KR102279510B1 - Apparatus for diagnosing virus - Google Patents

Abstract

Disclosed in the specification is a virus diagnosing device which conducts irradiation of laser having continuous pulses specific for a target virus, makes light pass through a specimen irradiated with the laser, and then diagnoses existence of the virus by using change in spectroscopic properties. According to the present invention, the target virus can be diagnosed in a short time.

Description

Virus diagnostic device {APPARATUS FOR DIAGNOSING VIRUS}

The present invention provides a virus diagnosis apparatus for diagnosing a target virus.

The method of diagnosing SARS-CoV-2 (SARS-CoV-2 or 2019-nCoV), which is the cause of the recent novel coronavirus infection-19 (hereinafter referred to as “COVID-19”), is to use a diagnostic reagent. There was a real-time gene amplification test (RT-PCR) and a test kit using an antibody-antigen reaction.

The real-time gene amplification test (RT-PCR), which is currently the most common diagnostic method, is a method of diagnosing the presence of SARS-coronavirus-2 through gene amplification after injecting a diagnostic reagent into a sample.

In this method, even if the time is shortened as much as possible, the diagnosis time is long because the gene amplification process is required. In addition, since this method requires a gene amplification device, it cannot be diagnosed immediately at an airport or a crowded area, and after collecting a sample, only a specialized diagnostic institution or hospital equipped with a gene amplification device diagnoses SARS-coronavirus-2 there was a problem with

In addition to the above-described SARS-Coronavirus-2, diagnostic methods for various types of viruses have a problem in that the diagnosis time is long and only a specialized diagnostic institution or hospital can diagnose the virus.

The present embodiments provide a virus diagnosis apparatus with a short diagnosis time for diagnosing a target virus.

The present embodiments provide a virus diagnosis apparatus for immediately diagnosing a virus at a sample collection site other than a specialized diagnostic institution or a hospital.

In the present specification, a laser (hereinafter referred to as a pulse laser) having a continuous pulse specific to a target virus is irradiated to a specimen to inactivate the virus contained in the specimen, and this results in a change in the chemical structure of the virus. A small change in optical properties is induced, and the laser beam, which has different wavelengths and is continuously output to the sample irradiated with this pulse laser, is divided into two light beams, one of them (hereinafter referred to as probe light). ) to change the amplitude and phase of the probe light, and measure the amplitude and phase change induced by the probe light with high sensitivity by interfering with other beams that do not pass through the sample (hereinafter referred to as reference light). Thus, a virus diagnosis device for diagnosing the presence of a virus by analyzing the change is disclosed.

In one embodiment, a neutralizing pulse irradiator that irradiates a laser having a continuous pulse specific to a target virus, a container that can accommodate a sample and is located on the irradiation path of the laser irradiated by the neutralizing pulse irradiator, and light toward the container A probe beam irradiator that irradiates, a beam splitter that separates the light irradiated from the probe light irradiator into a probe beam directed to a container and a reference beam that does not pass through the container, an interferometer that interferes with the probe beam that has passed through the container and the reference beam that does not pass through the container, and Provided is a virus diagnosis apparatus including a control unit for diagnosing whether a target virus is present in a sample according to a result of interference between probe light and reference light.

This interferometer may be an I/Q-interferometer that can measure the phase change and the amplitude change induced by the probe light at the same time.

Another embodiment is a neutralizing pulse irradiator that irradiates a laser having a continuous pulse specific to a target virus, a container that can accommodate a sample and is located on the irradiation path of the pulse irradiated by the neutralizing pulse irradiator, wavelength division multiplexing (wavelength) Division multiplexing (WDM) technology is applied to generate multi-wavelength probe light having two or more wavelengths, and it is irradiated by the multi-wavelength probe light irradiator and the multi-wavelength probe light emitter that irradiates the probe light toward the container A beam splitter that separates wavelength light into probe light directed to the container and reference light that does not pass through the container, an interferometer that interferes with the probe light that has passed through the container and the reference light that does not pass through the container, and re-wavelengths the interfered multi-wavelength probe light and reference light Provided is a virus diagnosis apparatus comprising a demultiplexing unit for demultiplexing each wavelength, and a control unit for diagnosing the presence or absence of a target virus in a sample according to a result of interference for each wavelength of probe light and reference light.

According to the virus diagnosis apparatus according to the present embodiments, the diagnosis time for diagnosing the target virus may be short.

According to the virus diagnosis apparatus according to the present embodiments, it is possible to immediately diagnose a virus at a sample collection site other than a specialized diagnosis institution or a hospital.

1 is a block diagram of a virus diagnosis apparatus according to an exemplary embodiment.
2 is a block diagram of a virus diagnosis apparatus according to another embodiment.
FIG. 3 is a diagram illustrating processes for diagnosing a virus using the virus diagnosis apparatus according to another embodiment of FIG. 2 .
FIG. 4 shows the result of modification of the phospholipid or protein of the target virus by the light irradiated by the neutralizing pulse irradiation unit of FIG. 2 .
5 is a block diagram of a virus diagnosis apparatus according to another embodiment.
6 is a block diagram of an example of the control unit of FIG. 5 .
FIG. 7 is a diagram illustrating an interference result between the probe light and the reference light of FIG. 5 .
8 is a block diagram of another example of the control unit of FIG. 5 .
9 is a block diagram of a virus diagnosis apparatus according to another embodiment.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS Hereinafter, embodiments of the present invention will be described in detail with reference to the accompanying drawings so that those skilled in the art can easily implement them. However, the present invention may be embodied in many different forms and is not limited to the embodiments described herein. And in order to clearly explain the present invention in the drawings, parts irrelevant to the description are omitted, and similar reference numerals are attached to similar parts throughout the specification.

Throughout the specification, when a part is "connected" to another part, it includes not only the case where it is "directly connected" but also the case where it is "electrically connected" with another element interposed therebetween. . Also, when a part "includes" a component, it means that other components may be further included, rather than excluding other components, unless otherwise stated, and one or more other features However, it is to be understood that the existence or addition of numbers, steps, operations, components, parts, or combinations thereof is not precluded in advance.

The terms "about", "substantially", etc. to the extent used throughout the specification are used in a sense at or close to the numerical value when the manufacturing and material tolerances inherent in the stated meaning are presented, and serve to enhance the understanding of the present invention. To help, precise or absolute figures are used to prevent unfair use by unscrupulous infringers of the stated disclosure. As used throughout the specification of the present invention, the term “step for (to)” or “step for” does not mean “step for”.

In this specification, a "part" includes a unit realized by hardware, a unit realized by software, and a unit realized using both. In addition, one unit may be implemented using two or more hardware, and two or more units may be implemented by one hardware.

1 is a block diagram of a virus diagnosis apparatus according to an exemplary embodiment.

Referring to FIG. 1 , the virus diagnosis apparatus 100 according to an embodiment irradiates a laser having a continuous pulse specific to a target virus, and a very small change in the structure of a virus contained in a sample irradiated with the laser. Disclosed is a virus diagnosis apparatus for diagnosing the presence or absence of a virus using a change in spectroscopic characteristics.

The virus diagnosis apparatus 100 according to an embodiment includes a neutralizing pulse irradiation unit 110 , a container 120 , a probe light irradiation unit 130 , and a control unit 140 .

The neutralizing pulse irradiation unit 110 irradiates a laser having a continuous pulse of a specific wavelength specific to the target virus. The neutralizing pulse irradiation unit 110 may irradiate a laser having a continuous pulse of a single wavelength specific to a target virus, or may irradiate a laser having a continuous pulse of multiple wavelengths specific to a target virus.

The neutralizing pulse irradiation unit 110 may include, for example, a laser diode-pumped mode-locked Ti-sapphire laser (laser diode-pumped mode-locked Ti-sapphire laser) device. This laser device is ^{a femtosecond laser capable of generating successive pulses with a pulse width shorter than 10 -12} seconds, and can also increase the energy per pulse by using an optical amplifier or the like.

In other words, the neutralization pulse irradiation unit 110 includes an optical amplifier, for example, an optical parametric amplifier, and specifically converts the intermediate wavelength of the neutralization pulse to a virus using the optical parametric amplifier to output it. can

A target virus is a contagious infectious agent that lives only in the living cells of other organisms and is an intermediate between living and non-living (anti-living). Depending on the type of host, target viruses can be divided into plant viruses, animal viruses, and bacterial viruses (phages). According to the type of nucleic acid, the target virus can be divided into a DNA virus or an RNA virus.

In the following, the target virus is exemplified by SARS-coronavirus-2 (SARS-CoV-2 or 2019-nCoV), which is the cause of the recently prevalent novel coronavirus infection-19 (COVID-19), as shown in FIG. 4 . However, the present specification is not limited thereto.

In addition, the laser specific to the target virus is ^{a femtosecond laser that typically generates a pulse shorter than 10 -12} seconds, but the present specification is not limited thereto. For example, a laser specific for SARS-CoV-2 (SARS-CoV-2 or 2019-nCoV) ^{may have a pulse of approximately several hundred femtoseconds (10 −15} sec), but with a pulse specific for the target virus. Any laser is free.

The container 120 can accommodate the specimen, and is located on the irradiation path of the laser irradiated from the neutralizing pulse irradiation unit 110 . The sample may be exhaled gas flowing out of the organism as a gas, but may also be a liquid such as blood or a solid object separated through a device. Hereinafter, the sample is exemplified as exhaled gas, but the present specification is not limited thereto.

The container 120 seals the specimen, such as exhaled gas, during the test period. Therefore, the exhaled gas may be accommodated in the container 120 through an exhaust port (not shown) of the container 120 before the inspection, and then discharged out of the container 120 through the exhaust port after the inspection.

When the sample is exhaled gas, the sample may be concentrated by using a method such as pressurizing the sample to increase the concentration of the target virus.

In the virus diagnosis apparatus 100 according to an embodiment, a sensor or device 122 for detecting exhaled gas may be installed in the exhaled gas inlet 121 spatially connected to the container 120 . Alternatively, in the virus diagnosis apparatus 100 according to an embodiment, a sensor or device 123 for detecting exhaled gas may be installed inside the container 120 .

The sensor or device (122, 123) for detecting exhaled gas is a dog nose sensor or electronic sensor for detecting exhaled gas used in lung disease testing, etc., or a mechatronic sensor for detecting temperature or pressure, carbon dioxide or It may be one or more than one gas analysis sensor that analyzes gas components such as methane.

The virus diagnosis apparatuses 200 , 300 , and 440 according to other embodiments to be described below may also include the sensors or devices 122 and 123 for detecting the exhaled gas described above, but a detailed description thereof will be omitted.

The container 120 may be made of a material such as glass through which the laser irradiated by the neutralization pulse irradiator 110 and the light irradiated from the probe light irradiator 130 can be transmitted, and the optical quality ( It may be composed of a window made of a material that can transmit the irradiated light, such as glass of optical quality, and the window may be coated with anti-reflection for the irradiated light.

The exploration light irradiation unit 130 irradiates light toward the container 120 . The probe light irradiator 130 is any device capable of generating light that can pass through the material of the container 120 and reach the control unit 140 , for example, a light emitting diode or laser diode, or wavelength multiplexed laser light. can At this time, the light irradiated by the probe light irradiation unit 130 may be any light such as visible light, infrared light, or ultraviolet light. In addition, the light irradiated by the probe light irradiator 130 may be multi-wavelength light transmitted to the container 120 along the same path with two or more wavelengths using the existing wavelength division multiplexing method. The control unit 140, in a state in which the container 120 accommodates the sample, the first absorption spectrum of the first light passing through the container 120, and the container 120 receives the sample and the laser neutralizes the pulse irradiation unit 110 ) in the state irradiated toward the sample in the container 120 , the second absorption spectrum of the second light passing through the container 120 is compared to diagnose the presence of the target virus in the sample. The controller 140 diagnoses the presence of a target virus in the sample by comparing the first and second absorption spectra of the first and second lights 135 and 136 passing through the sample before and after laser irradiation, as will be described later. .

The control unit 140 can know the interaction process between the virus and the laser pulse included in the sample from the change in intensity, pulse width, and spectroscopic characteristics of the laser pulse before and after transmitting the laser pulse to the sample, and Information on the size, concentration, structure, etc. of the scatterer can be obtained from the changes in the linear and nonlinear optical properties of the pulse. This will be described in detail in the virus diagnosis apparatus according to still other embodiments described with reference to FIGS. 5 and 8 .

The control unit 140 may additionally utilize the analysis result of the type, temperature, pressure, and gas components of the exhaled gas detected by the sensor or the devices 122 and 123 during virus diagnosis.

The virus diagnosis apparatus 100 according to the embodiment described with reference to FIG. 1 directly irradiates the light generated by the probe light irradiation unit 130 to the container 120, but another embodiment described with reference to FIGS. 2 and 3 . The light path is adjusted using the reflection units 132 and 134 as in the virus diagnosis apparatus 200 according to the present invention, or the reflection units 132 and 134 and the resonators 126 and 127, for example, a Harriot mirror. The container 120 may be repeatedly passed along the same path using a resonator mirror such as , and may be passed after successively repeated along several different paths within the container using a Harriet mirror.

2 is a block diagram of a virus diagnosis apparatus according to another embodiment.

Referring to FIG. 2 , the virus diagnosis apparatus 200 according to another embodiment irradiates a laser having a continuous pulse specific to a target virus, and a very small change in the structure of the virus contained in the sample to which the laser is irradiated The presence of virus can be diagnosed using an interferometer, especially an I/Q-interferometer that can measure the changes in spectroscopic characteristics by simultaneously discriminating and measuring the phase and amplitude changes of the probe light.

The virus diagnosis apparatus 200 according to another embodiment has a neutralizing pulse irradiation unit 110 , a container 120 , a probe light irradiation unit 130 , and a control unit 140 in the same manner as the virus diagnosis apparatus 100 described with reference to FIG. 1 . includes

In addition, the virus diagnosis apparatus 200 according to another embodiment includes a first reflector 132 and a container 120 that reflect the first and second lights irradiated from the probe light irradiation unit 130 and guide them to the container 120 . It may further include a second reflector 134 for reflecting the first and second light passing through. The first reflector 132 and the second reflector 134 may include a dichroic mirror that transmits light incident on one surface of both surfaces and transmits light incident on the other surface.

For example, the first reflector 132 may include a dichroic mirror that transmits the laser irradiated from the neutralization pulse irradiator 110 and reflects the light irradiated from the probe light irradiator 130 . The second reflecting unit 134 may also include a dichroic mirror.

Since the virus diagnosis apparatus 200 according to another embodiment adjusts the light path using the first and second reflectors 132 and 134 , the space efficiency of the virus diagnosis apparatus 200 may be improved.

In addition, the virus diagnosis apparatus 200 according to another embodiment includes the first resonator 126 and the second reflector 134 and the control unit 126 disposed between the probe light irradiation unit 130 and the first reflecting unit 132 . 140) may include a second resonator 127 disposed between.

Alternatively, the resonators 126 and 127 that are disposed between the first reflector 132 and the second reflector 134 so that the femtosecond pulse and the second light can reciprocate several times along the same path in the container 120, e.g. For example, as described above, it may include a first Harriot mirror and a second Harriot mirror.

The virus diagnosis apparatus 200 according to another embodiment causes the first and second lights to resonate between the first resonator 126 and the second resonator 127, so that the container 120 receives the first and second lights as many times as the number of resonances. 2 light can pass through.

FIG. 3 is a diagram illustrating processes for diagnosing a virus using the virus diagnosis apparatus according to another embodiment of FIG. 2 .

As shown in FIG. 3 , the controller 140 compares the first and second absorption spectra of the first and second lights 135 and 136 passing through the sample before and after irradiating the laser to determine whether the target virus is present in the sample. diagnose

Referring to FIG. 3 , as shown in FIG. 3A , the control unit 140 transmits the first light 135 passing through the container 120 in a state in which the container 120 accommodates the specimen. The first absorption spectrum is analyzed.

The first light 135 is a first resonator 126 disposed between the probe light irradiator 130 and the first reflecting unit 132 and a second resonator 126 disposed between the second reflecting unit 134 and the controller 140 . After resonance between the two resonator units 127 , the control unit 140 is reached.

As shown in (B) of FIG. 3 , the control unit 140 receives the specimen and the laser is irradiated from the neutralizing pulse irradiation unit 110 toward the specimen in the container 120 , the container A second absorption spectrum of the second light 136 passing through 120 may be analyzed.

The second light 136 is a first resonator 126 disposed between the probe light irradiator 130 and the first reflecting unit 132 and the second light 136 disposed between the second reflecting unit 134 and the controller 140 . After resonance between the two resonator units 127 , the control unit 140 is reached.

FIG. 4 shows the result of modification of the phospholipid or protein of the target virus by the light irradiated by the neutralizing pulse irradiation unit of FIG. 2 .

As shown in (A) of Figure 4, SARS-coronavirus-2, which is the cause of the recently popular novel coronavirus infection-19 (COVID-19), is wrapped in phospholipids, and proteins (aka spike proteins) attached to this phospholipid.

As shown in FIG. 4B, when a laser having a continuous pulse specific for SARS-coronavirus-2 is irradiated from the neutralizing pulse irradiation unit 110 toward the sample in the container 120, for example, It affects the hydro-binding included in the phospholipids or proteins of SARS-Coronavirus-2, and as a result, the phospholipids or proteins of SARS-Coronavirus-2 are modified.

If the sample is not included in SARS-coronavirus-2, when a laser having a continuous pulse specific for SARS-coronavirus-2 is irradiated from the neutralizing pulse irradiator 110 toward the sample in the container 120, the laser The first and second spectroscopic or optical characteristics of the first and second lights 135 and 136 passing through the specimen before and after irradiation are the same.

As shown in FIGS. 3 and 4 (A) and (B), the first and second spectroscopic or optical characteristics of the first and second lights 135 and 136 passing through the sample before and after irradiating the laser are -Coronavirus-2 is inevitably different depending on the modification of the phospholipids or proteins. Accordingly, the controller 140 compares the first and second optical characteristics of the first and second lights 135 and 136 to diagnose the presence of the target virus in the sample.

In summary, the virus diagnosis apparatuses 100 and 200 according to the embodiments modify the structure of a target virus with a laser having a continuous pulse specific to the target virus, and then perform spectroscopic or optical analysis before and after laser irradiation. Viruses can be detected by changing their characteristics.

The virus diagnosis apparatuses 100 and 200 according to embodiments have been described above with reference to FIGS. 1 to 4 . Hereinafter, an interferometer, for example, an I/Q-interferometer, is used to measure changes in spectroscopic and optical properties, such as changes in amplitude and phase of probe light, so that the sensitivity and specificity for diagnosing viruses contained in samples can be improved. Virus diagnosis apparatuses according to another embodiment will be described in detail.

5 is a block diagram of a virus diagnosis apparatus according to another embodiment.

Referring to FIG. 5 , the virus diagnosis apparatus 300 according to another embodiment irradiates a laser having a continuous pulse specific to a target virus, passes light through the irradiated sample, and divides it according to an absorption spectrum. The presence of virus is diagnosed using changes in optical properties.

The virus diagnosis apparatus 300 according to another embodiment includes a neutralizing pulse irradiation unit 310 , a container 320 , a probe light irradiation unit 330 , a beam splitter 332 , an interferometer 338 , and a control unit 340 . .

The neutralizing pulse irradiator 310 , the container 320 and the probe light irradiator 330 are substantially the same as the neutralization pulse irradiator 110 , the container 120 , and the probe light irradiator 130 described with reference to FIGS. 1 and 2 . can do.

In particular, the neutralizing pulse irradiator 310 includes an optical amplifier, and can amplify the output of a pulse specific to the target virus using the optical amplifier. Using an optical parametric oscillator, etc., the middle of the laser The wavelength (center wavelength) can be adjusted to a specific wavelength for the virus. The neutralization pulse irradiation unit 310 may increase the output of the pulse by amplifying the output of the pulse using an amplifier.

The beam splitter 332 separates the light irradiated from the probe light irradiation unit 330 into a probe light 339a directed to the container 320 and a reference light 339b that does not pass through the container 320 . .

The interferometer 338 interferes with the probe light 339a passing through the container 320 and the reference light 339b not passing through the container 320 .

The controller 340 diagnoses the presence or absence of a target virus in the sample according to the interference result of the probe light 339a and the reference light 339b.

In the virus diagnosis apparatus 300 according to another embodiment, the first reflector 336 and the beam splitter 332 reflect the probe light 339a separated from the beam splitter 332 and guide it to the container 320 . A second reflector 334 for guiding the separated reference light 339b to the interferometer 338 may be further included.

The virus diagnosis apparatus 300 according to another embodiment described with reference to FIG. 5 uses an interferometer, for example, an I/Q-interferometer, to measure changes in spectroscopic and optical properties such as changes in amplitude and phase of probe light. Compared to the virus diagnosis apparatuses 100 and 200 described with reference to FIGS. 1 and 2 , the sensitivity for diagnosing the virus included in the specimen and specificity may be improved.

6 is a block diagram of the control unit of FIG. 5 .

Referring to FIG. 6 , the control unit 340 compares the preprocessing unit 343 for preprocessing the first and second interference signals of the probe light 339a and the reference light 339b and the preprocessed first and second interference signals to obtain a sample. may include an analysis unit 344 for diagnosing the presence or absence of a target virus, and an output unit 346 for outputting a diagnosis result of the analysis unit 344 .

The analysis unit 344 compares the first and second interference signals preprocessed using artificial intelligence technology to diagnose the presence of the target virus in the sample.

FIG. 7 is a diagram illustrating an interference result between the probe light and the reference light of FIG. 5 .

Referring to FIG. 7 , one light irradiated by the probe light irradiation unit 330 is divided into a probe light 339a and a reference light 339b by the beam splitter 332 . The probe light 339a is reflected from the first reflector 336 , is irradiated toward the specimen in the container 320 , and finally reaches the interferometer 338 . The reference light 339b is reflected from the second reflector 334 and does not pass through the sample in the container 320 and arrives at an interferometer 338 composed of another beam splitter and a photodetector, where the interference signal between the probe light and the reference light is obtained. can be detected.

The two extreme cases of the interference signal are augmented interference in which the magnitude of the interference signal is maximized as the phases of the interfering probe light 339a and the reference light 339b are equal to each other as shown in FIG. 7(A) and FIG. 7(B). ) is destructive interference in which the magnitude of the interfered signal is minimized because the phase is staggered by 180 degrees, for example, and according to the phase difference between the probe light 339a and the reference light 339b, the interference signal is between the maximum value and the minimum value. have a value

Accordingly, the phase difference between the probe light 339a and the reference light 339b can be measured by measuring the magnitude of the interference signal. The phase difference between the probe light 339a and the reference light 339b is given by the refractive index, which is an optical characteristic of the transmitted medium. Therefore, by measuring the interference signal, it is possible to know information about the difference in refractive index between the media through which they each pass.

On the other hand, the size of the interference signal can be changed even by the size change of the probe light 339a. The size of the probe light 339a passing through the container 320 depends on the change in absorption coefficient, which is another characteristic of the sample. is given by That is, when the refractive index or absorption index changes as the virus is neutralized by the neutralization pulse 310a, the change can be measured with very high sensitivity using the interferometer 338 .

However, as described above, when the chemical structure of the virus is changed by the neutralization pulse 310a and, accordingly, the refractive index and the absorption index of the sample change at the same time, whether the change is due to the phase change of the probe light 339a according to the change in the refractive index or the absorption rate change It is not possible to distinguish whether it is caused by the amplitude change of the probe light 339b.

Since the I/Q-interferometer is an interferometer that can separate and measure the phase change and the intensity change of the probe light at the same time, the phase change induced by the probe light 339a, that is, the change in the refractive index of the sample and the probe light 339a By separately and simultaneously measuring the induced amplitude change, that is, the change in the absorption rate of the sample, it is possible to simultaneously measure the change in the refractive index and the absorption index occurring in the sample due to the virus whose chemical structure is changed by the neutralization pulse 310a. Therefore, more detailed information about the virus can be obtained when the I/Q-interferometer is applied.

The neutralizing pulse irradiation unit 110 irradiates a laser having a continuous pulse of a specific wavelength specific to the target virus. The neutralizing pulse irradiation unit 110 may irradiate a laser having a continuous pulse of a single wavelength specific to a target virus, or may irradiate a laser having a continuous pulse of multiple wavelengths specific to a target virus.

Since the neutralization pulse 310a selective and specific only to the target virus was irradiated to the specimen, if the target virus does not exist in the specimen, the first interference signal and the neutralization pulse 310a, which are the interference signals prior to irradiation of the neutralization pulse 310a, are irradiated There is no change in the second interference signal measured during the operation and the third interference signal measured after the neutralization pulse 310a.

On the other hand, if the target virus is present in the sample, the optical properties of the sample before virus neutralization from the above-described first interference signal, the dynamic change of the optical properties of the sample in the process of neutralization of the virus from the second interference signal, and the third It is possible to measure the optical change that occurred in the sample after virus neutralization occurred from the interference signal.

Therefore, it is possible to measure the change in the optical properties of the specimen according to the neutralization pulse condition, and show an interference result different from that of (A) or (B) in FIG. 7 as a result of the interference between the probe light 339a and the reference light 339b under the neutralization pulse condition. have. That is, the analyzer 344 may detect a target virus by irradiating a laser to the specimen and checking a change in phase and/or amplitude as a result of interfering waves of two paths using an interferometer.

As described above, the analysis unit 344 irradiates a single-wavelength laser pulse specific for a virus or a multi-wavelength laser pulse having two or more different wavelengths and output is synchronized with each other, and neutralizing conditions (pulse energy and width, wavelength) etc.), it provides various data systematically measuring the change in interference signal due to the spectral characteristics of a specific virus that appear differently depending on the spectral characteristics and the change in spectral characteristics due to its neutralization

Referring back to FIG. 5 , the virus diagnosis apparatus 310 according to another embodiment may further include a receiver 350 .

The receiver 350 receives the neutralization pulse 310b passing through the specimen, receives the neutralization pulse 310c scattered from the virus, or receives both pulses 310b and 310c. The receiver 350 includes a component (eg, a correlator) that receives the neutralization pulse 310b that has passed through the specimen and a component that receives the neutralization pulse 310c scattered from the virus (eg, a scattered light receiver). Each may be included.

8 is a block diagram of another example of the control unit of FIG. 5 .

The control unit 340 may be divided into a first control unit 340a and a second control unit 340b. The first control unit 340a may process the interference signal as described with reference to FIG. 5 , and the second control unit 340b may measure a change due to the laser pulse.

The first control unit 340a is electrically connected to the interferometer 338 as described above. The first control unit 340a includes a first preprocessor 343a , a first analysis unit 344a , and a second output unit 346a that are substantially the same as the control unit 340 described with reference to FIG. 6 .

The second controller 340b may be electrically connected to the receiver 350 . The second control unit 340b includes a second preprocessing unit 343b that preprocesses the neutralization pulse 310b passing through the specimen and the neutralization pulse 310c scattered from the virus received by the receiving unit 350, and the preprocessed pulse It may include a second analysis unit 344b for comparing the values, and a second output unit 346b for outputting the analysis result of the second analysis unit 344b.

If the target virus is not present in the sample, there is no interaction between the virus and the specific laser pulse for the virus, so there is no specific change in the width and energy of the laser pulse passing through the sample. There is no change induced by negative interactions.

The analysis unit 344b of the second control unit 340b compares the laser pulse 310a irradiated by the neutralization pulse irradiation unit 310 with the laser pulse 310b passing through the specimen. If the output unit 346b of the second control unit 340b confirms that there is no specific change in the width and energy of the laser pulse that has passed through the specimen, it outputs the comparison result as that the target virus does not exist in the specimen.

On the other hand, if a virus is present in the sample, a unique change in the width and energy of the neutralization pulse that has passed through the specimen is induced by the specific interaction with the neutralization pulse, and the neutralization pulse scattered from the virus also has a specific interaction between them. Linear and non-linear optical changes are induced under the influence of

Therefore, the virus diagnosis apparatus 300 according to another embodiment measures the linear and non-linear spectroscopic characteristics of light scattered from the specimen through the receiving unit 350 and the second control unit 340b and its change with time, By measuring the change in the width and energy of the neutralizing laser pulse that has passed through it, a lot of information about the virus that specifically interacts with the neutralizing pulse can be obtained.

The virus diagnosis apparatus 300 according to another embodiment secures basic data on volatile organic components included in the sample by using a conventional electronic nose or the like with respect to the sample collected from the examiner, and uses a laser pulse The presence or absence of a target virus is diagnosed based on big data analysis of the pre-processed signals of the first and second controllers 340a and 340b measured under various conditions such as power and wavelength of

The virus diagnosis apparatus 300 according to another embodiment includes changes in interference signals before, during, and after irradiation of the neutralization pulse, changes in width and energy of the neutralization pulse, statistical characteristics of the scattered neutralization pulse, and linear and scatter spectroscopic changes By analyzing big data collected using existing sensors such as , electronic nose, etc. using artificial intelligence, it is possible to confirm the presence of a target virus.

By measuring changes in spectroscopic and optical properties such as changes in amplitude and phase of probe light using an interferometer, for example, an I/Q-interferometer, the sensitivity and specificity for diagnosing viruses in a sample can be improved. Virus diagnosis apparatuses according to another embodiment have been described in detail.

9 is a block diagram of a virus diagnosis apparatus according to another embodiment.

Referring to FIG. 9 , a virus diagnosis apparatus 400 according to another embodiment includes a neutralizing pulse irradiator 410 that irradiates a laser having a continuous pulse specific to a target virus, and a neutralizing pulse irradiator that can accommodate a sample ( 410), the container 420 located on the irradiation path of the irradiated pulse, and wavelength division multiplexing (WDM) technology is applied to generate multi-wavelength probe light having two or more wavelengths, and The multi-wavelength probe light irradiator 430 irradiating the probe light toward the container 420 , the probe light 439a and the container 420 direct the multi-wavelength light irradiated from the multi-wavelength probe light irradiator 430 toward the container 420 . ), a beam splitter 432 that separates the reference light 439b that does not pass through, an interferometer 338 that interferes with the probe light passing through the container 420 and the reference light that does not pass through the container 420, and interfering multi-wavelength exploration The presence of the target virus in the sample according to the result of interference by the demultiplexing unit 441 for demultiplexing the light 439a and the reference light 439b again by wavelength, and the probe light 439a and the reference light 439b for each wavelength. and a control unit 440 for diagnosing whether or not there is.

The incapacitating pulse irradiation unit 410, the container 420, the beam splitter 432, the interferometer 438, and the control unit 440 are the neutralizing pulse irradiation unit 310, the container 320, the beam described with reference to FIGS. 5 to 8. The splitter 332 , the interferometer 338 , and the controller 340 may be substantially the same.

For example, the neutralization pulse irradiation unit 410 includes an optical amplifier, and can amplify the output of a pulse specific to the target virus by using the optical amplifier, and also uses a parametric vibrator. You can also change the intermediate wavelength.

The probe light 339a and the neutralizing laser pulse may be aligned to travel along the same path in the specimen.

As described above, the interferometer 338 may be an I/Q-interferometer capable of simultaneously measuring the phase change and the amplitude change induced by the detected light.

The multi-wavelength probe light irradiator 430 applies a wavelength division multiplexing (WDM) technology to generate multi-wavelength probe light having two or more wavelengths and emits the probe light toward the container 420 . investigate

The demultiplexer 442 demultiplexes the multi-wavelength probe light and the reference light interfered by the interferometer 438 for each wavelength again.

The control unit 440 compares the preprocessor 443 for preprocessing the interference signals of the probe light 439a and the reference light 439b demultiplexed by the demultiplexer 441 with the interference signals preprocessed using artificial intelligence technology. Thus, the analysis unit 444 for diagnosing the presence or absence of the target virus in the sample may include an output unit 446 for outputting the diagnosis result of the analysis unit 444 .

The virus diagnosis apparatus 400 according to another embodiment can increase specificity by applying a wavelength division multiplexing (WDM) technology to measure an optical change according to a wavelength by applying a multi-wavelength light source. have.

The virus diagnosis apparatuses 100 , 200 , 300 , and 400 according to the present embodiments have an effect that a diagnosis time for diagnosing a target virus is short.

The virus diagnosis apparatuses 100 , 200 , 300 , and 400 according to the present embodiments have an effect of immediately diagnosing a virus at a sample collection site other than a specialized diagnosis institution or a hospital.

In the aforementioned controllers 140, 340, and 440, the pre-processing unit (eg, 342) converts the interfered optical signals output from the interferometer into electrical signals, an opto-electronic conversion device, and It consists of various amplifiers and A/D converters for converting to digital signals.

In the aforementioned controllers 140 , 340 , and 440 , the analysis unit may be implemented by a computing device including at least a portion of a processor, a memory, a user input device, and a presentation device. A memory is a medium that stores computer-readable software, applications, program modules, routines, instructions, and/or data, etc. coded to perform specific tasks when executed by a processor. The processor may read and execute computer-readable software, applications, program modules, routines, instructions, and/or data stored in the memory and/or the like. The user input device may be a means for allowing the user to input a command to the processor to execute a specific task or to input data required for the execution of the specific task. The user input device may include a physical or virtual keyboard or keypad, a key button, a mouse, a joystick, a trackball, a touch-sensitive input means, or a microphone. The presentation device may include a display, a printer, a speaker, or a vibrator.

Computing devices may include various devices such as smartphones, tablets, laptops, desktops, servers, clients, and the like. The computing device may be a single stand-alone device, or may include a plurality of computing devices operating in a distributed environment comprising a plurality of computing devices cooperating with each other through a communication network.

The aforementioned control unit (140, 340, 440) is provided with a processor, and when executed by the processor, computer readable software, application, program module, routine, coded to perform virus diagnosis using a deep learning model, It may be executed by a computing device having a memory storing instructions, and/or data structures, and the like.

The above-described embodiments may be implemented through various means. For example, the present embodiments may be implemented by hardware, firmware, software, or a combination thereof.

In the case of hardware implementation, the image diagnosis method using the deep learning model according to the present embodiments may include one or more ASICs (Application Specific Integrated Circuits), DSPs (Digital Signal Processors), DSPDs (Digital Signal Processing Devices), It may be implemented by Programmable Logic Devices (PLDs), Field Programmable Gate Arrays (FPGAs), processors, controllers, microcontrollers or microprocessors, and the like.

For example, the aforementioned controllers 140 , 340 , and 440 may be implemented using an artificial intelligence semiconductor device in which neurons and synapses of a deep neural network are implemented with semiconductor elements. In this case, the semiconductor device may be currently used semiconductor devices, for example, SRAM, DRAM, NAND, or the like, or may be next-generation semiconductor devices, RRAM, STT MRAM, PRAM, or the like, or a combination thereof.

When the above-described control unit 140, 340, 440 is implemented using an artificial intelligence semiconductor device, the result (weight) of learning a deep learning model with software is transcribed into a synaptic mimic device arranged in an array or learned in an artificial intelligence semiconductor device. may proceed.

In the case of implementation by firmware or software, the above-described controllers 140 and 340 may be implemented in the form of an apparatus, procedure, or function that performs the functions or operations described above. The software code may be stored in the memory unit and driven by the processor. The memory unit may be located inside or outside the processor, and may transmit and receive data to and from the processor by various known means.

Also, as described above, terms such as "system", "processor", "controller", "component", "module", "interface", "model", or "unit" generally refer to computer-related entities hardware, hardware and software. may mean a combination of, software, or running software. For example, the aforementioned components may be, but are not limited to, a process run by a processor, a processor, a controller, a controlling processor, an object, a thread of execution, a program, and/or a computer. For example, both an application running on a controller or processor and a controller or processor can be a component. One or more components may reside within a process and/or thread of execution, and the components may be located on one device (eg, a system, computing device, etc.) or distributed across two or more devices.

Meanwhile, another embodiment provides a computer program stored in a computer recording medium for performing the above-described method. Another embodiment also provides a computer-readable recording medium in which a program for realizing the above-described method is recorded.

The program recorded on the recording medium can be read by a computer, installed, and executed to execute the above-described steps.

In this way, in order for the computer to read the program recorded on the recording medium and execute the functions implemented as the program, the above-described program is C, C++ that the computer's processor (CPU) can read through the computer's device interface (Interface). , JAVA, may include code coded in a computer language such as machine language.

Such code may include a function code related to a function defining the above-mentioned functions, etc., and may include an execution procedure related control code necessary for the processor of the computer to execute the above-mentioned functions according to a predetermined procedure.

In addition, this code may further include additional information necessary for the processor of the computer to execute the above functions or code related to memory reference for which location (address address) in the internal or external memory of the computer should be referenced. .

In addition, when the processor of the computer needs to communicate with any other computer or server located remotely in order to execute the functions described above, the code can be executed by the processor of the computer using the communication module of the computer. It may further include a communication-related code for how to communicate with other computers or servers, and what information or media to transmit and receive during communication.

The computer-readable recording medium in which the program as described above is recorded is, for example, ROM, RAM, CD-ROM, magnetic tape, floppy disk, optical media storage device, etc., and also carrier wave (eg, , transmission over the Internet) may be implemented in the form of.

In addition, the computer-readable recording medium is distributed in a computer system connected through a network, so that the computer-readable code can be stored and executed in a distributed manner.

And, in consideration of the system environment of a computer that reads a recording medium and executes a program by reading a recording medium, a functional program and related codes and code segments for implementing the present invention, programmers in the technical field to which the present invention belongs may be easily inferred or changed by

The above-described method may also be implemented in the form of a recording medium including instructions executable by a computer, such as an application or program module executed by a computer. Computer-readable media can be any available media that can be accessed by a computer and includes both volatile and nonvolatile media, removable and non-removable media. Also, computer-readable media may include all computer storage media. Computer storage media includes both volatile and nonvolatile, removable and non-removable media implemented in any method or technology for storage of information such as computer readable instructions, data structures, program modules or other data.

The above-described method may be executed by an application basically installed in the terminal (which may include a program included in a platform or operating system basically installed in the terminal), and the user may use an application store server, an application, or a service related to the corresponding service. It may be executed by an application (ie, a program) installed directly on the master terminal through an application providing server such as a web server. In this sense, the above-described method may be implemented as an application (ie, program) that is basically installed in a terminal or directly installed by a user, and may be recorded in a computer-readable recording medium such as a terminal.

The above description of the present invention is for illustration, and those of ordinary skill in the art to which the present invention pertains can understand that it can be easily modified into other specific forms without changing the technical spirit or essential features of the present invention. will be. Therefore, it should be understood that the embodiments described above are illustrative in all respects and not restrictive. For example, each component described as a single type may be implemented in a distributed manner, and likewise components described as distributed may be implemented in a combined form.

The scope of the present invention is indicated by the following claims rather than the above detailed description, and all changes or modifications derived from the meaning and scope of the claims and their equivalent concepts should be interpreted as being included in the scope of the present invention. do.

Claims (13)

A neutralizing pulse irradiation unit irradiating a laser having a continuous pulse specific to the target virus;
a container capable of accommodating a sample and positioned on the irradiation path of the laser irradiated from the neutralizing pulse irradiation unit;
an exploration light irradiation unit for irradiating light toward the container;
a beam splitter for splitting the light irradiated from the probe light irradiator into probe light directed to the container and reference light that does not pass through the container;
an interferometer for interfering the probe light passing through the container and the reference light not passing through the container; and
and a control unit for diagnosing the presence or absence of a target virus in the sample according to a result of interference between the probe light and the reference light.
According to claim 1,
a first reflector reflecting the probe light separated from the beam splitter and guiding it to the container; and a second reflector for guiding the reference light separated from the beam splitter to the interferometer.
According to claim 1,
The interferometer is an I/Q-interferometer that can measure the phase change and the amplitude change induced by the detected light at the same time.
According to claim 1,
The virus diagnosis device wherein the sample is exhaled gas.
According to claim 1,
The neutralizing pulse irradiation unit includes an optical amplifier, and a virus diagnosis apparatus for amplifying an output of a pulse specific to the target virus by using the optical amplifier.
According to claim 1,
The neutralizing pulse irradiation unit includes an optical parametric amplifier, and a virus diagnosis apparatus for specifically converting an intermediate wavelength of the neutralizing pulse to a virus and outputting the neutralizing pulse using the optical parametric amplifier.
According to claim 1,
The control unit includes a pre-processing unit for pre-processing the first and second interference signals of the probe light and the reference light, and an analysis unit for diagnosing the presence of a target virus in the sample by comparing the pre-processed first and second interference signals; and an output unit for outputting a diagnosis result of the analysis unit.
8. The method of claim 7,
The analysis unit is a virus diagnosis apparatus for diagnosing the presence of a target virus in the sample by comparing the preprocessed first and second interference signals using artificial intelligence technology.
According to claim 1,
Further comprising a receiver for receiving the neutralization pulse that has passed through the sample, or for receiving the neutralization pulse scattered from the virus,
The control unit includes a first control unit electrically connected to the interferometer and a second control unit electrically connected to the receiving unit,
The first control unit includes a first preprocessing unit that pre-processes the first and second interference signals of the probe light and the reference light, and compares the pre-processed first and second interference signals to determine whether a target virus is present in the sample a first analysis unit for diagnosing, and a first output unit for outputting a diagnosis result of the first analysis unit;
The second control unit includes a second preprocessing unit for preprocessing the neutralization pulses that have passed through the specimen or the neutralization pulses scattered from the virus and received by the receiving unit, a second analysis unit that compares the preprocessed pulses, and the second analysis unit Virus diagnosis apparatus including a second output unit for outputting an analysis result.
According to claim 1,
Further comprising an exhaled gas inlet connected spatially with the container or a sensor for detecting exhaled gas inside the container,
The control unit further utilizes the analysis result of the type, temperature, pressure, and gas components of the exhaled gas detected by the sensor or device during virus diagnosis.
A neutralizing pulse irradiation unit irradiating a laser having a continuous pulse specific to the target virus;
a container capable of accommodating a specimen and positioned on the irradiation path of the pulse irradiated by the neutralizing pulse irradiation unit;
a multi-wavelength probe light irradiator for generating multi-wavelength probe light having two or more wavelengths by applying a wavelength division multiplexing (WDM) technology and irradiating the probe light toward the container;
a beam splitter for splitting the multi-wavelength light irradiated from the multi-wavelength probe light irradiator into probe light directed to the container and reference light that does not pass through the container;
an interferometer for interfering the probe light passing through the container and the reference light not passing through the container;
a demultiplexer for demultiplexing the interfered multi-wavelength probe light and the reference light again for each wavelength; and
and a control unit for diagnosing the presence of a target virus in a sample according to a result of interference for each wavelength of the probe light and the reference light.
12. The method of claim 11,
The interferometer is an I/Q-interferometer that can measure the phase change and the amplitude change induced by the detected light at the same time.
12. The method of claim 11,
The neutralizing pulse irradiation unit includes an optical amplifier, and a virus diagnosis apparatus for amplifying an output of a pulse specific to the target virus by using the optical amplifier.

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