chamber 333 in which mineral oil is stored may be included.
  • the one or more cleaning solutions may include ethanol, wash buffer, or mineral oil.
  • the cleaning solution supply passage 340 connects the cleaning solution storage chamber 330 and the collecting chamber 320 .
  • One or more cleaning solutions stored in the cleaning solution storage chamber 330 may be supplied to the collection chamber 320 through the cleaning solution supply passage 340 .
  • ethanol, wash buffer, and mineral oil may be supplied to the collection chamber 320 in order to remove impurities from the sample collected in the collector 310 and to concentrate nucleic acids.
  • the cleaning solution discharge channel 350 discharges the cleaning solution discharged from the collector 310 .
  • the discharge chamber 360 collects the cleaning solution discharged through the cleaning solution discharge channel 350 .
  • the cleaning solution storage chamber 330 and the collection chamber are used to sequentially provide a plurality of cleaning solutions to the collector 310.
  • One or more valves may be disposed between the 320 to selectively connect the first to third sub-storage chambers with the collecting chamber 320 .
  • the first to third sub storage chambers 331 , 332 , and 333 may be connected to the cleaning solution supply channel 340 , respectively.
  • the mixing unit 400 is disposed between the enrichment unit 300 and the second heating unit 500 .
  • the mixing unit 400 mixes the exothermic material, the primer, and the polymerase with the sample transferred from the enrichment unit 300 .
  • the exothermic material may include exothermic particles.
  • the exothermic particles may be nanoparticles (eg, 10 nm to 1 ⁇ m in diameter).
  • the exothermic particles may be spherical, dumbbell, 2D, or mixed (core-shell, Janus, or combination) particles.
  • the exothermic particles may be micro particles (eg, 1 ⁇ m to 100 ⁇ m in diameter).
  • the exothermic particles may be integral type or mixed type (core-shell, Janus, combination type) particles.
  • the exothermic particles may include any one or more of magneto-plasmonic nanoparticles (MPN), plasmonic nanoparticles, magnetic nanoparticles, gold nanoparticles, and silver nanoparticles.
  • MPN magneto-plasmonic nanoparticles
  • plasmonic nanoparticles magnetic nanoparticles
  • gold nanoparticles e.g., gold nanoparticles, and silver nanoparticles.
  • the mixing unit 400 includes a separation solution storage chamber 410, a separation solution supply passage 420, a sample discharge passage 430, and a mixing chamber 440. can do.
  • the separation solution storage chamber 410 stores a separation solution for separating samples in a state in which impurities are removed from the collector 310 .
  • the separation solution may elute the sample from the collector 310 .
  • the separation solution may be water.
  • the separation solution supply passage 420 connects the separation solution storage chamber 410 and the collecting chamber 320 .
  • the separation solution may be supplied to the collection chamber 320 through the separation solution supply channel 420 .
  • the sample discharge channel 430 discharges the sample discharged together with the separation solution from the collection chamber 320 .
  • the mixing chamber 440 stores a mixed solution including the exothermic material, the primer, and the polymerase.
  • the sample introduced through the sample discharge channel 430 may be mixed with the mixed solution in the mixing chamber 440 .
  • one or more valves may be disposed between the separation solution supply passage 420 and the collection chamber 320 and between the sample discharge passage 430 and the collection chamber 320 to close or open the passage.
  • the sample discharge channel 430 may be provided as a microtubule or a tube having a diameter of several mm (eg, 1 mm to 5 mm).
  • the second heating unit 500 is disposed between the mixing unit 400 and the reaction unit 600 .
  • the second heating unit 500 heats the sample transferred to the reaction unit 600 to a second temperature so that reverse transcription of RNA included in the sample occurs.
  • the second temperature may be selected from 45 ⁇ 55 °C.
  • the second heating unit 500 may heat the sample to 52°C.
  • reverse transcription of RNA in the sample may proceed.
  • the target nucleic acid contained in the sample is DNA
  • reverse transcription is not required. Accordingly, when the target nucleic acid to be detected in the sample is DNA, the second heating unit 500 may be omitted.
  • the second heating part 500 may include a second heating passage 510 and a second heater 520 .
  • the second heating passage 510 connects the mixing unit 400 and the reaction unit 600 and is disposed so that the sample flows.
  • the second heating passage 510 may be provided as a microtubule in micro units or a tube having a diameter in units of several mm (eg, 1 mm to 5 mm).
  • the second heater 520 is disposed to heat the second heating passage 510 to a second temperature.
  • the second heater 520 may be a heater block disposed adjacent to the second heating passage 510 .
  • PCR of the sample proceeds.
  • the exothermic material mixed with the sample inside the reaction unit 600 heats the sample by generating heat when the first light is irradiated, and the exothermic material does not generate heat while not being irradiated with the first light.
  • the sample is cooled.
  • PCR may be performed while repeating such heating and cooling cycles.
  • the period length, irradiation time, and non-irradiation time may be equally set for each period.
  • the length of the period, the irradiation time, and the non-irradiation time of some periods may be set to be different from those of other periods, if necessary.
  • the reaction unit 600 includes a reaction passage 610 and a first light source 620 .
  • the reaction flow path 610 is arranged so that the sample flows or stays in a mixed state with the pyrogen, primer and polymerase.
  • the reaction channel 610 may be provided with a microtubule or a tube having a diameter of several millimeters (eg, 1 mm to 5 mm).
  • the first light source 620 radiates the first light to at least a portion of the reaction passage 610 .
  • the first light has a wavelength that heats the exothermic material. Heat may be generated by light of different wavelengths depending on the type of the heating material, and the wavelength range of the first light may vary depending on the type of the heating material. For example, the peak wavelength of the light may have an arbitrary range selected from 400 to 800 nm.
  • the reaction passage 610 may include an irradiation area 611 to which the first light is irradiated and a non-irradiation area 612 to which the first light is not irradiated. Also, the first light source 620 may radiate the first light to the irradiation area 611 .
  • the sample including the exothermic material flows through the reaction passage 610 , is heated when passing through the irradiation region 611 , and may be cooled when passing through the non-irradiated region 612 . Since heating and cooling cycles must be repeated in order for PCR to be repeatedly performed, one-way flow and opposite to the one-way flow allow the sample to repeatedly pass through the irradiated area 611 and the non-irradiated area 612 in the reaction passage 610 It is possible to repeat the flow in the other direction in one direction.
  • a plurality of irradiation areas 611 and non-irradiation areas 612 are alternately disposed in the reaction passage 610, and a first light source 620 is provided to irradiate the first light to the plurality of irradiation areas 611.
  • the sample flows in only one direction and it is possible to repeat heating and cooling cycles.
  • FIG. 7 is a graph showing temperature changes of samples repeating PCR cycles in a reaction unit of an on-site molecular diagnosis device according to an embodiment of the present invention.
  • the exothermic material while the sample is irradiated with the first light in the reaction passage 610 , the exothermic material generates heat, thereby heating the sample and increasing the temperature of the sample. Meanwhile, while the sample is not irradiated with the first light, the exothermic material does not generate heat and the sample is cooled. Accordingly, the temperature of the sample is lowered.
  • PCR consists of three steps: denaturation, annealing, and elongation.
  • denaturation is performed at a temperature of 94 to 98 ° C
  • bonding is performed at a temperature of 50 to 65 ° C
  • elongation may be performed at a temperature of 75 to 80 ° C.
  • the temperature of the sample is repeatedly raised and lowered depending on whether or not the first light is irradiated inside the reaction passage 610, and PCR cycles including denaturation, bonding, and elongation are repeated It can be.
  • the reaction unit 600a includes a reaction passage 610a and a first light source 620a, the reaction passage 610a does not have a separate non-irradiation area, and the first light is irradiated as a whole. placed so that In other words, the first light source 620a is disposed to radiate the first light to the entire area of the reaction passage 610a. In a modified example, the first light source 620a may intermittently radiate the first light to the reaction passage 610a.
  • the first light source 620a may intermittently repeat irradiating the first light to the reaction passage 610a for a predetermined time and blink. Accordingly, heating and cooling of the exothermic material mixed with the sample disposed inside the reaction passage 610a can be repeated, and the temperature of the sample can be repeatedly raised and lowered to proceed with PCR denaturation, bonding, and elongation steps. there is.
  • the exothermic particle may be a magneto-plasmonic nanoparticle (MPN).
  • MPN magneto-plasmonic nanoparticle
  • FIG. 9 shows a cross-sectional view of the magnetic plasmon nanoparticles 10 .
  • the magnetic plasmon nanoparticle 10 may include a core 11 and a shell 12 surrounding the core 11 . More specifically, the core 11 may have magnetism.
  • the core 11 may include any one or more of Fe3O4, Zn0.4Fe2.6O4, FexOy, ZnxFeyOz, and MnxFeyOz.
  • the shell 12 may include at least one of gold (Au), silver (Ag), and copper (Cu).
  • Magnetoplasmon nanoparticles 10 may have a nanoscale size.
  • the diameter of the core 11 may be 5 to 100 nm
  • the thickness of the shell 12 may be 1 to 20 nm.
  • the exothermic particles are magnetoplasmon nanoparticles 10 and the shell 12 is made of gold (Au) having a thickness of 12 nm
  • Au gold
  • the peak wavelength of the first light may be 530 to 540 nm (eg, 535 nm).
  • the first light sources 620 and 620a may radiate laser light having a peak wavelength of 530 to 540 nm toward the irradiation area.
  • the wavelength at which plasmon resonance occurs may be different.
  • the separator 700 separates the exothermic material from the sample transferred from the reaction unit 600 by fixing the exothermic material by magnetic force on the premise that the exothermic material has magnetism.
  • the pyrogen efficiently induces a PCR reaction by directly heating the sample within the sample, it may become an obstacle to detection of the target nucleic acid after completion of the PCR.
  • the pyrogenic substance may interfere with detection of the target nucleic acid by absorbing or reflecting (emitting light) light used for detection.
  • the separation unit 700 separates the pyrogen from the sample for which PCR has been completed in the reaction unit 600, so that the detection unit 800 at a later stage can effectively detect the target nucleic acid.
  • the separator 700 may be omitted.
  • the separation unit 700 may include a separation passage 710 and a magnet 720 .
  • the separation passage 710 is arranged so that the sample transferred from the reaction unit 600 stays or flows.
  • the separation passage 710 may be provided as a microtubule or a tube having a diameter of several millimeters (eg, 1 mm to 5 mm).
  • the magnet 720 provides magnetic force to the separation passage 710 to fix the exothermic material inside the separation passage 710 .
  • the magnet 720 may be disposed adjacent to the separation passage 710 .
  • the magnet 720 provides magnetic force so that the exothermic particles do not flow toward the detection unit 800 but are separated from the sample and stay in a predetermined area inside the separation passage 710 . Accordingly, the sample passing through the separation passage 710 may be in a state in which the exothermic particles are separated.
  • the separator 700 may further include a transfer means (not shown) for transferring the magnet 720 . If necessary, the magnet 720 can be displaced between a position adjacent to and separated from the separation passage 710 by the transfer means.
  • the detection unit 800 detects target nucleic acid present in the sample transferred from the reaction unit 600 .
  • the detection unit 800 may be disposed at the rear end of the separation unit 700 .
  • the detection unit 800 may include a detection passage 810 , a second light source 820 and a detector 830 .
  • the sample transported from the reaction unit 600 stays or flows in the detection passage 810 .
  • the sample transferred from the separator 700 stays or flows in the detection passage 810 .
  • the detection passage 810 may be provided as a microtubule or a tube having a diameter of several millimeters (eg, 1 mm to 5 mm).
  • the second light source 820 radiates a second light for detecting the target nucleic acid to the detection passage 810 .
  • the second light source 820 may irradiate the second light in a detection direction perpendicular to the flow direction of the sample.
  • the second light may have a wavelength that induces fluorescence excitation of the target nucleic acid.
  • the second light may have a wavelength selected from 100 to 350 nm.
  • the detector 830 detects the second light passing through the detection passage 810 . More specifically, the detector 830 detects fluorescence generated by the second light from the target nucleic acid in the sample.
  • the detector 800 may further include a display (not shown) displaying fluorescence detected by the detector 830 .
  • the pressure supply unit 900 provides fluidity to the sample.
  • the pressure supply unit 900 includes the input unit 100, the first heating unit 200, the enrichment unit 300, the mixing unit 400, the second heating unit 500, the reaction unit 600, and the separating unit 700. ) and the detection unit 800 and is disposed in communication, and supplies a positive pressure or a negative pressure to flow the sample. More specifically, the pressure supply unit 900 includes the input unit 100, the first heating passage 210, the cleaning solution supply passage 340, the washing solution discharge passage 350, the separation solution supply passage 420, and the sample discharge passage. Negative pressure or positive pressure may be supplied to the passage 430 , the second heating passage 510 , the reaction passage 610 , the separation passage 710 and the detection passage 810 .
  • the separation unit 700 and the detection unit 800 may be connected to a flow path. That is, the first heating passage 210, the cleaning solution supply passage 340, the washing solution discharge passage 350, the separation solution supply passage 420, the sample discharge passage 430, the second heating passage 510, the reaction
  • the passage 610 , the separation passage 710 and the detection passage 810 may communicate with each other.
  • one or more valves (not shown) may be disposed to connect or open and close the flow path therebetween.

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Abstract

Disclosed is a point-of-care molecular diagnostic device. A point-of-care molecular diagnostic device according to an embodiment of the present invention comprises: an input portion into which a sample for polymerase chain reaction (PCR) is inputted; and a reaction portion in which the PCR of the sample proceeds, wherein the reaction portion comprises: a reaction passage in which the sample, in a state of being mixed with an exothermic material that generates heat when irradiated with a first light, a primer, and a polymerase, flows or remains; and a first light source which radiates the first light to at least a part of the reaction passage, wherein while the sample is being irradiated with the first light inside the reaction passage, the exothermic material generates heat so that the sample is heated, and while the sample is not being irradiated with the first light, the exothermic material does not generate heat and the sample may be cooled.

Description

현장 중심형 분자진단 장치Field-oriented molecular diagnostic device

본 발명은 현장 중심형 분자진단 장치에 관한 것으로, 보다 상세하게는 진료 현장에서 PCR(Polymerase Chain Reaction)을 통해 타겟 핵산의 증폭을 수행할 수 있는 현장 중심형 분자진단 장치에 관한 것이다.The present invention relates to a field-oriented molecular diagnosis device, and more particularly, to a field-oriented molecular diagnosis device capable of performing amplification of a target nucleic acid through PCR (Polymerase Chain Reaction) in a medical field.

코로나 바이러스 감염증(COVID-19)의 팬데믹 상황 속에서 대규모 진단이 요구되고 있다. 질병의 팬데믹 기간 동안에는 증상 또는 무증상 감염자를 최대한 신속하게 많이 식별하여 격리시키는 것이 질병의 전파를 예방하는 데에 가장 효과적이기 때문이다.A large-scale diagnosis is required in the context of the pandemic of the coronavirus infection (COVID-19). During a disease pandemic, identifying and isolating as many symptomatic or asymptomatic infected people as quickly as possible is the most effective way to prevent disease transmission.

면역원성 측면 유동 분석(Immunogenic lateral flow assays)은 검사 장비가 소형이고, 결과가 신속하게 도출되며, 비용 측면에서 효율적이지만 초기 질병 단계에서 바이러스 검출에는 적합하지 않은 문제를 가지고 있다. 이와 비교하여 중합효소연쇄반응(PCR)을 기반으로 하는 핵산 증폭 테스트(Nucleic-acid amplification test, NAAT)는 바이러스 검출에 있어서 높은 분석 정확도(~99%)를 가지고 있다. 이에 따라 역전사 PCR(Reverse Transcription PCR, RT-PCR)이 코로나 바이러스 감염증의 진단에 있어 표준으로 사용되고 있다.Immunogenic lateral flow assays have small test equipment, rapid results, and cost-effectiveness, but have problems that are not suitable for virus detection in early disease stages. In comparison, the polymerase chain reaction (PCR)-based nucleic acid amplification test (NAAT) has high assay accuracy (~99%) in virus detection. Accordingly, reverse transcription PCR (RT-PCR) is used as a standard in the diagnosis of coronavirus infection.

그러나 대부분의 PCR 진단이 실험실에서 수행되기 때문에 샘플의 이송과 보존에 많은 비용이 소용되고, 결과를 얻기까지 최대 수일까지 소요되는 단점이 있다. 이러한 단점을 극복하고자 PCR 장비를 현장 중심형(POINT OF CARE, POC)으로 만들고자 하는 시도가 있다. 그러나 종래 현장 중심형 PCR 장비는 이송에 적합하지 않게 부피가 크고, 분석 시간도 1~2시간으로 다소 길어서 널리 사용되지 못하고 있는 실정이다. 또한, 검사의 정확도가 전통적인 PCR 장비에 비하여 다소 제한적인 것도 문제로 지적되고 있다.However, since most PCR diagnoses are performed in laboratories, there are disadvantages in that a lot of cost is required for transporting and preserving samples, and it takes up to several days to obtain results. In order to overcome these disadvantages, there is an attempt to make the PCR equipment site-oriented (POINT OF CARE, POC). However, conventional on-site PCR equipment is not widely used because it is bulky and unsuitable for transport, and the analysis time is rather long, 1 to 2 hours. In addition, it is pointed out as a problem that the accuracy of the test is somewhat limited compared to traditional PCR equipment.

본 발명은 상기와 같은 문제점을 해결하기 위한 것으로, 본 발명의 목적은 PCR을 통한 핵산 검출을 신속하고 효과적으로 수행할 수 있는 현장 중심형 분자진단 장치를 제공하는 것이다.The present invention is to solve the above problems, and an object of the present invention is to provide an in-situ molecular diagnostic device capable of quickly and effectively detecting nucleic acids through PCR.

본 발명의 다른 목적은 샘플의 투입 후 샘플의 전처리, PCR 및 타겟 핵산의 검출까지 연속적으로 수행되는 현장 중심형 분자진단 장치를 제공하는 것이다.Another object of the present invention is to provide an on-site molecular diagnosis device that continuously performs sample input, sample pretreatment, PCR, and target nucleic acid detection.

본 발명의 과제들은 이상에서 언급한 과제들로 제한되지 않으며, 언급되지 않은 또 다른 과제들은 아래의 기재로부터 본 발명이 속하는 기술분야의 통상의 기술자에게 명확하게 이해될 수 있을 것이다.The tasks of the present invention are not limited to the tasks mentioned above, and other tasks not mentioned will be clearly understood by those skilled in the art from the description below.

본 발명의 일 측면에 따르면, PCR(Polymerase Chain Reaction)용 샘플이 투입되는 투입부; 및 상기 샘플의 PCR이 진행되는 반응부;를 포함하고, 상기 반응부는, 상기 샘플이 제 1 광의 조사 시 열을 발생시키는 발열 물질, 프라이머(primer) 및 중합 효소와 혼합된 상태로 유동하거나 머무르는 반응 유로; 및 상기 반응 유로의 적어도 일부분에 상기 제 1 광을 조사하는 제 1 광원;을 포함하며, 상기 샘플이 상기 반응 유로의 내부에서 상기 제 1 광을 조사받는 동안에는 상기 발열 물질이 열을 발생시켜 상기 샘플이 가열되고, 상기 제 1 광을 조사받지 않는 동안에는 상기 발열 물질이 열을 발생시키지 않으며 상기 샘플이 냉각되는 현장 중심형 분자진단 장치가 제공된다.According to one aspect of the present invention, the input unit into which the sample for PCR (Polymerase Chain Reaction) is input; and a reaction unit in which the PCR of the sample proceeds, wherein the reaction unit is a reaction in which the sample flows or stays mixed with a pyrogen generating heat when irradiated with first light, a primer, and a polymerase. Euro; and a first light source for radiating the first light to at least a portion of the reaction passage, wherein while the sample is irradiated with the first light inside the reaction passage, the exothermic material generates heat so that the sample is irradiated with the first light. is heated, and while the exothermic material does not generate heat and the sample is cooled while not being irradiated with the first light, an in situ molecular diagnosis device is provided.

이때, 상기 현장 중심형 분자진단 장치는, 상기 투입부와 상기 반응부 사이에 배치되고, 이송된 샘플을 포집하며, 상기 샘플에 존재하는 불순물을 제거하고 상기 샘플에 존재하는 핵산을 농축시키는 농축부를 더 포함할 수 있다.At this time, the on-site molecular diagnosis device includes an enrichment unit disposed between the input unit and the reaction unit, collecting the transferred sample, removing impurities present in the sample, and concentrating nucleic acids present in the sample. can include more.

또한, 상기 농축부는, 상기 샘플을 포집하는 포집체; 상기 포집체가 배치되는 포집 챔버; 상기 샘플에 존재하는 불순물을 세척하기 위한 하나 이상의 세척 용액을 저장하는 세척 용액 저장 챔버; 상기 세척 용액 저장 챔버와 상기 포집 챔버를 연결하는 세척 용액 공급 유로;를 포함할 수 있다.In addition, the enrichment unit, the collection body for collecting the sample; a collecting chamber in which the collecting body is disposed; a washing solution storage chamber storing one or more washing solutions for washing impurities present in the sample; It may include; a cleaning solution supply passage connecting the cleaning solution storage chamber and the collection chamber.

또한, 상기 농축부는, 상기 포집체에서 배출되는 세척 용액을 배출하는 세척 용액 배출 유로; 및 상기 세척 용액 배출 유로를 통해 배출된 세척 용액을 수집하는 배출 챔버;를 더 포함할 수 있다.In addition, the enrichment unit may include a washing solution discharge channel for discharging the washing solution discharged from the collecting body; and a discharge chamber for collecting the cleaning solution discharged through the cleaning solution discharge passage.

또한, 상기 현장 중심형 분자진단 장치는, 상기 농축부와 상기 반응부 사이에 배치되고, 상기 농축부에서 이송된 샘플에 상기 발열 물질, 상기 프라이머 및 상기 중합 효소를 혼합시키는 혼합부를 더 포함할 수 있다.In addition, the in-situ molecular diagnosis device may further include a mixing unit disposed between the enrichment unit and the reaction unit and mixing the pyrogen, the primer, and the polymerase with the sample transferred from the enrichment unit. there is.

또한, 상기 혼합부는, 상기 포집체에서 불순물이 제거된 상태의 샘플을 분리시키는 분리 용액을 저장하는 분리 용액 저장 챔버; 상기 분리 용액 저장 챔버와 상기 포집 챔버를 연결하는 분리 용액 공급 유로; 상기 포집 챔버에서 분리 용액과 함께 배출되는 샘플을 배출하는 샘플 배출 유로; 및 상기 발열 물질, 상기 프라이머 및 상기 중합 효소를 포함하는 혼합 용액을 저장하고, 상기 샘플 배출 유로를 통해 유입된 샘플을 상기 혼합 용액과 혼합하는 혼합 챔버;를 포함할 수 있다.In addition, the mixing unit may include a separation solution storage chamber for storing a separation solution for separating a sample in which impurities are removed from the collection body; a separation solution supply passage connecting the separation solution storage chamber and the collecting chamber; a sample discharge passage through which the sample discharged together with the separation solution from the collection chamber is discharged; and a mixing chamber configured to store a mixed solution including the exothermic material, the primer, and the polymerase, and mix the sample introduced through the sample discharge channel with the mixed solution.

또한, 상기 현장 중심형 분자진단 장치는, 상기 투입부와 상기 농축부 사이에 배치되고, 상기 샘플에서 핵산이 추출되도록 상기 농축부로 이송되는 샘플을 제 1 온도로 가열하는 제 1 가열부를 더 포함할 수 있다.In addition, the in-situ molecular diagnosis device may further include a first heating unit disposed between the input unit and the enrichment unit and heating the sample transferred to the enrichment unit to a first temperature so that nucleic acid is extracted from the sample. can

또한, 상기 제 1 가열부는, 상기 투입부와 상기 농축부를 연결하며 상기 샘플이 유동하는 제 1 가열 유로; 및 상기 제 1 가열 유로를 제 1 온도로 가열하도록 배치되는 제 1 히터;를 포함할 수 있다.In addition, the first heating unit may include a first heating passage connecting the input unit and the enrichment unit and through which the sample flows; and a first heater disposed to heat the first heating passage to a first temperature.

또한, 상기 현장 중심형 분자진단 장치는, 상기 혼합부와 상기 반응부 사이에 배치되고, 상기 샘플에 포함된 RNA의 역전사가 일어나도록 상기 반응부로 이송되는 샘플을 제 2 온도로 가열하는 제 2 가열부를 더 포함할 수 있다.In addition, the in-situ molecular diagnosis device is disposed between the mixing unit and the reaction unit, and heats the sample transferred to the reaction unit to a second temperature so that reverse transcription of RNA included in the sample occurs. Wealth may be further included.

또한, 상기 제 2 가열부는, 상기 혼합부와 상기 반응부를 연결하고, 상기 샘플이 유동하는 제 2 가열 유로; 및 상기 제 2 가열 유로를 제 2 온도로 가열하도록 배치되는 제 2 히터;를 포함할 수 있다.In addition, the second heating unit may include a second heating passage connecting the mixing unit and the reaction unit and through which the sample flows; and a second heater disposed to heat the second heating passage to a second temperature.

또한, 상기 발열 물질은 자성을 가지며, 상기 현장 중심형 분자진단 장치는, 상기 발열 물질을 자력에 의해 고정시킴으로써 상기 반응부에서 이송된 샘플로부터 상기 발열 물질을 분리하는 분리부를 더 포함할 수 있다.In addition, the exothermic material has magnetism, and the on-site molecular diagnosis device may further include a separation unit that separates the exothermic material from the sample transferred from the reaction unit by fixing the exothermic material by magnetic force.

또한, 상기 분리부는, 상기 반응부에서 이송된 샘플이 머무르거나 유동하는 분리 유로; 및 상기 분리 유로에 자력을 제공하여 상기 발열 물질을 상기 분리 유로의 내부에 고정시키는 마그넷;을 포함할 수 있다.In addition, the separator may include a separation passage through which the sample transferred from the reaction unit stays or flows; and a magnet providing magnetic force to the separation passage to fix the exothermic material to the inside of the separation passage.

또한, 상기 현장 중심형 분자진단 장치는, 상기 반응부에서 이송된 샘플의 내부에 존재하는 타겟 핵산을 검출하는 검출부를 더 포함할 수 있다.In addition, the in-situ molecular diagnosis device may further include a detection unit for detecting target nucleic acid present in the sample transferred from the reaction unit.

또한, 상기 검출부는, 상기 반응부에서 이송된 샘플이 머무르거나 유동하는 검출 유로; 상기 검출 유로에 상기 타겟 핵산의 검출을 위한 제 2 광을 조사하는 제 2 광원; 및 상기 검출 유로를 통과한 제 2 광을 검출하는 디텍터;를 포함할 수 있다.In addition, the detection unit, a detection passage through which the sample transferred from the reaction unit stays or flows; a second light source radiating a second light for detecting the target nucleic acid to the detection channel; and a detector for detecting the second light passing through the detection passage.

또한, 상기 반응 유로는 상기 제 1 광이 조사되는 조사 영역과 상기 제 1 광이 조사되지 않는 비조사 영역을 포함하고, 상기 제 1 광원은 상기 조사 영역에 상기 제 1 광을 조사할 수 있다.The reaction channel may include an irradiated area irradiated with the first light and a non-irradiated area not irradiated with the first light, and the first light source may radiate the first light to the irradiated area.

또한, 상기 반응 유로는 전체적으로 상기 제 1 광이 조사되도록 배치되고, 상기 제 1 광원은 상기 반응 유로에 단속적으로 상기 제 1 광을 조사할 수 있다.In addition, the first light may be irradiated to the reaction channel as a whole, and the first light source may intermittently irradiate the first light to the reaction channel.

상기의 구성에 따라 본 발명에 따른 현장 중심형 분자진단 장치는 발열 물질과 혼합된 샘플이 반응기에서 승온과 냉각을 반복하며 PCR이 신속하고 효율적으로 이루어질 수 있게 해준다.According to the configuration described above, the in-situ molecular diagnosis device according to the present invention enables PCR to be performed quickly and efficiently by repeatedly heating and cooling a sample mixed with a pyrogen in a reactor.

또한, 본 발명의 실시예에 따른 현장 중심형 분자진단 장치는 샘플의 전처리, PCR 및 타겟 핵산의 검출이 연속적인 유로의 내부에서 순차적으로 수행될 수 있게 해줌으로써 병원체(pathogen) 검사의 효율성과 정확성을 높여준다.In addition, the on-site molecular diagnostic device according to an embodiment of the present invention enables sample pre-processing, PCR, and target nucleic acid detection to be sequentially performed inside a continuous flow path, thereby increasing the efficiency and accuracy of pathogen testing. raises

본 발명의 효과는 상기한 효과로 한정되는 것은 아니며, 본 발명의 상세한 설명 또는 청구범위에 기재된 발명의 구성으로부터 추론 가능한 모든 효과를 포함하는 것으로 이해되어야 한다.The effects of the present invention are not limited to the above effects, and should be understood to include all effects that can be inferred from the detailed description of the present invention or the configuration of the invention described in the claims.

도 1은 본 발명의 일 실시예에 따른 현장 중심형 분자진단 장치의 블록 구성도이다.1 is a block diagram of an on-site molecular diagnosis device according to an embodiment of the present invention.

도 2는 본 발명의 일 실시예에 따른 현장 중심형 분자진단 장치의 제 1 가열부의 구성을 나타낸 도면이다.2 is a diagram showing the configuration of a first heating unit of an on-site molecular diagnostic device according to an embodiment of the present invention.

도 3은 본 발명의 일 실시예에 따른 현장 중심형 분자진단 장치의 농축부의 구성을 나타낸 도면이다.3 is a diagram showing the configuration of an enrichment unit of an on-site molecular diagnostic device according to an embodiment of the present invention.

도 4는 본 발명의 일 실시예에 따른 현장 중심형 분자진단 장치의 혼합부의 구성을 나타낸 도면이다.4 is a diagram showing the configuration of a mixing unit of an on-site molecular diagnosis device according to an embodiment of the present invention.

도 5는 본 발명의 일 실시예에 따른 현장 중심형 분자진단 장치의 제 2 가열부의 구성을 나타낸 도면이다.5 is a diagram showing the configuration of a second heating unit of an on-site molecular diagnosis device according to an embodiment of the present invention.

도 6은 본 발명의 일 실시예에 따른 현장 중심형 분자진단 장치의 반응부의 구성을 나타낸 도면이다.6 is a diagram showing the configuration of a reaction unit of an on-site molecular diagnostic device according to an embodiment of the present invention.

도 7은 본 발명의 일 실시예에 따른 현장 중심형 분자진단 장치의 반응부에서 PCR 주기를 반복하는 샘플의 온도 변화를 나타낸 그래프이다.7 is a graph showing temperature changes of samples repeating PCR cycles in a reaction unit of an on-site molecular diagnosis device according to an embodiment of the present invention.

도 8은 본 발명의 일 실시예에 따른 현장 중심형 분자진단 장치의 반응부의 변형예의 구성을 나타낸 도면이다.8 is a view showing the configuration of a modified example of a reaction unit of an on-site molecular diagnostic device according to an embodiment of the present invention.

도 9는 자기플라즈몬 나노입자(Magneto-plasmonic nanoparticle, MPN)의 단면도이다.9 is a cross-sectional view of a magneto-plasmonic nanoparticle (MPN).

도 10은 본 발명의 일 실시예에 따른 현장 중심형 분자진단 장치의 분리부의 구성을 나타낸 도면이다.10 is a diagram showing the configuration of a separation unit of an on-site molecular diagnosis device according to an embodiment of the present invention.

도 11은 본 발명의 일 실시예에 따른 현장 중심형 분자진단 장치의 검출부의 구성을 나타낸 도면이다.11 is a diagram showing the configuration of a detection unit of an on-site molecular diagnosis device according to an embodiment of the present invention.

이하, 첨부한 도면을 참고로 하여 본 발명의 실시예에 대하여 본 발명이 속하는 기술분야에서 통상의 지식을 가진 자가 용이하게 실시할 수 있도록 상세히 설명한다. 본 발명은 여러 가지 상이한 형태로 구현될 수 있으며 여기에서 설명하는 실시예에 한정되지 않는다. 본 발명을 명확하게 설명하기 위해서 도면에서 설명과 관계없는 부분은 생략하였으며, 명세서 전체를 통하여 동일 또는 유사한 구성요소에 대해서는 동일한 참조부호를 붙였다.Hereinafter, with reference to the accompanying drawings, embodiments of the present invention will be described in detail so that those skilled in the art can easily carry out the present invention. This invention may be embodied in many different forms and is not limited to the embodiments set forth herein. In order to clearly describe the present invention, parts irrelevant to the description are omitted in the drawings, and the same reference numerals are assigned to the same or similar components throughout the specification.

본 명세서 및 청구범위에 사용된 단어와 용어는 통상적이거나 사전적인 의미로 한정 해석되지 않고, 자신의 발명을 최선의 방법으로 설명하기 위해 발명자가 용어와 개념을 정의할 수 있는 원칙에 따라 본 발명의 기술적 사상에 부합하는 의미와 개념으로 해석되어야 한다.Words and terms used in this specification and claims are not construed as limited in their ordinary or dictionary meanings, but in accordance with the principle that the inventors can define terms and concepts in order to best describe their inventions. It should be interpreted as a meaning and concept that corresponds to the technical idea.

본 명세서에서, "포함하다" 또는 "가지다" 등의 용어는 명세서상에 기재된 특징, 숫자, 단계, 동작, 구성 요소, 부품 또는 이들을 조합한 것이 존재함을 설명하려는 것이지, 하나 또는 그 이상의 다른 특징들이나 숫자, 단계, 동작, 구성 요소, 부품 또는 이들을 조합한 것들의 존재 또는 부가 가능성을 미리 배제하지 않는 것으로 이해되어야 한다.In this specification, terms such as "include" or "have" are intended to describe the presence of features, numbers, steps, operations, components, parts, or combinations thereof described in the specification, but one or more other features It should be understood that the presence or addition of numbers, steps, operations, components, parts, or combinations thereof is not precluded.

어떤 구성 요소가 다른 구성 요소의 "전방", "후방", "상부" 또는 "하부"에 있다는 것은 특별한 사정이 없는 한 다른 구성 요소와 바로 접하여 "전방", "후방", "상부" 또는 "하부"에 배치되는 것뿐만 아니라 그 중간에 또 다른 구성 요소가 배치되는 경우도 포함한다. 또한, 어떤 구성 요소가 다른 구성 요소와 "연결"되어 있다는 것은 특별한 사정이 없는 한 서로 직접 연결되는 것뿐만 아니라 간접적으로 서로 연결되는 경우도 포함한다.A component being in the "front", "rear", "above" or "below" of another component means that it is in direct contact with another component, unless there are special circumstances, and is "in front", "rear", "above" or "below". It includes not only those disposed at the lower part, but also cases in which another component is disposed in the middle. In addition, the fact that certain components are “connected” to other components includes cases where they are not only directly connected to each other but also indirectly connected to each other unless there are special circumstances.

도 1은 본 발명의 일 실시예에 따른 현장 중심형 분자진단 장치의 블록 구성도이다.1 is a block diagram of an on-site molecular diagnosis device according to an embodiment of the present invention.

본 발명의 일 실시예에 따른 현장 중심형 분자진단 장치(1)는 샘플에 혼합된 발열 물질이 승온과 냉각을 반복함으로써 PCR(Polymerase Chain Reaction)이 신속하고 효율적으로 이루어질 수 있게 해준다. 도 1을 참조하면, 본 발명의 일 실시예에 따른 현장 중심형 분자진단 장치(1)는 투입부(100), 제 1 가열부(200), 농축부(300), 혼합부(400), 제 2 가열부(500), 반응부(600), 분리부(700), 검출부(800) 및 압력 공급부(900)를 포함할 수 있다.The in-situ molecular diagnosis device 1 according to an embodiment of the present invention enables PCR (Polymerase Chain Reaction) to be performed quickly and efficiently by repeating heating and cooling of a heating material mixed in a sample. Referring to FIG. 1 , the on-site molecular diagnosis device 1 according to an embodiment of the present invention includes an inlet unit 100, a first heating unit 200, an enrichment unit 300, a mixing unit 400, It may include a second heating unit 500, a reaction unit 600, a separation unit 700, a detection unit 800, and a pressure supply unit 900.

투입부(100)를 통해 PCR용 샘플이 투입된다. 상기 샘플은 피검자의 구강, 비강 등에서 채취된 것일 수 있다. 투입부(100)는 샘플이 투입되는 투입구를 가지는 투입 유로로 형성될 수 있다. 본 발명의 일 실시예에서, 상기 샘플은 PCR을 통한 핵산 검출의 대상이 되며, 피검자의 타액에서 RNA 또는 DNA를 정제하여 제조된 것일 수 있다. 예를 들면, 검출 대상 핵산은 SARS-CoV-2 바이러스 검출을 위한 N1 및 N2 유전자와, 인간의 샘플임을 확인하기 위한 인간 RPP30 유전자가 될 수 있다. 물론, 이것은 하나의 예에 불과하며 진단하고자 하는 감염증의 종류에 따라 검출 대상 핵산은 달라질 수 있다.A sample for PCR is introduced through the input unit 100. The sample may be taken from the oral cavity or nasal cavity of the subject. The input unit 100 may be formed as an input passage having an input port into which a sample is input. In one embodiment of the present invention, the sample is subject to nucleic acid detection through PCR, and may be prepared by purifying RNA or DNA from saliva of a subject. For example, the nucleic acid to be detected may be the N1 and N2 genes for detecting the SARS-CoV-2 virus and the human RPP30 gene for confirming that the sample is a human sample. Of course, this is just one example, and the nucleic acid to be detected may vary depending on the type of infection to be diagnosed.

제 1 가열부(200)는 투입부(100)와 농축부(300) 사이에 배치되고, 상기 샘플에서 핵산이 추출되도록 농축부(300)로 이송되는 샘플을 제 1 온도로 가열한다. 이때, 제 1 온도는 90~100℃에서 선택될 수 있다. 예를 들면, 제 1 가열부(200)는 상기 샘플을 95℃로 가열할 수 있다. 제 1 가열부(200)의 내부에서 상기 샘플이 제 1 온도로 가열되면, 상기 샘플에서 바이러스가 용해(lysis)되고, RNA가 추출될 수 있다.The first heating unit 200 is disposed between the input unit 100 and the enrichment unit 300 and heats the sample transferred to the enrichment unit 300 to a first temperature so that nucleic acids are extracted from the sample. At this time, the first temperature may be selected from 90 ~ 100 ℃. For example, the first heating unit 200 may heat the sample to 95°C. When the sample is heated to a first temperature inside the first heating unit 200, viruses may be lysed and RNA may be extracted from the sample.

도 2는 본 발명의 일 실시예에 따른 현장 중심형 분자진단 장치의 제 1 가열부의 구성을 나타낸 도면이다. 도 2를 참조하면, 제 1 가열부(200)는 제 1 가열 유로(210) 및 제 1 히터(220)를 포함할 수 있다. 제 1 가열 유로(210)는 투입부(100)와 농축부(300)를 연결하며 상기 샘플이 유동하도록 배치된다. 이때, 제 1 가열 유로(210)는 마이크로단위의 미세소관이 될 수 있다. 또한, 제 1 가열 유로(210)는 수mm 단위(예를 들면, 1mm~5mm)의 직경을 가지는 관으로 구비될 수도 있다. 또한, 제 1 히터(220)는 제 1 가열 유로(210)를 제 1 온도로 가열하도록 배치된다. 제 1 히터(220)는 제 1 가열 유로(210)와 인접하여 배치되는 히터 블록이 될 수 있다.2 is a diagram showing the configuration of a first heating unit of an on-site molecular diagnostic device according to an embodiment of the present invention. Referring to FIG. 2 , the first heating unit 200 may include a first heating passage 210 and a first heater 220 . The first heating passage 210 connects the input unit 100 and the enrichment unit 300 and is arranged so that the sample flows. In this case, the first heating passage 210 may be microtubules. In addition, the first heating passage 210 may be provided as a tube having a diameter of several millimeters (eg, 1 mm to 5 mm). Also, the first heater 220 is disposed to heat the first heating passage 210 to a first temperature. The first heater 220 may be a heater block disposed adjacent to the first heating passage 210 .

농축부(300)는 제 1 가열부(200)와 혼합부(400) 사이에 배치된다. 농축부(300)는 제 1 가열부(200)를 통과하여 이송된 샘플을 포집하며, 상기 샘플에 존재하는 불순물을 제거하고 상기 샘플에 존재하는 핵산이 농축시킨다.The enrichment unit 300 is disposed between the first heating unit 200 and the mixing unit 400 . The enrichment unit 300 collects the sample transported through the first heating unit 200, removes impurities present in the sample, and concentrates nucleic acids present in the sample.

도 3은 본 발명의 일 실시예에 따른 현장 중심형 분자진단 장치의 농축부의 구성을 나타낸 도면이다. 도 3을 참조하면, 농축부(300)는 포집체(310), 포집 챔버(320), 세척 용액 저장 챔버(330), 세척 용액 공급 유로(340), 세척 용액 배출 유로(350) 및 배출 챔버(360)를 포함할 수 있다.3 is a diagram showing the configuration of an enrichment unit of an on-site molecular diagnostic device according to an embodiment of the present invention. Referring to FIG. 3 , the enrichment unit 300 includes a collecting body 310, a collecting chamber 320, a cleaning solution storage chamber 330, a cleaning solution supply channel 340, a cleaning solution discharge channel 350, and a discharge chamber. (360).

포집체(310)는 상기 샘플을 포집한다. 예를 들면, 포집체(310)는 레진(resin)으로 구성될 수 있다. 또한, 포집체(310)는 원기둥 형상을 가질 수 있다. 포집 챔버(320)는 내부에 포집체(310)가 배치된다. 포집 챔버(320)는 제 1 가열 유로(210)를 거치며 바이러스가 용해되고 RNA가 추출된 상태의 샘플이 이송되도록 제 1 가열 유로(210)와 연결될 수 있다.Collecting body 310 collects the sample. For example, the collection body 310 may be made of resin. In addition, the collector 310 may have a cylindrical shape. The collecting chamber 320 has a collecting body 310 disposed therein. The collection chamber 320 may be connected to the first heating passage 210 so that the sample in which the virus is dissolved and the RNA is extracted is transported through the first heating passage 210 .

세척 용액 저장 챔버(330)는 상기 샘플에 존재하는 불순물을 세척하기 위한 하나 이상의 세척 용액을 저장한다. 본 발명의 일 실시예에서, 세척 용액 저장 챔버(330)는 에탄올(ethanol)이 저장되는 제 1 서브 저장 챔버(331), 워시 버퍼(wash buffer)가 저장되는 제 2 서브 저장 챔버(332), 미네랄 오일(mineral oil)이 저장되는 제 3 서브 저장 챔버(333)를 포함할 수 있다. 다시 말하면, 하나 이상의 세척 용액은 에탄올, 워시 버퍼, 미네랄 오일을 포함할 수 있다.The cleaning solution storage chamber 330 stores one or more cleaning solutions for cleaning impurities present in the sample. In one embodiment of the present invention, the washing solution storage chamber 330 includes a first sub-storage chamber 331 storing ethanol, a second sub-storage chamber 332 storing a wash buffer, A third sub storage chamber 333 in which mineral oil is stored may be included. In other words, the one or more cleaning solutions may include ethanol, wash buffer, or mineral oil.

세척 용액 공급 유로(340)는 세척 용액 저장 챔버(330)와 포집 챔버(320)를 연결한다. 세척 용액 공급 유로(340)를 통해 세척 용액 저장 챔버(330)에 저장된 하나 이상의 세척 용액이 포집 챔버(320)로 공급될 수 있다. 예를 들면, 에탄올, 워시 버퍼 및 미네랄 오일의 순서로 포집 챔버(320)로 공급되어 포집체(310)에 포집된 상태의 샘플에서 불순물을 제거하고 핵산이 농축되도록 할 수 있다. 한편, 세척 용액 배출 유로(350)는 포집체(310)에서 배출되는 세척 용액을 배출한다. 또한, 배출 챔버(360)는 세척 용액 배출 유로(350)를 통해 배출된 세척 용액을 수집한다.The cleaning solution supply passage 340 connects the cleaning solution storage chamber 330 and the collecting chamber 320 . One or more cleaning solutions stored in the cleaning solution storage chamber 330 may be supplied to the collection chamber 320 through the cleaning solution supply passage 340 . For example, ethanol, wash buffer, and mineral oil may be supplied to the collection chamber 320 in order to remove impurities from the sample collected in the collector 310 and to concentrate nucleic acids. Meanwhile, the cleaning solution discharge channel 350 discharges the cleaning solution discharged from the collector 310 . In addition, the discharge chamber 360 collects the cleaning solution discharged through the cleaning solution discharge channel 350 .

앞서 살펴본 바와 같이, 세척 용액 저장 챔버(330)에 복수개의 서브 저장 챔버가 구비될 때, 복수개의 세척 용액이 순차적으로 포집체(310)에 제공되도록 하기 위해서 세척 용액 저장 챔버(330)와 포집 챔버(320) 사이에는 제 1 내지 3 서브 저장 챔버를 포집 챔버(320)와 선택적으로 연결하는 하나 이상의 밸브(미도시)가 배치될 수 있다. 또한, 제 1 내지 3 서브 저장 챔버(331, 332, 333)는 각각 세척 용액 공급 유로(340)와 연결될 수도 있다.As described above, when a plurality of sub-storage chambers are provided in the cleaning solution storage chamber 330, the cleaning solution storage chamber 330 and the collection chamber are used to sequentially provide a plurality of cleaning solutions to the collector 310. One or more valves (not shown) may be disposed between the 320 to selectively connect the first to third sub-storage chambers with the collecting chamber 320 . In addition, the first to third sub storage chambers 331 , 332 , and 333 may be connected to the cleaning solution supply channel 340 , respectively.

혼합부(400)는 농축부(300)와 제 2 가열부(500) 사이에 배치된다. 혼합부(400)는 농축부(300)에서 이송된 샘플에 상기 발열 물질, 상기 프라이머 및 상기 중합 효소를 혼합시킨다.The mixing unit 400 is disposed between the enrichment unit 300 and the second heating unit 500 . The mixing unit 400 mixes the exothermic material, the primer, and the polymerase with the sample transferred from the enrichment unit 300 .

본 발명의 일 실시예에서, 상기 발열 물질은 발열 입자를 포함할 수 있다. 예를 들면, 상기 발열 입자는 나노 입자(예를 들면, 직경 10nm~1㎛)가 될 수 있다. 이때, 상기 발열 입자는 구형, 아령형, 2D형, 혼합형(코어쉘, 야누스, 결합형) 입자가 될 수 있다. 또한, 상기 발열 입자는 마이크로 입자(예를 들면, 직경 1㎛~100㎛)가 될 수 있다. 이 경우, 상기 발열 입자는 일체형, 혼합형(코어쉘, 야누스, 결합형) 입자가 될 수 있다. 한편, 본 발명의 일 실시예에서, 상기 발열 입자는 자기플라즈몬 나노입자(Magneto-plasmonic nanoparticle, MPN), 플라스모닉 나노입자, 자기나노입자, 금나노입자, 은나노입자 중 어느 하나 이상을 포함할 수 있다.In one embodiment of the present invention, the exothermic material may include exothermic particles. For example, the exothermic particles may be nanoparticles (eg, 10 nm to 1 μm in diameter). In this case, the exothermic particles may be spherical, dumbbell, 2D, or mixed (core-shell, Janus, or combination) particles. In addition, the exothermic particles may be micro particles (eg, 1 μm to 100 μm in diameter). In this case, the exothermic particles may be integral type or mixed type (core-shell, Janus, combination type) particles. Meanwhile, in one embodiment of the present invention, the exothermic particles may include any one or more of magneto-plasmonic nanoparticles (MPN), plasmonic nanoparticles, magnetic nanoparticles, gold nanoparticles, and silver nanoparticles. can

도 4는 본 발명의 일 실시예에 따른 현장 중심형 분자진단 장치의 혼합부의 구성을 나타낸 도면이다. 도 4를 참조하면, 본 발명의 일 실시예에서, 혼합부(400)는 분리 용액 저장 챔버(410), 분리 용액 공급 유로(420), 샘플 배출 유로(430) 및 혼합 챔버(440)를 포함할 수 있다.4 is a diagram showing the configuration of a mixing unit of an on-site molecular diagnosis device according to an embodiment of the present invention. Referring to FIG. 4 , in one embodiment of the present invention, the mixing unit 400 includes a separation solution storage chamber 410, a separation solution supply passage 420, a sample discharge passage 430, and a mixing chamber 440. can do.

분리 용액 저장 챔버(410)는 포집체(310)에서 불순물이 제거된 상태의 샘플을 분리시키는 분리 용액을 저장한다. 분리 용액은 포집체(310)로부터 샘플을 용출(elution)시킬 수 있다. 예를 들면, 분리 용액은 물이 될 수 있다. 분리 용액 공급 유로(420)는 분리 용액 저장 챔버(410)와 포집 챔버(320)를 연결한다. 분리 용액 공급 유로(420)를 통해 분리 용액이 포집 챔버(320)로 공급될 수 있다.The separation solution storage chamber 410 stores a separation solution for separating samples in a state in which impurities are removed from the collector 310 . The separation solution may elute the sample from the collector 310 . For example, the separation solution may be water. The separation solution supply passage 420 connects the separation solution storage chamber 410 and the collecting chamber 320 . The separation solution may be supplied to the collection chamber 320 through the separation solution supply channel 420 .

샘플 배출 유로(430)는 포집 챔버(320)에서 분리 용액과 함께 배출되는 샘플을 배출한다. 또한, 혼합 챔버(440)는 상기 발열 물질, 상기 프라이머 및 상기 중합 효소를 포함하는 혼합 용액을 저장한다. 샘플 배출 유로(430)를 통해 유입된 샘플은 혼합 챔버(440)의 내부에서 상기 혼합 용액과 혼합될 수 있다.The sample discharge channel 430 discharges the sample discharged together with the separation solution from the collection chamber 320 . In addition, the mixing chamber 440 stores a mixed solution including the exothermic material, the primer, and the polymerase. The sample introduced through the sample discharge channel 430 may be mixed with the mixed solution in the mixing chamber 440 .

한편, 분리 용액 공급 유로(420)와 포집 챔버(320) 사이, 샘플 배출 유로(430)와 포집 챔버(320) 사이에는 유로의 폐쇄 또는 개방을 위한 하나 이상의 밸브(미도시)가 배치될 수 있다. 또한, 샘플 배출 유로(430)는 마이크로단위의 미세소관 또는 수mm 단위(예를 들면, 1mm~5mm)의 직경을 가지는 관으로 구비될 수 있다.Meanwhile, one or more valves (not shown) may be disposed between the separation solution supply passage 420 and the collection chamber 320 and between the sample discharge passage 430 and the collection chamber 320 to close or open the passage. . In addition, the sample discharge channel 430 may be provided as a microtubule or a tube having a diameter of several mm (eg, 1 mm to 5 mm).

제 2 가열부(500)는 혼합부(400)와 반응부(600) 사이에 배치된다. 제 2 가열부(500)는 상기 샘플에 포함된 RNA의 역전사가 일어나도록 반응부(600)로 이송되는 샘플을 제 2 온도로 가열한다. 이때, 제 2 온도는 45~55℃에서 선택될 수 있다. 예를 들면, 제 2 가열부(500)는 상기 샘플을 52℃로 가열할 수 있다. 제 2 가열부(500)의 내부에서 상기 샘플이 제 2 온도로 가열되면, 상기 샘플에서 RNA의 역전사가 진행될 수 있다.The second heating unit 500 is disposed between the mixing unit 400 and the reaction unit 600 . The second heating unit 500 heats the sample transferred to the reaction unit 600 to a second temperature so that reverse transcription of RNA included in the sample occurs. At this time, the second temperature may be selected from 45 ~ 55 ℃. For example, the second heating unit 500 may heat the sample to 52°C. When the sample is heated to the second temperature inside the second heating unit 500, reverse transcription of RNA in the sample may proceed.

한편, 샘플 내에 포함된 타겟 핵산이 DNA인 경우 역전사는 요구되지 않는다. 따라서 샘플 내에서 검출하고자 하는 타겟 핵산이 DNA인 경우 제 2 가열부(500)는 생략될 수 있다.On the other hand, when the target nucleic acid contained in the sample is DNA, reverse transcription is not required. Accordingly, when the target nucleic acid to be detected in the sample is DNA, the second heating unit 500 may be omitted.

도 5는 본 발명의 일 실시예에 따른 현장 중심형 분자진단 장치의 제 2 가열부의 구성을 나타낸 도면이다. 도 5를 참조하면, 제 2 가열부(500)는 제 2 가열 유로(510) 및 제 2 히터(520)를 포함할 수 있다. 제 2 가열 유로(510)는 혼합부(400)와 반응부(600)를 연결하며, 상기 샘플이 유동하도록 배치된다. 이때, 제 2 가열 유로(510)는 마이크로단위의 미세소관 또는 수mm 단위(예를 들면, 1mm~5mm)의 직경을 가지는 관으로 구비될 수 있다. 또한, 제 2 히터(520)는 제 2 가열 유로(510)를 제 2 온도로 가열하도록 배치된다. 제 2 히터(520)는 제 2 가열 유로(510)와 인접하여 배치되는 히터 블록이 될 수 있다.5 is a diagram showing the configuration of a second heating unit of an on-site molecular diagnosis device according to an embodiment of the present invention. Referring to FIG. 5 , the second heating part 500 may include a second heating passage 510 and a second heater 520 . The second heating passage 510 connects the mixing unit 400 and the reaction unit 600 and is disposed so that the sample flows. In this case, the second heating passage 510 may be provided as a microtubule in micro units or a tube having a diameter in units of several mm (eg, 1 mm to 5 mm). Also, the second heater 520 is disposed to heat the second heating passage 510 to a second temperature. The second heater 520 may be a heater block disposed adjacent to the second heating passage 510 .

반응부(600)에서는 상기 샘플의 PCR이 진행된다. 반응부(600)의 내부에서 상기 샘플에 혼합된 발열 물질은 제 1 광의 조사 시 열을 발생시켜 상기 샘플을 가열하며, 상기 제 1 광을 조사받지 않는 동안에는 상기 발열 물질이 열을 발생시키지 않으며 상기 샘플이 냉각된다. 이와 같은 승온 및 냉각 주기가 반복되면서 PCR이 수행될 수 있다. 이때, 주기의 길이, 조사 시간 및 비조사 시간은 각 주기별로 동일하게 설정될 수 있다. 물론, 필요에 따라 일부 주기는 주기의 길이, 조사 시간 및 비조사 시간이 다른 주기와 상이하게 설정될 수도 있다.In the reaction unit 600, PCR of the sample proceeds. The exothermic material mixed with the sample inside the reaction unit 600 heats the sample by generating heat when the first light is irradiated, and the exothermic material does not generate heat while not being irradiated with the first light. The sample is cooled. PCR may be performed while repeating such heating and cooling cycles. In this case, the period length, irradiation time, and non-irradiation time may be equally set for each period. Of course, the length of the period, the irradiation time, and the non-irradiation time of some periods may be set to be different from those of other periods, if necessary.

도 6은 본 발명의 일 실시예에 따른 현장 중심형 분자진단 장치의 반응부의 구성을 나타낸 도면이다. 도 6을 참조하면, 반응부(600)는 반응 유로(610) 및 제 1 광원(620)을 포함한다.6 is a diagram showing the configuration of a reaction unit of an on-site molecular diagnostic device according to an embodiment of the present invention. Referring to FIG. 6 , the reaction unit 600 includes a reaction passage 610 and a first light source 620 .

반응 유로(610)는 상기 샘플이 상기 발열 물질, 프라이머(primer) 및 중합 효소와 혼합된 상태로 유동하거나 머무르도록 배치된다. 예를 들면, 반응 유로(610)는 마이크로단위의 미세소관 또는 수mm 단위(예를 들면, 1mm~5mm)의 직경을 가지는 관으로 구비될 수 있다.The reaction flow path 610 is arranged so that the sample flows or stays in a mixed state with the pyrogen, primer and polymerase. For example, the reaction channel 610 may be provided with a microtubule or a tube having a diameter of several millimeters (eg, 1 mm to 5 mm).

제 1 광원(620)은 반응 유로(610)의 적어도 일부분에 상기 제 1 광을 조사한다. 상기 제 1 광은 상기 발열 물질을 발열시키는 파장을 가진다. 상기 발열 물질의 종류에 따라 상이한 파장대의 광에 의해 열이 발생될 수 있으며, 상기 제 1 광은 상기 발열 물질의 종류에 따라 그 파장대가 달라질 수 있다. 예를 들면, 상기 광의 피크 파장은 400~800nm에서 선택된 임의의 범위를 가질 수 있다.The first light source 620 radiates the first light to at least a portion of the reaction passage 610 . The first light has a wavelength that heats the exothermic material. Heat may be generated by light of different wavelengths depending on the type of the heating material, and the wavelength range of the first light may vary depending on the type of the heating material. For example, the peak wavelength of the light may have an arbitrary range selected from 400 to 800 nm.

본 발명의 일 실시예에서, 반응 유로(610)는 상기 제 1 광이 조사되는 조사 영역(611)과 상기 제 1 광이 조사되지 않는 비조사 영역(612)을 포함할 수 있다. 또한, 제 1 광원(620)은 조사 영역(611)에 상기 제 1 광을 조사할 수 있다.In one embodiment of the present invention, the reaction passage 610 may include an irradiation area 611 to which the first light is irradiated and a non-irradiation area 612 to which the first light is not irradiated. Also, the first light source 620 may radiate the first light to the irradiation area 611 .

상기 발열 물질을 포함하는 샘플은 반응 유로(610)를 유동하며, 조사 영역(611)을 통과할 때 가열되고, 비조사 영역(612)을 통과할 때 냉각될 수 있다. PCR이 반복적으로 수행되기 위해서는 가열과 냉각 주기가 반복되어야 하므로 반응 유로(610) 내에서 상기 샘플의 조사 영역(611)과 비조사 영역(612)을 반복적으로 통과하도록 일방향 유동과 상기 일방향 유동과 반대 방향으로 타방향 유동을 반복할 수 있다.The sample including the exothermic material flows through the reaction passage 610 , is heated when passing through the irradiation region 611 , and may be cooled when passing through the non-irradiated region 612 . Since heating and cooling cycles must be repeated in order for PCR to be repeatedly performed, one-way flow and opposite to the one-way flow allow the sample to repeatedly pass through the irradiated area 611 and the non-irradiated area 612 in the reaction passage 610 It is possible to repeat the flow in the other direction in one direction.

한편, 반응 유로(610)에 다수개의 조사 영역(611)과 비조사 영역(612)이 교번하여 배치되고 다수개의 조사 영역(611)에 상기 제 1 광이 조사되도록 제 1 광원(620)이 마련되는 경우에는 상기 샘플이 한방향으로만 유동하며 가열 및 냉각 주기를 반복하는 것도 가능하다.Meanwhile, a plurality of irradiation areas 611 and non-irradiation areas 612 are alternately disposed in the reaction passage 610, and a first light source 620 is provided to irradiate the first light to the plurality of irradiation areas 611. In this case, the sample flows in only one direction and it is possible to repeat heating and cooling cycles.

도 7은 본 발명의 일 실시예에 따른 현장 중심형 분자진단 장치의 반응부에서 PCR 주기를 반복하는 샘플의 온도 변화를 나타낸 그래프이다.7 is a graph showing temperature changes of samples repeating PCR cycles in a reaction unit of an on-site molecular diagnosis device according to an embodiment of the present invention.

도 7을 참조하면, 반응 유로(610)에서 상기 샘플에 상기 제 1 광이 조사되는 동안에는 상기 발열 물질이 열을 발생시킴으로써 상기 샘플의 가열이 이루어지고, 상기 샘플의 온도가 상승한다. 한편, 상기 샘플에 상기 제 1 광이 조사되지 않는 동안에는 상기 발열 물질이 열을 발생시키지 않으며 상기 샘플의 냉각이 이루어진다. 이에 따라 상기 샘플의 온도가 하강한다.Referring to FIG. 7 , while the sample is irradiated with the first light in the reaction passage 610 , the exothermic material generates heat, thereby heating the sample and increasing the temperature of the sample. Meanwhile, while the sample is not irradiated with the first light, the exothermic material does not generate heat and the sample is cooled. Accordingly, the temperature of the sample is lowered.

PCR은 변성(denaturation), 결합(annealing) 및 신장(elongation) 3단계로 이루어진다. 일반적으로 변성은 94~98℃의 온도에서 진행되고, 결합은 50~65℃의 온도에서 진행되며, 신장은 75~80℃의 온도에서 진행될 수 있다. 본 발명의 일 실시예에 의할 경우, 상기 샘플이 반응 유로(610)의 내부에서 상기 제 1 광의 조사 여부에 따라 온도의 상승과 하강을 반복하며 변성, 결합 및 신장을 포함하는 PCR 주기가 반복될 수 있다.PCR consists of three steps: denaturation, annealing, and elongation. In general, denaturation is performed at a temperature of 94 to 98 ° C, bonding is performed at a temperature of 50 to 65 ° C, and elongation may be performed at a temperature of 75 to 80 ° C. According to an embodiment of the present invention, the temperature of the sample is repeatedly raised and lowered depending on whether or not the first light is irradiated inside the reaction passage 610, and PCR cycles including denaturation, bonding, and elongation are repeated It can be.

도 8은 본 발명의 일 실시예에 따른 현장 중심형 분자진단 장치의 반응부의 변형예의 구성을 나타낸 도면이다. 도 8을 참조하면, 반응부(600a)는 반응 유로(610a) 및 제 1 광원(620a)을 포함하는데, 반응 유로(610a)는 별도의 비조사 영역을 가지지 않으며, 전체적으로 상기 제 1 광이 조사되도록 배치된다. 다시 말하면, 제 1 광원(620a)은 반응 유로(610a)의 전 영역에 상기 제 1 광을 조사하도록 배치되어 있다. 변형예에서, 제 1 광원(620a)은 반응 유로(610a)에 단속적으로 상기 제 1 광을 조사할 수 있다. 더욱 상세하게, 제 1 광원(620a)은 반응 유로(610a)에 상기 제 1 광을 소정 시간 조사하는 것을 단속적으로 반복하며 점멸 작동할 수 있다. 이에 따라 반응 유로(610a)의 내부에 배치된 샘플에 혼합된 발열 물질의 발열과 냉각이 반복될 수 있고, 상기 샘플의 온도가 상승과 하강을 반복하며 PCR의 변성, 결합 및 신장 단계가 진행될 수 있다.8 is a view showing the configuration of a modified example of a reaction unit of an on-site molecular diagnostic device according to an embodiment of the present invention. Referring to FIG. 8 , the reaction unit 600a includes a reaction passage 610a and a first light source 620a, the reaction passage 610a does not have a separate non-irradiation area, and the first light is irradiated as a whole. placed so that In other words, the first light source 620a is disposed to radiate the first light to the entire area of the reaction passage 610a. In a modified example, the first light source 620a may intermittently radiate the first light to the reaction passage 610a. More specifically, the first light source 620a may intermittently repeat irradiating the first light to the reaction passage 610a for a predetermined time and blink. Accordingly, heating and cooling of the exothermic material mixed with the sample disposed inside the reaction passage 610a can be repeated, and the temperature of the sample can be repeatedly raised and lowered to proceed with PCR denaturation, bonding, and elongation steps. there is.

전술한 바와 같이, 상기 발열 입자는 자기플라즈몬 나노입자(Magneto-plasmonic nanoparticle, MPN)가 될 수 있다. 이와 관련하여, 도 9에는 자기플라즈몬 나노입자(10)의 단면도가 도시되어 있다.As described above, the exothermic particle may be a magneto-plasmonic nanoparticle (MPN). In this regard, FIG. 9 shows a cross-sectional view of the magnetic plasmon nanoparticles 10 .

도 9를 참조하면, 자기플라즈몬 나노입자(10)는 코어(11)와, 코어(11)를 둘러싸는 쉘(12)을 포함할 수 있다. 더욱 상세하게, 코어(11)는 자성을 가질 수 있다. 코어(11)는 Fe3O4, Zn0.4Fe2.6O4, FexOy, ZnxFeyOz 및 MnxFeyOz 중 어느 하나 이상을 포함할 수 있다. 또한, 쉘(12)은 금(Au), 은(Ag) 및 구리(Cu) 중 어느 하나 이상을 포함할 수 있다.Referring to FIG. 9 , the magnetic plasmon nanoparticle 10 may include a core 11 and a shell 12 surrounding the core 11 . More specifically, the core 11 may have magnetism. The core 11 may include any one or more of Fe3O4, Zn0.4Fe2.6O4, FexOy, ZnxFeyOz, and MnxFeyOz. In addition, the shell 12 may include at least one of gold (Au), silver (Ag), and copper (Cu).

자기플라즈몬 나노입자(10)는 나노 스케일의 크기를 가질 수 있다. 예를 들면, 코어(11)의 직경은 5~100㎚, 쉘(12)의 두께는 1~20㎚가 될 수 있다.Magnetoplasmon nanoparticles 10 may have a nanoscale size. For example, the diameter of the core 11 may be 5 to 100 nm, and the thickness of the shell 12 may be 1 to 20 nm.

상기 발열 입자가 자기플라즈몬 나노입자(10)고, 쉘(12)이 12nm 두께의 금(Au)으로 이루어질 때, 535nm의 파장을 가지는 광에 대해 플라즈몬 공명을 보이는 것으로 확인되었다. 이 경우 상기 샘플의 효율적 가열을 위해 상기 제 1 광의 피크 파장은 530~540nm(예를 들면, 535nm)가 될 수 있다. 다시 말하면, 제 1 광원(620, 620a)은 530~540nm 피크 파장을 가지는 레이저 광을 조사 영역을 향해 조사할 수 있다. 물론, 상기 발열 물질로 다른 종류의 입자가 사용되었을 때, 플라즈몬 공명이 발생하는 파장은 달라질 수 있다.When the exothermic particles are magnetoplasmon nanoparticles 10 and the shell 12 is made of gold (Au) having a thickness of 12 nm, it has been confirmed that plasmon resonance is exhibited for light having a wavelength of 535 nm. In this case, for efficient heating of the sample, the peak wavelength of the first light may be 530 to 540 nm (eg, 535 nm). In other words, the first light sources 620 and 620a may radiate laser light having a peak wavelength of 530 to 540 nm toward the irradiation area. Of course, when different types of particles are used as the exothermic material, the wavelength at which plasmon resonance occurs may be different.

분리부(700)는 상기 발열 물질은 자성을 가짐을 전제로, 상기 발열 물질을 자력에 의해 고정시킴으로써 반응부(600)에서 이송된 샘플로부터 상기 발열 물질을 분리한다. 상기 발열 물질은 샘플 내에서 샘플을 직접적으로 가열함으로써 PCR 반응을 효율적으로 유도하지만, PCR의 완료 후 타겟 핵산의 검출 과정에서는 검출에 장애 요인이 될 수 있다. 예를 들면, 상기 발열 물질은 검출 시 사용되는 광을 흡수 또는 반사(발광)하여 타겟 핵산의 검출을 방해할 수 있다. 분리부(700)는 반응부(600)에서 PCR이 완료된 샘플에서 상기 발열 물질을 분리함으로써 후단의 검출부(800)에서 타겟 핵산의 검출이 효과적으로 이루어질 수 있게 해준다.The separator 700 separates the exothermic material from the sample transferred from the reaction unit 600 by fixing the exothermic material by magnetic force on the premise that the exothermic material has magnetism. Although the pyrogen efficiently induces a PCR reaction by directly heating the sample within the sample, it may become an obstacle to detection of the target nucleic acid after completion of the PCR. For example, the pyrogenic substance may interfere with detection of the target nucleic acid by absorbing or reflecting (emitting light) light used for detection. The separation unit 700 separates the pyrogen from the sample for which PCR has been completed in the reaction unit 600, so that the detection unit 800 at a later stage can effectively detect the target nucleic acid.

한편, 상기 발열 물질이 자성을 가지지 않거나 타겟 핵산의 검출 과정에서 장애 요인으로 작용하지 않는 경우 분리부(700)는 생략될 수 있다.On the other hand, if the heating material does not have magnetism or does not act as an obstacle in the process of detecting the target nucleic acid, the separator 700 may be omitted.

도 10은 본 발명의 일 실시예에 따른 현장 중심형 분자진단 장치의 분리부의 구성을 나타낸 도면이다. 도 10을 참조하면, 분리부(700)는 분리 유로(710) 및 마그넷(720)을 포함할 수 있다.10 is a diagram showing the configuration of a separation unit of an on-site molecular diagnosis device according to an embodiment of the present invention. Referring to FIG. 10 , the separation unit 700 may include a separation passage 710 and a magnet 720 .

분리 유로(710)는 반응부(600)에서 이송된 샘플이 머무르거나 유동하도록 배치된다. 분리 유로(710)는 마이크로단위의 미세소관 또는 수mm 단위(예를 들면, 1mm~5mm)의 직경을 가지는 관으로 구비될 수 있다.The separation passage 710 is arranged so that the sample transferred from the reaction unit 600 stays or flows. The separation passage 710 may be provided as a microtubule or a tube having a diameter of several millimeters (eg, 1 mm to 5 mm).

마그넷(720)은 분리 유로(710)에 자력을 제공하여 상기 발열 물질을 상기 분리 유로의 내부에 고정시킨다. 마그넷(720)은 분리 유로(710)에 인접하여 배치될 수 있다. 마그넷(720)은 상기 발열 입자가 검출부(800) 측으로 유동하지 않고 상기 샘플로부터 분리되어 분리 유로(710)의 내부 소정 영역에 머물도록 자력을 제공한다. 이에 따라 분리 유로(710)를 통과한 샘플은 상기 발열 입자가 분리된 상태가 될 수 있다.The magnet 720 provides magnetic force to the separation passage 710 to fix the exothermic material inside the separation passage 710 . The magnet 720 may be disposed adjacent to the separation passage 710 . The magnet 720 provides magnetic force so that the exothermic particles do not flow toward the detection unit 800 but are separated from the sample and stay in a predetermined area inside the separation passage 710 . Accordingly, the sample passing through the separation passage 710 may be in a state in which the exothermic particles are separated.

한편, 분리부(700)는 마그넷(720)의 이송을 위한 이송수단(미도시)을 더 포함할 수 있다. 필요한 경우, 마그넷(720)은 상기 이송수단에 의해 분리 유로(710)에 인접한 위치 및 떨어진 위치 사이를 변위할 수 있다.Meanwhile, the separator 700 may further include a transfer means (not shown) for transferring the magnet 720 . If necessary, the magnet 720 can be displaced between a position adjacent to and separated from the separation passage 710 by the transfer means.

검출부(800)는 반응부(600)에서 이송된 샘플의 내부에 존재하는 타겟 핵산을 검출한다. 본 발명의 일 실시예에서, 검출부(800)는 분리부(700)의 후단에 배치될 수 있다.The detection unit 800 detects target nucleic acid present in the sample transferred from the reaction unit 600 . In one embodiment of the present invention, the detection unit 800 may be disposed at the rear end of the separation unit 700 .

도 11은 본 발명의 일 실시예에 따른 현장 중심형 분자진단 장치의 검출부의 구성을 나타낸 도면이다. 도 11을 참조하면, 검출부(800)는 검출 유로(810), 제 2 광원(820) 및 디텍터(830)를 포함할 수 있다.11 is a diagram showing the configuration of a detection unit of an on-site molecular diagnosis device according to an embodiment of the present invention. Referring to FIG. 11 , the detection unit 800 may include a detection passage 810 , a second light source 820 and a detector 830 .

검출 유로(810)는 반응부(600)에서 이송된 샘플이 머무르거나 유동한다. 본 발명의 일 실시예에서, 검출 유로(810)에는 분리부(700)로부터 이송된 샘플이 머무르거나 유동하게 된다. 한편, 검출 유로(810)는 마이크로단위의 미세소관 또는 수mm 단위(예를 들면, 1mm~5mm)의 직경을 가지는 관으로 구비될 수 있다.The sample transported from the reaction unit 600 stays or flows in the detection passage 810 . In one embodiment of the present invention, the sample transferred from the separator 700 stays or flows in the detection passage 810 . Meanwhile, the detection passage 810 may be provided as a microtubule or a tube having a diameter of several millimeters (eg, 1 mm to 5 mm).

제 2 광원(820)은 검출 유로(810)에 상기 타겟 핵산의 검출을 위한 제 2 광을 조사한다. 제 2 광원(820)은 샘플의 유동 방향과 수직한 검출 방향으로 상기 제 2 광을 조사할 수 있다. 본 발명의 일 실시예에서, 상기 제 2 광은 상기 타겟 핵산의 형광 여기를 유도하는 파장을 가질 수 있다. 예를 들면, 상기 제 2 광은 100~350nm에서 선택된 범위의 파장을 가질 수 있다.The second light source 820 radiates a second light for detecting the target nucleic acid to the detection passage 810 . The second light source 820 may irradiate the second light in a detection direction perpendicular to the flow direction of the sample. In one embodiment of the present invention, the second light may have a wavelength that induces fluorescence excitation of the target nucleic acid. For example, the second light may have a wavelength selected from 100 to 350 nm.

디텍터(830)는 검출 유로(810)를 통과한 제 2 광을 검출한다. 더욱 상세하게, 디텍터(830)는 상기 샘플 내에서 타겟 핵산이 상기 제 2 광에 의해 발생시키는 형광을 검출한다. 이와 관련하여 검출부(800)는 디텍터(830)가 검출한 형광을 디스플레이하는 디스플레이(미도시)를 더 포함할 수 있다.The detector 830 detects the second light passing through the detection passage 810 . More specifically, the detector 830 detects fluorescence generated by the second light from the target nucleic acid in the sample. In this regard, the detector 800 may further include a display (not shown) displaying fluorescence detected by the detector 830 .

압력 공급부(900)는 상기 샘플에 유동력을 제공한다. 압력 공급부(900)는 투입부(100), 제 1 가열부(200), 농축부(300), 혼합부(400), 제 2 가열부(500), 반응부(600), 분리부(700) 및 검출부(800)와 연통되어 배치되고, 양압 또는 음압을 공급하여 상기 샘플을 유동시킨다. 더욱 상세하게, 압력 공급부(900)는 투입부(100), 제 1 가열 유로(210), 세척 용액 공급 유로(340), 세척 용액 배출 유로(350), 분리 용액 공급 유로(420), 샘플 배출 유로(430), 제 2 가열 유로(510), 반응 유로(610), 분리 유로(710) 및 검출 유로(810)에 음압 또는 양압을 공급할 수 있다.The pressure supply unit 900 provides fluidity to the sample. The pressure supply unit 900 includes the input unit 100, the first heating unit 200, the enrichment unit 300, the mixing unit 400, the second heating unit 500, the reaction unit 600, and the separating unit 700. ) and the detection unit 800 and is disposed in communication, and supplies a positive pressure or a negative pressure to flow the sample. More specifically, the pressure supply unit 900 includes the input unit 100, the first heating passage 210, the cleaning solution supply passage 340, the washing solution discharge passage 350, the separation solution supply passage 420, and the sample discharge passage. Negative pressure or positive pressure may be supplied to the passage 430 , the second heating passage 510 , the reaction passage 610 , the separation passage 710 and the detection passage 810 .

한편, 본 발명의 일 실시예에서, 투입부(100), 제 1 가열부(200), 농축부(300), 혼합부(400), 제 2 가열부(500), 반응부(600), 분리부(700) 및 검출부(800)는 유로로 연결될 수 있다. 즉, 제 1 가열 유로(210), 세척 용액 공급 유로(340), 세척 용액 배출 유로(350), 분리 용액 공급 유로(420), 샘플 배출 유로(430), 제 2 가열 유로(510), 반응 유로(610), 분리 유로(710) 및 검출 유로(810)는 서로 연통될 수 있다. 또한, 이들 사이의 유로를 연결하거나 개폐하는 하나 이상의 밸브(미도시)가 배치될 수 있다.Meanwhile, in one embodiment of the present invention, the input unit 100, the first heating unit 200, the enrichment unit 300, the mixing unit 400, the second heating unit 500, the reaction unit 600, The separation unit 700 and the detection unit 800 may be connected to a flow path. That is, the first heating passage 210, the cleaning solution supply passage 340, the washing solution discharge passage 350, the separation solution supply passage 420, the sample discharge passage 430, the second heating passage 510, the reaction The passage 610 , the separation passage 710 and the detection passage 810 may communicate with each other. In addition, one or more valves (not shown) may be disposed to connect or open and close the flow path therebetween.

본 발명의 실시예에 대하여 설명하였으나, 본 발명의 사상은 본 명세서에 제시되는 실시예에 의해 제한되지 아니하며, 본 발명의 사상을 이해하는 당업자는 동일한 사상의 범위 내에서, 구성요소의 부가, 변경, 삭제, 추가 등에 의해서 다른 실시예를 용이하게 제안할 수 있을 것이나, 이 또한 본 발명의 사상범위 내에 든다고 할 것이다.Although the embodiments of the present invention have been described, the spirit of the present invention is not limited by the embodiments presented herein, and those skilled in the art who understand the spirit of the present invention may add or change components within the scope of the same spirit. Other embodiments can be easily proposed by adding, deleting, adding, etc., but this will also be said to be within the scope of the present invention.

Claims (16)

PCR(Polymerase Chain Reaction)용 샘플이 투입되는 투입부; 및An input unit into which samples for PCR (Polymerase Chain Reaction) are input; and 상기 샘플의 PCR이 진행되는 반응부;를 포함하고,Including; a reaction unit in which the PCR of the sample proceeds, 상기 반응부는,The reaction part, 상기 샘플이 제 1 광의 조사 시 열을 발생시키는 발열 물질, 프라이머(primer) 및 중합 효소와 혼합된 상태로 유동하거나 머무르는 반응 유로; 및a reaction channel in which the sample flows or stays in a state in which the sample is mixed with an exothermic material, a primer, and a polymerase that generate heat when irradiated with a first light; and 상기 반응 유로의 적어도 일부분에 상기 제 1 광을 조사하는 제 1 광원;을 포함하며,A first light source radiating the first light to at least a portion of the reaction passage; includes, 상기 샘플이 상기 반응 유로의 내부에서 상기 제 1 광을 조사받는 동안에는 상기 발열 물질이 열을 발생시켜 상기 샘플이 가열되고, 상기 제 1 광을 조사받지 않는 동안에는 상기 발열 물질이 열을 발생시키지 않으며 상기 샘플이 냉각되는 현장 중심형 분자진단 장치.While the sample is irradiated with the first light inside the reaction passage, the exothermic material generates heat and the sample is heated, and while the sample is not irradiated with the first light, the exothermic material does not generate heat and A field-oriented molecular diagnostic device where samples are cooled. 제 1 항에 있어서,According to claim 1, 상기 투입부와 상기 반응부 사이에 배치되고, 이송된 샘플을 포집하며, 상기 샘플에 존재하는 불순물을 제거하고 상기 샘플에 존재하는 핵산을 농축시키는 농축부를 더 포함하는 현장 중심형 분자진단 장치.An in-situ molecular diagnosis device further comprising an enrichment unit disposed between the input unit and the reaction unit, collecting the transferred sample, removing impurities present in the sample, and concentrating nucleic acid present in the sample. 제 2 항에 있어서,According to claim 2, 상기 농축부는,The enrichment unit, 상기 샘플을 포집하는 포집체;a collection body for collecting the sample; 상기 포집체가 배치되는 포집 챔버;a collecting chamber in which the collecting body is disposed; 상기 샘플에 존재하는 불순물을 세척하기 위한 하나 이상의 세척 용액을 저장하는 세척 용액 저장 챔버;a washing solution storage chamber storing one or more washing solutions for washing impurities present in the sample; 상기 세척 용액 저장 챔버와 상기 포집 챔버를 연결하는 세척 용액 공급 유로;를 포함하는 현장 중심형 분자진단 장치.A field-oriented molecular diagnostic device comprising: a washing solution supply passage connecting the washing solution storage chamber and the collection chamber. 제 3 항에 있어서,According to claim 3, 상기 농축부는,The enrichment unit, 상기 포집체에서 배출되는 세척 용액을 배출하는 세척 용액 배출 유로; 및a washing solution discharge passage through which the washing solution discharged from the collecting body is discharged; and 상기 세척 용액 배출 유로를 통해 배출된 세척 용액을 수집하는 배출 챔버;를 더 포함하는 현장 중심형 분자진단 장치.The field-oriented molecular diagnostic device further comprising a discharge chamber for collecting the cleaning solution discharged through the cleaning solution discharge passage. 제 3 항에 있어서,According to claim 3, 상기 농축부와 상기 반응부 사이에 배치되고, 상기 농축부에서 이송된 샘플에 상기 발열 물질, 상기 프라이머 및 상기 중합 효소를 혼합시키는 혼합부를 더 포함하는 현장 중심형 분자진단 장치.and a mixing unit disposed between the enrichment unit and the reaction unit and mixing the pyrogen, the primer, and the polymerase with the sample transferred from the enrichment unit. 제 5 항에 있어서,According to claim 5, 상기 혼합부는,The mixing part, 상기 포집체에서 불순물이 제거된 상태의 샘플을 분리시키는 분리 용액을 저장하는 분리 용액 저장 챔버;a separation solution storage chamber for storing a separation solution for separating a sample in which impurities are removed from the collection body; 상기 분리 용액 저장 챔버와 상기 포집 챔버를 연결하는 분리 용액 공급 유로;a separation solution supply passage connecting the separation solution storage chamber and the collection chamber; 상기 포집 챔버에서 분리 용액과 함께 배출되는 샘플을 배출하는 샘플 배출 유로; 및a sample discharge passage through which the sample discharged together with the separation solution from the collection chamber is discharged; and 상기 발열 물질, 상기 프라이머 및 상기 중합 효소를 포함하는 혼합 용액을 저장하고, 상기 샘플 배출 유로를 통해 유입된 샘플을 상기 혼합 용액과 혼합하는 혼합 챔버;를 포함하는 현장 중심형 분자진단 장치.and a mixing chamber for storing a mixed solution including the pyrogen, the primer, and the polymerase, and mixing the sample introduced through the sample discharge channel with the mixed solution. 제 2 항에 있어서,According to claim 2, 상기 투입부와 상기 농축부 사이에 배치되고, 상기 샘플에서 핵산이 추출되도록 상기 농축부로 이송되는 샘플을 제 1 온도로 가열하는 제 1 가열부를 더 포함하는 현장 중심형 분자진단 장치.The in situ molecular diagnosis device further comprises a first heating unit disposed between the input unit and the enrichment unit and heating the sample transferred to the enrichment unit to a first temperature so that nucleic acids are extracted from the sample. 제 7 항에 있어서,According to claim 7, 상기 제 1 가열부는,The first heating part, 상기 투입부와 상기 농축부를 연결하며 상기 샘플이 유동하는 제 1 가열 유로; 및a first heating passage connecting the input unit and the enrichment unit and through which the sample flows; and 상기 제 1 가열 유로를 제 1 온도로 가열하도록 배치되는 제 1 히터;를 포함하는 현장 중심형 분자진단 장치.and a first heater arranged to heat the first heating passage to a first temperature. 제 5 항에 있어서,According to claim 5, 상기 혼합부와 상기 반응부 사이에 배치되고, 상기 샘플에 포함된 RNA의 역전사가 일어나도록 상기 반응부로 이송되는 샘플을 제 2 온도로 가열하는 제 2 가열부를 더 포함하는 현장 중심형 분자진단 장치.A second heating unit disposed between the mixing unit and the reaction unit and heating the sample transferred to the reaction unit to a second temperature so that reverse transcription of RNA included in the sample occurs. 제 9 항에 있어서,According to claim 9, 상기 제 2 가열부는,The second heating part, 상기 혼합부와 상기 반응부를 연결하고, 상기 샘플이 유동하는 제 2 가열 유로; 및a second heating passage connecting the mixing part and the reaction part and through which the sample flows; and 상기 제 2 가열 유로를 제 2 온도로 가열하도록 배치되는 제 2 히터;를 포함하는 현장 중심형 분자진단 장치.and a second heater arranged to heat the second heating passage to a second temperature. 제 1 항에 있어서,According to claim 1, 상기 발열 물질은 자성을 가지며,The exothermic material has magnetism, 상기 발열 물질을 자력에 의해 고정시킴으로써 상기 반응부에서 이송된 샘플로부터 상기 발열 물질을 분리하는 분리부를 더 포함하는 현장 중심형 분자진단 장치.The in-situ molecular diagnosis device further comprises a separator for separating the pyrogen from the sample transferred from the reaction unit by fixing the pyrogen by magnetic force. 제 11 항에 있어서,According to claim 11, 상기 분리부는,the separation unit, 상기 반응부에서 이송된 샘플이 머무르거나 유동하는 분리 유로; 및a separation passage through which the sample transported from the reaction unit stays or flows; and 상기 분리 유로에 자력을 제공하여 상기 발열 물질을 상기 분리 유로의 내부에 고정시키는 마그넷;을 포함하는 현장 중심형 분자진단 장치.and a magnet for providing magnetic force to the separation passage to fix the exothermic substance inside the separation passage. 제 1 항에 있어서,According to claim 1, 상기 반응부에서 이송된 샘플의 내부에 존재하는 타겟 핵산을 검출하는 검출부를 더 포함하는 현장 중심형 분자진단 장치.The in-situ molecular diagnostic device further comprising a detection unit for detecting target nucleic acid present in the sample transferred from the reaction unit. 제 13 항에 있어서,According to claim 13, 상기 검출부는,The detecting unit, 상기 반응부에서 이송된 샘플이 머무르거나 유동하는 검출 유로;a detection passage through which the sample transported from the reaction unit stays or flows; 상기 검출 유로에 상기 타겟 핵산의 검출을 위한 제 2 광을 조사하는 제 2 광원; 및a second light source radiating a second light for detecting the target nucleic acid to the detection channel; and 상기 검출 유로를 통과한 제 2 광을 검출하는 디텍터;를 포함하는 현장 중심형 분자진단 장치.An in-situ molecular diagnosis device comprising: a detector for detecting the second light passing through the detection passage. 제 1 항에 있어서,According to claim 1, 상기 반응 유로는 상기 제 1 광이 조사되는 조사 영역과 상기 제 1 광이 조사되지 않는 비조사 영역을 포함하고,The reaction passage includes an irradiated area irradiated with the first light and a non-irradiated area not irradiated with the first light, 상기 제 1 광원은 상기 조사 영역에 상기 제 1 광을 조사하는 현장 중심형 분자진단 장치.The first light source irradiates the first light to the irradiation area. 제 1 항에 있어서,According to claim 1, 상기 반응 유로는 전체적으로 상기 제 1 광이 조사되도록 배치되고,The reaction channel is disposed so that the first light is irradiated as a whole, 상기 제 1 광원은 상기 반응 유로에 단속적으로 상기 제 1 광을 조사하는 현장 중심형 분자진단 장치.The first light source intermittently irradiates the first light to the reaction passage.
PCT/KR2022/018756 2021-12-29 2022-11-24 Point-of-care molecular diagnostic device Ceased WO2023128298A1 (en)

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