WO2021201635A1 - Analysis system and method - Google Patents

Analysis system and method Download PDF

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Publication number
WO2021201635A1
WO2021201635A1 PCT/KR2021/004085 KR2021004085W WO2021201635A1 WO 2021201635 A1 WO2021201635 A1 WO 2021201635A1 KR 2021004085 W KR2021004085 W KR 2021004085W WO 2021201635 A1 WO2021201635 A1 WO 2021201635A1
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WIPO (PCT)
Prior art keywords
electromagnet unit
electromagnet
analyte
magnetic field
unit
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PCT/KR2021/004085
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French (fr)
Korean (ko)
Inventor
강민희
김은주
김한비
최영만
Original Assignee
사회복지법인 삼성생명공익재단
아주대학교 산학협력단
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Publication of WO2021201635A1 publication Critical patent/WO2021201635A1/en

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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00—Sampling; Preparing specimens for investigation
    • G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
    • G01N1/38—Diluting, dispersing or mixing samples
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/65—Raman scattering
    • 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 separation apparatus and method for separating an analyte and an interfering material from a complex sample, and to an analysis system and method for detecting a target gene and confirming the presence or absence of a specific disease using the same.
  • a method of detecting a nucleic acid uses a labeled detection method using a second probe labeled with fluorescence, which allows a target nucleic acid to complementarily bind to a first probe for a probe and confirm it.
  • a detection method is easy to analyze a trace amount of nucleic acid, it is necessary to use different sensor chips to which a probe is immobilized, and a nucleic acid amplification technique such as a PCR amplification method must be preceded. ) may occur.
  • the method using a fluorescently labeled probe in PCR is one of the methods to detect only a specific amplification product using the 5' nuclease activity of Taq DNA polymerase.
  • Loop-mediated isothermal amplification is a simple and fast isothermal PCR. Instead of using Taq DNA polymerase used in existing PCR methods, Bst DNA with exonuclease function This is a method using a polymerase (Bst DNA polymerase). Since this isothermal PCR method does not require a change in temperature during gene amplification, it enables gene amplification at a fixed temperature easily without specialized equipment.
  • An object of the present invention is to provide a separation device capable of separating interfering substances other than analytes by using an electromagnet, and it is also an object of the present invention to provide an analysis system capable of integrating sample amplification, analyte separation and detection is to provide
  • the analysis system includes a separation device for agitating and separating a sample including an analyte, an interference material, and magnetic particles bound to the interference material, and is connected to the separation device and provides light to the sample. and an analysis device for irradiating light and detecting the analyte using an emitted light signal, wherein the separation device includes a body, a receiving unit detachably disposed on the body, and a receiving unit for accommodating the sample; A first electromagnet part disposed on the body and generating a magnetic field, and a second electron disposed to face the first electromagnet part around the receiving part on the body, and generating a magnetic field in a different direction from that of the first electromagnet part and a magnet, wherein at least one of the first electromagnet unit and the second electromagnet unit applies a magnetic field to the magnetic particles to agitate at least a portion of the analyte, the interference material, and the magnetic particles.
  • the first electromagnet unit and the second electromagnet unit may alternately apply a magnetic field to the magnetic particles at a preset period.
  • the first electromagnet unit and the second electromagnet unit may simultaneously apply a magnetic field to the magnetic particles at a preset period.
  • At least one of the first electromagnet unit and the second electromagnet unit may separate the analyte and the interference material by continuously applying a magnetic field to the magnetic particles.
  • the separated interfering material is located in a first region in the accommodating part, and the separated analyte is located in a second region different from the first region in the accommodating part, and the first The region may be a region adjacent to at least one of the first electromagnet unit and the second electromagnet unit, and the second region may be a region spaced apart from the first region.
  • an incident hole for guiding the light to the second region may be formed in the body of the separation device.
  • the optical signal may be a surface-enhanced Raman scattering (SERS) signal.
  • SERS surface-enhanced Raman scattering
  • the receiving part may be made of a transparent material.
  • the present invention is disposed on the body, and at least one additional electromagnet unit for generating a magnetic field in a different direction from the first electromagnet unit and the second electromagnet unit; further comprising, the additional electromagnet unit
  • a plurality of the additional electromagnet parts may be provided, and the plurality of additional electromagnet parts may be disposed to be spaced apart from the first electromagnet part and the second electromagnet part.
  • the analysis method comprises the steps of: preparing a sample containing an analyte, an interfering material, and magnetic particles in a receiving unit; amplifying the analyte and the interfering material; Separating the interfering material, irradiating light to the sample, and detecting the analyte using an emitted light signal, wherein separating the analyte and the interfering material includes the receiving generating a magnetic field by operating at least one of the first electromagnet unit and the second electromagnet unit disposed to face each other around the unit; It may include agitating the sample so that it binds, and separating the analyte and the interfering material in the receiving unit using the magnetic field.
  • the step of agitating the sample so that the magnetic particles bind to any one of the analyte or the interference material accommodated in the receiver using the magnetic field, the first electromagnet and the second electromagnet may include applying a magnetic field to the magnetic particles alternately at a preset period.
  • the step of stirring the sample so that the magnetic particles bind to any one of the analyte or the interfering material accommodated in the receiving unit using the magnetic field comprises: the first electromagnet unit and the second The electromagnet unit may simultaneously apply a magnetic field to the magnetic particles at a preset period.
  • At least one of the first electromagnet unit and the second electromagnet unit is the magnetic particle
  • the separated interference material is located in a first region in the accommodating part, the separated analyte is located in a second region in the accommodating part, and the first region is the first electron
  • the region may be adjacent to at least one of the magnet and the second electromagnet, and the second region may be a region spaced apart from the first region.
  • the light in the detecting of the analyte using the optical signal, the light may be guided to the second region through an incident hole formed in the body of the separation device.
  • the optical signal may be a surface-enhanced Raman scattering signal.
  • the receiving part may be made of a transparent material.
  • the present invention is disposed on the body, and at least one additional electromagnet unit for generating a magnetic field in a different direction from the first electromagnet unit and the second electromagnet unit; further comprising, the additional electromagnet unit
  • a plurality of the additional electromagnet parts may be provided, and the plurality of additional electromagnet parts may be disposed to be spaced apart from the first electromagnet part and the second electromagnet part.
  • the separation apparatus and separation method according to the embodiments of the present invention bind magnetic particles to an interference material using probe materials that specifically bind to an analyte and an interference material, respectively, and magnetic particles by means of symmetrically arranged electromagnets.
  • a magnetic field to the accommodating part to agitate the sample, it is possible to facilitate the binding of the magnetic particles and the probe.
  • the separation process and time can be shortened by separating the analyte and the interfering material directly in the accommodating part using the magnetic field generated by the symmetrically arranged electromagnets.
  • the analyte is separated from the interfering material in the receiving unit using a magnetic field, and then the analyte is performed by the analysis device without a separate process of discharging the interfering material.
  • FIG. 1 is a perspective view showing a separation device according to an embodiment of the present invention.
  • Figure 2 is an exploded view showing the separation device of Figure 2;
  • FIG. 3 is a schematic cross-sectional view of the separation device of FIG. 1 .
  • FIG. 4 is a graph showing the intensity and period of a magnetic field applied to magnetic particles.
  • FIG. 5 shows a stirring process using the separation device of FIG. 1 .
  • FIG. 6 illustrates a separation process using the separation device of FIG. 1 .
  • FIG. 7 is a flowchart illustrating a sequence of stirring and separating a sample according to an embodiment of the present invention.
  • FIG. 8 is a perspective view illustrating an analysis system according to an embodiment of the present invention.
  • FIG. 9 is a graph showing a surface-enhanced Raman scattering analysis signal of an analyte according to an embodiment of the present invention.
  • FIG. 10 is a flowchart illustrating an analysis procedure of a sample using the analysis system according to an embodiment of the present invention.
  • FIG. 1 is a perspective view showing a separation device according to an embodiment of the present invention.
  • FIG. 2 is an exploded view illustrating the separation device of FIG. 2
  • FIG. 3 is a cross-sectional view schematically illustrating the separation device of FIG. 1 .
  • 4 is a graph showing the intensity and period of a magnetic field applied to magnetic particles.
  • FIG. 5 shows a stirring process using the separation device of FIG. 1
  • FIG. 6 shows a separation process using the separation device of FIG. 1 .
  • the separation device 10 may include a body 100 , an accommodating part 110 , a first electromagnet part 120 , and a second electromagnet part 130 .
  • the body 100 may have a space for accommodating the accommodating part 110 therein.
  • the body 100 may have various shapes such as a hemisphere, a cylinder, a polygon, etc., but for convenience of explanation, hereinafter, the body 100 will be described mainly in an embodiment in which the body 100 is a rectangular parallelepiped shape with a space formed therein.
  • the accommodating part 110 is disposed in the inner space of the body 100 , and a sample may be accommodated in the accommodating part 110 .
  • the sample may be obtained from a biological sample of the subject, for example, from a tissue extract, cell lysate, whole blood, plasma, serum, saliva, ocular fluid, cerebrospinal fluid, sweat, urine, milk, ascites fluid, synovial fluid, or peritoneal fluid. It may be a nucleic acid sample obtained, but is not limited thereto. In this case, the subject may be a mammal including a human.
  • the sample may include an analyte to be detected, an interfering material not to be detected, and a magnetic material binding to any one of the analyte or the interfering material, and the sample may include a probe material and a liquid.
  • the magnetic particles may bind to the analyte or to the interfering material, but for convenience of description, an embodiment in which the magnetic particles bind to the interfering material will be mainly described.
  • the analyte may be a reporter material for diagnosing a specific disease
  • the interfering material may be a material other than the analyte included in the sample.
  • the probe material may include a first probe and a second probe that specifically bind to a target gene (infectious disease-specific gene).
  • the first probe is for detection of a target gene
  • a reporter material may be bound to the first probe
  • the reporter material may be a fluorophore or a Raman active material. Since the fluorescent material or Raman active material shows a specific spectrum, a target material to be detected can be analyzed more effectively.
  • Fluorescent material or Raman active material capable of binding to the first probe is, for example, FAM (5'-Fluorescein phosphoramidite), TAMRA (5'-TAMRA phosphoramidite), VIC (2'-chloro-7''phenyl-1) ,4-dichloro-6-carboxy-fluorescein), Cy5(2-[5-[1,3-Dihydro-1-[3-(4-methoxytriphenylmethoxy)propyl]-3, 3-dimethyl-2H-indol-2) -ylidene]-1, 3-pentadien-1-yl]-1-[3-[N,N-diisopropylamino(2-cyanoethoxy)phosphinoxy]propyl]-3, 3-dimethyl-3H-indolium), JOE (6 -Carboxy-4', 5'-Dichloro-2', 7'-Dimethoxyfluorescein, Succinimidyl Ester),
  • the second probe is for separating substances other than the analyte, and the second probe may be a substance capable of specifically binding to a residue of a magnetic particle or a substance bound to the magnetic particle.
  • the magnetic particles may be, for example, magnetite (Magnetite; Fe 3 O 4 ), maghemite (Fe 2 O 3 ), or hematite (Hematite; Fe 2 O 3 ).
  • Magnetite may include r-Fe 2 O 3 in a core-shell structure, and r may be made of Si, ZnO, Fe, Co and Mg.
  • the present invention is not limited thereto, and any magnetic particles known in the art may be used as the magnetic particles.
  • the PCR amplification process may proceed.
  • the reporter material bound to the first probe in the PCR amplification product may be separated from the first probe by the restriction enzyme activated during the PCR amplification process.
  • the probe material (ie, the second probe) other than the first probe bound to the target gene is specifically bound to the magnetic particle, the magnetic particle may be bound to the interference material.
  • Separation device 10 for generating a magnetic field can be used to separate interfering substances.
  • the analyte (ie, the reporter material) from which the interfering material is separated may be detected by the analysis device 20 such as a Raman spectrometer.
  • the reporter material is not separated from the first probe, and thus the reporter material may remain bound to the probe material.
  • the second probe which is another material included in the probe material, is combined with the magnetic particles, the analyte (ie, the reporter material) may be separated by the separation device 10 together with the interfering material.
  • the analyte since the analyte is separated together by the separation device 10 in a state of being bound to the interference substance, the analyte may not be detected by the analysis device 20 .
  • the receiving part 110 may be disposed on the body 100 .
  • the accommodating part 110 is detachably connected to the body 100, and when the user needs to change the test target sample, the accommodating part 110 is separated from the body 100 and replaced with a new accommodating part 110.
  • the receiving unit 110 It is possible to prevent a decrease in analysis accuracy due to residues of existing experiments that may remain in the .
  • the receiving part 110 may be supported by the supporting part 101 of the body 100 .
  • the receiving part 110 may be fixed to the support part 101 after being inserted into the body 100 . Accordingly, it is possible to improve the stability of the analysis by preventing the receiving unit 110 from shaking due to vibration, shock, etc. that may occur in the process of performing analysis such as stirring and separation.
  • the accommodating part 110 may be made of a transparent material through which light can pass.
  • the receiving part 110 made of a transparent material may have a high transmittance. Thereby, the light emitted from the analysis device 20 can be incident into a target area in the separation device 10 . Details on this will be described later.
  • the first electromagnet unit 120 may generate a magnetic field by receiving a current from a current applying unit (not shown) disposed outside or inside the separation device 10 .
  • the first electromagnet unit 120 may be disposed on one side of the body 100 .
  • the first electromagnet part 120 may include a first base part 121 , a first electromagnet unit 122 , and a first protrusion part 123 .
  • the first base part 121 may be a part of one side surface of the body 100 on which the first electromagnet part 120 is disposed, and the first electromagnet unit 122 may be disposed on the first base part 121 . have.
  • the first electromagnet unit 122 may include an electromagnet having a plurality of coils C1 wound therein.
  • a current is applied to the first electromagnet unit 122 from a current applying unit (not shown)
  • the first electromagnet unit 122 may generate a magnetic field.
  • the direction and strength of the current applied to the first electromagnet unit 122 or the number and winding direction of the coil C1 can be adjusted. have.
  • the first protrusion 123 may be disposed between the first electromagnet unit 122 and the receiving part 110 inserted into the body 100 .
  • the first protrusion 123 may protrude from one end of the first electromagnet unit 122 toward the receiving unit 110 in a direction perpendicular to the radial direction of the first electromagnet unit 122 .
  • the first protrusion 123 may support the receiving unit 110 by contacting one side of the receiving unit 110 .
  • the first electromagnet unit 120 may apply a magnetic field generated by the first electromagnet unit 122 to the receiving unit 110 . Specifically, the first electromagnet unit 120 may apply a magnetic field to the sample (eg, magnetic particles) accommodated in the receiving unit 110 .
  • the second electromagnet unit 130 may generate a magnetic field by receiving a current from a current applying unit (not shown) disposed outside or inside the separation device 10 .
  • the second electromagnet unit 130 may be disposed on one side and the other side of the body 100 on which the first electromagnet unit 120 is disposed. In this case, the second electromagnet unit 130 may be disposed on the side of the body 100 on which the first electromagnet unit 120 is not disposed.
  • An embodiment that is disposed on the other side of the body 100 so as to face the first electromagnet unit 120 disposed on one side of the body 100 will be mainly described.
  • the second electromagnet unit 130 may include a second base unit 131 , a second electromagnet unit 132 , and a second protrusion 133 .
  • the second electromagnet unit 132 may include an electromagnet in which a plurality of coils C2 are wound.
  • the second electromagnet unit 132 may generate a magnetic field.
  • the direction and strength of the current applied to the second electromagnet unit 132 or the number and winding direction of the coil C2 can be adjusted. .
  • the second protrusion 133 may be disposed between the second electromagnet unit 132 and the receiving part 110 inserted into the body 100 .
  • the second protrusion 133 may protrude from one end of the second electromagnet unit 132 toward the receiving unit 110 in a direction perpendicular to the radial direction of the second electromagnet unit 132 .
  • the second protrusion 133 may be disposed to be symmetrical with the first protrusion 123 with the accommodating part 110 interposed therebetween to support the accommodating part 110 in both directions. Thereby, the stability of agitation and separation of the sample can be improved.
  • each component included in the second electromagnet unit 130 is the same as or similar to those of the first electromagnet unit 120 , and thus a redundant description thereof will be omitted.
  • the second electromagnet unit 130 may apply a magnetic field generated by the second electromagnet unit 132 to the receiving unit 110 . Specifically, the second electromagnet unit 130 may apply a magnetic field to the sample accommodated in the receiving unit 110 (eg, magnetic particles in the receiving unit 110).
  • At least one of the first electromagnet unit 120 and the second electromagnet unit 130 may apply a magnetic field to the magnetic particles accommodated in the receiving unit 110 . Accordingly, at least a portion of the analyte, the interfering material, and the magnetic particles may be stirred in the receiving unit 110 . In this case, the direction and strength of the magnetic field applied by the first electromagnet unit 120 and the magnetic field applied by the second electromagnet unit 130 may be different from each other. However, the present invention is not limited thereto, and the directions and strengths of the magnetic fields may be the same.
  • the direction of the magnetic field generated by the first electromagnet unit 120 and the second electromagnet unit 130 is the winding direction of the coils C1 and C2 wound on each electromagnet unit or the coils C1 and C2 as described above. It can be adjusted by changing the direction of the current applied to it.
  • Stirring by the magnetic field can be controlled by changing a predetermined condition.
  • the intensity of agitation may be adjusted by changing the intensity of the direct current applied to the first electromagnet unit 120 and the second electromagnet unit 130 and the number of turns of the coils C1 and C2.
  • the frequency of the alternating current applied to the first electromagnet unit 120 and the second electromagnet unit 130 and the duty cycle of the first electromagnet unit 120 and the second electromagnet unit 130 The cycle of agitation can be adjusted.
  • the stirring by the magnetic field may be adjusted to change over time.
  • the first electromagnet unit 120 and the second electromagnet unit 130 may apply a magnetic field to the magnetic particles at a preset period (T).
  • the preset period (T) is the first electromagnet unit 120 or the second electromagnet unit from a point in time when any one of the first electromagnet unit 120 or the second electromagnet unit 130 starts to apply a magnetic field to the magnetic particles.
  • Any one of 130 may mean a time before starting to apply a magnetic field to the magnetic particles again, and the preset period T includes a plurality of the first period T1, the second period T2, and the like. It can be repeated in cycles.
  • the first electromagnet unit 120 and the second electromagnet unit 130 may alternately apply a magnetic field to the magnetic particles.
  • any one of the first electromagnet unit 120 and the second electromagnet unit 130 may first apply a magnetic field to the magnetic particles for the first time t1 .
  • the other of the first electromagnet unit 120 and the second electromagnet unit 130 may apply a magnetic field to the magnetic particles for a second time t2.
  • the first electromagnet unit 120 applies a magnetic field to the magnetic particles for a first time t1, and then the second electromagnet unit 130 generates magnetic particles for a second time t2.
  • An embodiment in which a magnetic field is applied will be mainly described.
  • a first time t1 in which the first electromagnet unit 120 applies a magnetic field and a second time t2 in which the second electromagnet unit 130 applies a magnetic field may be continuous (refer to FIG. 4A ).
  • the magnetic particles by any of the first electromagnet unit 120 and the second electromagnet unit 130 may be an unattended application time (to) in which no magnetic field is applied (see FIG. 4B ).
  • the first time t1 and the second time t2 may be the same, but as another example, the first time t1 and the second time t2 may be different.
  • the unattended time to may be the same as or different from any one of the first time t1 and the second time t2.
  • the first electromagnet unit 120 and the second electromagnet unit 130 continuously alternate to apply a magnetic field to the magnetic particles so that there is no time when the magnetic field is not applied to the magnetic particles while the stirring is in progress. It can also be applied (see Fig. 4c).
  • any one of the first electromagnet unit 120 or the second electromagnet unit 130 continuously applies a magnetic field a plurality of times, one of the first electromagnet unit 120 or the second electromagnet unit 130 .
  • the other may apply a magnetic field (not shown).
  • the magnetic particles in the receiving unit 110 are generated by the magnetic field in the first electromagnet unit 120 ) and the movement toward the second electromagnet unit 130 may be repeated.
  • the movement of the magnetic particles stirs the liquid accommodated in the accommodating part to generate a flow of the liquid in the accommodating part 110 .
  • the analyte and the interfering material accommodated in the receiving unit 110 are uniformly mixed with the magnetic particles, so that the sample can be stirred in the receiving unit 110 .
  • the magnetic particles can be effectively bound to the interference substance (or the binding material bound to the interference substance), thereby increasing the amount of magnetic particles bound to the interference substance.
  • the first electromagnet unit 120 and the second electromagnet unit 130 may simultaneously apply a magnetic field to the magnetic particles at a preset period.
  • the first electromagnet unit 120 and the second electromagnet unit 130 may simultaneously apply a magnetic field to the magnetic particles for the same application time ts. For example, between the application time ts1 by the first electromagnet unit 120 and the second electromagnet unit 130 and the next application time ts2, there is an unattended time to in which a magnetic field is not applied to the magnetic particles. can be (see Figure 4d).
  • the magnetic particles before the stirring of the sample is started by the magnetic field, the magnetic particles may be in a state of sinking to the lower part of the inside of the receiving unit 110 . Thereafter, when a current is applied to the first electromagnet unit 120 and the second electromagnet unit 130 to apply a magnetic field to the magnetic particles, the magnetic particles are generated in the receiving unit 110 by the magnetic field in the first electromagnet unit 120 . By repeating the movement toward and movement toward the second electromagnet unit 130 , a flow may be formed in the liquid inside the receiving unit 110 . When the magnetic field is applied to the magnetic particles for a sufficient time and the application of the magnetic field is stopped after the stirring is progressed, the magnetic particles may be uniformly dispersed in the receiving unit 110 .
  • the first electromagnet unit 120 and the second electromagnet unit 130 may re-apply a magnetic field to the magnetic particles in the receiving unit 110 .
  • the first electromagnet unit 120 and the second electromagnet unit 130 continuously apply a magnetic field to the magnetic particles at the same time, whereby some of the magnetic particles are part of the first electromagnet unit in the receiving unit 110 by the magnetic field. It may move toward 120 and may be located on the periphery of the inner wall of the accommodating part 110 adjacent to the first electromagnet part 120 .
  • the other part of the magnetic particles moves toward the second electromagnet unit 130 within the receiving unit 110 by the magnetic field to be located in the inner wall periphery of the receiving unit 110 adjacent to the second electromagnet unit 130 .
  • the interference material to which the magnetic particles are bound and the analyte to which the magnetic particles are not bound may be separated into different regions (eg, the first region and the second region) inside the receiving unit 110 .
  • the first electromagnet unit 120 and the second electromagnet unit 130 simultaneously apply a magnetic field to the magnetic particles
  • the first electromagnet unit 120 and the second electromagnet unit 130 alternately generate a magnetic field.
  • a stronger force can be applied to the magnetic particles compared to the case of applying
  • the flow of the liquid in the accommodating part 110 is reduced.
  • the analyte and the interfering material in the accommodating unit 110 may be uniformly mixed with the magnetic particles. Accordingly, it is possible to facilitate the binding of the magnetic particles to the interference material.
  • the separation device 10 may further include at least one additional electromagnet (not shown).
  • the first electromagnet unit 120 , the second electromagnet unit 130 , and at least one additional electromagnet unit may be disposed on the body 100 , and the perimeter of the receiving unit 110 with the receiving unit 110 as the center Accordingly, they may be disposed to be spaced apart from each other.
  • the first electromagnet unit 120 , the second electromagnet unit 130 , and at least one additional electromagnet unit may generate a magnetic field, and may apply the generated magnetic field to the magnetic particles accommodated in the receiving unit 110 .
  • the first electromagnet unit 120 and the second electromagnet unit 130 are disposed to face each other with the receiving unit 110 as the center as described above, and in this case, the additional electromagnet unit The part may be disposed on a side opposite to one surface of the body 100 to which the analysis device 20 is coupled.
  • the method of applying the magnetic field to the magnetic particles by the first electromagnet unit 120 , the second electromagnet unit 130 , and at least one additional electromagnet unit is the same as the above-described first electromagnet unit 120 and the second electromagnet unit 130 . or similar, overlapping description thereof will be omitted.
  • a plurality of electromagnet units disposed to surround the accommodating unit 110 applies magnetic fields in various directions different from each other to the magnetic particles accommodated in the accommodating unit 110 . can do. Thereby, the effect of stirring and separation by the magnetic field can be improved.
  • At least one of the first electromagnet unit 120 and the second electromagnet unit 130 may apply a magnetic field to the sample to separate the analyte and the interfering material.
  • the first electromagnet unit 120 and the second electromagnet unit 130 may continuously apply a magnetic field to the magnetic particles in the receiving unit 110 after the sample is stirred by the magnetic field and the magnetic particles are coupled to the interference material. .
  • the continuous application of the magnetic field is performed with the first electromagnet unit 120 and the first electromagnet unit 120 from after the sample is stirred and the magnetic particles are bound to the interfering material until the separation of the analyte and the interfering material in the receiving unit 110 is completed.
  • This may mean that the second electromagnet unit 130 operates to generate a magnetic field, and a state of applying the magnetic field to the sample (particularly, magnetic particles) in the receiving unit 110 is maintained.
  • the first electromagnet unit 120 and the second electromagnet unit 130 may continuously apply a magnetic field to the magnetic particles at the same time. Only the interference material to which the magnetic particles are bound by the applied magnetic field may be moved in the receiving unit 110 . Specifically, a part of the interference material to which the magnetic particles are bonded is attracted toward the first electromagnet unit 120 , and another part of the interference material to which the magnetic particles are bonded is attracted toward the second electromagnet unit 130 , and magnetic particles Since the analyte to which is not bound is not affected by the magnetic field, positional movement by the magnetic field may not occur. Accordingly, the analyte and the interfering material may be separated in the receiving unit 110 .
  • the first region may be a region adjacent to at least one of the first electromagnet unit 120 and the second electromagnet unit 130
  • the second region may be a region spaced apart from the first region.
  • the first region may be an inner wall periphery of the accommodating part 110 adjacent to the first electromagnet part 120 and an inner wall periphery of the accommodating part 110 adjacent to the second electromagnet part 130 .
  • the second region may be a region between the peripheral portions of both inner walls of the accommodating part 110 , or may be an inlet 111 side region of the accommodating part 110 .
  • the interference of the interfering material in the detection step of the analyte is minimized and the accuracy of the analyte detection is improved.
  • the analysis process can be simplified and the time required for the analysis can be shortened.
  • either the first electromagnet unit 120 or the second electromagnet unit 130 is continuously applied to the magnetic particles in the receiving unit 110 to separate the analyte and the interference material to which the magnetic particles are combined. may do it
  • FIG. 7 is a flowchart illustrating a sequence of stirring and separating a sample according to an embodiment of the present invention.
  • a method for stirring and separating a sample according to an embodiment of the present invention may be as follows.
  • a user may prepare a sample including an analyte, an interfering material, and magnetic particles in the receiving unit (S100).
  • the sample may include a probe material (eg, a first probe and a second probe).
  • At least one of the first electromagnet unit 120 and the second electromagnet unit 130 may be operated to generate a magnetic field (S200).
  • a magnetic field S200
  • the first electromagnet unit 120 and the second electromagnet unit 130 may generate a magnetic field.
  • This magnetic field may be applied to the magnetic particles accommodated in the receiving unit (110).
  • a magnetic field may be used to stir the sample so that the magnetic particles bind to the interfering material (S300).
  • a current applying unit (not shown) alternately applies current to the first electromagnet unit 120 and the second electromagnet unit 130 , and accordingly, the first electromagnet unit 120 and the second electromagnet unit 130 . 130 may apply a magnetic field to the magnetic particles in the receiving unit 110 by alternating with each other.
  • the magnetic particles in the accommodating part 110 are generated by a magnetic field, thereby generating a flow of the liquid in the accommodating part 110, and the analytes, interfering substances and magnetic particles accommodated in the accommodating part 110 by this flow can be stirred. have. Accordingly, it may be easy for the magnetic particles to bind to the interference material.
  • the analyte and the interfering material may be separated in the receiving unit 110 by using a magnetic field (S400).
  • a magnetic field S400
  • the first electromagnet unit 120 and the second electromagnet unit 130 provide a magnetic field to the magnetic particles of the stirred sample. can be continuously approved. Accordingly, the interference material to which the magnetic particles are bound may move to a first region in the accommodating unit 110 , and the analyte to which the magnetic particles are not bound may move to a second region in the accommodating unit 110 . Accordingly, the analyte and the interfering material may be separated in the receiving unit 110 .
  • the probe materials eg, the first probe and the second probe
  • the probe materials that specifically bind to the analyte and the magnetic particle, respectively
  • the separation process and time can be shortened by directly separating the analyte and the interfering material in the accommodating unit 110 using the magnetic field generated by the symmetrically arranged electromagnets 120 and 130 .
  • FIG. 8 is a perspective view illustrating an analysis system according to an embodiment of the present invention.
  • FIG. 9 is a graph showing a surface-enhanced Raman scattering analysis signal of an analyte according to an embodiment of the present invention.
  • 10 is a flowchart illustrating an analysis procedure of a sample using the analysis system according to an embodiment of the present invention.
  • the analysis system 1 may include a separation device 10 and an analysis device 20 .
  • the separation device 10 may stir and separate the sample including the analyte, the interference material, and the magnetic particle as described above.
  • the separation device 10 may include the body 100 , the accommodating part 110 , the first electromagnet part 120 , and the second electromagnet part 130 .
  • an incident hole 102 for guiding the light emitted from the analysis device 20 to either the first region or the second region in the receiving unit 110 may be formed.
  • the incident hole 102 is the analysis device
  • the light emitted from the light source of (20) may be guided to the analyte located in the second region.
  • the accommodating unit 110 is made of a transparent material that allows light to pass therethrough, whereby the light emitted from the light source 21 may be irradiated with the analyte contained in the accommodating unit 110 .
  • the incident hole 102 may be disposed on one side of the body 100 of the separation device 10 .
  • one side of the body 100 may be one side of the body 100 facing the analysis device 20 .
  • the incident hole 102 is disposed on a straight line with the light source of the analysis device 20 , and light emitted from the light source may travel toward the analyte through the incident hole 102 .
  • the analysis device 20 may measure an optical signal to detect an analyte present in the sample.
  • the analysis apparatus 20 may include a light source unit 21 and an optical signal detection unit (not shown), and in this case, the light source unit 21 and the optical signal detection unit may be disposed in the analysis apparatus 20 .
  • the light emitted from the light source unit 21 may be irradiated to the sample accommodated in the receiving unit 110 of the separation device 10 .
  • the light may be irradiated to the analyte in the second region of the receiving unit 110 through the incident hole 102 of the separation device 10 .
  • the optical signal detector may measure an optical signal generated when the irradiated light is scattered by the sample.
  • the analysis device 20 may measure the optical signal by various methods such as fluorescence or Raman spectroscopy, infrared spectroscopy, etc., but hereinafter, the analysis device 20 detects an analyte using Raman spectroscopy will be mainly described. decide to do
  • Raman scattering refers to a phenomenon in which when light passes through a medium, the wavelength of light is changed, so that a part of the light deviates from the direction of travel and proceeds in a different direction.
  • Raman spectroscopy is useful for obtaining molecular level information by irradiating a short-wavelength laser to a sample and detecting scattered light, and Raman spectroscopy provides information on the vibrational state of molecules.
  • absorbed radiation is re-radiated at the same wavelength, where the energy difference between the re-radiated beams is a shift in wavelength between them, and the degree of this difference is It is measured as a unit of wavenumber (the reciprocal of wavelength) and expressed as a Raman shift (RS).
  • the analysis device 20 may detect an analyte by measuring a surface-enhanced Raman scattering (SERS) signal.
  • the Raman signal may be measured by separating an analyte (eg, a fluorescent material or a Raman active material) from the first probe accommodated in the receiving unit 110 .
  • the analyte can be detected by irradiating the light emitted from the light source unit 21 of the analysis device 20 to the analyte accommodated in the receiving unit 110 to obtain a Raman signal of a fluorescent material or a Raman active material.
  • a specific peak is observed from the measured Raman signal, it can be determined that the individual has a marker of an infectious disease, and accordingly, whether the individual is infected can be confirmed.
  • the analysis device 20 may specify and detect any one target gene desired to be detected.
  • the receiving unit 110 includes a first probe material (eg, a first probe and a second probe of the first probe material) specifically binding to a first target gene, a second target gene, A second probe material that specifically binds (eg, the first probe and the second probe of the second probe material) may be included.
  • the reporter material ie, the analyte
  • the interfering material is separated by the magnetic field.
  • the reporter material is not dropped from the first probe of the second probe material, and the reporter material of the second probe material is combined with the second probe material. It can be separated from the analyte by the magnetic particles and the magnetic field applied to the magnetic particles. Accordingly, it can be seen that the light signal by the reporter material of the second probe material gradually decreases (for example, refer to FIG. 9A ). According to this method, multiple diagnosis may be possible from a single light source according to the fluorescent material introduced into the first probe.
  • the analysis device 20 may be detachably connected to the separation device 10 .
  • the analysis device 20 when analyzing a sample stirred and separated by the separation device 10 , the analysis device 20 may be connected to the separation device 10 .
  • the analysis device 20 when the analysis of the sample is completed by the analysis device 20 , the analysis device 20 may be separated from the separation device 10 .
  • the present invention is not limited thereto, and the analysis device 20 may analyze the sample by irradiating light toward the sample in the separation device 10 while being spaced apart from the separation device 10 .
  • the analysis device 20 may further include a power switch 22 and a display unit 23 of the analysis device 20 .
  • the display unit 23 may further include displaying information on whether an analyte is present and a diagnosis result of a specific disease of the subject based on the sample analysis result. Based on the information displayed on the display unit 23, the user may check whether the object has a disease.
  • a method of analyzing a sample using the analysis system 1 may be as follows, and for convenience of explanation, the following will focus on an embodiment in which a target gene is present in a sample accommodated in the receiving unit 110 . to be explained as
  • a user may prepare a sample including an analyte, an interference material, and magnetic particles in the receiving unit 110 of the separation device 10 ( S10 ).
  • the sample may include a liquid and a probe material including the first probe and the second probe that specifically bind to the target gene.
  • An analyte may be bound to the first probe, and magnetic particles may be bound to the second probe.
  • the analyte and the interfering material included in the sample may be amplified ( S20 ).
  • the analyte and the interfering material may be amplified through the PCR amplification process as described above.
  • the present invention is not limited thereto, and the analyte and the interfering material may be amplified by an isothermal amplification method.
  • the temperature in the accommodating unit 110 is used to amplify the By maintaining a specific temperature, analytes and interfering substances can be amplified without the need for an additional heat supply.
  • an analyte and an interfering material may be separated using a magnetic field in the separation device 10 ( S30 ).
  • the specific method of stirring and separating the analyte and the interfering material in the receiving unit 110 is the same as described above, the separated interfering material is located in the first region in the receiving unit 110, and the separated analyte is It may be located in the second area in the receiving unit 110 .
  • the analysis device 20 may measure the optical signal to detect the analyte present in the receiving unit 110 ( S40 ).
  • the analysis device 20 connected to the separation device 10 may irradiate the light emitted from the light source unit 21 as an analyte through the incident hole 102 , and measure a light signal of the light scattered by the analyte.
  • the optical signal may be a surface-enhanced Raman scattering signal, and by observing a specific peak from the measured Raman signal, it is possible to determine whether an individual is infected with a disease.
  • the analysis system 1 and the analysis method according to the embodiments of the present invention separate the analyte and the interfering material in the receiving unit 110 using a magnetic field and then discharging the interfering material.
  • the analysis device 20 By detecting the analyte by the analysis device 20 without the above process, the amplification and separation of the analyte and the interfering material and the detection of the analyte may be continuously performed. Accordingly, it is possible to reduce the time required for analysis by unifying the analysis steps, and to increase the convenience of analysis.

Abstract

The present invention provides an analysis system. Specifically, the present invention provides an analysis system comprising: a separating apparatus which stirs and separates a sample including an analyte, an interfering substance, and magnetic particles which binds to the interfering substance; and an analysis apparatus which is connected to the separating apparatus and irradiates the sample with light to detect the analyte by using an optical signals emitted therefrom. The separating apparatus comprises: a body; a receiving part which is detachably disposed on the body and receives the sample; a first electromagnet part which is disposed on the body and generates a magnetic field; and a second electromagnet part which is disposed on the body to face the first electromagnet part with the receiving part in the center and generates a magnetic field in a different direction from that of the first electromagnet part, wherein at least one of the first electromagnet part and the second electromagnet part applies a magnetic field to the magnetic particles so that the analyte, the interfering substance, and at least some of the magnetic particles are stirred.

Description

분석 시스템 및 방법Analytical Systems and Methods
본 발명은 복합 시료에서 분석물질과 간섭물질을 분리하는 분리 장치 및 방법에 관한 것이고, 이를 이용하여 표적 유전자를 검출하고 특정 질병의 유무를 확인하는 분석 시스템 및 방법에 관한 것이다.The present invention relates to a separation apparatus and method for separating an analyte and an interfering material from a complex sample, and to an analysis system and method for detecting a target gene and confirming the presence or absence of a specific disease using the same.
핵산의 검출 방법은 탐침용 제1 프로브에 표적 핵산이 상보적으로 결합하고 이를 확인하게 하는 형광이 표지된 제2 프로브를 사용하는 표지화 탐지(labeled detection) 방식을 사용한다. 이와 같은 검출 방법은 극미량의 핵산 분석에 용이하지만, 탐침 프로브를 고정시킨 서로 다른 센서 칩을 사용해야 할 뿐만 아니라, PCR 증폭 방법과 같은 핵산 증폭 기술이 선행되어야 하므로 이 과정에서 교차 오염(carry-over contamination)이 발생할 수 있다. A method of detecting a nucleic acid uses a labeled detection method using a second probe labeled with fluorescence, which allows a target nucleic acid to complementarily bind to a first probe for a probe and confirm it. Although such a detection method is easy to analyze a trace amount of nucleic acid, it is necessary to use different sensor chips to which a probe is immobilized, and a nucleic acid amplification technique such as a PCR amplification method must be preceded. ) may occur.
PCR에서 형광 표지 프로브를 이용하는 방법(TaqMan 프로브 방법)은 Taq DNA 증합효소의 5’뉴클레아제 활성을 이용하여 특정 증폭 산물만을 검출하는 방법 중 하나이다. The method using a fluorescently labeled probe in PCR (TaqMan probe method) is one of the methods to detect only a specific amplification product using the 5' nuclease activity of Taq DNA polymerase.
루프매개 등온증폭법(Loop-mediated isothermal amplification, LAMP)는 단순하고 빠른 등온 PCR로, 기존 PCR 방법에 사용되는 Taq DNA 중합효소를 사용하는 대신, 핵산말단가수분해(exonuclease) 기능을 갖고 있는 Bst DNA 중합효소(Bst DNA polymerase)를 이용한 방법이다. 이러한 등온 PCR법은 유전자를 증폭하는 동안 온도의 변화를 필요로 하지 않기 때문에 전문장비 없이 손쉽게 고정된 온도에서 유전자 증폭을 가능하게 한다.Loop-mediated isothermal amplification (LAMP) is a simple and fast isothermal PCR. Instead of using Taq DNA polymerase used in existing PCR methods, Bst DNA with exonuclease function This is a method using a polymerase (Bst DNA polymerase). Since this isothermal PCR method does not require a change in temperature during gene amplification, it enables gene amplification at a fixed temperature easily without specialized equipment.
본 발명의 목적은 전자석을 이용하여 분석물질을 제외한 간섭물질을 분리할 수 있는 분리 장치를 제공하는 것이며, 또한 본 발명의 목적은 시료의 증폭, 분석물질의 분리 및 검출을 일체화할 수 있는 분석 시스템을 제공하는 것이다.An object of the present invention is to provide a separation device capable of separating interfering substances other than analytes by using an electromagnet, and it is also an object of the present invention to provide an analysis system capable of integrating sample amplification, analyte separation and detection is to provide
본 발명의 일 실시예에 따른 분석 시스템은, 분석물질, 간섭물질 및 상기 간섭물질에 결합되는 자성입자를 포함하는 시료를 교반 및 분리하는 분리 장치와, 상기 분리 장치에 연결되고, 상기 시료에 광을 조사하고, 출사되는 광 신호를 이용하여 상기 분석물질을 검출하는 분석 장치를 포함하고, 상기 분리 장치는, 바디와, 상기 바디에 분리가능하게 배치되고, 상기 시료를 수용하는 수용부와, 상기 바디에 배치되고, 자기장을 발생시키는 제1 전자석부와, 상기 바디에 상기 수용부를 중심으로 상기 제1 전자석부와 마주보도록 배치되고, 상기 제1 전자석부와 상이한 방향의 자기장을 발생시키는 제2 전자석부;를 포함하고, 상기 제1 전자석부와 상기 제2 전자석부 중 적어도 하나는 상기 자성입자에 자기장을 인가하여 상기 분석물질, 상기 간섭물질 및 상기 자성입자 중 적어도 일부를 교반시킬 수 있다.The analysis system according to an embodiment of the present invention includes a separation device for agitating and separating a sample including an analyte, an interference material, and magnetic particles bound to the interference material, and is connected to the separation device and provides light to the sample. and an analysis device for irradiating light and detecting the analyte using an emitted light signal, wherein the separation device includes a body, a receiving unit detachably disposed on the body, and a receiving unit for accommodating the sample; A first electromagnet part disposed on the body and generating a magnetic field, and a second electron disposed to face the first electromagnet part around the receiving part on the body, and generating a magnetic field in a different direction from that of the first electromagnet part and a magnet, wherein at least one of the first electromagnet unit and the second electromagnet unit applies a magnetic field to the magnetic particles to agitate at least a portion of the analyte, the interference material, and the magnetic particles.
본 발명의 일 실시예에 있어서, 상기 제1 전자석부와 상기 제2 전자석부는 기 설정된 주기로 교번하여 상기 자성입자에 자기장을 인가할 수 있다.In an embodiment of the present invention, the first electromagnet unit and the second electromagnet unit may alternately apply a magnetic field to the magnetic particles at a preset period.
본 발명의 일 실시예에 있어서, 상기 제1 전자석부와 상기 제2 전자석부는 기 설정된 주기로 동시에 상기 자성입자에 자기장을 인가할 수 있다.In an embodiment of the present invention, the first electromagnet unit and the second electromagnet unit may simultaneously apply a magnetic field to the magnetic particles at a preset period.
본 발명의 일 실시예에 있어서, 상기 제1 전자석부와 상기 제2 전자석부 중 적어도 하나는 상기 자성입자에 자기장을 계속적으로 인가하여 상기 분석물질과 상기 간섭물질을 분리시킬 수 있다.In an embodiment of the present invention, at least one of the first electromagnet unit and the second electromagnet unit may separate the analyte and the interference material by continuously applying a magnetic field to the magnetic particles.
본 발명의 일 실시예에 있어서, 분리된 상기 간섭물질은 상기 수용부 내의 제1 영역에 위치하고, 분리된 상기 분석물질은 상기 수용부 내의 상기 제1 영역과 다른 제2 영역에 위치하고, 상기 제1 영역은 상기 제1 전자석부와 상기 제2 전자석부 중 적어도 하나와 인접한 영역이고, 상기 제2 영역은 상기 제1 영역과 이격된 영역일 수 있다.In an embodiment of the present invention, the separated interfering material is located in a first region in the accommodating part, and the separated analyte is located in a second region different from the first region in the accommodating part, and the first The region may be a region adjacent to at least one of the first electromagnet unit and the second electromagnet unit, and the second region may be a region spaced apart from the first region.
본 발명의 일 실시예에 있어서, 상기 분리 장치의 상기 바디에는 상기 광을 상기 제2 영역으로 안내하기 위한 입사홀이 형성될 수 있다.In an embodiment of the present invention, an incident hole for guiding the light to the second region may be formed in the body of the separation device.
본 발명의 일 실시예에 있어서, 상기 광 신호는 표면-증강 라만 산란(surface-enhanced Raman scattering, SERS) 신호일 수 있다.In an embodiment of the present invention, the optical signal may be a surface-enhanced Raman scattering (SERS) signal.
본 발명의 일 실시예에 있어서, 상기 수용부는 투명 재질로 이루어질 수 있다.In one embodiment of the present invention, the receiving part may be made of a transparent material.
본 발명의 일 실시예에 있어서, 상기 바디에 배치되고, 상기 제1 전자석부 및 상기 제2 전자석부와 상이한 방향으로 자기장을 발생시키는 적어도 하나의 추가 전자석부;를 더 포함하고, 상기 추가 전자석부는 복수개 구비되며, 복수개의 상기 추가 전자석부는 상기 제1 전자석부 및 상기 제2 전자석부와 이격되어 배치될 수 있다.In one embodiment of the present invention, it is disposed on the body, and at least one additional electromagnet unit for generating a magnetic field in a different direction from the first electromagnet unit and the second electromagnet unit; further comprising, the additional electromagnet unit A plurality of the additional electromagnet parts may be provided, and the plurality of additional electromagnet parts may be disposed to be spaced apart from the first electromagnet part and the second electromagnet part.
본 발명의 일 실시예에 따른 분석 방법은, 수용부 내에 분석물질, 간섭물질 및 자성입자를 포함하는 시료를 마련하는 단계와, 상기 분석물질과 상기 간섭물질을 증폭시키는 단계와, 상기 분석물질과 상기 간섭물질을 분리하는 단계와, 상기 시료에 광을 조사하고, 출사되는 광 신호를 이용하여 상기 분석물질을 검출하는 단계를 포함하고, 상기 분석물질과 상기 간섭물질을 분리하는 단계는, 상기 수용부를 중심으로 마주보도록 배치되는 제1 전자석부와 제2 전자석부 중 적어도 하나를 작동시켜 자기장을 발생시키는 단계와, 상기 자기장을 이용하여 상기 수용부에 수용된 분석물질, 간섭물질 중 어느 하나에 자성입자가 결합하도록, 상기 시료를 교반하는 단계와, 상기 자기장을 이용하여 상기 수용부 내에서 상기 분석물질과 상기 간섭물질을 분리하는 단계를 포함할 수 있다.The analysis method according to an embodiment of the present invention comprises the steps of: preparing a sample containing an analyte, an interfering material, and magnetic particles in a receiving unit; amplifying the analyte and the interfering material; Separating the interfering material, irradiating light to the sample, and detecting the analyte using an emitted light signal, wherein separating the analyte and the interfering material includes the receiving generating a magnetic field by operating at least one of the first electromagnet unit and the second electromagnet unit disposed to face each other around the unit; It may include agitating the sample so that it binds, and separating the analyte and the interfering material in the receiving unit using the magnetic field.
본 발명의 일 실시예에 있어서, 상기 자기장을 이용하여 수용부에 수용된 분석물질 또는 간섭물질 중 어느 하나에 및 자성입자가 결합하도록, 상기 시료를 교반하는 단계는, 제1 전자석부와 제2 전자석부가 기 설정된 주기로 교번하여 상기 자성입자에 자기장을 인가하는 단계를 포함할 수 있다.In one embodiment of the present invention, the step of agitating the sample so that the magnetic particles bind to any one of the analyte or the interference material accommodated in the receiver using the magnetic field, the first electromagnet and the second electromagnet The addition may include applying a magnetic field to the magnetic particles alternately at a preset period.
본 발명의 일 실시예에 있어서, 상기 자기장을 이용하여 수용부에 수용된 분석물질 또는 간섭물질 중 어느 하나에 자성입자가 결합하도록, 상기 시료를 교반하는 단계는, 상기 제1 전자석부와 상기 제2 전자석부가 기 설정된 주기로 동시에 상기 자성입자에 자기장을 인가할 수 있다.In one embodiment of the present invention, the step of stirring the sample so that the magnetic particles bind to any one of the analyte or the interfering material accommodated in the receiving unit using the magnetic field comprises: the first electromagnet unit and the second The electromagnet unit may simultaneously apply a magnetic field to the magnetic particles at a preset period.
본 발명의 일 실시예에 있어서, 상기 자기장을 이용하여 상기 수용부 내에서 상기 분석물질과 상기 간섭물질을 분리하는 단계는, 상기 제1 전자석부와 상기 제2 전자석부 중 적어도 하나가 상기 자성입자에 자기장을 계속적으로 인가하여 상기 분석물질과 상기 간섭물질을 분리할 수 있다.In one embodiment of the present invention, in the step of separating the analyte and the interference material in the receiving unit using the magnetic field, at least one of the first electromagnet unit and the second electromagnet unit is the magnetic particle By continuously applying a magnetic field to the analyte and the interference material can be separated.
본 발명의 일 실시예에 있어서, 분리된 상기 간섭물질은 상기 수용부 내의 제1 영역에 위치하고, 분리된 상기 분석물질은 상기 수용부 내의 제2 영역에 위치하고, 상기 제1 영역은 상기 제1 전자석부와 상기 제2 전자석부 중 적어도 하나와 인접한 영역이고, 상기 제2 영역은 상기 제1 영역과 이격된 영역일 수 있다.In an embodiment of the present invention, the separated interference material is located in a first region in the accommodating part, the separated analyte is located in a second region in the accommodating part, and the first region is the first electron The region may be adjacent to at least one of the magnet and the second electromagnet, and the second region may be a region spaced apart from the first region.
본 발명의 일 실시예에 있어서, 상기 광 신호를 이용하여 상기 분석물질을 검출하는 단계는, 상기 분리 장치의 상기 바디에 형성된 입사홀을 통해 상기 광이 상기 제2 영역으로 안내될 수 있다.In an embodiment of the present invention, in the detecting of the analyte using the optical signal, the light may be guided to the second region through an incident hole formed in the body of the separation device.
본 발명의 일 실시예에 있어서, 상기 광 신호는 표면-증강 라만 산란 신호일 수 있다.In an embodiment of the present invention, the optical signal may be a surface-enhanced Raman scattering signal.
본 발명의 일 실시예에 있어서, 상기 수용부는 투명 재질로 이루어질 수 있다.In one embodiment of the present invention, the receiving part may be made of a transparent material.
본 발명의 일 실시예에 있어서, 상기 바디에 배치되고, 상기 제1 전자석부 및 상기 제2 전자석부와 상이한 방향으로 자기장을 발생시키는 적어도 하나의 추가 전자석부;를 더 포함하고, 상기 추가 전자석부는 복수개 구비되며, 복수개의 상기 추가 전자석부는 상기 제1 전자석부 및 상기 제2 전자석부와 이격되어 배치될 수 있다.In one embodiment of the present invention, it is disposed on the body, and at least one additional electromagnet unit for generating a magnetic field in a different direction from the first electromagnet unit and the second electromagnet unit; further comprising, the additional electromagnet unit A plurality of the additional electromagnet parts may be provided, and the plurality of additional electromagnet parts may be disposed to be spaced apart from the first electromagnet part and the second electromagnet part.
본 발명의 실시예들에 따른 분리 장치 및 분리 방법은 분석물질과 간섭물질에 각각 특이적으로 결합하는 탐침물질들을 이용하여 간섭물질에 자성입자를 결합시키고, 대칭으로 배치된 전자석부들에 의해 자성입자에 자기장을 인가하여 수용부 내의 시료를 교반 시킴으로써 자성입자와 프로브의 결합을 용이하게 할 수 있다. 또한, 대칭으로 배치된 전자석부들에서 발생된 자기장을 이용하여 수용부 내에서 바로 분석물질과 간섭물질을 분리함으로써, 분리 과정 및 시간을 단축시킬 수 있다.The separation apparatus and separation method according to the embodiments of the present invention bind magnetic particles to an interference material using probe materials that specifically bind to an analyte and an interference material, respectively, and magnetic particles by means of symmetrically arranged electromagnets. By applying a magnetic field to the accommodating part to agitate the sample, it is possible to facilitate the binding of the magnetic particles and the probe. In addition, the separation process and time can be shortened by separating the analyte and the interfering material directly in the accommodating part using the magnetic field generated by the symmetrically arranged electromagnets.
또한, 본 발명의 실시예들에 따른, 분석 시스템 및 분석 방법은, 자기장을 이용하여 수용부 내에서 분석물질과 간섭물질을 분리한 후 간섭물질을 배출하는 별도의 과정 없이 분석 장치에 의해 분석물질을 검출함으로써, 분석물질 및 간섭물질의 증폭과 분리 및 분석물질의 검출을 연속하여 진행할 수 있다. 이에 의해 분석 단계를 일체화하여 분석에 소요되는 시간을 단축시키고, 분석의 편의성을 증대시킬 수 있다.In addition, in the analysis system and analysis method according to the embodiments of the present invention, the analyte is separated from the interfering material in the receiving unit using a magnetic field, and then the analyte is performed by the analysis device without a separate process of discharging the interfering material. By detecting , amplification and separation of analytes and interfering substances and detection of analytes can be continuously performed. Accordingly, it is possible to reduce the time required for analysis by unifying the analysis steps, and to increase the convenience of analysis.
도 1은 본 발명의 일 실시예에 따른 분리 장시를 도시한 사시도이다.1 is a perspective view showing a separation device according to an embodiment of the present invention.
도 2는 도 2의 분리 장치를 도시한 분해도이다.Figure 2 is an exploded view showing the separation device of Figure 2;
도 3은 도 1의 분리 장치를 간략히 도시한 단면도이다.FIG. 3 is a schematic cross-sectional view of the separation device of FIG. 1 .
도 4는 자성입자에 인가되는 자기장의 세기 및 주기를 나타내는 그래프이다.4 is a graph showing the intensity and period of a magnetic field applied to magnetic particles.
도 5는 도 1의 분리 장치를 이용한 교반 과정을 도시한다. FIG. 5 shows a stirring process using the separation device of FIG. 1 .
도 6은 도 1의 분리 장치를 이용한 분리 과정을 도시한다.6 illustrates a separation process using the separation device of FIG. 1 .
도 7은 본 발명의 일 실시예에 따른 시료의 교반 및 분리 순서를 도시한 흐름도이다.7 is a flowchart illustrating a sequence of stirring and separating a sample according to an embodiment of the present invention.
도 8은 본 발명의 일 실시예에 따른 분석 시스템을 도시한 사시도이다.8 is a perspective view illustrating an analysis system according to an embodiment of the present invention.
도 9는 본 발명의 일 실시예에 따른 분석물질의 표면-증강 라만 산란 분석 신호를 나타낸 그래프이다.9 is a graph showing a surface-enhanced Raman scattering analysis signal of an analyte according to an embodiment of the present invention.
도 10은 본 발명의 일 실시예에 따른 분석 시스템을 이용한 시료의 분석 순서를 나타내는 흐름도이다.10 is a flowchart illustrating an analysis procedure of a sample using the analysis system according to an embodiment of the present invention.
본 발명은 다양한 변환을 가할 수 있고 여러 가지 실시예를 가질 수 있는 바, 특정 실시예들을 도면에 예시하고 상세한 설명에 상세하게 설명하고자 한다. 그러나, 이는 본 발명을 특정한 실시 형태에 대해 한정하려는 것이 아니며, 본 발명의 사상 및 기술 범위에 포함되는 모든 변환, 균등물 내지 대체물을 포함하는 것으로 이해되어야 한다. 본 발명을 설명함에 있어서 관련된 공지 기술에 대한 구체적인 설명이 본 발명의 요지를 흐릴 수 있다고 판단되는 경우 그 상세한 설명을 생략한다. Since the present invention can apply various transformations and can have various embodiments, specific embodiments are illustrated in the drawings and described in detail in the detailed description. However, this is not intended to limit the present invention to specific embodiments, and it should be understood to include all modifications, equivalents and substitutes included in the spirit and scope of the present invention. In describing the present invention, if it is determined that a detailed description of a related known technology may obscure the gist of the present invention, the detailed description thereof will be omitted.
제1, 제2 등의 용어는 다양한 구성요소들을 설명하는데 사용될 수 있지만, 구성요소들은 용어들에 의해 한정되어서는 안 된다. 용어들은 하나의 구성요소를 다른 구성요소로부터 구별하는 목적으로만 사용된다.Terms such as first, second, etc. may be used to describe various elements, but the elements should not be limited by the terms. The terms are used only for the purpose of distinguishing one component from another.
본 출원에서 사용한 용어는 단지 특정한 실시예를 설명하기 위해 사용된 것으로, 본 발명을 한정하려는 의도가 아니다. 단수의 표현은 문맥상 명백하게 다르게 뜻하지 않는 한, 복수의 표현을 포함한다. 또한 각 도면에서, 구성요소는 설명의 편의 및 명확성을 위하여 과장되거나 생략되거나 또는 개략적으로 도시되었으며, 각 구성요소의 크기는 실제크기를 전적으로 반영하는 것은 아니다.The terms used in the present application are only used to describe specific embodiments, and are not intended to limit the present invention. The singular expression includes the plural expression unless the context clearly dictates otherwise. In addition, in each drawing, components are exaggerated, omitted, or schematically illustrated for convenience and clarity of description, and the size of each component does not fully reflect the actual size.
각 구성요소의 설명에 있어서, 상(on)에 또는 하(under)에 형성되는 것으로 기재되는 경우에 있어, 상(on)과 하(under)는 직접 또는 다른 구성요소를 개재하여 형성되는 것을 모두 포함하며, 상(on) 및 하(under)에 대한 기준은 도면을 기준으로 설명한다.In the description of each component, in the case where it is described as being formed on or under, both on and under are formed directly or through other components. Including, the standards for the upper (on) and the lower (under) will be described with reference to the drawings.
이하, 본 발명의 실시 예를 첨부도면을 참조하여 상세히 설명하기로 하며, 첨부 도면을 참조하여 설명함에 있어, 동일하거나 대응하는 구성 요소는 동일한 도면번호를 부여하고 이에 대한 중복되는 설명은 생략하기로 한다.Hereinafter, embodiments of the present invention will be described in detail with reference to the accompanying drawings, and in the description with reference to the accompanying drawings, the same or corresponding components are given the same reference numerals, and the overlapping description thereof will be omitted. do.
도 1은 본 발명의 일 실시예에 따른 분리 장시를 도시한 사시도이다. 도 2는 도 2의 분리 장치를 도시한 분해도이고, 도 3은 도 1의 분리 장치를 간략히 도시한 단면도이다. 도 4는 자성입자에 인가되는 자기장의 세기 및 주기를 나타내는 그래프이다. 도 5는 도 1의 분리 장치를 이용한 교반 과정을 도시하고, 도 6은 도 1의 분리 장치를 이용한 분리 과정을 도시한다.1 is a perspective view showing a separation device according to an embodiment of the present invention. FIG. 2 is an exploded view illustrating the separation device of FIG. 2 , and FIG. 3 is a cross-sectional view schematically illustrating the separation device of FIG. 1 . 4 is a graph showing the intensity and period of a magnetic field applied to magnetic particles. FIG. 5 shows a stirring process using the separation device of FIG. 1 , and FIG. 6 shows a separation process using the separation device of FIG. 1 .
도 1 내지 도 4를 참조하면, 분리 장치(10)는 바디(100)와, 수용부(110)와, 제1 전자석부(120)와, 제2 전자석부(130)를 포함할 수 있다.1 to 4 , the separation device 10 may include a body 100 , an accommodating part 110 , a first electromagnet part 120 , and a second electromagnet part 130 .
바디(100)는 내부에 수용부(110)를 수용하기 위한 공간이 배치될 수 있다. 바디(100)는 반구, 원기둥, 다각면체 등 다양한 형상을 가질 수 있으나, 설명의 편의를 위해, 이하에서는 바디(100)가 내부에 공간이 형성된 직육면체 형상인 실시예를 중심으로 설명하기로 한다.The body 100 may have a space for accommodating the accommodating part 110 therein. The body 100 may have various shapes such as a hemisphere, a cylinder, a polygon, etc., but for convenience of explanation, hereinafter, the body 100 will be described mainly in an embodiment in which the body 100 is a rectangular parallelepiped shape with a space formed therein.
수용부(110)는 바디(100)의 내부 공간에 배치되고, 수용부(110)에는 시료가 수용될 수 있다. 여기서 시료는 개체의 생물학적 시료로부터 수득될 수 있으며, 예를 들어 조직 추출물, 세포 용해물, 전혈, 혈장, 혈청, 침, 안구액, 뇌척수액, 땀, 뇨, 젖, 복수액, 활액 또는 복막액에서 확보된 핵산 시료일 수 있으나 이에 제한되는 것은 아니다. 이때 개체는 인간을 포함한 포유동물일 수 있다. The accommodating part 110 is disposed in the inner space of the body 100 , and a sample may be accommodated in the accommodating part 110 . wherein the sample may be obtained from a biological sample of the subject, for example, from a tissue extract, cell lysate, whole blood, plasma, serum, saliva, ocular fluid, cerebrospinal fluid, sweat, urine, milk, ascites fluid, synovial fluid, or peritoneal fluid. It may be a nucleic acid sample obtained, but is not limited thereto. In this case, the subject may be a mammal including a human.
시료는 검출 대상이 되는 분석물질과, 검출 대상이 아닌 간섭물질과, 분석물질 또는 간섭물질 중 어느 하나에 결합하는 자성물질을 포함할 수 있으며, 또한 시료는 탐침물질과 액체를 포함할 수 있다. 이러한 경우, 자성입자는 분석물질에 결합하거나, 또는 간섭물질에 결합할 수 있으나, 설명의 편의를 위해 자성입자가 간섭물질에 결합하는 실시예를 중심으로 설명하기로 한다. The sample may include an analyte to be detected, an interfering material not to be detected, and a magnetic material binding to any one of the analyte or the interfering material, and the sample may include a probe material and a liquid. In this case, the magnetic particles may bind to the analyte or to the interfering material, but for convenience of description, an embodiment in which the magnetic particles bind to the interfering material will be mainly described.
분석물질은 특정 질환을 진단하기 위한 리포터 물질일 수 있고, 간섭물질은 시료에 포함된 분석물질을 제외한 물질일 수 있다. 또한, 탐침물질은 표적 유전자(감염 질환 특이 유전자)에 특이적으로 결합하는 제1 프로브와, 제2 프로브를 포함할 수 있다. 이때, 제1 프로브는 표적 유전자의 검출을 위한 것으로, 제1 프로브에는 리포터 물질이 결합될 수 있으며, 리포터 물질은 형광물질(fluorophore) 또는 라만 활성 물질일 수 있다. 이러한 형광물질 또는 라만 활성 물질은 특정 스펙트럼을 보여주기 때문에 검출하고자 하는 표적 물질을 보다 효과적으로 분석할 수 있다. The analyte may be a reporter material for diagnosing a specific disease, and the interfering material may be a material other than the analyte included in the sample. In addition, the probe material may include a first probe and a second probe that specifically bind to a target gene (infectious disease-specific gene). In this case, the first probe is for detection of a target gene, and a reporter material may be bound to the first probe, and the reporter material may be a fluorophore or a Raman active material. Since the fluorescent material or Raman active material shows a specific spectrum, a target material to be detected can be analyzed more effectively.
제1 프로브에 결합될 수 있는 형광물질 또는 라만 활성 물질은 예를 들어, FAM(5'-Fluorescein phosphoramidite), TAMRA(5'-TAMRA phosphoramidite), VIC(2’-chloro-7’'phenyl-1,4-dichloro-6-carboxy-fluorescein), Cy5(2-[5-[1,3-Dihydro-1-[3-(4-methoxytriphenylmethoxy)propyl]-3, 3-dimethyl-2H-indol-2-ylidene]-1, 3-pentadien-1-yl]-1-[3-[N,N-diisopropylamino(2-cyanoethoxy)phosphinoxy]propyl]-3, 3-dimethyl-3H-indolium), JOE(6-Carboxy-4', 5'-Dichloro-2', 7'-Dimethoxyfluorescein, Succinimidyl Ester), HEX([6 - carboxy - 2', 4, 4', 5', 7, 7' -hexachlorofluorescein]), ROX(Rhodamine X, Rhodamine 101), 4-MBA(4-mercaptobenzoic acid), MMC(2, 7-mercapto-4-methylcoumarin), MMTAA(2-mercapto-4-methyl-5-thiazoleacetic acid), TFMBA(2, 3, 5, 6-Tetrafluoro-4-mercaptobenzoic acid), 및 MGITC(malachite Green Isothiocyantate) 및 이들의 조합으로 이루어진 군으로부터 선택된 것을 포함할 수 있으나, 이에 한정하는 것은 아니다.Fluorescent material or Raman active material capable of binding to the first probe is, for example, FAM (5'-Fluorescein phosphoramidite), TAMRA (5'-TAMRA phosphoramidite), VIC (2'-chloro-7''phenyl-1) ,4-dichloro-6-carboxy-fluorescein), Cy5(2-[5-[1,3-Dihydro-1-[3-(4-methoxytriphenylmethoxy)propyl]-3, 3-dimethyl-2H-indol-2) -ylidene]-1, 3-pentadien-1-yl]-1-[3-[N,N-diisopropylamino(2-cyanoethoxy)phosphinoxy]propyl]-3, 3-dimethyl-3H-indolium), JOE (6 -Carboxy-4', 5'-Dichloro-2', 7'-Dimethoxyfluorescein, Succinimidyl Ester), HEX([6 - carboxy - 2', 4, 4', 5', 7, 7' -hexachlorofluorescein]), ROX (Rhodamine X, Rhodamine 101), 4-MBA (4-mercaptobenzoic acid), MMC (2, 7-mercapto-4-methylcoumarin), MMTAA (2-mercapto-4-methyl-5-thiazoleacetic acid), TFMBA ( 2, 3, 5, 6-Tetrafluoro-4-mercaptobenzoic acid), and malachite green isothiocyantate (MGITC), and combinations thereof may include, but are not limited to.
제2 프로브는 분석물질 이외의 물질을 분리하기 위한 것으로, 제2 프로브는 자성입자의 잔기(residue) 또는 자성입자에 결합된 물질에 특이적으로 결합 할 수 있는 물질일 수 있다. 이때 자성입자는 예를 들어, 마그네타이트(Magnetite; Fe3O4), 마그헤마이트(Maghemite; Fe2O3) 또는 헤마타이트(Hematite; Fe2O3) 등 일 수 있다. 마그네타이트는 코어-쉘(core-shell) 구조로 r-Fe2O3도 포함될 수 있고 r은 Si, ZnO, Fe, Co 및 Mg 등으로 이루어질 수 있다. 다만, 본 발명은 이에 한정되는 것은 아니며, 자성입자는 당업계에서 알려진 어떠한 자성입자도 이용될 수 있다.The second probe is for separating substances other than the analyte, and the second probe may be a substance capable of specifically binding to a residue of a magnetic particle or a substance bound to the magnetic particle. In this case, the magnetic particles may be, for example, magnetite (Magnetite; Fe 3 O 4 ), maghemite (Fe 2 O 3 ), or hematite (Hematite; Fe 2 O 3 ). Magnetite may include r-Fe 2 O 3 in a core-shell structure, and r may be made of Si, ZnO, Fe, Co and Mg. However, the present invention is not limited thereto, and any magnetic particles known in the art may be used as the magnetic particles.
시료에 표적 유전자가 존재하면 PCR 증폭 과정이 진행될 수 있다. 이러한 경우, PCR 증폭산물 중 제1 프로브에 결합된 리포터 물질은 PCR 증폭 과정에서 활성화된 제한 효소에 의해 제1 프로브로부터 분리될 수 있다. 또한 표적 유전자에 결합된 제1 프로브를 제외한 탐침 물질(즉, 제2 프로브)이 자성입자와 특이적으로 결합됨으로써, 간섭물질에 자성입자가 결합될 수 있다.자기장을 발생시키는 분리 장치(10)를 이용하여 간섭물질을 분리할 수 있다. 이러한 경우 간섭물질이 분리된 분석물질(즉, 리포터 물질)은 라만 분광기 등의 분석 장치(20)에 의해 검출될 수 있다.If the target gene is present in the sample, the PCR amplification process may proceed. In this case, the reporter material bound to the first probe in the PCR amplification product may be separated from the first probe by the restriction enzyme activated during the PCR amplification process. In addition, since the probe material (ie, the second probe) other than the first probe bound to the target gene is specifically bound to the magnetic particle, the magnetic particle may be bound to the interference material. Separation device 10 for generating a magnetic field can be used to separate interfering substances. In this case, the analyte (ie, the reporter material) from which the interfering material is separated may be detected by the analysis device 20 such as a Raman spectrometer.
시료에 표적 유전자가 존재하지 않으면, 리포터 물질은 제1 프로브로부터 분리되지 않고, 이에 따라 리포터 물질은 탐침물질에 결합된 상태로 유지될 수 있다. 이때 탐침물질에 포함되어 있는 또 다른 물질인 제2 프로브와 자성입자가 결합됨으로써, 분석물질(즉, 리포터 물질)은 간섭물질과 함께 분리 장치(10)에 의해 분리될 수 있다. 이러한 경우 분석물질은 간섭물질에 결합된 상태로 분리 장치(10)에 의해 함께 분리되므로, 분석 장치(20)에 의해 분석물질이 검출되지 않을 수 있다.If the target gene is not present in the sample, the reporter material is not separated from the first probe, and thus the reporter material may remain bound to the probe material. At this time, since the second probe, which is another material included in the probe material, is combined with the magnetic particles, the analyte (ie, the reporter material) may be separated by the separation device 10 together with the interfering material. In this case, since the analyte is separated together by the separation device 10 in a state of being bound to the interference substance, the analyte may not be detected by the analysis device 20 .
수용부(110)는 바디(100)에 배치될 수 있다. 이때 수용부(110)는 바디(100)에 분리 가능하도록 연결되고, 사용자는 검사 대상 시료의 변경이 필요한 경우 수용부(110)를 바디(100)로부터 분리하여 새로운 수용부(110)로 교체할 수 있다. 이에 의해, 새로운 시료의 분석을 진행할 때마다 수용부(110)를 세척해야 하는 불편함을 줄일 수 있으며, 매번 실험마다 새로운 수용부(110)로 교체하여 검사를 진행할 수 있기에, 수용부(110)에 남아있을 수 있는 기존 실험의 잔여물에 의한 분석 정확도가 하락하는 것을 방지할 수 있다.The receiving part 110 may be disposed on the body 100 . At this time, the accommodating part 110 is detachably connected to the body 100, and when the user needs to change the test target sample, the accommodating part 110 is separated from the body 100 and replaced with a new accommodating part 110. can Accordingly, it is possible to reduce the inconvenience of having to wash the receiving unit 110 every time a new sample is analyzed, and since the examination can be performed by replacing the receiving unit 110 with a new receiving unit 110 for every experiment, the receiving unit 110 It is possible to prevent a decrease in analysis accuracy due to residues of existing experiments that may remain in the .
수용부(110)는 바디(100)의 지지부(101)에 의해 지지될 수 있다. 일 실시예로서, 수용부(110)는 바디(100)의 내부에 삽입된 후 지지부(101)에 고정될 수 있다. 이에 의해, 교반 및 분리 등의 분석을 진행하는 과정에서 발생할 수 있는 진동, 충격 등에 의해 수용부(110)가 흔들리는 것을 방지하여 분석의 안정성을 향상시킬 수 있다.The receiving part 110 may be supported by the supporting part 101 of the body 100 . As an embodiment, the receiving part 110 may be fixed to the support part 101 after being inserted into the body 100 . Accordingly, it is possible to improve the stability of the analysis by preventing the receiving unit 110 from shaking due to vibration, shock, etc. that may occur in the process of performing analysis such as stirring and separation.
수용부(110)는 빛이 투과할 수 있는 투명한 재질로 이루어질 수 있다. 이때, 투명한 재질의 수용부(110)는 높은 투과율을 가질 수 있다. 이에 의해, 분석 장치(20)에서 방출된 광이 분리 장치(10)내의 목표 영역 내로 입사될 수 있다. 이에 대한 자세한 내용은 후술하기로 한다.The accommodating part 110 may be made of a transparent material through which light can pass. In this case, the receiving part 110 made of a transparent material may have a high transmittance. Thereby, the light emitted from the analysis device 20 can be incident into a target area in the separation device 10 . Details on this will be described later.
제1 전자석부(120)는 분리 장치(10)의 외부 또는 내부에 배치된 전류 인가부(미도시)로부터 전류를 인가받아 자기장을 발생시킬 수 있다. 제1 전자석부(120)는 바디(100)의 일 측면에 배치될 수 있다.The first electromagnet unit 120 may generate a magnetic field by receiving a current from a current applying unit (not shown) disposed outside or inside the separation device 10 . The first electromagnet unit 120 may be disposed on one side of the body 100 .
제1 전자석부(120)는 제1 베이스부(121)과, 제1 전자석 유닛(122)과, 제1 돌출부(123)를 포함할 수 있다. 이때 제1 베이스부(121)는 제1 전자석부(120)가 배치되는 바디(100)의 일 측면의 일부일 수 있으며, 제1 베이스부(121)에는 제1 전자석 유닛(122)이 배치될 수 있다.The first electromagnet part 120 may include a first base part 121 , a first electromagnet unit 122 , and a first protrusion part 123 . In this case, the first base part 121 may be a part of one side surface of the body 100 on which the first electromagnet part 120 is disposed, and the first electromagnet unit 122 may be disposed on the first base part 121 . have.
제1 전자석 유닛(122)은 내부에 복수의 코일(C1)이 권선된 형태의 전자석을 포함할 수 있다. 전류 인가부(미도시)로부터 제1 전자석 유닛(122)에 전류가 인가되면 제1 전자석 유닛(122)은 자기장을 발생시킬 수 있다. 이때, 제1 전자석 유닛(122)에 인가되는 전류의 방향과 세기 또는 코일(C1)의 권선수 및 권선 방향을 조절하여, 제1 전자석 유닛(122)에서 발생되는 자기장의 방향 및 세기를 조절할 수 있다.The first electromagnet unit 122 may include an electromagnet having a plurality of coils C1 wound therein. When a current is applied to the first electromagnet unit 122 from a current applying unit (not shown), the first electromagnet unit 122 may generate a magnetic field. At this time, by adjusting the direction and strength of the current applied to the first electromagnet unit 122 or the number and winding direction of the coil C1, the direction and strength of the magnetic field generated in the first electromagnet unit 122 can be adjusted. have.
제1 돌출부(123)는 제1 전자석 유닛(122)과 바디(100)에 삽입된 수용부(110) 사이에 배치될 수 있다. 이때 제1 돌출부(123)는 제1 전자석 유닛(122)의 일단으로부터 제1 전자석 유닛(122)의 반경방향에 수직한 방향으로 수용부(110)를 향해 돌출될 수 있다. 이때 제1 돌출부(123)는 수용부(110)의 일측면에 접촉하여 수용부(110)를 지지할 수 있다.The first protrusion 123 may be disposed between the first electromagnet unit 122 and the receiving part 110 inserted into the body 100 . In this case, the first protrusion 123 may protrude from one end of the first electromagnet unit 122 toward the receiving unit 110 in a direction perpendicular to the radial direction of the first electromagnet unit 122 . In this case, the first protrusion 123 may support the receiving unit 110 by contacting one side of the receiving unit 110 .
제1 전자석부(120)는 제1 전자석 유닛(122)에 의해 발생된 자기장을 수용부(110)에 인가할 수 있다. 구체적으로 제1 전자석부(120)는 수용부(110) 내에 수용된 시료(예를 들어, 자성입자)에 자기장을 인가할 수 있다.The first electromagnet unit 120 may apply a magnetic field generated by the first electromagnet unit 122 to the receiving unit 110 . Specifically, the first electromagnet unit 120 may apply a magnetic field to the sample (eg, magnetic particles) accommodated in the receiving unit 110 .
제2 전자석부(130)는 분리 장치(10)의 외부 또는 내부에 배치된 전류 인가부(미도시)로부터 전류를 인가받아 자기장을 발생시킬 수 있다. 제2 전자석부(130)는 제1 전자석부(120)가 배치된 바디(100)의 일 측면과 다른 측면에 배치될 수 있다. 이때 제2 전자석부(130)는 제1 전자석부(120)가 배치되지 않은 바디(100)의 측면에 배치될 수 있으나, 설명의 편의를 위해 제2 전자석부(130)가 수용부(110)를 중심으로 바디(100)의 일 측면에 배치된 제1 전자석부(120)와 마주보도록, 바디(100)의 다른 측면에 배치된 실시예를 중심으로 설명하기로 한다.The second electromagnet unit 130 may generate a magnetic field by receiving a current from a current applying unit (not shown) disposed outside or inside the separation device 10 . The second electromagnet unit 130 may be disposed on one side and the other side of the body 100 on which the first electromagnet unit 120 is disposed. In this case, the second electromagnet unit 130 may be disposed on the side of the body 100 on which the first electromagnet unit 120 is not disposed. An embodiment that is disposed on the other side of the body 100 so as to face the first electromagnet unit 120 disposed on one side of the body 100 will be mainly described.
제2 전자석부(130)는 제2 베이스부(131)과, 제2 전자석 유닛(132)과, 제2 돌출부(133)를 포함할 수 있다. The second electromagnet unit 130 may include a second base unit 131 , a second electromagnet unit 132 , and a second protrusion 133 .
제2 전자석 유닛(132)은 내부에 복수의 코일(C2)이 권선된 형태의 전자석을 포함할 수 있다. 전류 인가부(미도시)로부터 제2 전자석 유닛(132)에 전류가 인가되면 제2 전자석 유닛(132)은 자기장을 발생시킬 수 있다. 이때 제2 전자석 유닛(132)에 인가되는 전류의 방향과 세기 또는 코일(C2)의 권선수 및 권선 방향을 조절하여, 제2 전자석 유닛(132)에서 발생되는 자기장의 방향 및 세기를 조절할 수 있다.The second electromagnet unit 132 may include an electromagnet in which a plurality of coils C2 are wound. When a current is applied to the second electromagnet unit 132 from the current applying unit (not shown), the second electromagnet unit 132 may generate a magnetic field. At this time, by adjusting the direction and strength of the current applied to the second electromagnet unit 132 or the number and winding direction of the coil C2, the direction and strength of the magnetic field generated in the second electromagnet unit 132 can be adjusted. .
제2 돌출부(133)는 제2 전자석 유닛(132)과 바디(100)에 삽입된 수용부(110) 사이에 배치될 수 있다. 이때 제2 돌출부(133)는 제2 전자석 유닛(132)의 일단으로부터 제2 전자석 유닛(132)의 반경방향에 수직한 방향으로 수용부(110)를 향해 돌출될 수 있다. 이때 제2 돌출부(133)는 수용부(110)를 사이에 두고 제1 돌출부(123)와 대칭되도록 배치되어, 수용부(110)를 양 방향에서 지지할 수 있다. 이에 의해 시료의 교반 및 분리의 안정성을 향상시킬 수 있다.The second protrusion 133 may be disposed between the second electromagnet unit 132 and the receiving part 110 inserted into the body 100 . In this case, the second protrusion 133 may protrude from one end of the second electromagnet unit 132 toward the receiving unit 110 in a direction perpendicular to the radial direction of the second electromagnet unit 132 . In this case, the second protrusion 133 may be disposed to be symmetrical with the first protrusion 123 with the accommodating part 110 interposed therebetween to support the accommodating part 110 in both directions. Thereby, the stability of agitation and separation of the sample can be improved.
제2 전자석부(130)에 포함된 각 구성의 구체적인 특징은 제1 전자석부(120)와 동일 또는 유사하므로, 이에 대해 중복되는 설명은 생략하기로 한다.Specific features of each component included in the second electromagnet unit 130 are the same as or similar to those of the first electromagnet unit 120 , and thus a redundant description thereof will be omitted.
제2 전자석부(130)는 제2 전자석 유닛(132)에 의해 발생된 자기장을 수용부(110)에 인가할 수 있다. 구체적으로 제2 전자석부(130)는 수용부(110) 내에 수용된 시료(예를 들어, 수용부(110) 내의 자성입자)에 자기장을 인가할 수 있다.The second electromagnet unit 130 may apply a magnetic field generated by the second electromagnet unit 132 to the receiving unit 110 . Specifically, the second electromagnet unit 130 may apply a magnetic field to the sample accommodated in the receiving unit 110 (eg, magnetic particles in the receiving unit 110).
앞서 설명한 바와 같이, 제1 전자석부(120)와 제2 전자석부(130) 중 적어도 하나는 수용부(110)에 수용된 자성입자에 자기장을 인가할 수 있다. 이에 의해 수용부(110) 내에서 분석물질, 간섭물질 및 자성입자 중 적어도 일부를 교반시킬 수 있다. 이러한 경우, 제1 전자석부(120)에 의해 인가되는 자기장과 제2 전자석부(130)에 의해 인가되는 자기장의 방향 및 세기는 서로 상이할 수 있다. 다만, 본 발명은 이에 한정되는 것이 아니며, 상기한 자기장들의 방향 및 세기가 동일할 수도 있다. 이때 제1 전자석부(120) 및 제2 전자석부(130)에서 발생되는 자기장의 방향은, 전술한 바와 같이 각 전자석부에 권선된 코일(C1, C2)의 권선 방향 또는 코일(C1, C2)에 인가되는 전류의 방향을 변경하여 조절할 수 있다.As described above, at least one of the first electromagnet unit 120 and the second electromagnet unit 130 may apply a magnetic field to the magnetic particles accommodated in the receiving unit 110 . Accordingly, at least a portion of the analyte, the interfering material, and the magnetic particles may be stirred in the receiving unit 110 . In this case, the direction and strength of the magnetic field applied by the first electromagnet unit 120 and the magnetic field applied by the second electromagnet unit 130 may be different from each other. However, the present invention is not limited thereto, and the directions and strengths of the magnetic fields may be the same. At this time, the direction of the magnetic field generated by the first electromagnet unit 120 and the second electromagnet unit 130 is the winding direction of the coils C1 and C2 wound on each electromagnet unit or the coils C1 and C2 as described above. It can be adjusted by changing the direction of the current applied to it.
자기장에 의한 교반은 소정의 조건을 변경하여 조절할 수 있다. 구체적으로, 제1 전자석부(120)와 제2 전자석부(130)에 인가되는 직류 전류의 세기 및 코일(C1, C2)의 권선수를 변경하여 교반의 세기를 조절할 수 있다. 또한, 제1 전자석부(120)와 제2 전자석부(130)에 인가되는 교류 전류의 주파수, 제1 전자석부(120)와 제2 전자석부(130)의 듀티 사이클(duty cycle)을 변경하여 교반의 주기를 조절할 수 있다. 일 실시예로서, 시간에 따라 상기한 바와 같은 조건들을 시간에 따라 변경하여 전자석부들(120, 130)에 인가함으로써, 자기장에 의한 교반이 시간에 따라 변경되도록 조절할 수도 있다.Stirring by the magnetic field can be controlled by changing a predetermined condition. Specifically, the intensity of agitation may be adjusted by changing the intensity of the direct current applied to the first electromagnet unit 120 and the second electromagnet unit 130 and the number of turns of the coils C1 and C2. In addition, by changing the frequency of the alternating current applied to the first electromagnet unit 120 and the second electromagnet unit 130 and the duty cycle of the first electromagnet unit 120 and the second electromagnet unit 130 , The cycle of agitation can be adjusted. As an embodiment, by changing the conditions as described above over time and applying them to the electromagnets 120 and 130 , the stirring by the magnetic field may be adjusted to change over time.
제1 전자석부(120)와 제2 전자석부(130)는 기 설정된 주기(T)로 자성입자에 자기장을 인가할 수 있다. 이때 기 설정된 주기(T)는 제1 전자석부(120)또는 제2 전자석부(130) 중 어느 하나가 자성입자에 자기장을 인가하기 시작한 시점부터, 제1 전자석부(120)또는 제2 전자석부(130) 중 어느 하나가 다시 자성입자에 자기장의 인가를 시작하기 전까지의 시간을 의미할 수 있으며, 기 설정된 주기(T)는 제1 주기(T1), 제2 주기(T2) 등의 복수의 주기로 반복될 수 있다.The first electromagnet unit 120 and the second electromagnet unit 130 may apply a magnetic field to the magnetic particles at a preset period (T). At this time, the preset period (T) is the first electromagnet unit 120 or the second electromagnet unit from a point in time when any one of the first electromagnet unit 120 or the second electromagnet unit 130 starts to apply a magnetic field to the magnetic particles. Any one of 130 may mean a time before starting to apply a magnetic field to the magnetic particles again, and the preset period T includes a plurality of the first period T1, the second period T2, and the like. It can be repeated in cycles.
일 실시예로서, 제1 전자석부(120)와 제2 전자석부(130)는 서로 교번하여 자성입자에 자기장을 인가할 수 있다. 이러한 경우 제1 전자석부(120)와 제2 전자석부(130) 중 어느 하나가 먼저 제1 시간(t1)동안 자성입자에 자기장을 인가할 수 있다. 그런 다음 제1 전자석부(120)와 제2 전자석부(130) 중 다른 하나가 자성입자에 제2 시간(t2)동안 자기장을 인가할 수 있다. 이하에서는 설명의 편의를 위해, 제1 전자석부(120)가 제1 시간(t1) 동안 자성입자에 자기장을 인가하고, 그런 다음 제2 전자석부(130)가 제2 시간(t2) 동안 자성입자에 자기장을 인가하는 실시예를 중심으로 설명하기로 한다.As an embodiment, the first electromagnet unit 120 and the second electromagnet unit 130 may alternately apply a magnetic field to the magnetic particles. In this case, any one of the first electromagnet unit 120 and the second electromagnet unit 130 may first apply a magnetic field to the magnetic particles for the first time t1 . Then, the other of the first electromagnet unit 120 and the second electromagnet unit 130 may apply a magnetic field to the magnetic particles for a second time t2. Hereinafter, for convenience of explanation, the first electromagnet unit 120 applies a magnetic field to the magnetic particles for a first time t1, and then the second electromagnet unit 130 generates magnetic particles for a second time t2. An embodiment in which a magnetic field is applied will be mainly described.
제1 전자석부(120)가 자기장을 인가하는 제1 시간(t1)과, 제2 전자석부(130)가 자기장을 인가하는 제2 시간(t2)은 연속될 수 있다(도 4a를 참조). 그러나 다른 실시예로서, 기 설정된 주기(T)동안에, 제1 시간(t1)과 제2 시간(t2) 사이에는 제1 전자석부(120)와 제2 전자석부(130) 중 어느 것에 의해서도 자성입자에 자기장에 인가되지 않는 무인가 시간(to)이 존재할 수도 있다(도 4b를 참조). 일 예로, 제1 시간(t1)과 제2 시간(t2)은 동일할 수 있으나, 다른 예로, 제1 시간(t1)과 제2 시간(t2)은 상이할 수도 있다. 무인가 시간(to)은 제1 시간(t1)과 제2 시간(t2) 중 어느 하나와 동일 또는 상이할 수 있다. 또 다른 실시예로서, 제1 전자석부(120)와 제2 전자석부(130)는 교반이 진행되는 동안 자성입자에 자기장이 인가되지 않는 시간이 존재하지 않도록, 연속적으로 교번하여 자성입자에 자기장을 인가할 수도 있다(도 4c를 참조). 또 다른 예로서, 제1 전자석부(120) 또는 제2 전자석부(130) 중 어느 하나가 연속하여 복수회 자기장을 인가한 후에, 제1 전자석부(120) 또는 제2 전자석부(130) 중 다른 하나가 자기장을 인가할 수도 있다(미도시).A first time t1 in which the first electromagnet unit 120 applies a magnetic field and a second time t2 in which the second electromagnet unit 130 applies a magnetic field may be continuous (refer to FIG. 4A ). However, as another embodiment, during the preset period (T), between the first time (t1) and the second time (t2), the magnetic particles by any of the first electromagnet unit 120 and the second electromagnet unit 130 . There may be an unattended application time (to) in which no magnetic field is applied (see FIG. 4B ). As an example, the first time t1 and the second time t2 may be the same, but as another example, the first time t1 and the second time t2 may be different. The unattended time to may be the same as or different from any one of the first time t1 and the second time t2. As another embodiment, the first electromagnet unit 120 and the second electromagnet unit 130 continuously alternate to apply a magnetic field to the magnetic particles so that there is no time when the magnetic field is not applied to the magnetic particles while the stirring is in progress. It can also be applied (see Fig. 4c). As another example, after any one of the first electromagnet unit 120 or the second electromagnet unit 130 continuously applies a magnetic field a plurality of times, one of the first electromagnet unit 120 or the second electromagnet unit 130 . The other may apply a magnetic field (not shown).
상술한 바와 같이, 제1 전자석부(120)와 제2 전자석부(130)가 교번하여 자성입자에 자기장을 인가함에 따라 수용부(110)내에서 자성입자는 자기장에 의해 제1 전자석부(120)를 향한 이동과 제2 전자석부(130)를 향한 이동을 반복할 수 있다. 이러한 자성입자의 운동은 수용부에 수용된 액체를 휘저어 수용부(110) 내에서 액체의 유동을 발생시킬 수 있다. 이러한 유동에 의해 수용부(110)에 수용된 분석물질과 간섭물질은 자성입자와 골고루 믹싱(mixing)됨으로써 수용부(110) 내에서 시료가 교반될 수 있다. 이에 의해, 자성입자는 간섭물질(또는 간섭물질에 결합된 결합물질)에 효과적으로 결합될 수 있어, 간섭물질에 결합되는 자성입자의 양을 증가시킬 수 있다.As described above, as the first electromagnet unit 120 and the second electromagnet unit 130 alternately apply a magnetic field to the magnetic particles, the magnetic particles in the receiving unit 110 are generated by the magnetic field in the first electromagnet unit 120 ) and the movement toward the second electromagnet unit 130 may be repeated. The movement of the magnetic particles stirs the liquid accommodated in the accommodating part to generate a flow of the liquid in the accommodating part 110 . By this flow, the analyte and the interfering material accommodated in the receiving unit 110 are uniformly mixed with the magnetic particles, so that the sample can be stirred in the receiving unit 110 . Thereby, the magnetic particles can be effectively bound to the interference substance (or the binding material bound to the interference substance), thereby increasing the amount of magnetic particles bound to the interference substance.
다른 실시예로서, 제1 전자석부(120)와 제2 전자석부(130)는 기 설정된 주기로 동시에 자성입자에 자기장을 인가할 수 있다. 이러한 경우, 제1 전자석부(120)와 제2 전자석부(130)는 동일한 인가 시간(ts) 동안 동시에 자성입자에 자기장을 인가할 수 있다. 일 예로, 제1 전자석부(120)와 제2 전자석부(130)에 의한 인가시간(ts1)과 그 다음 인가 시간(ts2) 사이에는 자성입자에 자기장이 인가되지 않는 무인가 시간(to)이 존재할 수 있다(도 4d를 참조).As another embodiment, the first electromagnet unit 120 and the second electromagnet unit 130 may simultaneously apply a magnetic field to the magnetic particles at a preset period. In this case, the first electromagnet unit 120 and the second electromagnet unit 130 may simultaneously apply a magnetic field to the magnetic particles for the same application time ts. For example, between the application time ts1 by the first electromagnet unit 120 and the second electromagnet unit 130 and the next application time ts2, there is an unattended time to in which a magnetic field is not applied to the magnetic particles. can be (see Figure 4d).
도 5를 참조하면, 자기장에 의해 시료의 교반이 시작되기 전에 자성입자가 수용부(110) 내부의 하부에 가라앉은 상태로 있을 수 있다. 이후, 제1 전자석부(120)와 제2 전자석부(130)에 전류가 인가되어 자성입자에 자기장을 인가하면, 자성입자는 자기장에 의해 수용부(110) 내에서 제1 전자석부(120)를 향한 이동 및 제2 전자석부(130)를 향한 이동을 반복하며, 수용부(110) 내부의 액체에 유동을 형성할 수 있다. 충분한 시간 동안 자성입자에 자기장이 인가됨으로써 교반이 진행된 후 자기장의 인가를 중단하면, 자성입자는 수용부(110) 내에서 고르게 분산된 상태가 될 수 있다.Referring to FIG. 5 , before the stirring of the sample is started by the magnetic field, the magnetic particles may be in a state of sinking to the lower part of the inside of the receiving unit 110 . Thereafter, when a current is applied to the first electromagnet unit 120 and the second electromagnet unit 130 to apply a magnetic field to the magnetic particles, the magnetic particles are generated in the receiving unit 110 by the magnetic field in the first electromagnet unit 120 . By repeating the movement toward and movement toward the second electromagnet unit 130 , a flow may be formed in the liquid inside the receiving unit 110 . When the magnetic field is applied to the magnetic particles for a sufficient time and the application of the magnetic field is stopped after the stirring is progressed, the magnetic particles may be uniformly dispersed in the receiving unit 110 .
도 6을 참조하면, 도 5와 같은 방식으로 수용부(110) 내부에서 교반이 진행된 후, 제1 전자석부(120)와 제2 전자석부(130)에 다시 전류가 인가되어 자기장이 발생할 수 있다. 이에 따라, 제1 전자석부(120)와 제2 전자석부(130)는 수용부(110) 내의 자성입자에 자기장을 다시 인가해줄 수 있다. 이때, 제1 전자석부(120)와 제2 전자석부(130)는 동시에 자성입자에 자기장을 계속적으로 인가하고, 이에 의해 자성입자의 일부는 자기장에 의해 수용부(110) 내에서 제1 전자석부(120)를 향해 이동하여 제1 전자석부(120)에 인접한 수용부(110)의 내측벽 주변부에 위치할 수 있다. 그리고, 자성입자의 다른 일부는 자기장에 의해 수용부(110) 내에서 제2 전자석부(130)를 향해 이동하여 제2 전자석부(130)에 인접한 수용부(110)의 내측벽 주변부에 위치할 수 있다. 이에 의해, 자성입자가 결합된 간섭물질과, 자성입자가 결합되지 않은 분석물질은 수용부(110) 내부에서 각각 상이한 영역(예를 들어, 제1 영역 및 제2 영역)으로 분리될 수 있다. Referring to FIG. 6 , after stirring is performed inside the receiving unit 110 in the same manner as in FIG. 5 , current is applied again to the first electromagnet unit 120 and the second electromagnet unit 130 to generate a magnetic field. . Accordingly, the first electromagnet unit 120 and the second electromagnet unit 130 may re-apply a magnetic field to the magnetic particles in the receiving unit 110 . At this time, the first electromagnet unit 120 and the second electromagnet unit 130 continuously apply a magnetic field to the magnetic particles at the same time, whereby some of the magnetic particles are part of the first electromagnet unit in the receiving unit 110 by the magnetic field. It may move toward 120 and may be located on the periphery of the inner wall of the accommodating part 110 adjacent to the first electromagnet part 120 . In addition, the other part of the magnetic particles moves toward the second electromagnet unit 130 within the receiving unit 110 by the magnetic field to be located in the inner wall periphery of the receiving unit 110 adjacent to the second electromagnet unit 130 . can Accordingly, the interference material to which the magnetic particles are bound and the analyte to which the magnetic particles are not bound may be separated into different regions (eg, the first region and the second region) inside the receiving unit 110 .
상술한 바와 같이, 제1 전자석부(120)와 제2 전자석부(130)가 동시에 자성입자에 자기장을 인가하는 경우, 제1 전자석부(120)와 제2 전자석부(130)가 교대로 자기장을 인가하는 경우에 비해 자성입자에 보다 강한 힘을 인가할 수 있다. 이에 의해, 수용부(110)에 수용된 자성입자가 전자석부들(120, 130)로부터 멀어지는 방향으로, 또는 전자석부들(120, 130)을 향하는 방향으로 이동함으로써, 수용부(110) 내의 액체의 흐름을 발생시켜, 수용부(110) 내의 분석물질과 간섭물질이 자성입자와 골고루 믹싱될 수 있다. 이에 따라, 자성입자가 간섭물질과 결합되는 것을 용이하게 할 수 있다.As described above, when the first electromagnet unit 120 and the second electromagnet unit 130 simultaneously apply a magnetic field to the magnetic particles, the first electromagnet unit 120 and the second electromagnet unit 130 alternately generate a magnetic field. A stronger force can be applied to the magnetic particles compared to the case of applying Thereby, by moving the magnetic particles accommodated in the accommodating part 110 in a direction away from the electromagnets 120 and 130 or in a direction toward the electromagnets 120 and 130, the flow of the liquid in the accommodating part 110 is reduced. As a result, the analyte and the interfering material in the accommodating unit 110 may be uniformly mixed with the magnetic particles. Accordingly, it is possible to facilitate the binding of the magnetic particles to the interference material.
한편, 분리 장치(10)는 적어도 하나의 추가 전자석부(미도시)를 더 포함할 수 있다. 이때 제1 전자석부(120)와 제2 전자석부(130) 및 적어도 하나의 추가 전자석부는 바디(100)에 배치될 수 있으며, 또한 수용부(110)를 중심으로 수용부(110)의 둘레를 따라 서로 이격되어 배치될 수 있다. 이러한 경우, 제1 전자석부(120)와 제2 전자석부(130) 및 적어도 하나의 추가 전자석부는 자기장을 발생시키고, 발생된 자기장을 수용부(110)에 수용된 자성입자에 인가할 수 있다. 예를 들어, 추가 전자석부가 한 개 구비되는 경우라면 제1 전자석부(120)와 제2 전자석부(130)는 상술한 바와 같이 수용부(110)를 중심으로 서로 마주보도록 배치되고, 이때 추가 전자석부는 분석 장치(20)가 결합되는 바디(100)의 일면에 대향하는 측면에 배치될 수 있다. 제1 전자석부(120)와 제2 전자석부(130) 및 적어도 하나의 추가 전자석부가 자성입자에 자기장을 인가하는 방법은 상술한 제1 전자석부(120) 및 제2 전자석부(130)와 동일 또는 유사하므로, 이에 대해 중복되는 설명은 생략하기로 한다.Meanwhile, the separation device 10 may further include at least one additional electromagnet (not shown). At this time, the first electromagnet unit 120 , the second electromagnet unit 130 , and at least one additional electromagnet unit may be disposed on the body 100 , and the perimeter of the receiving unit 110 with the receiving unit 110 as the center Accordingly, they may be disposed to be spaced apart from each other. In this case, the first electromagnet unit 120 , the second electromagnet unit 130 , and at least one additional electromagnet unit may generate a magnetic field, and may apply the generated magnetic field to the magnetic particles accommodated in the receiving unit 110 . For example, if one additional electromagnet unit is provided, the first electromagnet unit 120 and the second electromagnet unit 130 are disposed to face each other with the receiving unit 110 as the center as described above, and in this case, the additional electromagnet unit The part may be disposed on a side opposite to one surface of the body 100 to which the analysis device 20 is coupled. The method of applying the magnetic field to the magnetic particles by the first electromagnet unit 120 , the second electromagnet unit 130 , and at least one additional electromagnet unit is the same as the above-described first electromagnet unit 120 and the second electromagnet unit 130 . or similar, overlapping description thereof will be omitted.
상술한 바와 같이 분리 장치(10)에 추가 전자석부가 구비되는 경우, 수용부(110)를 둘러싸도록 배치된 복수개의 전자석부들이 수용부(110)에 수용된 자성입자에 서로 상이한 다양한 방향으로 자기장을 인가할 수 있다. 이에 의해, 자기장에 의한 교반 및 분리 효과를 향상시킬 수 있다.As described above, when the separation device 10 is provided with an additional electromagnet unit, a plurality of electromagnet units disposed to surround the accommodating unit 110 applies magnetic fields in various directions different from each other to the magnetic particles accommodated in the accommodating unit 110 . can do. Thereby, the effect of stirring and separation by the magnetic field can be improved.
제1 전자석부(120)와 제2 전자석부(130) 중 적어도 하나는 시료에 자기장을 인가하여 분석물질과 간섭물질을 분리할 수 있다.At least one of the first electromagnet unit 120 and the second electromagnet unit 130 may apply a magnetic field to the sample to separate the analyte and the interfering material.
제1 전자석부(120)와 제2 전자석부(130)는 자기장에 의한 시료가 교반되고, 자성입자가 간섭물질에 결합된 후 수용부(110) 내의 자성입자에 자기장을 계속적으로 인가할 수 있다. 이때, 자기장을 계속적으로 인가하는 것은 시료가 교반되고 자성입자가 간섭물질에 결합된 후부터, 수용부(110) 내에서 분석물질과 간섭물질의 분리가 완료될 때까지 제1 전자석부(120)와 제2 전자석부(130)가 작동하여 자기장을 발생시키고, 이러한 자기장을 수용부(110) 내의 시료(특히, 자성입자)에 인가하는 상태가 유지되는 것을 의미할 수 있다.The first electromagnet unit 120 and the second electromagnet unit 130 may continuously apply a magnetic field to the magnetic particles in the receiving unit 110 after the sample is stirred by the magnetic field and the magnetic particles are coupled to the interference material. . At this time, the continuous application of the magnetic field is performed with the first electromagnet unit 120 and the first electromagnet unit 120 from after the sample is stirred and the magnetic particles are bound to the interfering material until the separation of the analyte and the interfering material in the receiving unit 110 is completed. This may mean that the second electromagnet unit 130 operates to generate a magnetic field, and a state of applying the magnetic field to the sample (particularly, magnetic particles) in the receiving unit 110 is maintained.
제1 전자석부(120)와 제2 전자석부(130)는 동시에 자성입자에 자기장을 계속적으로 인가할 수 있다. 인가되는 자기장에 의해 자성입자가 결합된 간섭물질만이 수용부(110) 내에서 이동될 수 있다. 구체적으로, 자성입자가 결합된 간섭물질의 일부는 제1 전자석부(120)를 향해 끌려가고, 자성입자가 결합된 간섭물질의 다른 일부는 제2 전자석부(130)를 향해 끌려가며, 자성입자가 결합되지 않은 분석물질은 자기장의 영향을 받지 않아 자기장에 의한 위치 이동이 발생하지 않을 수 있다. 이에 의해, 분석물질과 간섭물질이 수용부(110) 내에서 분리될 수 있다.The first electromagnet unit 120 and the second electromagnet unit 130 may continuously apply a magnetic field to the magnetic particles at the same time. Only the interference material to which the magnetic particles are bound by the applied magnetic field may be moved in the receiving unit 110 . Specifically, a part of the interference material to which the magnetic particles are bonded is attracted toward the first electromagnet unit 120 , and another part of the interference material to which the magnetic particles are bonded is attracted toward the second electromagnet unit 130 , and magnetic particles Since the analyte to which is is not bound is not affected by the magnetic field, positional movement by the magnetic field may not occur. Accordingly, the analyte and the interfering material may be separated in the receiving unit 110 .
자기장에 의해 이동된 간섭물질은 수용부(110) 내의 제1 영역에 위치되고, 자성입자가 결합되지 않아 자기장의 영향을 받지 않는 분석물질은 수용부 내에서 제1 영역과 다른 제2 영역에 위치될 수 있다. 이때 제1 영역은 제1 전자석부(120)와 제2 전자석부(130) 중 적어도 하나와 인접한 영역이며, 제2 영역은 제1 영역과 이격된 영역일 수 있다. 예를 들어, 제1 영역은 제1 전자석부(120)와 인접하는 수용부(110)의 내측벽 주변부와 제2 전자석부(130)와 인접하는 수용부(110)의 내측벽 주변부일 수 있다. 제2 영역은 상기한 수용부(110)의 양쪽 내측벽 주변부 사이의 영역이거나, 수용부(110)의 입구(111)측 영역일 수 있다.The interfering material moved by the magnetic field is located in the first region in the accommodating part 110, and the analyte that is not affected by the magnetic field because the magnetic particles are not combined is located in the second region different from the first region in the accommodating part can be In this case, the first region may be a region adjacent to at least one of the first electromagnet unit 120 and the second electromagnet unit 130 , and the second region may be a region spaced apart from the first region. For example, the first region may be an inner wall periphery of the accommodating part 110 adjacent to the first electromagnet part 120 and an inner wall periphery of the accommodating part 110 adjacent to the second electromagnet part 130 . . The second region may be a region between the peripheral portions of both inner walls of the accommodating part 110 , or may be an inlet 111 side region of the accommodating part 110 .
상술한 바와 같이, 자기장을 이용하여 분석물질과 간섭물질을 수용부(110) 내의 서로 상이한 영역으로 분리시킴으로써, 분석물질을 검출 단계에서 간섭물질의 간섭을 최소화하고, 분석물질 검출의 정확성을 향상시킬 수 있다. 또한, 분리된 간섭물질을 수용부(110)로부터 배출시키기 위한 별도의 구성 또는 과정을 필요로 하지 않으므로 분석 과정을 단순화하고 분석에 소요되는 시간을 단축시킬 수 있다. As described above, by separating the analyte and the interfering material into different regions in the receiving unit 110 using a magnetic field, the interference of the interfering material in the detection step of the analyte is minimized and the accuracy of the analyte detection is improved. can In addition, since a separate configuration or process for discharging the separated interfering material from the receiving unit 110 is not required, the analysis process can be simplified and the time required for the analysis can be shortened.
다른 실시예로서, 제1 전자석부(120) 또는 제2 전자석부(130) 중 어느 하나가 수용부(110) 내의 자성입자에 계속적으로 인가하여 분석물질과, 자성입자가 결합된 간섭물질을 분리시킬 수도 있다.In another embodiment, either the first electromagnet unit 120 or the second electromagnet unit 130 is continuously applied to the magnetic particles in the receiving unit 110 to separate the analyte and the interference material to which the magnetic particles are combined. may do it
도 7은 본 발명의 일 실시예에 따른 시료의 교반 및 분리 순서를 도시한 흐름도이다.7 is a flowchart illustrating a sequence of stirring and separating a sample according to an embodiment of the present invention.
도 7을 참조하면, 본 발명의 일 실시예에 따른 시료를 교반 및 분리하는 방법은 아래와 같을 수 있다.Referring to FIG. 7 , a method for stirring and separating a sample according to an embodiment of the present invention may be as follows.
우선, 사용자는 수용부 내에 분석물질, 간섭물질 및 자성입자를 포함하는 시료를 마련할 수 있다(S100). 이때 시료에는 탐침물질(예를 들어, 제1 프로브, 제2 프로브)이 포함될 수 있다.First, a user may prepare a sample including an analyte, an interfering material, and magnetic particles in the receiving unit (S100). In this case, the sample may include a probe material (eg, a first probe and a second probe).
다음, 제1 전자석부(120)와 제2 전자석부(130) 중 적어도 하나를 작동시켜 자기장을 발생시킬 수 있다(S200). 전류 인가부(미도시)로부터 제1 전자석부(120)와 제2 전자석부(130)로 전류가 인가되면 제1 전자석부(120)와 제2 전자석부(130)는 자기장을 발생시킬 수 있다. 이러한 자기장은 수용부(110)에 수용된 자성입자에 인가될 수 있다.Next, at least one of the first electromagnet unit 120 and the second electromagnet unit 130 may be operated to generate a magnetic field (S200). When current is applied from the current applying unit (not shown) to the first electromagnet unit 120 and the second electromagnet unit 130 , the first electromagnet unit 120 and the second electromagnet unit 130 may generate a magnetic field. . This magnetic field may be applied to the magnetic particles accommodated in the receiving unit (110).
다음, 자기장을 이용하여 자성입자가 간섭물질에 결합하도록 시료를 교반시킬 수 있다(S300). 일 실시예로서, 전류 인가부(미도시)는 제1 전자석부(120)와 제2 전자석부(130)에 번갈아가며 전류를 인가하고, 이에 따라 제1 전자석부(120)와 제2 전자석부(130)는 서로 교번하여 자기장을 수용부(110) 내의 자성입자에 인가할 수 있다. 수용부(110) 내의 자성입자는 자기장에 의해 함으로써, 수용부(110) 내의 액체의 유동을 발생시키고, 이러한 유동에 의해 수용부(110)에 수용된 분석물질, 간섭물질 및 자성입자가 교반될 수 있다. 이에 따라, 자성입자가 간섭물질에 결합하는 것이 용이해질 수 있다.Next, a magnetic field may be used to stir the sample so that the magnetic particles bind to the interfering material (S300). As an embodiment, a current applying unit (not shown) alternately applies current to the first electromagnet unit 120 and the second electromagnet unit 130 , and accordingly, the first electromagnet unit 120 and the second electromagnet unit 130 . 130 may apply a magnetic field to the magnetic particles in the receiving unit 110 by alternating with each other. The magnetic particles in the accommodating part 110 are generated by a magnetic field, thereby generating a flow of the liquid in the accommodating part 110, and the analytes, interfering substances and magnetic particles accommodated in the accommodating part 110 by this flow can be stirred. have. Accordingly, it may be easy for the magnetic particles to bind to the interference material.
다음, 자기장을 이용하여 수용부(110) 내에서 분석물질과 간섭물질을 분리할 수 있다(S400). S300 단계에서 제1 전자석부(120)와 제2 전자석부(130)에 의해 시료를 교반시킨 후, 제1 전자석부(120)와 제2 전자석부(130)는 교반된 시료의 자성입자에 자기장을 계속적으로 인가할 수 있다. 이에 의해, 자성입자가 결합된 간섭물질은 수용부(110) 내의 제1 영역으로 이동하고, 자성입자가 결합되지 않은 분석물질은 수용부(110) 내의 제2 영역으로 이동할 수 있다. 이에 따라, 수용부(110) 내에서 분석물질과 간섭물질이 분리될 수 있다.Next, the analyte and the interfering material may be separated in the receiving unit 110 by using a magnetic field (S400). After stirring the sample by the first electromagnet unit 120 and the second electromagnet unit 130 in step S300, the first electromagnet unit 120 and the second electromagnet unit 130 provide a magnetic field to the magnetic particles of the stirred sample. can be continuously approved. Accordingly, the interference material to which the magnetic particles are bound may move to a first region in the accommodating unit 110 , and the analyte to which the magnetic particles are not bound may move to a second region in the accommodating unit 110 . Accordingly, the analyte and the interfering material may be separated in the receiving unit 110 .
전술한 바와 같이, 본 발명의 실시예들에 따른, 분리 장치(10) 및 분리방법은 분석물질과 자성입자에 각각 특이적으로 결합하는 탐침물질들(예를 들어, 제1 프로브 및 제2 프로브)을 이용하여 간섭물질에만 자성입자를 결합시키고, 대칭으로 배치된 전자석부들(120, 130)로 자성입자에 자기장을 인가하여 수용부(110) 내의 시료를 교반시킴으로써 자성입자와 제2 프로브의 결합을 용이하게 할 수 있다. 또한, 대칭으로 배치된 전자석부들(120, 130)에서 발생된 자기장을 이용하여 수용부(110) 내에서 바로 분석물질과 간섭물질을 분리함으로써, 분리 과정 및 시간을 단축시킬 수 있다.As described above, in the separation apparatus 10 and the separation method according to the embodiments of the present invention, the probe materials (eg, the first probe and the second probe) that specifically bind to the analyte and the magnetic particle, respectively ) to bind the magnetic particles only to the interfering material, and apply a magnetic field to the magnetic particles with the symmetrically arranged electromagnets 120 and 130 to agitate the sample in the receiving unit 110, thereby combining the magnetic particles and the second probe. can facilitate In addition, the separation process and time can be shortened by directly separating the analyte and the interfering material in the accommodating unit 110 using the magnetic field generated by the symmetrically arranged electromagnets 120 and 130 .
도 8은 본 발명의 일 실시예에 따른 분석 시스템을 도시한 사시도이다.8 is a perspective view illustrating an analysis system according to an embodiment of the present invention.
도 9는 본 발명의 일 실시예에 따른 분석물질의 표면-증강 라만 산란 분석 신호를 나타낸 그래프이다. 도 10은 본 발명의 일 실시예에 따른 분석 시스템을 이용한 시료의 분석 순서를 나타내는 흐름도이다.9 is a graph showing a surface-enhanced Raman scattering analysis signal of an analyte according to an embodiment of the present invention. 10 is a flowchart illustrating an analysis procedure of a sample using the analysis system according to an embodiment of the present invention.
도 8 및 도 9를 참조하면, 분석 시스템(1)은 분리 장치(10)와, 분석 장치(20)를 포함할 수 있다.8 and 9 , the analysis system 1 may include a separation device 10 and an analysis device 20 .
분리 장치(10)는 상술한 바와 같이 분석물질, 간섭물질 및 자성입자를 포함하는 시료를 교반 및 분리할 수 있다. 이러한 경우 분리 장치(10)는 바디(100)와, 수용부(110)와, 제1 전자석부(120)와, 제2 전자석부(130)를 포함할 수 있다. The separation device 10 may stir and separate the sample including the analyte, the interference material, and the magnetic particle as described above. In this case, the separation device 10 may include the body 100 , the accommodating part 110 , the first electromagnet part 120 , and the second electromagnet part 130 .
분리 장치(10)의 바디(100)에는 분석 장치(20)에서 방출된 광을 수용부(110) 내의 제1 영역 또는 제2 영역 중 어느 하나로 안내하기 위한 입사홀(102)이 형성될 수 있다. 일 실시예로서, 자기장에 의해 분리된 간섭물질이 수용부(110) 내의 제1 위치에 위치하고, 분석물질이 수용부(110) 내의 제2 영역에 위치하는 경우, 입사홀(102)은 분석 장치(20)의 광원으로부터 방출된 광을 제2 영역에 위치하는 분석물질로 안내할 수 있다. 이때, 수용부(110)는 빛을 통과시킬 수 있는 투명한 재질로 이루어지며, 이에 의해 광원부(21)에서 방출된 빛은 수용부(110)에 수용된 분석물질로 조사될 수 있다.In the body 100 of the separation device 10 , an incident hole 102 for guiding the light emitted from the analysis device 20 to either the first region or the second region in the receiving unit 110 may be formed. . As an embodiment, when the interference material separated by the magnetic field is located at a first position in the accommodating unit 110 and the analyte is located in the second region within the accommodating unit 110 , the incident hole 102 is the analysis device The light emitted from the light source of (20) may be guided to the analyte located in the second region. In this case, the accommodating unit 110 is made of a transparent material that allows light to pass therethrough, whereby the light emitted from the light source 21 may be irradiated with the analyte contained in the accommodating unit 110 .
입사홀(102)은 분리 장치(10)의 바디(100)의 일 측면에 배치될 수 있다. 이때 바디(100)의 일 측면은 분석 장치(20)와 마주보는 바디(100)의 일 측면일 수 있다. 입사홀(102)은 분석 장치(20)의 광원과 일직선 상에 배치되고, 광원으로부터 방출된 광은 입사홀(102)을 통해 분석물질을 향해 나아갈 수 있다.The incident hole 102 may be disposed on one side of the body 100 of the separation device 10 . In this case, one side of the body 100 may be one side of the body 100 facing the analysis device 20 . The incident hole 102 is disposed on a straight line with the light source of the analysis device 20 , and light emitted from the light source may travel toward the analyte through the incident hole 102 .
분리 장치(10)에 포함된 바디(100), 수용부(110), 제1 전자석부(120) 및 제2 전자석부(130)의 구체적인 특징은 상술한 바와 동일 또는 유사하므로, 이에 대한 중복되는 설명은 생략하기로 한다.Specific features of the body 100, the accommodating part 110, the first electromagnet part 120 and the second electromagnet part 130 included in the separation device 10 are the same as or similar to those described above. A description will be omitted.
분석 장치(20)는 광 신호를 측정하여 시료에 존재하는 분석물질을 검출할 수 있다. 이러한 경우, 분석 장치(20)는 광원부(21) 및 광신호검출부(미도시)를 포함할 수 있으며, 이때 광원부(21)와 광신호검출부는 분석 장치(20) 내에 배치될 수 있다.The analysis device 20 may measure an optical signal to detect an analyte present in the sample. In this case, the analysis apparatus 20 may include a light source unit 21 and an optical signal detection unit (not shown), and in this case, the light source unit 21 and the optical signal detection unit may be disposed in the analysis apparatus 20 .
광원부(21)에서 방출된 광은 분리 장치(10)의 수용부(110)에 수용된 시료에 조사될 수 있다. 이때 광은 분리 장치(10)의 입사홀(102)을 통해 수용부(110)의 제2 영역 내의 분석물질로 조사될 수 있다. 광신호검출부는 조사된 광이 시료에 의해 산란됨으로써 발생하는 광신호를 측정할 수 있다.The light emitted from the light source unit 21 may be irradiated to the sample accommodated in the receiving unit 110 of the separation device 10 . In this case, the light may be irradiated to the analyte in the second region of the receiving unit 110 through the incident hole 102 of the separation device 10 . The optical signal detector may measure an optical signal generated when the irradiated light is scattered by the sample.
분석 장치(20)는 형광 또는 라만 분광법, 적외선 분광법 등 다양한 방법에 의해 광 신호를 측정할 수 있으나, 이하에서는 분석 장치(20)가 라만 분광법을 이용하여 분석물질을 검출하는 실시예를 중심으로 설명하기로 한다.The analysis device 20 may measure the optical signal by various methods such as fluorescence or Raman spectroscopy, infrared spectroscopy, etc., but hereinafter, the analysis device 20 detects an analyte using Raman spectroscopy will be mainly described. decide to do
라만 산란은 빛이 어떤 매질을 통과할 때 빛의 파장을 변화시켜 빛의 일부가 진행 방향에서 이탈해 다른 방향으로 진행하는 현상을 의미한다. 라만 분광법은 시료에 단파장의 레이저를 조사하여 산란된 빛을 검출하여 분자 수준의 정보를 얻어내는 유용하며, 라만 분광법은 분자들의 진동 상태(vibrational state)에 대한 정보를 제공한다. 대부분의 경우, 흡수된 광선(radiation)이 동일한 파장에서 재-방사(re-radiated)되는데, 이때 재-방사된 광선간의 에너지 차이는 이들 간의 파장에서의 이동(shift)으로 나타나고 이러한 차이의 정도는 파수(파장의 역수)의 단위로서 측정되어 라만 쉬프트(Raman shift, RS)로 표현된다.Raman scattering refers to a phenomenon in which when light passes through a medium, the wavelength of light is changed, so that a part of the light deviates from the direction of travel and proceeds in a different direction. Raman spectroscopy is useful for obtaining molecular level information by irradiating a short-wavelength laser to a sample and detecting scattered light, and Raman spectroscopy provides information on the vibrational state of molecules. In most cases, absorbed radiation is re-radiated at the same wavelength, where the energy difference between the re-radiated beams is a shift in wavelength between them, and the degree of this difference is It is measured as a unit of wavenumber (the reciprocal of wavelength) and expressed as a Raman shift (RS).
일 실시예로서, 분석 장치(20)는 표면-증강 라만 산란(surface-enhanced Raman scattering, SERS) 신호를 측정하여 분석물질을 검출할 수 있다. 이때, 수용부(110)에 수용된 제1 프로브로부터 분석물질(예를 들어, 형광물질 또는 라만 활성 물질)을 분리하여 라만 신호를 측정할 수 있다. 이러한 경우, 분석 장치(20)의 광원부(21)로부터 방출된 광을 수용부(110)에 수용된 분석물질에 조사하여, 형광물질 또는 라만 활성 물질의 라만 신호를 획득함으로써 분석물질을 검출할 수 있다. 측정된 라만 신호로부터 특정 피크가 관찰되면, 개체가 감염 질환의 마커를 가지고 있는 것으로 판단할 수 있고, 이에 따라 개체의 감염 여부를 확인할 수 있다. As an embodiment, the analysis device 20 may detect an analyte by measuring a surface-enhanced Raman scattering (SERS) signal. In this case, the Raman signal may be measured by separating an analyte (eg, a fluorescent material or a Raman active material) from the first probe accommodated in the receiving unit 110 . In this case, the analyte can be detected by irradiating the light emitted from the light source unit 21 of the analysis device 20 to the analyte accommodated in the receiving unit 110 to obtain a Raman signal of a fluorescent material or a Raman active material. . When a specific peak is observed from the measured Raman signal, it can be determined that the individual has a marker of an infectious disease, and accordingly, whether the individual is infected can be confirmed.
한편, 분석 장치(20)는 시료 내에 서로 다른 표적 유전자와 특이적으로 결합하는 복수의 탐침물질이 포함된 경우 검출을 원하는 어느 하나의 표적 유전자를 특정하여 검출할 수 있다. 일 실시예로서, 수용부(110)에는 제1 표적 유전자와 특이적으로 결합하는 제 1 탐침물질(예를 들어, 제1 탐침물질의 제1 프로브와 제2 프로브)과, 제2 표적 유전자와 특이적으로 결합하는 제 2 탐침물질(예를 들어, 제2 탐침물질의 제1 프로브 및 제2 프로브)이 포함될 수 있다. 이때 시료에 제1 표적 유전자만이 존재하면, 제1 탐침물질 중 제1 프로브로부터 리포터 물질(즉, 분석물질)이 탈락되고, 자기장에 의해 간섭물질만이 분리가 진행됨에 따라, 수용부(110) 내의 분석물질에 의한 광 신호가 점차적으로 증가(예를 들어, 도 9의 B, C를 참조)할 수 있다. 반면에, 수용부(110) 내에는 제2 표적 유전자는 존재하지 않으므로, 제2 탐침물질의 제1 프로브에서 리포터 물질이 탈락되지 않고, 제2 탐침물질의 리포터 물질은 제2 탐침물질과 결합된 자성입자와 이러한 자성입자에 인가된 자기장에 의해 상기한 분석물질로부터 분리될 수 있다. 이에 따라 제 2 탐침물질의 리포터 물질에 의한 광 신호가 점차 감소(예를 들어, 도 9의 A 참조)하는 것을 확인할 수 있다. 이러한 방법에 의하면 제1 프로브에 도입된 형광 물질에 따라 단일 광원에서 다중 진단이 가능할 수 있다.Meanwhile, when a plurality of probe materials specifically binding to different target genes are included in the sample, the analysis device 20 may specify and detect any one target gene desired to be detected. As an embodiment, the receiving unit 110 includes a first probe material (eg, a first probe and a second probe of the first probe material) specifically binding to a first target gene, a second target gene, A second probe material that specifically binds (eg, the first probe and the second probe of the second probe material) may be included. At this time, if only the first target gene is present in the sample, the reporter material (ie, the analyte) is dropped from the first probe among the first probe material, and only the interfering material is separated by the magnetic field. ) may gradually increase (see, for example, B and C of FIG. 9 ) by an analyte in the . On the other hand, since the second target gene does not exist in the receiving unit 110, the reporter material is not dropped from the first probe of the second probe material, and the reporter material of the second probe material is combined with the second probe material. It can be separated from the analyte by the magnetic particles and the magnetic field applied to the magnetic particles. Accordingly, it can be seen that the light signal by the reporter material of the second probe material gradually decreases (for example, refer to FIG. 9A ). According to this method, multiple diagnosis may be possible from a single light source according to the fluorescent material introduced into the first probe.
분석 장치(20)는 분리 장치(10)에 탈부착 가능하게 연결될 수 있다. 일 실시예로서, 분리 장치(10)에 의해 교반 및 분리된 시료를 분석할 때 분석 장치(20)가 분리 장치(10)에 연결될 수 있다. 다른 실시예로서, 분석 장치(20)에 의해 시료의 분석을 완료한 경우에는 분석 장치(20)를 분리 장치(10)로부터 분리할 수 있다. 다만, 본 발명은 이에 한정되는 것은 아니며, 분석 장치(20)는 분리 장치(10)로부터 이격되어 배치된 상태로 분리 장치(10) 내의 시료를 향해 광을 조사하여 시료를 분석할 수도 있다.The analysis device 20 may be detachably connected to the separation device 10 . As an embodiment, when analyzing a sample stirred and separated by the separation device 10 , the analysis device 20 may be connected to the separation device 10 . As another embodiment, when the analysis of the sample is completed by the analysis device 20 , the analysis device 20 may be separated from the separation device 10 . However, the present invention is not limited thereto, and the analysis device 20 may analyze the sample by irradiating light toward the sample in the separation device 10 while being spaced apart from the separation device 10 .
분석 장치(20)는 분석 장치(20)의 전원 스위치(22)와 디스플레이부(23)를 더 포함할 수 있다. 이러한 경우, 디스플레이부(23)는 시료 분석 결과에 기초한 분석물질의 존재 여부 및 개체의 특정 질병의 진단 결과 정보를 보여주는 것을 더 포함할 수 있다. 사용자는 디스플레이부(23)이 표시된 정보에 기초하여, 개체의 질병 여부를 확인할 수 있다.The analysis device 20 may further include a power switch 22 and a display unit 23 of the analysis device 20 . In this case, the display unit 23 may further include displaying information on whether an analyte is present and a diagnosis result of a specific disease of the subject based on the sample analysis result. Based on the information displayed on the display unit 23, the user may check whether the object has a disease.
도 10을 참조하면, 분석 시스템(1)을 이용하여 시료를 분석하는 방법은 아래와 같을 수 있으며, 이하에서는 설명의 편의를 위해 수용부(110)에 수용된 시료에 표적 유전자가 존재하는 실시예를 중심으로 설명하기로 한다.Referring to FIG. 10 , a method of analyzing a sample using the analysis system 1 may be as follows, and for convenience of explanation, the following will focus on an embodiment in which a target gene is present in a sample accommodated in the receiving unit 110 . to be explained as
우선, 사용자는 분리 장치(10)의 수용부(110) 내에 분석물질, 간섭물질 및 자성입자를 포함하는 시료를 마련할 수 있다(S10). 이때, 시료에는 표적 유전자에 특이적으로 결합하는 제1 프로브와 제2 프로브를 포함하는 탐침물질과 액체가 포함될 수 있다. 제1 프로브에는 분석물질이 결합되고, 제2 프로브에는 자성입자가 결합될 수 있다.First, a user may prepare a sample including an analyte, an interference material, and magnetic particles in the receiving unit 110 of the separation device 10 ( S10 ). In this case, the sample may include a liquid and a probe material including the first probe and the second probe that specifically bind to the target gene. An analyte may be bound to the first probe, and magnetic particles may be bound to the second probe.
다음, 수용부(110) 내의 시료에 표적 유전자가 존재하는 경우 시료에 포함된 분석물질과 간섭물질은 증폭될 수 있다(S20). 이때, 분석물질과 간섭물질은 전술한 바와 같은 PCR 증폭 과정을 통해 증폭될 수 있다. 그러나 본 발명은 이에 한정되는 것이 아니며, 분석물질과 간섭물질은 등온 증폭법에 의해 증폭될 수도 있다. 이러한 경우, 전류 인가부(미도시)에서 제1 전자석부(120)와 제2 전자석부(130)로 전류가 인가될 때 발생하는 열을 이용하여 수용부(110) 내의 온도를 등옥 증폭을 위한 특정 온도로 유지시킴으로써, 추가적인 열 공급 장치 없이도 분석물질 및 간섭물질을 증폭시킬 수 있다.Next, when the target gene is present in the sample in the receiving unit 110 , the analyte and the interfering material included in the sample may be amplified ( S20 ). In this case, the analyte and the interfering material may be amplified through the PCR amplification process as described above. However, the present invention is not limited thereto, and the analyte and the interfering material may be amplified by an isothermal amplification method. In this case, using the heat generated when current is applied from the current applying unit (not shown) to the first electromagnet unit 120 and the second electromagnet unit 130 , the temperature in the accommodating unit 110 is used to amplify the By maintaining a specific temperature, analytes and interfering substances can be amplified without the need for an additional heat supply.
다음, 분리 장치(10)에서 자기장을 이용하여 분석물질과 간섭물질을 분리할 수 있다(S30). 이때, 수용부(110) 내에서 분석물질과 간섭물질을 교반 및 분리하는 구체적인 방법은 전술한 바와 동일하며, 분리된 간섭물질은 수용부(110) 내의 제1 영역에 위치하고, 분리된 분석물질은 수용부(110) 내의 제2 영역에 위치할 수 있다.Next, an analyte and an interfering material may be separated using a magnetic field in the separation device 10 ( S30 ). At this time, the specific method of stirring and separating the analyte and the interfering material in the receiving unit 110 is the same as described above, the separated interfering material is located in the first region in the receiving unit 110, and the separated analyte is It may be located in the second area in the receiving unit 110 .
다음, 분석 장치(20)는 광 신호를 측정하여 수용부(110) 내에 존재하는 분석물질을 검출할 수 있다(S40). 분리 장치(10)에 연결된 분석 장치(20)는 광원부(21)에서 방출된 광을 입사홀(102)을 통해 분석물질로 조사하고, 분석물질에 의해 산란된 광의 광 신호를 측정할 수 있다. 이때, 광 신호는 표면-증강 라만 산란 신호일 수 있으며, 측정된 라만 신호로부터 특정 피크를 관찰하여 개체의 질병 감염 여부를 확인할 수 있다.Next, the analysis device 20 may measure the optical signal to detect the analyte present in the receiving unit 110 ( S40 ). The analysis device 20 connected to the separation device 10 may irradiate the light emitted from the light source unit 21 as an analyte through the incident hole 102 , and measure a light signal of the light scattered by the analyte. In this case, the optical signal may be a surface-enhanced Raman scattering signal, and by observing a specific peak from the measured Raman signal, it is possible to determine whether an individual is infected with a disease.
전술한 바와 같이, 본 발명의 실시예들에 따른, 분석 시스템(1) 및 분석 방법은, 자기장을 이용하여 수용부(110) 내에서 분석물질과 간섭물질을 분리한 후 간섭물질을 배출하는 별도의 과정 없이, 분석 장치(20)에 의해 분석물질을 검출함으로써, 분석물질 및 간섭물질의 증폭과 분리 및 분석물질의 검출을 연속하여 진행할 수 있다. 이에 의해 분석 단계를 일체화하여 분석에 소요되는 시간을 단축시키고, 분석의 편의성을 증대시킬 수 있다. As described above, the analysis system 1 and the analysis method according to the embodiments of the present invention separate the analyte and the interfering material in the receiving unit 110 using a magnetic field and then discharging the interfering material. By detecting the analyte by the analysis device 20 without the above process, the amplification and separation of the analyte and the interfering material and the detection of the analyte may be continuously performed. Accordingly, it is possible to reduce the time required for analysis by unifying the analysis steps, and to increase the convenience of analysis.
이상에서는 도면에 도시된 실시예를 참고로 설명되었으나 이는 예시적인 것에 불과하며, 당해 기술 분야에서 통상의 지식을 가진 자라면 이로부터 다양한 변형 및 균등한 다른 실시예가 가능하다는 점을 이해할 것이다. 따라서, 본 발명의 진정한 기술적 보호 범위는 첨부된 특허청구범위의 기술적 사상에 의하여 정해져야 할 것이다.In the above, the embodiments shown in the drawings have been described with reference to, but these are merely exemplary, and those skilled in the art will understand that various modifications and equivalent other embodiments are possible therefrom. Accordingly, the true technical protection scope of the present invention should be determined by the technical spirit of the appended claims.

Claims (18)

  1. 분석물질, 간섭물질 및 상기 간섭물질에 결합되는 자성입자를 포함하는 시료를 교반 및 분리하는 분리 장치; 및a separation device for stirring and separating a sample including an analyte, an interfering material, and magnetic particles bound to the interfering material; and
    상기 분리 장치에 연결되고, 상기 시료에 광을 조사하고, 출사되는 광 신호를 이용하여 상기 분석물질을 검출하는 분석 장치;를 포함하고,an analysis device connected to the separation device, irradiating light to the sample, and detecting the analyte using the emitted light signal;
    상기 분리 장치는,The separation device is
    바디;body;
    상기 바디에 분리가능하게 배치되고, 상기 시료를 수용하는 수용부;a receiving part that is detachably disposed on the body and receives the sample;
    상기 바디에 배치되고, 자기장을 발생시키는 제1 전자석부; 및a first electromagnet unit disposed on the body and generating a magnetic field; and
    상기 바디에 상기 수용부를 중심으로 상기 제1 전자석부와 마주보도록 배치되고, 상기 제1 전자석부와 상이한 방향의 자기장을 발생시키는 제2 전자석부;를 포함하고,and a second electromagnet part disposed on the body to face the first electromagnet part around the receiving part, and generating a magnetic field in a different direction from that of the first electromagnet part;
    상기 제1 전자석부와 상기 제2 전자석부 중 적어도 하나는 상기 자성입자에 자기장을 인가하여 상기 분석물질, 상기 간섭물질 및 상기 자성입자 중 적어도 일부를 교반하는, 분석 시스템.At least one of the first electromagnet unit and the second electromagnet unit applies a magnetic field to the magnetic particles to stir at least a portion of the analyte, the interference material, and the magnetic particles.
  2. 제1항에 있어서,According to claim 1,
    상기 제1 전자석부와 상기 제2 전자석부는 기 설정된 주기로 교번하여 상기 자성입자에 자기장을 인가하는, 분석 시스템.The first electromagnet unit and the second electromagnet unit alternately with a preset period to apply a magnetic field to the magnetic particles, the analysis system.
  3. 제1항에 있어서,According to claim 1,
    상기 제1 전자석부와 상기 제2 전자석부는 기 설정된 주기로 동시에 상기 자성입자에 자기장을 인가하는, 분석 시스템.The first electromagnet unit and the second electromagnet unit apply a magnetic field to the magnetic particles at the same time at a preset period, analysis system.
  4. 제1항에 있어서,According to claim 1,
    상기 제1 전자석부와 상기 제2 전자석부 중 적어도 하나는 상기 자성입자에 자기장을 계속적으로 인가하여 상기 분석물질과 상기 간섭물질을 분리하는, 분석 시스템.At least one of the first electromagnet unit and the second electromagnet unit continuously applies a magnetic field to the magnetic particles to separate the analyte and the interfering material.
  5. 제4항에 있어서, 5. The method of claim 4,
    분리된 상기 간섭물질은 상기 수용부 내의 제1 영역에 위치하고, 분리된 상기 분석물질은 상기 수용부 내의 상기 제1 영역과 다른 제2 영역에 위치하고, The separated interfering substance is located in a first region in the accommodating part, and the separated analyte is located in a second region different from the first region in the accommodating part,
    상기 제1 영역은 상기 제1 전자석부와 상기 제2 전자석부 중 적어도 하나와 인접한 영역이고, 상기 제2 영역은 상기 제1 영역과 이격된 영역인, 분석 시스템.The first region is a region adjacent to at least one of the first electromagnet unit and the second electromagnet unit, and the second region is a region spaced apart from the first region.
  6. 제5항에 있어서,6. The method of claim 5,
    상기 분리 장치의 상기 바디에는 상기 광을 상기 제2 영역으로 안내하기 위한 입사홀이 형성되는, 분석 시스템.An incident hole for guiding the light to the second region is formed in the body of the separation device.
  7. 제1항에 있어서,According to claim 1,
    상기 광 신호는 표면-증강 라만 산란(surface-enhanced Raman scattering, SERS) 신호인, 분석 시스템.wherein the optical signal is a surface-enhanced Raman scattering (SERS) signal.
  8. 제1항에 있어서,According to claim 1,
    상기 수용부는 투명 재질로 이루어진, 분석 시스템.The accommodating part is made of a transparent material, analysis system.
  9. 제1항에 있어서,According to claim 1,
    상기 바디에 배치되고, 상기 제1 전자석부 및 상기 제2 전자석부와 상이한 방향으로 자기장을 발생시키는 적어도 하나의 추가 전자석부;를 더 포함하고, At least one additional electromagnet unit disposed on the body and generating a magnetic field in a direction different from that of the first electromagnet unit and the second electromagnet unit;
    상기 추가 전자석부는 복수개 구비되며, The additional electromagnet unit is provided in plurality,
    복수개의 상기 추가 전자석부는 상기 제1 전자석부 및 상기 제2 전자석부와 이격되어 배치되는, 분석 시스템.A plurality of the additional electromagnet unit is disposed spaced apart from the first electromagnet unit and the second electromagnet unit, analysis system.
  10. 수용부 내에 분석물질, 간섭물질 및 자성입자를 포함하는 시료를 마련하는 단계;providing a sample containing an analyte, an interfering material, and a magnetic particle in the receiving unit;
    상기 분석물질과 상기 간섭물질을 증폭시키는 단계;amplifying the analyte and the interfering material;
    상기 분석물질과 상기 간섭물질을 분리하는 단계; 및separating the analyte and the interfering material; and
    상기 시료에 광을 조사하고, 출사되는 광 신호를 이용하여 상기 분석물질을 검출하는 단계;를 포함하고, Including; irradiating light to the sample and detecting the analyte using the emitted light signal;
    상기 분석물질과 상기 간섭물질을 분리하는 단계는Separating the analyte and the interfering material
    상기 수용부를 중심으로 마주보도록 배치되는 제1 전자석부와 제2 전자석부 중 적어도 하나를 작동시켜 자기장을 발생시키는 단계;generating a magnetic field by operating at least one of a first electromagnet unit and a second electromagnet unit disposed to face each other around the receiving unit;
    상기 자기장을 이용하여 상기 수용부에 수용된 분석물질, 간섭물질 중 어느 하나에 자성입자가 결합하도록, 상기 시료를 교반하는 단계; 및agitating the sample so that the magnetic particles bind to any one of the analyte and the interference material accommodated in the receiving unit using the magnetic field; and
    상기 자기장을 이용하여 상기 수용부 내에서 상기 분석물질과 상기 간섭물질을 분리하는 단계;를 포함하는, 분석 방법.Separating the analyte and the interfering material in the accommodating part using the magnetic field;
  11. 제10항에 있어서,11. The method of claim 10,
    상기 자기장을 이용하여 수용부에 수용된 분석물질 또는 간섭물질 중 어느 하나에 및 자성입자가 결합하도록, 상기 시료를 교반하는 단계는, 제1 전자석부와 제2 전자석부가 기 설정된 주기로 교번하여 상기 자성입자에 자기장을 인가하는 단계를 포함하는, 분석 방법.Agitating the sample so that the magnetic particles bind to any one of the analyte or the interfering material accommodated in the receiver using the magnetic field, the first electromagnet unit and the second electromagnet unit alternate at a preset period to alternate the magnetic particles An analysis method comprising the step of applying a magnetic field to the .
  12. 제10항에 있어서,11. The method of claim 10,
    상기 자기장을 이용하여 수용부에 수용된 분석물질 또는 간섭물질 중 어느 하나에 자성입자가 결합하도록, 상기 시료를 교반하는 단계는, 상기 제1 전자석부와 상기 제2 전자석부가 기 설정된 주기로 동시에 상기 자성입자에 자기장을 인가하는, 분리 방법.Agitating the sample so that the magnetic particles bind to any one of the analyte or the interfering material accommodated in the receiving unit by using the magnetic field includes the first electromagnet unit and the second electromagnet unit at the same time at a preset cycle. A separation method by applying a magnetic field to the
  13. 제10항에 있어서,11. The method of claim 10,
    상기 자기장을 이용하여 상기 수용부 내에서 상기 분석물질과 상기 간섭물질을 분리하는 단계는, 상기 제1 전자석부와 상기 제2 전자석부 중 적어도 하나가 상기 자성입자에 자기장을 계속적으로 인가하여 상기 분석물질과 상기 간섭물질을 분리하는, 분석 방법.In the step of separating the analyte and the interference material in the receiving unit using the magnetic field, at least one of the first electromagnet unit and the second electromagnet unit continuously applies a magnetic field to the magnetic particles for the analysis An analysis method for separating a substance and the interfering substance.
  14. 제10항에 있어서,11. The method of claim 10,
    분리된 상기 간섭물질은 상기 수용부 내의 제1 영역에 위치하고, 분리된 상기 분석물질은 상기 수용부 내의 제2 영역에 위치하고,The separated interfering substance is located in a first region in the accommodating part, and the separated analyte is located in a second region in the accommodating part,
    상기 제1 영역은 상기 제1 전자석부와 상기 제2 전자석부 중 적어도 하나와 인접한 영역이고, 상기 제2 영역은 상기 제1 영역과 이격된 영역인, 분석 방법.The first region is a region adjacent to at least one of the first electromagnet unit and the second electromagnet unit, and the second region is a region spaced apart from the first region.
  15. 제14항에 있어서,15. The method of claim 14,
    상기 광 신호를 이용하여 상기 분석물질을 검출하는 단계는, 상기 분리 장치의 상기 바디에 형성된 입사홀을 통해 상기 광이 상기 제2 영역으로 안내되는, 분석 방법.In the detecting of the analyte using the optical signal, the light is guided to the second region through an incident hole formed in the body of the separation device.
  16. 제10항에 있어서,11. The method of claim 10,
    상기 광 신호는 표면-증강 라만 산란 신호인, 분석 방법.wherein the optical signal is a surface-enhanced Raman scattering signal.
  17. 제10항에 있어서,11. The method of claim 10,
    상기 수용부는 투명 재질로 이루어진, 분석 방법.The receiving part is made of a transparent material, analysis method.
  18. 제10항에 있어서,11. The method of claim 10,
    상기 바디에 배치되고, 상기 제1 전자석부 및 상기 제2 전자석부와 상이한 방향으로 자기장을 발생시키는 적어도 하나의 추가 전자석부;를 더 포함하고, At least one additional electromagnet unit disposed on the body and generating a magnetic field in a direction different from that of the first electromagnet unit and the second electromagnet unit;
    상기 추가 전자석부는 복수개 구비되며, The additional electromagnet unit is provided in plurality,
    복수개의 상기 추가 전자석부는 상기 제1 전자석부 및 상기 제2 전자석부와 이격되어 배치되는, 분석 방법.A plurality of the additional electromagnet parts are arranged to be spaced apart from the first electromagnet part and the second electromagnet part, the analysis method.
PCT/KR2021/004085 2020-04-03 2021-04-01 Analysis system and method WO2021201635A1 (en)

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JP2011158334A (en) * 2010-01-29 2011-08-18 Beckman Coulter Inc Analyzing method, analyzer, and analyzing program
KR101195957B1 (en) * 2009-03-26 2012-10-30 한양대학교 에리카산학협력단 Combinational surface-enhanced raman scattering probe and method for detecting target substance by using the same
KR101907267B1 (en) * 2016-10-10 2018-10-11 서울대학교산학협력단 A kit for detecting the target materials using porous wall and magnets
KR20190016066A (en) * 2019-02-08 2019-02-15 서울대학교산학협력단 A kit for detecting target materials comprising image sensors and magnets
KR20200034725A (en) * 2017-07-19 2020-03-31 암젠 인크 Self-assisted separation device and related methods

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR101195957B1 (en) * 2009-03-26 2012-10-30 한양대학교 에리카산학협력단 Combinational surface-enhanced raman scattering probe and method for detecting target substance by using the same
JP2011158334A (en) * 2010-01-29 2011-08-18 Beckman Coulter Inc Analyzing method, analyzer, and analyzing program
KR101907267B1 (en) * 2016-10-10 2018-10-11 서울대학교산학협력단 A kit for detecting the target materials using porous wall and magnets
KR20200034725A (en) * 2017-07-19 2020-03-31 암젠 인크 Self-assisted separation device and related methods
KR20190016066A (en) * 2019-02-08 2019-02-15 서울대학교산학협력단 A kit for detecting target materials comprising image sensors and magnets

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