KR101191233B1 - bio chip and system for detecting bio materials - Google Patents

Abstract

Biochips and biomaterial detection systems are provided. The biochip may include a biological sample injection unit into which a biological sample is injected, a biological sample injection unit spaced apart from the biological sample injection unit, a reaction sample injection unit into which a reaction sample reacting with the biological sample is injected, and a biological sample injection unit and a reaction sample injection unit through fluid channels; It is connected, and includes a sample reaction unit which is a closed space where the biological sample and the reaction sample is mixed and reacted, and a sample discharge unit for discharging the biological sample and the reaction sample.

Biochips, biological samples, reaction samples

Description

Bio chip and system for detecting bio materials

The present invention relates to a biochip and a biomaterial detection system, and more particularly, to a biochip and a biomaterial detection system capable of detecting a biomaterial through mixing between a biological sample to be analyzed and a reaction sample.

The present invention is derived from a study conducted as part of the IT growth engine technology development project of the Ministry of Knowledge Economy and the Ministry of Information and Communication Research and Development. [Task management number: 2008-S-014-01, Assignment name: Household high sensitivity urination analysis sensor module] .

Creatinine, which occurs during muscle metabolism and is excreted in the urine, is not only a label for dysfunction of the kidneys, but also a very constant total daily discharge per day, providing a reference for analysis of other substances in urination. Creatinine is affected by muscle mass and its level of use, and by detecting the concentration of creatinine in urine, diagnosing nephritis, muscle mass-increasing diseases (eg, hypertrophy, acromegaly), urinary tract obstruction and muscular atrophy .

As a detection method of creatinine in urine, chemical detection, an enzyme reaction, an immunological detection method, etc. are used. Among these, the Jaffe method using picric acid is used as a chemical detection method. By the way, the detection method of creatinine using picric acid has difficulty in detecting creatinine by using picric acid which has explosive properties during drying.

The problem to be solved by the present invention is to provide a biochip that can analyze biomaterials more safely.

Another object of the present invention is to provide a biomaterial detection system capable of analyzing biomaterials more safely.

The problems to be solved by the present invention are not limited to the above-mentioned problems, and other problems not mentioned can be clearly understood by those skilled in the art from the following description.

In order to achieve the above object, a biochip according to an embodiment of the present invention is a biological sample injection unit into which a biological sample is injected, a biological sample injection unit spaced apart from the reaction sample, and a reaction sample into which the reaction sample reacts with the biological sample is injected. It is connected to the biological sample injector and the reaction sample injector through the injection unit, the fluid channels, and includes a sample reaction unit which is a closed space where the biological sample and the reaction sample are mixed and reacted, and a sample discharge unit for discharging the biological sample and the reaction sample. do.

In order to achieve the above object, a biomaterial detection system according to an embodiment of the present invention is a biological sample injection unit into which a biological sample is injected, a biological sample injection unit is spaced apart, and a reaction sample reacting with the biological sample is injected It is connected to the biological sample injector and the reaction sample injector through the reaction sample injector, the fluid channels, and discharges the sample reaction unit and the biological sample and the reaction sample, which are enclosed spaces where the biological sample and the reaction sample are mixed and reacted. A biochip including a sample discharge unit, a light source unit providing incident light to the sample reaction unit, and a detection unit receiving the incident light passing through the sample reaction unit and detecting a change in the optical signal.

Specific details of other embodiments are included in the detailed description and the drawings.

According to the biochip and biomaterial detection system of the present invention, since samples can be supplied and reacted in a confined space, biomaterials can be detected more safely when detecting biomaterials using dangerous chemicals, such as picric acid samples. .

BRIEF DESCRIPTION OF THE DRAWINGS The advantages and features of the present invention, and how to accomplish them, will become apparent by reference to the embodiments described in detail below with reference to the accompanying drawings. The present invention may, however, be embodied in many different forms and should not be construed as being limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the concept of the invention to those skilled in the art. Is provided to fully convey the scope of the invention to those skilled in the art, and the invention is only defined by the scope of the claims. Like reference numerals refer to like elements throughout the specification.

The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. In this specification, the singular also includes the plural unless specifically stated otherwise in the phrase. As used herein, the terms 'comprises' and / or 'comprising' mean that the stated element, step, operation and / or element does not imply the presence of one or more other elements, steps, operations and / Or additions.

In addition, the embodiments described herein will be described with reference to cross-sectional views and / or plan views, which are ideal illustrations of the present invention. In the drawings, the thicknesses of films and regions are exaggerated for effective explanation of technical content. Thus, the regions illustrated in the figures have schematic attributes, and the shapes of the regions illustrated in the figures are intended to illustrate specific types of regions of the elements and are not intended to limit the scope of the invention.

Hereinafter, a biochip according to embodiments of the present invention will be described in detail with reference to the drawings.

1 is a schematic block diagram showing a biochip according to an embodiment of the present invention.

Referring to FIG. 1, the biochip 100 includes a reaction sample injector 110, a biological sample injector 120, a sample reaction unit 130, and a sample discharger 140.

In detail, the biochip 100 includes a reaction sample injecting unit 110 and a biological sample injecting unit 120 capable of separately supplying a reaction sample reacting with a specific biomaterial and a biological sample to be analyzed, respectively. . The reaction sample injected into the reaction sample injection unit 110 may be a chemical liquid that reacts with a specific biomaterial in the biological sample. For example, the reaction sample may be an explosive substance. The biological sample injected into the biological sample injection unit 120 is a material obtained from the living body, and includes various kinds of biomaterials representing a specific substrate. The biological sample may be, for example, a body fluid such as blood, serum, plasma, interstitial fluid, lavage, sweat, urine or saliva.

Each of the reaction sample injecting unit 110 and the biological sample injecting unit 120 is connected to the sample reaction unit 130, and the biological sample and the reaction sample may be mixed and reacted in the sample reaction unit 130. In addition, the sample reaction unit 130 is formed of a closed space, the biological sample and the reaction sample may be mixed and reacted in the closed space.

In addition, the biological sample injection unit 120 may be connected to the sample discharge unit 140 for discharging the mixed sample to the outside. That is, the biological sample and the reaction sample mixed and reacted in the biological sample injector 120 may be discharged to the outside through the sample discharger 140.

Such a biochip 100 may be isolated from the outside, except for the reaction sample injector 110, the biological sample injector 120, and the sample discharger 140. Therefore, upon detection of a specific biomaterial, the biological sample and the reaction samples can be handled safely, and it is possible to prevent the biological sample and the reaction samples from being contaminated or deforming the characteristics of the biological sample or the reaction samples.

Hereinafter, a biochip according to an embodiment of the present invention will be described in more detail with reference to FIGS. 2 to 4.

2 is a plan view of a biochip according to an embodiment of the present invention. 3 is a cross-sectional view of a biochip according to an embodiment of the present invention. 4 illustrates a biochip according to an embodiment of the present invention.

2 to 4, the biochip 100 includes a reaction sample injector 110, a biological sample injector 120, a sample reaction unit 130, a signal detector 135, and a sample discharger 140. Include them.

In more detail, the reaction sample injector 110 may be connected to the sample reaction unit 130 through the first fluid channel 151, and the biological sample injection unit 120 may be connected through the second fluid channels 152. It may be connected to the sample reaction unit 130. Accordingly, the reaction sample and the biological sample may be supplied to the sample reaction unit 130 through the first or second fluid channels 151 and 152, respectively. In addition, the first and second fluid channels 151 and 152 are passages that are isolated from the outside, and can prevent the characteristics of biological samples and reaction samples from being changed or contaminated.

Meanwhile, the first and second fluid channels 151 and 152 may be connected to the sample reaction unit 130 through the confluence channel 153. That is, one side of the first and second fluid channels 151 and 152 separated from each other may be connected to the confluence channel 153, and the confluence channel 153 is connected to the sample reaction part 130. That is, the first and second fluid channels 151, 152 branch off from the confluence channel 153.

In addition, the first washing liquid injection unit 162 may be connected to the first fluid channel 151, and after the analysis of the biological sample, the washing liquid may be injected into the first fluid channel 151. In detail, when the biological sample is supplied to the sample reaction unit 130, at the point where the first fluid channel 151 and the second fluid channel 152 join, the biological sample of the second fluid channel 152 is formed. It can flow back to the first fluid channel 151. Accordingly, after the analysis of the biological sample, the first washing solution injection unit 162 may be connected to the first fluid channel 151 in order to remove the biological sample flowed back to the first fluid channel 151.

In addition, the second washing liquid injection unit 164 may be connected to the second fluid channel 152 through which the biological sample flows, and the washing liquid may be injected into the second fluid channel 152 after the analysis of the biological sample. That is, by supplying the washing liquid through the second washing liquid injecting unit 164, after the analysis of the biological sample is finished, the biological sample remaining in the biochip 100 may be removed.

Between the reaction sample injector 110 and the sample reaction unit 130, a reaction sample storage unit 115 capable of storing a predetermined amount of the reaction sample may be formed. The reaction sample storage unit 115 may be a space isolated from the outside, and may be connected to the sample reaction unit 130 through the first fluid channel 151 and the confluence channel 153. That is, a reaction sample, for example, a picric acid sample may be supplied from the reaction sample storage unit 115 to the sample reaction unit 130.

In addition, a biological sample storage unit 125 capable of storing a predetermined amount of biological samples may be formed between the biological sample injection unit 120 and the sample reaction unit 130. The biological sample storage unit 125 may be a space isolated from the outside, and the biological sample storage unit 125 may be connected to the sample reaction unit 130 through the second fluid channel 152 and the confluence channels 153. . That is, a biological sample, for example, urine, may be supplied from the biological sample storage unit 125 to the sample reaction unit 130.

Meanwhile, when the biological sample storage unit 125 is formed between the biological sample injection unit 120 and the sample reaction unit 130, the second washing solution is injected between the biological sample injection unit 120 and the biological sample storage unit 125. The unit 164 may be connected. In addition, when analyzing biomaterials using various kinds of reaction samples, a washing solution injection unit (not shown) may be connected between the reaction sample injection unit 110 and the reaction sample storage unit 115.

The sample reaction unit 130 may have a confluence channel 153 connected to one side and a third fluid channel 154 connected to the other side. In the sample reaction unit 130, the biological sample and the reaction sample supplied from the reaction sample storage unit 115 and the biological sample storage unit 125 are mixed and reacted. For example, samples mixed in the sample reaction unit 130 may have different optical characteristics according to specific biomaterials, for example, creatinine in a biological sample. In addition, the biological sample and the reaction sample supplied through the confluence channel 153 may be mixed and reacted in the sample reaction unit 130 and then discharged through the third fluid channel 154.

The signal detector 135 receives a mixed sample from the sample reaction unit 130 through the third fluid channel 154, and changes in optical characteristics of the samples mixed in the sample reaction unit 130 may be detected.

The signal detector 135 may be selectively formed in the biochip 100. When the signal detector 135 is not formed, a change in optical characteristics of the mixed samples may be detected by the sample reaction unit 130. . In addition, the sample reaction unit 130 may be directly connected to the sample discharge unit 140 through the third fluid channel 154.

As such, the reaction sample injector 110, the biological sample injector 120, the sample reaction unit 130, the signal detector 135, the sample discharger 140, and the fluid channels 151, 152, 153 and 154. ) And the biochip 100 including the cleaning solution injection parts 162 and 164 may be formed by bonding the first and second plates 100a and 100b. That is, the analysis of the biological sample may be performed in the biochip 100 isolated from the outside.

In detail, the first and second plates 100a and 100b may be formed of a transparent material through which light can be transmitted. For example, the first and second plates 100a and 100b may be plastic, glass, or silicon substrates. In addition, the first and second plates 100a and 100b may include polydimethylsiloxane (PDMS), polymethylmethacrylate (PMMA), polycarbonate (PC), cyclic olefin copolymer (COC), polyamide (PA), polyethylene (PE), and polypropylene (PP). ), PPE (polyphenylene ether), PS (polystyrene), POM (polyoxymethylene), PEEK (polyetheretherketone), PTFE (polytetrafluoroethylene), PVC (polyvinylchloride), PVDF (polyvinylidene fluoride), PBT (polybutyleneterephthalate), FEP (fluorinated ethylenepropylene), It may be made of a polymer such as perfluoralkoxyalkane (PFA).

Each of the reaction sample storage unit 115, the biological sample storage unit 125, the sample reaction unit 130, and the signal detection unit 135 is formed by spaced apart from the first and second plates 100a and 100b by a predetermined interval. It can be formed in space. In detail, the first plate 100a is recessed in regions corresponding to each of the reaction sample storage 115, the biological sample storage 125, the sample reaction unit 130, and the signal detector 135. Have portions 101.

The first plate 100a with the recessed portions 101 may be formed using photo lithography, electron beam lithography or imprint techniques. The method of forming the first plate 100a will be briefly described. A silicon substrate is prepared, a photolithography and an etching process are performed to form an embossed mold. Thereafter, the mold may be prepared by filling a polymer material (eg PDMS) and curing the polymer material.

In addition, the second plate 100b may be bonded to the first plate 100a by being spaced apart from the upper surface of the first plate 100a by a predetermined distance h. The second plate 100b has a flat surface, and holes may be formed in predetermined regions. That is, a hole penetrating the second plate 100b in each of the regions in which the reaction sample injecting unit 110, the biological sample injecting unit 120, the sample discharging unit 140, and the cleaning liquid injecting units 162 and 164 are formed. This can be formed.

In addition, the fluid channels 151, 152, 153, and 154 may be formed by the upper surface of the first plate 100a and the lower surface of the second plate 100b spaced apart from each other by a predetermined distance h. At this time, the interval h between the first and second plates 100a and 100b may be adjusted to allow the capillary force to fully function. Accordingly, the samples may pass through the fluid channels 151, 152, 153, 154 by capillary force. In addition, the upper surface of the first plate (100a) and the lower surface of the second plate (100b) may be hydrophilic surface treatment so that the samples can be moved smoothly.

As such, the biochip 100 according to an embodiment of the present invention may be supplied and reacted with samples in a closed space, such as picric acid sample, and more safely when detecting a biomaterial using a hazardous chemical solution. Can be detected.

Hereinafter, a biomaterial detection system according to an embodiment of the present invention will be described with reference to FIG. 5.

5 illustrates a biomaterial detection system according to an embodiment of the present invention.

Referring to FIG. 5, the biomaterial detection system includes a biochip 100, a light source unit 200, and a detector 300.

As described with reference to FIGS. 2 to 4, the biochip has a reaction sample injector 110, a biological sample injector 120, a sample reaction unit 130, a signal detector 135, and a sample discharger 140. ). The biological sample and the reaction sample supplied to the biochip, respectively, may be mixed and reacted in the sample reaction unit 130, and the mixed and reacted sample may have optical properties changed according to the biomaterial in the biological sample. For example, when urine is supplied as a biological sample and picric acid sample is supplied as a reaction sample, creatinine and picric acid in the urine may react to turn red. Then, the mixed and reacted sample is moved from the sample reaction unit 130 to the signal detection unit 135. In addition, after detecting the optical characteristics of the sample mixed and reacted by the signal detector 135, the cleaning solution is supplied through the first or second cleaning solution injection section (162, 164), and the biological sample and the reaction sample in the biochip Can be removed.

The light source unit 200 irradiates incident light having a specific wavelength to the signal detection unit 135 of the biochip in order to detect optical characteristics of the mixed and reacted sample. For example, to detect creatinine in urination, incident light having a wavelength of about 515 nm to 525 nm can be irradiated. The light source unit 200 may include, for example, a Xenon lamp that outputs polychromatic light, a laser diode that outputs a monochromatic light source having a specific wavelength, and a white light source or a light emitting diode (LED). Can be used.

The detector 300 detects incident light passing through the signal detector 135 of the biochip, and measures optical characteristics, that is, absorbance of the mixed and reacted samples. The detector 300 may measure the absorbance of the mixed and reacted sample using a light sensing element, for example, an optical sensor. As the detector 300, a UV spectrometer may be used. The UV spectrometer can detect the absorbance of light having a wide wavelength band. In addition, the detection unit 300 may analyze the change in absorbance of the reacted sample to quantify the concentration of a specific biomaterial in the biological sample.

6A and 6B illustrate a biological sample detection process using a biochip according to an embodiment of the present invention. 6A illustrates a biochip in which a biological sample and a reaction sample are injected, and FIG. 6B illustrates a biochip in which the biological sample and the reaction sample are mixed and reacted and moved from the sample reaction unit to the signal detection unit.

In FIG. 6A, creatinine was dissolved in water at a concentration of 100 mg / ml and injected into a biological sample, and 1.17% picric acid including 0.25 N NaOH was injected into the reaction sample. And, as shown in Figure 6b, it is possible to confirm the change in color according to the mixing and reaction of the biological sample and the reaction sample. Therefore, according to the mixing and reaction of the biological sample and the reaction sample, the absorbance may change, and the concentration of the creatinine in the biological sample may be detected by quantifying the change in absorbance.

FIG. 7 is a graph showing absorbance changes according to reactions of a biological sample and a reaction sample in each of the biochip and the test tube according to the general technique.

Referring to FIG. 7, absorbance measured by reacting a biological sample without creatinine and a picric acid sample was represented by noise, and the same concentration and amount of creatinine and picric acid samples were reacted in a test tube and a biochip, respectively. The absorbance measured is expressed as a signal to noise ratio. That is, it can be seen that there is no difference between the absorbance measured by reacting a biological sample and a reaction sample in a test tube in the past, and the absorbance measured by reacting a biological sample and a reaction sample in a biochip of the present invention. Therefore, in the biochip according to an embodiment of the present invention, it can be seen that the biological sample can be analyzed accurately and safely.

Although the embodiments of the present invention have been described above with reference to the accompanying drawings, those skilled in the art to which the present invention belongs may be embodied in other specific forms without changing the technical spirit or essential features of the present invention. You will understand that. It is therefore to be understood that the above-described embodiments are illustrative and not restrictive in every respect.

1 is a schematic block diagram showing a biochip according to an embodiment of the present invention.

2 is a plan view of a biochip according to an embodiment of the present invention.

3 is a cross-sectional view of a biochip according to an embodiment of the present invention.

4 illustrates a biochip according to an embodiment of the present invention.

5 illustrates a biomaterial detection system according to an embodiment of the present invention.

6A and 6B illustrate a biological sample detection process using a biochip according to an embodiment of the present invention.

FIG. 7 is a graph showing absorbance changes according to reactions of a biological sample and a reaction sample in each of the biochip and the test tube according to the general technique.

DESCRIPTION OF THE REFERENCE NUMERALS

100: biochip 110: reaction sample injection unit

120: biological sample injection unit 130: sample reaction unit

135: signal detection unit 140: sample discharge unit

151, 152, 153, 154: fluid channels 162, 164: washing liquid inlet

Claims (19)

A biological sample injection unit into which a biological sample is injected; A reaction sample injector spaced apart from the biological sample injector and into which a reaction sample reacting with the biological sample is injected; A sample reaction part connected to the biological sample injector and the reaction sample injector through fluid channels, the sample reaction part being an enclosed space in which the biological sample and the reaction sample are mixed and reacted; And Biochip comprising a sample discharge unit for discharging the biological sample and the reaction sample. The method of claim 1, The biochip is formed by joining first and second plates, wherein the planes of the first and second plates facing each other are spaced apart by a predetermined interval. The method of claim 2, And the first plate has a recessed portion defining the sample reaction portion. The method of claim 2, And said fluid channels are formed by surfaces of said first and second plates facing each other. The method of claim 2, The second plate has a through hole formed in regions corresponding to the biological sample injector, the reaction sample injector, and the sample outlets. The method of claim 2, The fluid channels may include a first fluid channel connected to the biological sample injector, a second fluid channel connected to the reaction sample injector, and a confluence channel connecting the first and second fluid channels to the sample reactant. Bio chip. The method of claim 2, And the first and second plates are formed of a transparent material. The method of claim 2, And said surfaces of said first and second plates facing each other are hydrophilic. The method of claim 1, The reaction sample is a biochip, characterized in that the explosive substance. The method of claim 9, The reaction sample is a biochip, characterized in that the picric acid reacted with creatinine. The method of claim 1, And a signal detection unit connected to the sample reaction unit and emitting an optical signal changed by the reaction of the biological sample and the reaction sample. The method of claim 1, wherein the biochip, A biological sample storage unit for storing the biological sample between the biological sample injection unit and the sample reaction unit; And And a reaction sample storage unit for storing the reaction sample between the reaction sample injection unit and the sample reaction unit. 13. The method of claim 12, The biochip further includes a first washing solution injection unit in which a washing solution is injected between the reaction sample storage unit and the sample reaction unit. The method of claim 13, The biochip further comprises a second cleaning solution injecting unit, the cleaning solution is injected between the biological sample injection unit and the biological sample storage unit. A biological sample injection unit into which a biological sample is injected; A biochip connected to the at least one bioreactor, the biochip including a sample reaction part which is a sealed space where the biological sample and the reaction sample are mixed and reacted, and a sample discharge part which discharges the biological sample and the reaction sample; A light source unit providing incident light to the sample reaction unit; And And a detector configured to receive the incident light passing through the sample reaction part and detect a change in an optical signal. 16. The method of claim 15, The detection unit detects a change in absorbance from the incident light passing through the sample reaction unit. 16. The method of claim 15, And the light source unit is a light-emitting diode or a light emitting laser. 16. The method of claim 15, The detection unit is a biomaterial detection system, characterized in that the UV spectrometer. 16. The method of claim 15, The biochip further includes a signal detection unit connected to the sample reaction unit and detecting an optical signal that is changed by the reaction of the biological sample and the reaction sample. The light source unit provides incident light to the sample reaction unit or the signal detection unit, And the detection unit receives the incident light passing through the sample reaction unit or the signal detection unit to detect a change in an optical signal.

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