KR20180047853A - Virus detecting device with chaotic sensor and virus detecting method using the same - Google Patents

Abstract

An embodiment of the present invention provides an apparatus for detecting a virus, capable of rapidly estimating the virus, the virus concentration and a type of the virus at low costs by using a temporal correlation of a laser speckle. The apparatus includes: a sample arrangement unit for containing a sample; a virus marker application part for applying a virus marker including magnetic particles to the sample to form a detection complex in which the virus marker is combined with the virus in the sample; a magnetic field forming unit disposed adjacent to the sample arrangement unit and forming a magnetic field around the sample arrangement unit to impart a motion to the detection composite; a wave source for irradiating a wave toward the sample in the sample arrangement unit; at least one detector for detecting a laser speckle, which is generated by multiple scattering of the irradiated waves due to the movement of the detection complex, at predetermined time points; and a control unit acquiring a temporal correlation of the detected laser speckle and determining whether the virus is present in the sample or estimating the concentration of the virus based on the obtained time correlation in real-time.

Description

[0001] The present invention relates to a virus detecting device using a chaos wave sensor and a virus detecting device using the same,

Embodiments of the present invention relate to a virus detection device using a chaos wave sensor and a virus detection method using the same.

Viruses are infectious pathogens that are smaller in size than bacteria. It consists of RNA or DNA, a genetic material, and a protein that surrounds the genetic material. Viruses can be classified into plant viruses, animal viruses, and bacterial viruses (phage) depending on the type of host. However, in most cases, depending on the type of nucleic acid, it is divided into DNA viruses and RNA viruses.

Among these viruses, avian influenza is an acute viral infectious disease caused by an infection of avian influenza virus in chickens, ducks, or wild birds, and rarely causes infections in humans. There are three types of avian influenza virus, which are highly pathogenic, low pathogenic, and non-pathogenic depending on their pathogenicity. Human avian influenza virus (H5N1), which is highly pathogenic avian influenza virus (H5N1) More than 640 cases have been reported. Avian influenza causes high mortality due to high mortality and low egg production rate of birds, and it is not high possibility of human infection but it shows high mortality rate when it is infected to human body. Because it is difficult to develop a basic vaccine and the spread rate is very fast, it is necessary to minimize the spread of disease and economic loss through early diagnosis.

Immunological detection methods such as enzyme-linked immunosorbent assay (ELISA), enzyme immunoassay (EIA) and immunofluorescence assay (IFA), and RNA detection by RT-PCR are known as diagnostic methods for such viruses. Such a method has problems such as excessive time for virus diagnosis, high cost of testing, low specificity and sensitivity due to nonspecific reaction, and the like. Therefore, it is necessary to develop a method for efficiently detecting viruses in a short time at a low cost.

In order to solve the above-mentioned problems and / or limitations, it is an object of the present invention to provide a virus detection apparatus using a chaos wave sensor and a virus detection method using the same.

One embodiment of the present invention is a detection complex comprising a sample placement part for accommodating a sample and a virus marker including magnetic particles applied to the sample to bind the virus marker and the virus in the sample, A magnetic field forming unit disposed adjacent to the sample arrangement unit to form a magnetic field around the sample arrangement unit to impart motion to the detection composite, A wave source for irradiating a wave toward the sample, a laser speckle generated by multiple scattering of the irradiated wave due to the movement of the detection complex, The detection unit and the detected laser speckle are used to determine a time correlation of the detected laser speckle n) and estimating in real time the presence or absence of virus in the sample based on the obtained time correlation.

In one embodiment of the present invention, the virus marker may include an antibody conjugated with the virus in the sample and the magnetic particles bound to the antibody.

In one embodiment of the present invention, the sample includes a plurality of kinds of viruses, and the virus marker application unit includes the antibody conjugated with any one of the plurality of kinds of viruses and the magnetic particles bonded to the antibody A plurality of types of virus markers can be applied to the sample.

In one embodiment of the present invention, the sample arrangement part can support the sample while restricting movement of the sample itself.

In one embodiment of the present invention, the magnetic field generator may change the direction or intensity of the magnetic field every predetermined first time period to impart motion to the detection complex.

In one embodiment of the present invention, the controller receives magnetic field information about the direction or strength of the magnetic field to be changed by the magnetic field forming unit, acquires time correlation of the detected laser speckle using the magnetic field information can do.

In an embodiment of the present invention, the time interval of the predetermined time points detected by the detection unit may be shorter than the first time.

In one embodiment of the present invention, the magnetic field forming unit may use micro-NMR.

One embodiment of the present invention relates to a method for detecting a virus, comprising: forming a detection complex in which a virus marker in the sample is combined with a virus marker by applying a virus marker containing magnetic particles to the sample; Forming a magnetic field around the sample to impart motion to the detection complex; Detecting a laser speckle generated by multiple scattering of the irradiated waves due to the movement of the detection complex at predetermined time points by irradiating the waves toward the specimen; Obtaining a temporal correlation of the detected laser speckle using the detected laser speckle; And estimating, based on the obtained time correlation, whether there is a virus in the sample or the concentration of the virus in a real-time manner.

In one embodiment of the present invention, the virus marker may include an antibody conjugated with the virus in the sample and the magnetic particles bound to the antibody.

In one embodiment of the present invention, the step of forming the complex for detection includes a step of immersing the sample containing a plurality of kinds of viruses into the sample, the antibody conjugated with any one of the plurality of kinds of viruses, A plurality of kinds of virus markers including the magnetic particles can be applied.

In one embodiment of the present invention, the movement of the sample itself may be restricted by the sample arrangement part.

In one embodiment of the present invention, the step of imparting motion to the detecting complex may change the direction or intensity of the magnetic field at a constant first time interval.

In one embodiment of the present invention, the acquiring of the time correlation may include receiving magnetic field information about the direction or intensity of the magnetic field, obtaining a time correlation of the detected laser speckle using the magnetic field information, can do.

In one embodiment of the present invention, in the step of detecting the laser speckle, the time interval of the predetermined time points may be shorter than the first time.

Other aspects, features, and advantages will become apparent from the following drawings, claims, and detailed description of the invention.

The virus detecting apparatus according to the embodiments of the present invention can detect the presence or absence of the virus, the concentration, and the viruses of the virus by using the change of the time correlation of the laser speckle by the detection complex comprising viruses and magnetic particles. Can be estimated.

1 is a conceptual diagram schematically showing a virus detection apparatus according to an embodiment of the present invention.
2 is a block diagram schematically showing the virus detection apparatus of FIG.
3A and 3B are diagrams schematically illustrating a process of applying a virus marker in the virus marker application unit of FIG.
4 is a flowchart sequentially illustrating a virus detection method according to an embodiment of the present invention.
5 is a view for explaining a method of analyzing time correlation of laser speckles in a controller according to an embodiment of the present invention.
6 is a graph showing the time correlation coefficient according to the type of virus in the sample.
6 is a view for explaining a method of analyzing time correlation of laser speckles in a controller according to an embodiment of the present invention.
7 is a graph showing a standard deviation distribution of light intensity of a laser speckle measured over time through an individual identification apparatus according to an embodiment of the present invention.
8 is a view for explaining the principle of a chaotic wave sensor according to an embodiment of the present invention.
9A and 9B are conceptual diagrams schematically showing a virus detection apparatus according to another embodiment of the present invention.

Hereinafter, embodiments of the present invention will be described in detail with reference to the accompanying drawings, wherein like reference numerals refer to like or corresponding parts throughout the drawings, and a duplicate description thereof will be omitted.

These embodiments are capable of various transformations, and specific embodiments are illustrated in the drawings and described in detail in the detailed description. The effects and features of the embodiments, and how to achieve them, will be apparent from the following detailed description taken in conjunction with the drawings. However, the embodiments are not limited to the embodiments described below, but may be implemented in various forms.

In the following embodiments, the terms first, second, and the like are used for the purpose of distinguishing one element from another element, not the limitative meaning.

In the following examples, the singular forms "a", "an" and "the" include plural referents unless the context clearly dictates otherwise.

In the following embodiments, terms such as inclusive or having mean that a feature or element described in the specification is present, and do not exclude the possibility that one or more other features or elements are added in advance.

In the following embodiments, when a unit, a region, an element, or the like is on or on another portion, not only the case where the portion is directly on another portion but also another unit, region, .

In the following embodiments, terms such as joining or joining do not necessarily mean a direct and / or fixed connection or coupling of two members unless the context clearly indicates otherwise, and it is understood that other members are interposed between the two members It is not excluded.

Means that there is a feature or element described in the specification and does not preclude the possibility that one or more other features or components will be added.

In the drawings, components may be exaggerated or reduced in size for convenience of explanation. For example, the sizes and thicknesses of the components shown in the drawings are arbitrarily shown for convenience of explanation, and therefore, the following embodiments are not necessarily drawn to scale.

Hereinafter, the principle of the chaos wave sensor of the present invention will be described with reference to Fig.

8 is a view for explaining the principle of a chaotic wave sensor according to an embodiment of the present invention.

In the case of a material having a homogeneous internal refractive index like glass, refraction occurs in a certain direction when light is irradiated. However, when a coherent light such as a laser is irradiated on an object having an inhomogeneous internal refractive index, a very complex multiple scattering occurs inside the material.

Referring to FIG. 8, a portion of a wave scattered by a complex path through multiple scattering among light or waves (hereinafter referred to as waves for simplification) irradiated from a wave source passes through the surface to be inspected. The waves passing through various points on the surface to be inspected cause mutual constructive interference or destructive interference and the reinforcement / destructive interference of these waves causes a speckle do.

In this specification, the waves scattered by this complex path are named as "Chaotic wave", and chaotic waves can be detected through laser speckle.

8 is a view showing a state in which a stable medium is irradiated with a laser. Stable speckle patterns with no change can be observed when irradiating a stable medium with no movement of the internal constituent material with interference light (for example, laser).

However, as shown in the right diagram of FIG. 8, when the unstable medium containing movement of internal constituent substances such as bacteria is included therein, the speckle pattern is changed.

That is, microscopic life activity of an organism (for example, intracellular movement, microbial movement, mite movement, etc.) may cause microscopic changes in the optical path over time. Since the speckle pattern is a phenomenon caused by wave interference, a change in the minute light path can cause a change in the speckle pattern. Thus, by measuring the temporal change of the speckle pattern, the movement of the creature can be measured quickly. As described above, when the change of the speckle pattern with time is measured, it is possible to know the presence or concentration of the organism, and furthermore, the kind of the organism.

In the present specification, a configuration for measuring the change of the speckle pattern is defined as a Chaotic Wave Sensor.

Hereinafter, Fig. 1, which is one embodiment of the present invention, will be described based on the principle of the chaos wave sensor described above. FIG. 1 is a conceptual diagram schematically showing a virus detection apparatus 100 according to an embodiment of the present invention, and FIG. 2 is a block diagram schematically showing the virus detection apparatus 100 of FIG. 3A and 3B are diagrams schematically illustrating a process of applying a virus marker in the virus marker application unit 120 of FIG.

1 and 2, a sample placement unit 110, a virus marker application unit 120, a magnetic field formation unit 150, a wave source 130, a detection unit 140, And a control unit 160. [0029]

The sample arrangement unit 110 can receive the sample S. At this time, the sample (S) may be a sample such as a saliva, a blood, a tissue of an individual, or a sample such as a stool, a urine, or a keratin which is discharged from the body to the outside of the body. The sample may be an organic sample such as food or a sample taken from a surface of an object using a cotton swab or tape. The sample (S) may be prepared by using the entire sample as a sample, or by means of a virus, such as a tape, a membrane, or the like. The sample arrangement part 110 may be in the form of a container capable of receiving the sample S. The sample placement unit 110 can support the sample S while restricting the movement of the sample itself. In other words, the sample S itself is detected in a state in which the motion is limited.

The virus marker application unit 120 may apply a virus marker containing magnetic particles to the sample S to form a detection complex in which the virus marker and the virus in the sample are combined. The virus marker application unit 120 may be disposed adjacent to the sample placement unit 110. In another embodiment, the virus detection apparatus 100 may perform the step of moving the sample placement unit 110 to the virus marker application unit 120 to apply the virus marker. In another embodiment, the virus detection apparatus 100 may move the collected sample S to the virus marker application unit 120 and apply the virus marker to the sample placement unit 110. As described above, the position of the virus marker application unit 120 is not limited in the present invention.

Referring to FIG. 3A, the virus marker (A1) may be formed by binding magnetic particles (A13) to a substance that forms a gene pair with a specific virus. Specifically, the virus marker A1 may include an antibody (A11) conjugated with the virus (V1) in the sample (S) and a magnetic particle (A13) bonded to the antibody (A11). The antibody (A11) of the virus marker (A1) can bind to the virus (V1) in the sample (S) through the antigen-antibody reaction whereby the virus (V1) To form a detection complex (C1) combined with the detection complex (C1).

The magnetic particles may be particles having a particle diameter in the nanometer range. Since the magnetic particles have a large scattering of the waves irradiated from the wave source, the laser speckle can be easily detected. On the other hand, the magnetic particles may be specifically a super-magnetic nanoparticle. Here, the superpowder magnetic nanoparticle means a material having strong magnetism when a magnetic field is applied from the outside. For example, at least one selected from the group consisting of Fe (III), Mg, Mg, Ni, Zn and Co. The super-magnetic nanoparticles according to one embodiment may have an average particle size of 3 to 100 nm and may be particles having 4 to 30 nm. In addition, the super magnet nanoparticles may have an average magnetizing power of 60 emu / g to 150 emu / g, and 80 emu / g to 130 emu / g.

Referring to FIG. 3B, the collected sample S may include a plurality of kinds of viruses. In order to detect such a plurality of kinds of viruses, the virus marker application unit 120 may include a plurality of types of virus markers, including an antibody conjugated with any one of a plurality of kinds of viruses and magnetic particles bonded to the antibody, . In the figure, for convenience of explanation, a case where two kinds of viruses are included in the sample S is shown as an example. Since it is not possible to visually check what kind of virus is contained in the sample (S) actually collected, plural kinds of virus markers can be applied to the sample (S) for virus detection.

At this time, the number of kinds of virus markers need not be equal to the number of kinds of viruses in the sample (S). For example, as shown in FIG. 3B, the virus marker application unit 120 may apply the first virus marker A1, the second virus marker A2, and the third virus marker A3, which are three kinds of virus markers, . When the sample S contains the first virus V1 paired with the first virus marker A1 and the second virus V2 paired with the second virus marker A2, The first detection complex C1 in which the first virus marker V1 and the first virus marker A1 are combined and the second detection complex C2 in which the second virus V2 and the second virus marker A2 are combined can be formed have. The virus detecting apparatus 100 can detect not only the presence but also the type of virus in the sample S through the first detecting complex (C1) and the second detecting complex (C2).

On the other hand, the virus marker application unit 120 can remove the virus marker that is not coupled with the virus from the sample S. For example, the virus marker application unit 120 can remove the magnetic particles that are not coupled with the virus from the sample S by using a porous filter. Here, the porous filter may be an object for filtering a detection complex in which a virus marker and a virus marker are combined with each other. Specifically, as an example, the virus marker application unit 120 may remove the third virus marker A3 that is not paired with the sample S using a porous filter (not shown). As a result, only the first detection complex (C1) and the second detection complex (C2) combined with the virus marker including magnetic particles remain in the sample (S), and accurate virus detection can be performed.

1 and 2, the magnetic field forming unit 150 is disposed adjacent to the sample arranging unit 110 to form a magnetic field around the sample arranging unit 110 to move the detecting complex . The magnetic field forming unit 150 can move the magnetic particles included in the detecting complex by using a magnetic force. At this time, the virus bound to the magnetic particles can move together. Since the virus does not move in the same way as a microorganism such as a bacterium, even if a sample (S) to which a virus marker is not applied is irradiated with a wave, the virus can not be detected due to no laser speckle. Therefore, when the virus is present in the sample S, the detection complex can be formed in which the magnetic particles are bound to the virus through the virus marker application unit 120, and the detection complex can be moved to the virus . At this time, the magnetic field forming unit 150 may form a magnetic field by using the RF coil 155 surrounding the sample arrangement unit 110, as shown in the figure. However, it is only one embodiment, and the present invention is not limited thereto. A magnetic field may be formed in the sample S of the sample arrangement part 110 simply by using the permanent magnet. The magnetic field forming unit 150 may use micro-nuclear magnetic resonance (micro-NMR).

The magnetic field forming unit 150 may change the direction or strength of the magnetic field every predetermined first time period to impart movement to the detecting complex. When the magnetic field forming unit 150 applies a magnetic field having a constant direction and intensity to the sample S, the detecting complex C1 can move in one direction and stop moving again, so that accurate virus detection can be difficult. Therefore, the magnetic field forming unit 150 may change the direction or intensity of the magnetic field at a predetermined first time to continuously impart motion while the virus detecting apparatus 100 detects the virus.

The wave source 130 can irradiate a wave toward the sample S in the sample arrangement part 110. [ The wave source 130 may be any type of source device capable of generating waves, for example, a laser capable of emitting light of a specific wavelength band. The present invention is not limited to the kind of the wave source, but the following description will focus on the case of a laser for convenience of explanation.

For example, a laser having good coherence can be used as the wave source 130 in order to form speckles in the sample arrangement unit 110. In this case, the shorter the spectral bandwidth of the wave source that determines the coherence of the laser source, the greater the measurement accuracy. That is, the longer the coherence length, the greater the measurement accuracy. Accordingly, the laser beam whose spectral bandwidth of the wave source is less than the predetermined reference bandwidth can be used as the wave source 130, and the measurement accuracy can be increased as it is shorter than the reference bandwidth. For example, the spectral bandwidth of the wave source may be set such that the condition of Equation (1) below is maintained.

According to Equation (1), in order to measure the pattern change of the laser speckle, the spectral bandwidth of the wave source 130 can be kept less than 1 nm when irradiating the light in the culture dish every reference time.

The detection unit 140 detects the laser speckle generated by multiple scattering of the irradiated waves due to the movement of the detection complex C1 in the sample S at predetermined time points can do. Here, time refers to any one of continuous time flows, and time points can be set in advance at the same time interval, but are not limited thereto, and may be set in advance at an arbitrary time interval . The detection unit 140 may include detection means corresponding to the type of the wave source 130. For example, when a light source of a visible light wavelength band is used, a CCD camera, which is a photographing apparatus for photographing an image, . The detection unit 140 may detect the laser speckle at the first time point and may detect the laser speckle at the second time point and provide the laser speckle to the control unit 160. [ Meanwhile, the first and second points of view are merely examples selected for the convenience of explanation, and the detector 140 can detect laser speckles at a plurality of points of view greater than the first point and the second point of time.

Specifically, when a sample is irradiated with a wave, the incident wave can form laser speckles by multiple scattering. Since the laser speckle is caused by the light interference phenomenon, if there is no movement in the sample, it can always show a constant interference pattern with time. In contrast, when the detection complex is present in the sample S, the laser speckle may change with time due to the movement of the detection complex. The detection unit 140 may detect the laser speckles varying according to the time, and may provide the detected laser speckles to the control unit 160 at predetermined time points. The detection unit 140 can detect the laser speckle at such a speed as to detect the motion of the detection complex, and can detect the laser speckle at a speed of, for example, 25 frames to 30 frames per second.

Meanwhile, the time interval of preset points of time detected by the detector 140 may be shorter than the first time of giving motion to the complex for detection in the magnetic field generator 150. In other words, fast movement of the detecting complex may act as noise if the movement of the detecting complex is shorter than the interval of the measuring points. Therefore, the detection unit 140 can detect the laser speckle at intervals shorter than the first time for changing the direction or strength of the magnetic field in the magnetic field forming unit 150 for accurate detection.

Meanwhile, when the image sensor is used as the detector 140, the image sensor may be arranged such that the size d of one pixel of the image sensor is smaller than or equal to the grain size of the speckle pattern. For example, the image sensor may be disposed in the optical system included in the detection unit 140 so as to satisfy the following condition (2).

If the size d of one pixel of the image sensor is less than the grain size of the speckle pattern as shown in Equation (2), if the size of the pixel becomes too small, undersampling occurs and the pixel resolution There may be difficulties in utilizing Accordingly, the image sensor can be arranged so that no more than five pixels are located in the speckle grain size to achieve an effective SNR (Signal to Noise Ratio).

The controller 160 can obtain a temporal correlation of the detected laser speckle using the detected laser speckle. The controller 160 may estimate the presence or absence of the virus in the sample S or the concentration of the virus in a real-time based on the obtained time correlation. At this time, the controller 160 receives the magnetic field information about the direction or intensity of the magnetic field of the magnetic field generator 150, and obtains the time correlation of the detected laser speckle using the magnetic field information. In this specification, real-time means to estimate the presence or absence of a virus or the concentration of a virus within one hour, and preferably the presence or absence of the virus can be estimated within 5 minutes. More preferably, the virus can be detected within 20 seconds. A method of acquiring the time correlation of the laser speckle in the controller 160 will be described later.

Meanwhile, the virus detection apparatus 100 may further include a display unit 190. The display unit 190 may display the results of the presence, concentration, and type of the virus estimated by the controller 160 as an external information.

4 is a flowchart sequentially illustrating a virus detection method according to an embodiment of the present invention.

Referring to FIG. 4, a virus marker containing magnetic particles is applied to a sample to form a detection complex in which a virus marker and a virus in the sample S are bound (S10). Since there may be a plurality of types of viruses in the sample S, the number of types of virus markers may be plural, and the number of virus types and the number of types of virus marker need not necessarily be the same. At this time, the virus marker may be different in the type of antibody corresponding to the virus, and the magnetic particles bound to the antibody may use the same magnetic particles. Accordingly, when a magnetic field is formed in the sample (S) to impart motion to the detection complex, movement differences may occur depending on the type of the virus, so that the virus can be classified according to the type of virus.

Thereafter, a magnetic field is formed around the sample S to impart movement to the detection complex (S20). The magnetic field forming unit 150 may change the direction or strength of the magnetic field every predetermined first time period, thereby inducing continuous movement of the detecting complex.

Thereafter, the laser beam is irradiated toward the sample S, and the laser speckle generated by multiplying the irradiated wave by the motion of the detection complex is detected at a preset time (S30). At this time, the interval of the predetermined time points may be shorter than the first time for changing the direction or strength of the magnetic field in the magnetic field forming unit 150.

Thereafter, the control unit 160 acquires the time correlation of the detected laser speckle using the detected laser speckle, and determines the presence or concentration of the virus in the sample S based on the obtained time correlation It can be estimated in real time (S40).

Hereinafter, a method of acquiring time correlation of laser speckles in the controller 160 according to an embodiment will be described with reference to FIG.

5 is a view for explaining a method of analyzing time correlation of laser speckles in a controller according to an embodiment of the present invention.

Referring to FIG. 5, in one embodiment, the controller 160 determines whether the first image information of the laser speckle detected at the first point of time and the second image information of the laser speckle detected at the second point of time other than the first point of view The presence of the virus can be estimated using the information difference. Here, the first image information and the second image information may be at least one of pattern information of the laser speckle and intensity information of the wave. Meanwhile, the embodiment of the present invention does not use only the difference between the first image information at the first time point and the second image information at the second time point, but extends the image information of the plurality of laser speckles Information is available. The control unit 160 may calculate the temporal correlation coefficient between images using the image information of the laser speckles generated at a plurality of predetermined points in time, Whether or not the concentration of the virus can be estimated. The temporal correlation of the detected laser speckle image can be calculated using the following equation (3).

은 시간 상관 관계 계수,

은 표준화된 빛 세기, (x,y)는 카메라의 픽셀 좌표, t는 측정된 시간, T는 총 측정 시간,

는 타임래그(time lag)를 나타낸다. In Equation 3,

Time correlation coefficient,

(X, y) is the pixel coordinates of the camera, t is the measured time, T is the total measurement time,

Represents a time lag.

The time correlation coefficient may be calculated according to Equation (3). In one embodiment, the concentration of the virus can be estimated through an analysis in which the temporal correlation coefficients fall below a preset reference value. Specifically, it can be estimated that the virus exists because the temporal correlation coefficient falls below the reference value beyond the predetermined error range. Also, as the concentration of the virus increases, the time correlation coefficient falls below the reference value becomes shorter, so that the virus concentration can be estimated through the slope value of the graph showing the time correlation coefficient. The reference value may vary depending on the type of virus, but a constant reference value can be applied when estimating the average concentration. In the graph of FIG. 5, the solid line S1 represents the time correlation coefficient of the sample in which the virus is not present, and the dotted line S2 represents the time correlation coefficient of the sample in the presence of the virus. If the concentration of the virus differs, the slope value of the dotted line S2 may also vary.

6 is a graph showing the time correlation coefficient according to the type of virus in the sample. In the graph of Fig. 6, the solid line S1 represents the time correlation coefficient of the sample in which no virus exists, and the first dashed line C1 represents the time correlation coefficient of the sample in which only the first virus V1 exists. The third dashed line C2 represents the temporal correlation coefficient of the sample in which only the second virus V2 exists and the second dashed line C1 + C2 represents the time correlation coefficient between the first virus V1 and the second virus V2 The time correlation coefficient of the sample is shown. At this time, when the first virus (V1) and the second virus (V2) coexist, it can be assumed that the concentration is the same as the case where only the first virus exists or only the second virus exists. In FIG. 3B, the first virus (V1) and the second virus (V2) are shown in the same circle, but the first virus (V1) and the second virus (V2) may have different shapes and different weights. Therefore, the first detection complex (C1) containing the first virus (V1) and the second detection complex (C2) containing the second virus (V2) can show different motions even if they are placed on the same magnetic field . The time correlation of the laser speckle may be different from this other movement. By using these differences, the kinds of viruses in the sample (S) can be distinguished.

Hereinafter, with reference to FIG. 7, a method of determining the concentration of the virus in the sample using the laser speckle in the control unit 160 will be described in detail.

7 is a graph showing a standard deviation distribution of light intensity of a laser speckle measured over time through an individual identification apparatus according to an embodiment of the present invention.

Referring to FIG. 7, the controller 160 may calculate the standard deviation of the intensity of the laser speckle with respect to the laser speckle image measured for each reference time. As the viruses in the sample continue to move, constructive interference and destructive interference can change in response to the movement. At this time, as the constructive interference and the destructive interference change, the degree of light intensity may vary greatly. Then, the control unit 160 can measure the location of the virus in the measurement target by obtaining the standard deviation indicating the degree of change of the light intensity, and the distribution of the virus can be measured.

For example, the control unit 160 may synthesize the laser speckle images measured at predetermined time intervals, and calculate the light intensity standard deviation of the laser speckle over time in the synthesized image. The light intensity standard deviation of the laser speckle over time can be calculated based on Equation (4) below.

: 시간에 따른 평균 빛 세기를 나타낼 수 있다.In Equation 4, S: standard deviation, (x, y): camera pixel coordinates, T: total measurement time, t: measurement time,

: It can indicate the average light intensity over time.

The strength and the destructive interference pattern are changed according to the movement of the detection complex, and the standard deviation value calculated based on Equation (4) becomes larger, so that the concentration of the virus can be measured based on this. However, the present invention is not limited to the method of measuring the concentration of virus according to Equation (4) above, and the concentration of the virus can be measured by any method using the difference of detected laser speckle.

The control unit 160 can estimate the distribution of viruses included in the subject, that is, the concentration based on the linear relationship between the magnitude of the standard deviation of the light intensity of the laser speckle and the virus concentration.

As described above, the virus detecting device according to the embodiments of the present invention can detect the presence of viruses at a low cost and at a low cost by using the change in the time correlation of the laser speckles by the detecting complex comprising viruses and magnetic particles. Whether or not, concentration and kind of virus can be estimated.

9A and 9B are conceptual diagrams schematically showing a virus detection device 200 according to another embodiment of the present invention.

Referring to FIGS. 9A and 9B, the virus detection apparatus 200 is configured to detect a first wave signal scattered from a sample by using an optical unit for modulating a wave of the wave source 230 into a second optical signal before being scattered by the sample (35). In this case, the optical unit 35 may include a spatial light modulator (SLM) 351 and a detection unit 240. When the scattered wave is incident from the measurement object, the optical unit 35 controls the wavefront of the scattered wave, restores the wave to the scattered wave (light), and provides the wave to the detection unit 240.

The spatial light modulator 351 can receive waves (light) scattered from the sample. The spatial light modulator 351 can control the wavefront of the scattered wave in the sample and provide it to the lens 352. The lens 352 can collect the controlled light and provide it to the detector 240 again. The detection unit 240 may detect the wave condensed in the lens and may restore the waveform output from the original wave source to be scattered and output.

Here, the optical unit 35 can restore the first optical signal scattered from the sample to light before the scattering, when there is no stable movement of the living body, that is, the movement of the living things in the measurement object. However, when the virus exists in the measurement object, the first optical signal changes due to the motion of the detection complex, so that the phase control wavefront can not be detected, and therefore, the second optical signal having the phase conjugate wavefront can not be modulated . The virus detecting apparatus 200 including the optical unit 35 may estimate the presence or the concentration of the virus more finely using the difference of the second optical signal.

The present invention has been described above with reference to preferred embodiments. It will be understood by those skilled in the art that the present invention may be embodied in various other forms without departing from the spirit or essential characteristics thereof. Therefore, the above-described embodiments should be considered in an illustrative rather than a restrictive sense. The scope of the present invention is indicated by the appended claims rather than by the foregoing description, and all differences within the scope of equivalents thereof should be construed as being included in the present invention.

100: Virus detection device 110: Sample arrangement part
120: Virus marker applying unit 130: Wave marker
140: detecting part 150: magnetic field forming part
155: RF coil 160:
190: display unit 200: virus detection device
240:

Claims (15)

A sample placement part for receiving the sample;
A virus marker application unit applying a virus marker including magnetic particles to the sample to form a detection complex in which the virus marker and the virus in the sample are bound;
A magnetic field forming unit disposed adjacent to the sample arranging unit to form a magnetic field around the sample arranging unit to impart motion to the detecting complex;
A wave source for irradiating a wave in the sample arrangement part toward the sample;
At least one detector for detecting a laser speckle generated by multiple scattering of the irradiated waves due to the movement of the detection complex at predetermined time points; And
Acquiring a temporal correlation of the detected laser speckle using the detected laser speckle and determining whether the virus is present in the sample or the concentration of the virus based on the obtained time correlation, and estimating the real time of the virus detection unit. The method according to claim 1,
Wherein the virus marker comprises an antibody conjugated with the virus in the sample and the magnetic particles bound to the antibody. 3. The method of claim 2,
Wherein the sample contains plural kinds of viruses,
Wherein the virus marker application unit applies to the sample a plurality of types of virus markers including the antibody conjugated with any one of the plurality of kinds of viruses and the magnetic particles bonded to the antibody. The method according to claim 1,
And the sample placement unit supports the sample while restricting movement of the sample itself. The method according to claim 1,
Wherein the magnetic field generator changes the direction or intensity of the magnetic field every predetermined first time period to impart motion to the detection complex. 6. The method of claim 5,
Wherein the controller receives the magnetic field information about the direction or strength of the magnetic field to be changed by the magnetic field forming unit and acquires the time correlation of the detected laser speckle using the magnetic field information. 6. The method of claim 5,
Wherein the time interval of the predetermined time points detected by the detection unit is shorter than the first time. The method according to claim 1,
Wherein the magnetic field forming unit uses a micro-nuclear magnetic resonance apparatus (micro-NMR). Applying a virus marker containing magnetic particles to the sample to form a detection complex in which the virus marker and the virus in the sample are bound;
Forming a magnetic field around the sample to impart motion to the detection complex;
Detecting a laser speckle generated by multiple scattering of the irradiated waves due to the movement of the detection complex at predetermined time points by irradiating the waves toward the specimen;
Obtaining a temporal correlation of the detected laser speckle using the detected laser speckle; And
Estimating the presence or absence of a virus in the sample based on the obtained time correlation or a concentration of the virus in a real-time manner. 10. The method of claim 9,
Wherein the virus marker comprises an antibody conjugated with the virus in the sample and the magnetic particles bound to the antibody. 11. The method of claim 10,
Wherein the step of forming the detecting complex comprises:
Wherein a plurality of types of virus markers including the antibody conjugated with any one of the plural kinds of viruses and the magnetic particles bound to the antibody are applied to the sample containing plural kinds of viruses. 10. The method of claim 9,
Wherein the movement of the sample itself is restricted by the sample arrangement part of the sample. 10. The method of claim 9,
Wherein the step of imparting motion to the detecting complex changes the direction or strength of the magnetic field at a constant first time interval. 14. The method of claim 13,
Wherein the acquiring of the temporal correlation acquires the time correlation of the detected laser speckle using the magnetic field information on the direction or intensity of the magnetic field. 14. The method of claim 13,
Wherein the step of detecting the laser speckle is such that the time interval of the predetermined time points is shorter than the first time.

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