KR20110068066A - Apparatus for detecting bio contents using optical coherence - Google Patents

Abstract

PURPOSE: A biochemical material detecting apparatus using light interference is provided to make detection and quantitative analysis for a biochemical material included in sample by using a light detection method and a quantitative analysis method simultaneously. CONSTITUTION: A biochemical material detecting apparatus using light interference comprises: a first vibration device(20) coupled with a standard receptor, which is intercepted to react to sample containing a biochemical material to be detected, and resonating; a second vibration device(30) located at a certain distance from the first vibration device and coupled with a detection receptor which is possible to react to the sample, and resonating according to the same resonance frequency as the first vibration device; a light source(40) irradiating light toward the first vibration device and the second vibration device; a light imaging unit(50) imaging optical interference patterns generated by the interference between first reflected light, which is reflected from the surface of the first vibration device by the light irradiated from the light source, and second reflected light, reflected from the surface of the second vibration device; and a detection confirmation unit(60) checking whether or not the biochemical material is detected from the imaged light interference patterns.

Description

Apparatus for detecting bio contents using optical coherence

The present invention relates to a biochemical detection device using optical interference. More specifically, the present invention relates to a biochemical detection device using optical interference capable of detecting a biochemical from a sample containing a biochemical to be detected.

In general, a biosensor is a device used for the detection of biochemicals, and a basic principle is to convert biochemicals into measurable signals such as optical signals or electrical signals.

As such, methods for converting the detection of biochemicals from the biosensor into measurable signals include photodetection, mass spectrometry, and conductivity change measurement.

First, the photodetection method is a method of detecting biochemicals using a fluorescent material that generates a fluorescent signal when irradiated with light of a specific wavelength, and has the advantages of high sensitivity and low noise, but is the most widely used method. In addition to a sample containing a biochemical and a receptor reacting with the sample, an additional fluorescent marker, which is a fluorescent substance for generating a fluorescent signal by being irradiated with light of a specific wavelength, needs to be additionally added, thus requiring an additional reaction process. There is a problem.

Next, the mass spectrometry method is one of the non-label methods capable of detecting biochemicals without attaching a separate fluorescent marker, and attaches a receptor for a biochemical to be detected on a thin vibrator having a natural frequency and detects the biochemical. Reacting the sample containing the material with the receptor increases the weight of the receptor due to the biochemicals attached to the receptor and accordingly decreases the resonance frequency of the vibrator to measure the degree of change in the resonance frequency and includes it in the sample. Refers to the way of detecting biochemicals.

At this time, the vibrator used in the mass spectrometry method is a QCM (Quarts Crystal Microbalance) that can detect fine molecular adsorption using the resonant frequency of the quartz crystal, and is a thin metal film processed in micro units. The cantilever sensor in which is changed, and the piezoelectric element which is an electromechanical or mechanical-electrical conversion element, etc. are mainly used.

However, in the case of mass spectrometry, the resonant frequency of resonance of the vibrator is typically about several tens of KHz, while the variation of the resonator frequency due to the attachment of biochemicals to be detected is about several hundred Hz, which is compared with the resonant frequency. In order to facilitate the detection of biochemicals by using the variation of the resonant frequency having a small range, the detection device having such a complicated structure is required. Since the noise due to external stimulus is easily mixed in the detection process, the detection error is increased. There is a problem that becomes large.

The present invention has been made to solve the above problems, the optical interference which can perform the detection and quantitative analysis of the biochemicals contained in the sample by using the light detection method using a light source and the mass spectrometry method of the non-labeling method at the same time An object of the present invention is to provide a biochemical detection apparatus using the same.

Biochemical detection apparatus using optical interference according to the present invention for achieving the above object is the first vibration element coupled to the reference receptor blocked the reaction with the sample containing the biochemical to be detected, the first vibration A second vibration device, which is spaced apart from the device and coupled with a detection receptor capable of reacting with the sample and resonates according to the same resonance frequency as that of the first vibration device, irradiates light toward the first vibration device and the second vibration device. The first reflected light reflected from the surface of the first vibrating element and the second reflected light reflected from the surface of the second vibrating element by the light source, the light emitted from the light source, the first reflected light and the second reflected light An optical imaging unit for photographing the optical interference fringe generated in accordance with the interference phenomenon of the optical signal and the presence or absence of imaging of the optical interference fringe Detection check to determine whether the detection of a substance characterized in that it comprises a.

Also, when the detection of the interference fringe is not confirmed from the driver and the detection confirming unit for resonating the first vibrating element and the second vibrating element, the resonant frequency of the second vibrating element may be adjusted toward the second vibrating element. The apparatus may further include a feedback voltage supply unit supplying a feedback voltage.

The apparatus may further include a quantitative analyzer configured to perform quantitative analysis on the biochemical material using the magnitude information after receiving the magnitude information of the feedback voltage supplied from the feedback voltage supply unit to the second vibration device.

The optical imaging unit may be a charge-coupled device (CCD).

In addition, the first vibration element and the second vibration element may be a QCM (Quartz Crystal Microbalance), a cantilever sensor, or a piezoelectric sensor.

In addition, the first vibration element and the second vibration element may have a thickness of 10um to 100um.

In addition, the first vibration device and the second vibration device may be the same device.

According to the present invention, a detection circuit having a complicated configuration for detecting a small change in resonant frequency generated by an additional attachment of a fluorescent label for fluorescence generation or a vibration element by using a photodetection method and a mass spectrometry method simultaneously is not required. Is improved and the configuration is simplified.

In addition, since the minute mass change due to the detection of the biochemical can be detected from the presence or absence of the generation of the optical interference pattern due to the change in the resonance frequency, it has the effect of improving the detection accuracy of the biochemical.

Hereinafter, embodiments of the present invention will be described in detail with reference to the accompanying drawings. First, in adding reference numerals to the components of each drawing, it should be noted that the same reference numerals are used as much as possible even if displayed on different drawings. In the following description of the present invention, a detailed description of known functions and configurations incorporated herein will be omitted when it may make the subject matter of the present invention rather unclear. In addition, preferred embodiments of the present invention will be described below, but the technical idea of the present invention may be implemented by those skilled in the art without being limited or limited thereto.

1 is a block diagram of a light detecting apparatus according to a preferred embodiment of the present invention.

1 shows a biochemical detection apparatus 10 according to a preferred embodiment of the present invention, the first vibration device 20, the second vibration device 30, the light source 40, the optical imaging unit 50 And a detection confirming unit 60, a driving unit 70, a feedback voltage supply unit 80, and a quantitative analysis unit 90.

The first vibration device 20 is coupled to the reference receptor that is blocked from the reaction with the sample containing the biochemicals to be detected on the top and resonates.

In this case, the biochemical to be detected may be a protein, a pathogen, or a virus, and the reference receptor is an antibody whose functional group is blocked to block a reaction with a sample containing a biochemical such as a protein, a pathogen, or a virus to be detected. Or an aptamer.

The second vibrating device 30 is spaced apart from the first vibrating device 20 and is coupled with a detection receptor capable of reacting with a sample containing the biochemical to be detected and according to the same resonance frequency as the first vibrating device 20. Resonates.

Therefore, the first vibrating element 20 and the second vibrating element 30 may vibrate at the same resonance frequency.

At this time, the first vibrating element 20 and the second vibrating element 30 are QCM (Quarts Crystal Microbalance), which can detect fine molecular adsorption using the resonant frequency of the quartz crystal, and are a thin metal film processed in micro units. It may be a cantilever sensor in which the natural frequency changes when the external material contacts, or a piezoelectric element such as a piezoelectric ceramic capable of converting mechanical vibration into electrical vibration or converting electrical vibration into mechanical vibration using a piezoelectric effect.

In addition, the first vibrating device 20 and the second vibrating device 30 may be a thin film type vibration device having a thickness of 10μm to 100μm.

Here, the range of 10μm to 100μm presented as the thickness of the first vibrating device 20 and the second vibrating device 30 is whether the detection of the biochemical during the reaction between the sample containing the biochemical to be detected and the detection receptor It is presented as the minimum range that can be detected.

In addition, the first vibrating device 20 and the second vibrating device 30 may use the same device to vibrate at the same resonant frequency according to the same resonant frequency.

The light source 40 irradiates the light L1 to the first vibrating device 20 and the second vibrating device 30.

In this case, the light source 40 may be a laser or a laser diode which is an incoherent light source composed of neat sine waves having the same wavelength.

The optical imaging unit 50 reflects the first reflected light L2 reflected from the surface of the first vibrating element 20 by the light irradiated from the light source 40 and the second reflected from the surface of the second vibrating element 30. When the reflected light L3 is irradiated, the optical interference pattern generated by the interference phenomenon between the first reflected light L2 and the second reflected light L3 is captured.

In this case, the optical imaging unit 50 may be a charge-coupled device (CCD).

The detection confirmation unit 60 confirms the presence or absence of optical interference pattern imaging by the optical imaging unit 50 and confirms the presence or absence of detection of a biochemical according to the presence or absence of optical interference pattern imaging.

In this case, the detection of the biochemical material according to the imaging of the optical interference pattern is performed by the first reflected light L2 reflected from the surfaces of the first vibration element 20 and the second vibration element 30 in the case of the optical interference pattern. By using the principle that occurs only when the characteristics of the optical wavefront of the second reflected light L3 are the same, the detection confirmation unit 60 detects the presence or absence of the detection of the biochemical material from the optical interference pattern imaging in the optical imaging unit 50. Detailed process of confirming will be described in Figures 2 to 4 below.

The driving unit 70 resonates the first vibrating device 20 and the second vibrating device 30.

At this time, the driving unit 70 is a resonant circuit for resonating the first vibrating device 20 and the second vibrating device 30, and since the configuration of the resonant circuit is known in the art, detailed description thereof will be omitted.

The feedback voltage supply unit 80 operates when the detection of the optical interference pattern on the optical image pickup unit 50 is not confirmed by the detection confirming unit 60 to operate the resonance frequency of the second vibration element 30 toward the second vibration element 30. Supply additional feedback voltage for compensation.

At this time, when the feedback voltage supply unit 80 does not confirm the detection of the interference fringes in the optical imaging unit 50 from the detection confirmation unit 60, the resonance frequency compensation of the second vibration element 30 toward the second vibration element 30 is performed. A detailed process of additionally supplying a feedback voltage for the above will be described with reference to FIGS. 2 to 4.

The quantitative analysis unit 90 receives the magnitude information of the feedback voltage supplied from the feedback voltage supply unit 80 to the second vibrating device 30 and performs quantitative analysis on the biochemical to be detected using the magnitude information. do.

In this case, the detailed process of performing the quantitative analysis on the biochemicals to be detected by the quantitative analyzer 90 will be described with reference to FIGS. 2 to 4.

2 to 4 is a reference diagram for the operation of the biochemical detection apparatus according to a preferred embodiment of the present invention.

In this case, in order to explain the operation of the biochemical detection apparatus 10 in FIGS. 2 to 4, some components of the biochemical detection apparatus 10 are omitted.

Referring to Figure 2 to 4 will be described the operation of the biochemical detection apparatus according to a preferred embodiment of the present invention.

As shown in FIG. 2, in a state in which the sample is not added to the reference receptor a1 coupled to the upper portion of the first vibrating element 20 and the detection receptor a2 coupled to the upper portion of the second vibrating element 30. When light L1 is irradiated from the light source 40 to the first vibrating device 20 and the second vibrating device 30, the light is radiated from the light source 40 to the first vibrating device 20 and the second vibrating device 30. The optical imaging unit 50 includes the first reflected light L2 reflected from the surface of the first vibrating element 20 and the second reflected light L3 reflected from the surface of the second vibrating element 30 by the light L1. Can be irradiated to the side.

At this time, since the first vibrating element 20 and the second vibrating element 30 resonate according to the same resonant frequency, the resonant frequencies of the first vibrating element 20 and the second vibrating element 30 are the same. In the case of the first reflected light L2 and the second reflected light L3 irradiated to the imaging unit 50, the characteristics of the optical wavefront are the same, so that the optical phenomenon occurs in the optical scratching unit 50, thereby causing optical interference. A pattern may be picked up by the optical imaging unit 50.

Therefore, when the optical interference pattern is picked up by the optical imaging unit 50, it may be confirmed that the detection of the biochemical is not performed.

As shown in FIG. 3, the sample S is injected into the detection receptor a2 coupled to the upper portion of the second vibrating element 30, and the biochemical material contained in the detection receptor a2 and the sample S reacts. When the biochemical is attached to the detection receptor (a2) to increase the mass of the detection receptor (a2).

In this case, the blocking part b is formed on the reference receptor a1 to prevent a part of the sample S from reacting with the reference receptor a1 while the sample S is introduced into the detection receptor a2. can do.

As such, when the biochemical to be detected is attached to the detection receptor a2 and the mass of the detection receptor a2 is increased, the mass of the second vibrating element 30 having the detection receptor a2 coupled thereon is also increased. As a result, the resonance frequency for resonance of the second vibrating element 30 is lowered.

Therefore, when the detection receptor a2 and the biochemical to be detected react, the first vibration element 20 and the second vibration element 30 are resonated according to different resonance frequencies, so a difference in resonance frequency occurs. Done.

At this time, when the light L1 is irradiated from the light source 40 toward the first vibrating device 20 and the second vibrating device 30, the first vibrating device 20 and the second vibrating device 30 from the light source 40. Reflected from the surface of the first vibrating element 20 by light L1 irradiated to the side) and reflected from the surfaces of the first reflected light L2 and the second vibrating element 30 irradiated to the optical imaging unit 50 side. Since the optical wavefront characteristics of the second reflected light L3 irradiated toward the optical image pickup unit 50 are not the same, interference between the first reflected light L2 and the second reflected light L3 does not occur in the optical image pickup unit 5. Therefore, the optical interference pattern is not picked up by the optical image pickup unit 50.

Therefore, when the optical interference pattern is not captured by the optical imaging unit 50, it may be determined that the biochemical material included in the sample S is detected by the detection receptor a2 coupled to the second vibration device 30. .

As shown in FIG. 4, when the optical interference pattern is not captured by the optical imaging unit 50, the detection checker 60 may detect the detection receptor a2 coupled to the upper portion of the second vibration device 30. The sample S containing the biochemical reacts to determine that the biochemical is detected, and accordingly, the feedback voltage supply unit 80 operates to perform a second vibration from the feedback voltage supply unit 80 to the second vibration element 30. The feedback voltage for the resonant frequency compensation of the device 30 is additionally supplied.

As such, the reason why the feedback voltage is supplied from the feedback voltage supply unit 80 to the second vibrating device 30 is that the resonant frequency of the vibrating device can be adjusted by adjusting the voltage in a resonant state in the general vibrating device. The first vibration device 20 and the second vibration device 30 are provided in such a manner as to compensate the resonance frequency of the second vibration device 30 by additionally supplying a feedback voltage from the feedback voltage supply unit 80 to the second vibration device 30. This is to adjust the resonant frequency of

When the feedback voltage is additionally supplied from the feedback voltage supply unit 80 to the second vibrating element 30 to adjust the resonant frequencies of the first vibrating element 20 and the second vibrating element 30 to be irradiated from the light source 40. The optical characteristics of the first reflected light L2 reflected from the surface of the first vibrating element 20 and the second reflected light L3 reflected from the surface of the second vibrating element 30 by the light L1 are the same. Since the interference phenomenon between the first reflected light L2 and the second reflected light L3 occurs again, the optical interference pattern can be captured by the optical image pickup unit 50 again.

In addition, the quantitative analysis unit 90 may perform quantitative analysis on the detected biochemical material using the magnitude of the feedback voltage additionally supplied from the feedback voltage supply unit 80 to the second vibrating device 30.

Here, the reason why the quantitative analysis unit 90 may perform the quantitative analysis on the detected biochemical material using the magnitude of the feedback voltage additionally supplied from the feedback voltage supply unit 80 to the second vibrating element 30 is the feedback voltage. The magnitude of the feedback voltage additionally supplied from the supply unit 80 to the second vibration element 30 is equal to the resonance frequency of the second vibration element 30 corrected to be equal to the magnitude of the resonance frequency of the first vibration element 20. This is because it is proportional to the mass of the detected biochemical attached to the detection receptor (a2).

Therefore, the quantitative analysis unit 90 can quantitatively measure the reaction amount of the biochemical contained in the sample S by using the magnitude of the voltage supplied from the feedback voltage supply unit 80 to the second vibration element 30. Become.

The biochemical detection apparatus 10 of the present invention includes the first reflected light L2 and the second vibrating device 30 reflected from the surface of the first vibrating device 20 according to the light L1 irradiated from the light source 30. In accordance with the interference phenomenon between the second reflected light (L3) reflected from the surface of the optical imaging unit 50, whether or not the detection of the biochemical substance to be detected according to the presence or absence of the imaging of the optical interference pattern that can be picked up.

In addition, when it is confirmed whether the biochemical is detected, the second vibration device is supplied with feedback power from the feedback power supply unit 80 to the second vibration device 30 to have the same resonance frequency as that of the first vibration device 20. The resonance frequency of 30 is corrected, and quantitative analysis of the reaction amount of the biochemical substance detected by the quantitative analyzer 90 is possible by using the magnitude of the feedback voltage supplied from the feedback power supply 80.

Therefore, according to the present invention, a separate circuit for attaching a separate fluorescent marker for fluorescence generation or a complex circuit for detecting minute resonance frequency changes occurring in a vibrating element are not required by using a photodetection method and a mass spectrometry method simultaneously. The detection speed can be improved and the configuration of the biochemical detection device can be simplified.

In addition, the minute mass change of the second vibrating element 30 due to the biochemical substance detected by the detection receptor is easily obtained from the presence or absence of optical interference pattern imaging of the optical imaging unit 50 according to the change of the resonance frequency of the second vibrating element 30. Since it can detect, it has an effect of improving the detection accuracy of the biochemical compared with the conventional.

The above description is merely illustrative of the technical idea of the present invention, and various modifications, changes, and substitutions may be made by those skilled in the art without departing from the essential characteristics of the present invention. It will be possible. Therefore, the scope of the technical spirit of the present invention is not limited by the embodiments disclosed in the present invention and the accompanying drawings. The protection scope of the present invention should be interpreted by the following claims, and all technical ideas within the equivalent scope should be interpreted as being included in the scope of the present invention.

According to the present invention, it is possible to provide a biochemical detection device that can be miniaturized and has a high sensitivity by using a light detection method and a mass spectrometry at the same time as a simpler structure than the existing biosensors, and thus can be used to replace the biosensors previously used. Can be.

1 is a block diagram of a biochemical detection apparatus according to a preferred embodiment of the present invention, and

2 to 4 is a reference diagram for the operation of the biochemical detection apparatus according to a preferred embodiment of the present invention.

<Brief description of the main parts of the drawings>

(10): biochemical detection device (20): first vibrating element

30: second vibration element 40: light source

50: optical imaging unit 60: detection confirmation unit

70: drive unit 80: feedback voltage supply unit

(90): quantitative analysis unit

Claims (7)

A first vibrating element coupled to and resonating with a reference receptor blocked from reaction with a sample containing a biochemical to be detected; A second vibrating element which is spaced apart from the first vibrating element and coupled with a detection receptor capable of reacting with the sample and resonates according to the same resonant frequency as the first vibrating element; A light source for irradiating light to the first vibrating element and the second vibrating element; Interference phenomenon between the first reflected light and the second reflected light by receiving the first reflected light reflected from the surface of the first vibrating element and the second reflected light reflected from the surface of the second vibrating element by the light emitted from the light source An optical imaging unit for capturing an optical interference pattern generated according to the present invention; And And a detection confirming unit for confirming whether or not the biochemical is detected from the imaging of the optical interference pattern. The method of claim 1, A feedback voltage for adjusting the resonant frequency of the second vibrating element toward the second vibrating element when the detection of the interference fringe is not confirmed from the driving unit for resonating the first vibrating element and the second vibrating element and the detection confirming unit; Biochemical detection apparatus using optical interference further comprising a feedback voltage supply for supplying a. 3. The method of claim 2, And an quantitative analysis unit configured to receive quantitative analysis of the biochemical material using the magnitude information after receiving the magnitude information of the feedback voltage supplied from the feedback voltage supply unit to the second vibration device. Biochemical detection device using. The method of claim 1, The optical imaging unit is a biochemical detection device using optical interference, characterized in that the CCD (Charge-Coupled Device). The method of claim 1, The first vibration device and the second vibration device is a biochemical detection device using optical interference, characterized in that the QCM (Quartz Crystal Microbalance), cantilever sensor, or piezoelectric sensor. The method of claim 1, The first vibration device and the second vibration device has a thickness of 10um to 100um biochemical detection device using optical interference, characterized in that. The method of claim 1, The first vibration device and the second vibration device is a biochemical detection device using optical interference, characterized in that the same device.

Images