KR20160015495A - Analysis system for composite sample using multi wavelength light - Google Patents

Abstract

The present invention relates to an analysis system of a composite sample using multi-wavelength light and, more specifically, relates to a system capable of quantitatively analyzing concentration of each substance by analyzing a sample mixed with a plurality of substances to be analyzed using multi-wavelength light. According to the present invention, the analysis system rapidly and accurately quantifies a concentration on each substance contained in the mixed sample by analyzing a change in wavelength and strength of a predetermined wavelength signal selectively radiated onto the mixed sample containing the substances injected into a biochip. Also, in accordance with the present invention, the analysis system prevents denaturation of the substance in accordance with an analysis time difference by performing a quantitative analysis on each substance among the mixed sample containing the substances through real-time monitoring.

Description

Technical Field [0001] The present invention relates to an analysis system for multi-wavelength light,

The present invention relates to a system for analyzing a mixed sample using light of multiple wavelengths, more specifically, by analyzing a sample in which a plurality of analyte materials to be analyzed are analyzed using light of multiple wavelengths, To a system that can be analyzed.

Recently, there is an increasing need to periodically measure the amount of blood glucose in diagnosis and prevention of diabetes. The measurement of blood sugar can be easily performed using a portable measuring device. However, since the amount of blood sugar varies greatly depending on the dietary state of the patient and the condition of the body, it also involves pain in the process of collecting the blood necessary for the measurement, so that it is difficult for the patient to accurately measure the measurement.

It has been reported that when a protein reacts with glucose in body fluids over a long period of time, a modified protein such as a glycated protein can be produced, and these glycated proteins are closely related to an average of blood glucose levels over a period of 2 to 3 months. In other words, glycated proteins are less likely to be misdiagnosed as fasting and taking drugs, and their specificity is high, which is considered to be a better indicator of diabetes mellitus and complications.

Optical, electrochemical, thermal, and mechanical systems can be used to diagnose these biomarkers, that is, glycated proteins. Among them, optical measurement Systems and electrochemical measurement systems are preferred.

Electrochemical methods of diagnosis include electrophoresis or electrophoretic methods whereby proteins extracted from cell or tissue samples can be separated into individual proteins by gel or capillary electrophoresis or affinity techniques. In particular, two-dimensional gel electrophoresis is the most recently adopted method for separating individual proteins from cells or tissue samples.

However, since bands or spots appearing in electrophoresis include all the changes due to expression, modification, degradation, etc. of proteins in cells or tissues, it is difficult to identify individual characteristics of proteins contained in protein bands or spots, Among proteins contained in a band or a spot, a protein having a characteristic meaning, that is, a target specific protein, is very difficult and remains an important technical problem.

Optical spectroscopy is preferred as a simple, fast and accurate diagnostic method using optical methods. This has the advantage of being able to analyze the measurement substance by obtaining the signal of Absorbance value or% Reflectance value based on the interaction between the biological biomaterial to be analyzed and the light.

In the conventional optical detection system using the optical spectrum as described above, in order to scan a plurality of biochips, it is troublesome to remove a biochip after it has been scanned and then load a new biochip again Or even if a plurality of biochips can be scanned at the same time, it is complicated that detection is performed by combining the results after scanning for each biochip.

In such a conventional system, even if the biochip is scanned at a rapid and uniform speed, if each sample moves during the scan or the sample changes due to the scan time, It was difficult to detect and analyze accurately.

In addition, since most conventional systems detect only a fluorescent signal, a light source is used as a laser, and the wavelength of a usable light source is limited. Therefore, in order to detect a sample using a light source, a dye for reacting with the light source must be combined with a sample. However, since the wavelength of a usable light source is limited, available dyes are limited. It has also been difficult to selectively bind a dye to any of the mixed samples containing a plurality of substances.

In addition, since the wavelength of the light source for exciting the phosphors and the interval between the emission wavelengths of the phosphors are not wide, an unusual phenomenon in which the analysis results depend on the performance of the filter used for the photodetector part also occurs.

In order to solve the above problems, attempts have been made to use a light outgoing source in which multiple wavelengths without wavelength selectivity are emitted. However, there is no problem in analyzing one sample. However, in a mixed sample containing a plurality of substances When applied, noises due to substances other than the detection target were generated, so that it was almost impossible to selectively detect any one of the substances contained in the mixed sample.

Korean Patent Laid-Open No. 10-2011-0002350 discloses a prior art.

Korean Patent Laid-Open No. 10-2011-0002350

The present inventors have solved the problems of the conventional optical detection system by excluding a factor that may affect the analysis result such as a change in the waiting time from the sample movement or analysis by irradiating multiple wavelength light sources to the detection point of the biochip We have tried for years to develop a system capable of accurate quantitative analysis of mixed samples containing multiple substances.

As a result, the present inventors have found that by irradiating the biochip with multi-wavelength light having at least one wavelength, the intensity of the optical signal by the sample, the wavelength of the light passing through the sample, The intensity of the optical signal, the change of the wavelength of the light passing through the sample to which the dye is bound, and the like are detected and analyzed.

That is, in order to provide a system capable of quantitatively analyzing the concentration of each substance contained in a sample containing a plurality of substances, the present invention eliminates the necessity of using a light source having a wide wavelength, And an object of the present invention is to provide an analysis system having a plurality of light sources selectively providing light.

In order to solve the above technical problem,

According to an aspect of the present invention, there is provided a biochip comprising: a light source part for emitting at least one light; a light mixing part for mixing at least one light emitted from the light source part; A lower stage including an optical focusing portion; And a top stage including a wavelength separation unit for separating at least one light having passed through the biochip, and a detection unit for detecting light separated from the wavelength separation unit, wherein the upper stage and the lower stage A chip insertion unit for inserting a biochip can be provided in the analysis system of the mixed sample using the multi-wavelength light.

According to the present invention, by analyzing a change in the intensity and wavelength of a specific wavelength signal selectively irradiated to a mixed sample containing a plurality of substances injected into a biochip, the concentration of each substance contained in the mixed sample It can be quantified quickly and accurately.

In addition, according to the present invention, it is possible to quantitatively analyze each substance in a mixed sample containing a plurality of substances through real-time monitoring, .

1 is a perspective view of an analysis system 100 according to an embodiment of the present invention.
2 and 3 illustrate a light mixing section 122 of the analysis system 100 according to an embodiment of the present invention.
4 illustrates a cross-sectional view of an analysis system 100 in accordance with another embodiment of the present invention.
5 shows a side view of an analysis system 100 according to another embodiment of the present invention.

Certain terms are hereby defined for convenience in order to facilitate a better understanding of the present invention. Unless otherwise defined herein, scientific and technical terms used in the present invention shall have the meanings commonly understood by one of ordinary skill in the art. Also, unless the context clearly indicates otherwise, the singular form of the term also includes plural forms thereof, and plural forms of the term should be understood as including its singular form.

Hereinafter, the present invention will be described in more detail with reference to embodiments and drawings. It should be understood, however, that these examples are for illustrative purposes only and are not to be construed as limiting the scope of the present invention.

According to an aspect of the present invention, there is provided an optical device including a light source unit 121 for emitting at least one light, a light mixing unit 122 for mixing at least one light emitted from the light source unit 121, And an optical focusing unit 123 for irradiating the bio-chip 501 with light mixed by the lower stage 120. And a detection unit (112) for detecting light separated from the wavelength separation unit (111), wherein the wavelength separation unit (111) separates at least one light having passed through the biochip (501) And a chip inserting part 130 for inserting the bio-chip 501 is formed between the upper stage 110 and the lower stage 120. The multi- An analysis system 100 of the present invention can be provided.

Hereinafter, the configuration of the analysis system 100 according to the present invention will be described in more detail with reference to the accompanying drawings.

1, an analysis system 100 according to an embodiment of the present invention includes an upper stage 110 and a lower stage 120, And a chip inserting portion 130 formed between the stage 110 and the lower stage 120.

The lower stage 120 is configured to include a light source unit 121, a light mixing unit 122, and an optical focusing unit 123 in the housing.

The light source unit 121 may include a laser diode (LED) or a light emitting diode (LED) for emitting at least one light.

In one embodiment, the light source unit 121 may include a plurality of light source units 121 for emitting a plurality of light sources having different wavelengths.

The number of the light source units 121 may vary depending on the type and number of the target substances included in the sample to be analyzed, and may include a plurality of light sources preferably within 6, more preferably within 4 , But are not necessarily limited thereto.

Also, it is preferable that the wavelength of light provided by the light source included in the light source unit 121 is determined according to the type and number of the target substance to be analyzed.

At this time, it is particularly preferable that the wavelengths are determined so as to facilitate detection of separation as having wavelength bands that do not overlap with each other as much as possible.

In another embodiment, the light source unit 121 may be configured to independently select and emit a plurality of light sources having different wavelengths.

Here, the term "independent" means that a plurality of light sources having different wavelengths are configured to emit light individually, and the term "independent" means that a plurality of light sources having different wavelengths emit light at the same time, Only a part of the light sources of the light source is selected to emit light.

As described above, the configuration of the light source unit 121 included in the analysis system 100 according to the specific embodiment of the present invention is not limited to that of the conventional optical detection scanner in which it is difficult to impart wavelength selectivity by simultaneously providing light of a wide wavelength band We want to overcome the limit.

The wavelength selectivity means providing light of only one wavelength to independently and selectively detect a target substance to be detected and analyzed, and the analysis system 100 according to an embodiment of the present invention provides efficient wavelength selectivity It is possible to independently and selectively detect an optical signal with respect to a target substance to be detected among a plurality of target substances and effectively suppress the noise generated by a substance which is not a detection target.

In one embodiment, if the light source unit 121 includes two light source units 121 for emitting two light sources having different wavelengths, the light source unit 121 may be disposed within a wavelength range of 610 to 625 nm And a second light source unit 121b that emits a second light having a wavelength selected from a wavelength range of 410 nm to 420 nm.

The wavelength ranges of the first and second light sources 121a and 121b are determined in consideration of the type of the target material as described above. When the first and second light sources 121a and 121b are in the wavelength range The subject substance may preferably be a mixture of a glycated protein and a non-glycated protein containing a dye containing a boronic acid group to induce a target specific interaction with the glycated protein.

Here, the protein may be hemoglobin. In addition, the target substance is a separated body fluid (for example, blood), and the glycated protein may be hemoglobin or glycated hemoglobin or glycated albumin in which glucose is bound to albumin.

At this time, the glycated protein and the non-glycated protein may have an absorbance value within a wavelength range of 410 to 420 nm in an aqueous solution. In addition, the dyes containing the boronate groups may have absorbance values in the wavelength range of 610 to 625 nm on the aqueous solution. Accordingly, the glycated protein bound through the cis-diol reaction with the dye containing the boronate group can also have an absorbance value in the wavelength range of 610 to 625 nm on the aqueous solution.

As described above, the glycated protein and the non-glycosylated protein may have an absorbance value in a wavelength range of 410 to 420 nm on an aqueous solution. Here, the glycated protein may have an absorbance value within a wavelength range of 610 to 625 nm by binding to the dye containing the boronic acid group through a cis-diol reaction, but the non-glycosylated protein includes the boronic acid group It does not have absorbance values within the wavelength range of 610 to 625 nm because it can not interact with the dye specifically with the target.

Therefore, according to one embodiment of the present invention, the concentration of whole proteins in the sample can be measured through the absorbance value using the first light within a wavelength range of 410 to 425 nm emitted from the first light source section 121a, The concentration of the glycated protein contained in the whole protein can be measured through the absorbance value using the second light within the wavelength range of 610 to 625 nm emitted from the second light source part 121b.

The light expanding unit 124 may further include a light expanding unit 124 extending between the light source unit 121 and the optical mixing unit 122 to enlarge the size of the light emitted by the light source unit 121, The traveling directions of a plurality of lights to be emitted are parallel to each other. The light passing through the light expanding part 124 enters the light mixing part 122.

The light mixing unit 122 is configured to uniformly mix a plurality of lights supplied from the plurality of light source units 121.

The light mixing unit 122 may include a mirror unit 201 for vertically reflecting the light emitted from the first light source unit 121a and a light source unit for combining the light incident by the mirror unit 201, And a total reflection prism 202 for mixing the light emitted from the two light sources 121b (see FIG. 2).

The optical mixer 122 includes a mirror unit 201 for vertically reflecting the light emitted from the second light source unit 121b and a light source unit for combining the light incident by the mirror unit 201 and the light And a total reflection prism 202 for mixing the light emitted from the light source unit 121a.

It is preferable that the total reflection prism 202 is configured such that a deflection angle of the light 301 incident on the mirror unit 201 and the light mixed and emitted in the total reflection prism 202 is 90 degrees, The prism 202 may be, for example, in the form of a pentaprism.

A virtual reflection surface 302 is present inside the total reflection prism 202. The reflection surface 302 does not refract the light 301 incident on the mirror portion 201 The prism may reflect a part of the incident light but may not be incident again at an angle within the prism due to the angle of the reflecting surface 302 and the refractive index of the prism, 3).

According to yet another embodiment, the light mixing part 122 may include a first mirror part for reflecting the first light emitted from the first light source part 121a, A second mirror portion 401b for reflecting the second light emitted from the second light source portion 121b and a second mirror portion 401b for reflecting the first light reflected from the first mirror portion 401a and the second mirror portion 401b, And a third mirror part 402 for reflecting the second light to the homogenizing part 403 (see FIG. 4).

The first light and the second light reflected by the homogenizing part 403 are uniformly mixed in the homogenizing part 403 and exited to the optical focusing part 123.

The optical focusing unit 123 irradiates the light mixed uniformly by the optical mixing unit 122 to the bio-chip 501. The focusing may be dot focussing, linear focussing or surface focusing.

The angle of incidence of light irradiated to the bio-chip 501 by the optical focusing unit 123 is preferably 2.5 degrees / 10 cm or less, and preferably 0 degrees.

The optical path of the light passing through the refractive index of the medium of the biochip 501 is refracted by the Snell's law. At this time, When the incident angle of the light irradiated to the biochip 501 exceeds 2.5 degrees / 10 cm, the light entering the detection unit 112 is lost and it is impossible to detect a change in the amount of light.

Between the upper stage 110 and the lower stage 120, a chip inserting unit 130 is formed for inserting a biochip 501 into which a sample containing an analyte to be analyzed is to be developed.

At this time, the bio-chip 501 inserted into the chip inserting unit 130 includes a sample developing unit formed of a microfluidic channel, a sample injecting unit for injecting a sample to one side of the sample developing unit, (502), and the optical focusing portion (123) is configured to irradiate the mixed light to the detection point (502).

Here, a single or a plurality of detection points 502 may be set on the sample development unit. The detection point 502 is a region irradiated by the optical focusing unit 123 with light of multiple wavelengths mixed by the light mixing unit 122 and is injected into one side of the sample development unit through the sample injection unit The sample is developed on the sample development unit by an electric or mechanical method and moves to the detection point 502. The sample moved to the detection point 502 is irradiated with the mixed light.

For example, when one detection point 502 is included on the sample development unit, the analysis system 100 according to an exemplary embodiment of the present invention performs analysis on a sample that is finally developed on the sample development unit . In the case where a plurality of detection points 502 are included on the sample development unit, the analysis system 100 according to an embodiment of the present invention analyzes the changed characteristics of the mixed sample developed on the sample development unit .

The upper stage 110 includes a wavelength separation unit 111 and a detection unit 112.

The lower stage of the upper stage 110 is positioned adjacent to the bio-chip 501 inserted into the chip insertion unit 130 and the sample injected through the sample injection unit is electrically or mechanically And a sample loading unit 131 for expanding the sample loading unit.

Here, the electrical method may preferably be an electrophoresis method, and the electrophoresis method may be a two-dimensional or non-two-dimensional electrophoresis method. As the mechanical method, a development method using a pump or a capillary force may be used.

The wavelength separating unit 111 separates the mixed multi-wavelength light having passed through the detection point 502 of the bio-chip 501 into individual lights, and the light having a specific wavelength range is reflected, Is configured to be transmitted.

When the number of lights mixed by the light mixing unit 122 is n (where n≥2), it is preferable that the number of the wavelength division units 111 for separating the light is n-1.

The detection unit 112 may include at least one photoconductor selected from a CCD (Charge Coupled Device), a CMOS (Complementary Metal Oxide Semiconductor), a PD (Photodiode) and a PMT (Photo Multiplier Tube).

It will be apparent to those skilled in the art that various modifications and variations can be made in the present invention without departing from the spirit of the invention as set forth in the appended claims. The present invention can be variously modified and changed by those skilled in the art, and it is also within the scope of the present invention.

110: upper stage 111: wavelength separator
112: detecting unit 120: lower stage
121: light source part 122: light mixing part
123: optical focusing section 130: chip insertion section

Claims (17)

A light source for emitting at least one light,
A light mixing section for mixing at least one light emitted from the light source section, and
A lower stage including an optical focusing part for irradiating light mixed by the light mixing part to the biochip; And
A wavelength separation unit for separating at least one light having passed through the biochip,
And a detector for detecting light separated from the wavelength demultiplexing unit,
And a chip insertion portion for inserting a bio-chip is formed between the upper stage and the lower stage.
The method according to claim 1,
The bio-
A sample development unit formed of a microfluidic channel;
A sample injection unit for injecting the sample into one side of the sample development unit; And
And a detection point formed on the other side of the sample development unit,
Wherein the optical focusing unit irradiates the mixed light to the detection point.
3. The method of claim 2,
In the lower portion of the upper stage,
A chip insertion unit disposed adjacent to the bio-chip inserted in the chip insertion unit,
Further comprising a sample loading unit for spreading the sample injected through the sample injecting unit to the detection point by an electric or mechanical method.
The method according to claim 1,
The light source unit includes:
And a laser diode (LED) or a light emitting diode (LED) for emitting at least one light.
The method according to claim 1,
The light source unit includes:
And a plurality of light sources for emitting a plurality of light sources having different wavelengths.
6. The method of claim 5,
The light source unit includes:
And a plurality of light sources having different wavelengths are independently selected and emitted. The system for analyzing a mixed sample using multi-wavelength light.
6. The method of claim 5,
The light source unit includes:
A first light source for emitting a first light having a wavelength selected within a wavelength range of 610 to 625 nm; And a second light source unit for emitting a second light having a wavelength selected within a wavelength range of 410 to 420 nm.
6. The method of claim 5,
Between the plurality of light source portions and the light mixing portion,
Further comprising a light expanding section for expanding the size of light emitted by the plurality of light source sections,
Wherein a direction of travel of a plurality of lights emitted through the optical expanding unit is parallel to each other.
8. The method of claim 7,
Wherein the light mixing unit comprises:
A mirror unit for vertically reflecting the light emitted from the first light source unit; And
And a total reflection prism for mixing the light incident by the mirror unit and the light emitted from the second light source unit.
8. The method of claim 7,
Wherein the light mixing unit comprises:
A mirror unit for vertically changing the traveling direction of the light emitted from the second light source unit; And
And a total reflection prism for mixing the light incident by the mirror unit and the light emitted from the first light source unit.
11. The method according to claim 9 or 10,
The total reflection prism,
Wherein the deflection angle of the light incident on the mirror portion and the light mixed and emitted in the total reflection prism is 90 degrees.
12. The method of claim 11,
Wherein the total reflection prism is a penta prism.
8. The method of claim 7,
Wherein the light mixing unit comprises:
A first mirror unit for reflecting the first light emitted from the first light source unit;
A second mirror part for reflecting the second light emitted from the second light source part;
And a third mirror part for reflecting the first light and the second light reflected from the first mirror part and the second mirror part to the homogenizing part,
Wherein the homogenizing unit mixes the first light and the second light and outputs the mixed light to the optical focusing unit.
The method according to claim 1,
The optical focusing unit includes:
Wherein the multi-wavelength light mixed by the optical mixing unit is focused through point focusing, linear focusing or surface focusing to irradiate the multi-wavelength light onto the bio-chip.
The method according to claim 1,
Wherein an angle of incidence of light irradiated to the bio-chip by the optical focusing unit is 2.5 degrees / 10 cm or less.
The method according to claim 1,
When the number of lights mixed by the light mixing unit is n (where n ≥ 2)
And the number of the wavelength division units for separating the plurality of wavelength division parts is n-1.
The method according to claim 1,
Wherein:
Wherein the at least one photoreceptor is at least one photoreceptor selected from a CCD (Charge Coupled Device), a CMOS (Complementary Metal Oxide Semiconductor), a PD (Photodiode) and a PMT (Photo Multiplier Tube).

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