Standard material composition for verifying a bioanalyzer and standard strip using the same

Abstract

The present application relates to a standard material composition for verifying a bioanalysis device, which comprises nanoparticles containing quantum dots. The present application can improve the analytical accuracy of the bioanalysis device through a standard strip and / or a standard tray made of the standard material composition.

Description

Technical Field

[0001] The present application relates to a standard material composition capable of verifying (calibrating) the analytical accuracy of a biological analysis device and a standard strip using the same. Background Art

[0002] Optical detection methods for measuring the radiant energy transmitted, reflected, and refracted by an object according to wavelength are easy to use, accurate, compact or portable, and can be used for various reactions at a low price. Accordingly, optical detection methods are used in various fields such as chemistry, physics, biochemistry, immunology, enzymology, molecular biology, biology, etc.

[0003] Examples of the optical detection method may include a detection (analysis) method in which a lateral flow strip or a microfluidic chip is applied to a bioanalysis device equipped with optical components.

[0004] However, in the manufacture of analytical devices, although the hardware configuration equipped in each analytical device is designed to be the same, there is a problem that due to various variables such as deviations in each configuration combination and deviations in the electromagnetic properties of the components, several manufactured analytical devices will not obtain the same data for the same fluorescent signal. This reduces the analytical accuracy (reliability) of the results of quantitative diagnosis and analysis of the detection material by measuring the intensity of the fluorescent signal.

[0005] Therefore, when detection is performed by several analysis devices, a verification process is required to correct the fluorescence intensity deviation of the analysis devices using a standard material as a reference to indicate the required fluorescence signal intensity. Accordingly, in the prior art, the verification process of the analysis device is performed by using a mixed ink with gold, latex or the like or a fluorescent substance such as europium as a standard material.

[0006] However, the ink has several problems, since it is manufactured as a standard material through a printing process based on a color map, an error in color expression occurs whenever the printing process is performed, and since it is easily contaminated when exposed to the outside, its life is not long. In addition, the fluorescent substance has several problems, since photobleaching occurs during the manufacturing process of the standard material, or it is sensitive to changes in light, temperature or humidity, so its reproducibility is poor.

[0007] Accordingly, there is a need to develop improved standard materials in order to enhance the analytical accuracy of bioanalytical equipment. Summary of the invention

[0008] [public]

[0009] [Technical issues]

[0010] One object of the present application is to provide a standard material composition for verifying a bioanalysis device, which can verify (calibrate) the analytical accuracy of the bioanalysis device.

[0011] Another object of the present application is to provide a standard strip prepared from a standard material composition.

[0012] Another object of the present application is to provide a standard pallet made from a standard material composition.

[0013] Another object of the present application is to provide a method for validating a bioanalytical device using a standard strip and / or a standard tray.

[0014] [Technical solution]

[0015] In order to achieve the above-mentioned object, the present application provides a standard material composition for verifying a bioanalysis device, which comprises nanoparticles containing quantum dots.

[0016] The quantum dot-containing nanoparticle may include a core portion; a quantum dot portion bonded to the surface of the core portion; and a shell portion for protecting the core portion and the quantum dot portion.

[0017] The quantum dot portion may include a plurality of quantum dot embedding layers.

[0018] The shell portion may include a plurality of silicon dioxide shell layers.

[0019] The quantum dot-containing nanoparticle may further include a supporting portion for supporting the combination of the core portion and the shell portion.

[0020] Meanwhile, the present application provides a standard strip comprising one or more luminescent lines formed by a standard material composition for verifying a bioanalysis device.

[0021] Multiple light emitting lines may be provided, and the concentration of quantum dots may be different between the multiple light emitting lines.

[0022] A plurality of light emitting lines may be provided, and the intensity of the fluorescent signal may be different between the plurality of light emitting lines.

[0023] In addition, the present application provides a standard tray including a light emitting portion formed of a standard material composition for verifying a bioanalysis device.

[0024] In addition, the present application provides a method for verifying a bioanalysis device, comprising the steps of: irradiating a light source onto a standard tray, wherein the standard tray comprises a light-emitting portion formed by a standard material composition for verifying the bioanalysis device; judging whether a fluorescence intensity value of the light-emitting portion emitted by the irradiating light source falls within a range of a standard fluorescence intensity value of an optical component input to the bioanalysis device; and first correcting the range of the standard fluorescence intensity value input to the optical component so that the fluorescence intensity value falls within the range of the standard fluorescence intensity value through the judgment.

[0025] The method of verifying a bioanalysis device of the present application may further comprise the step of performing secondary correction on a standard fluorescence intensity value input to the optical component by means of a standard strip comprising one or more luminescent lines formed by a standard material composition for verifying a bioanalysis device.

[0026] [Advantageous Effects]

[0027] According to the present application, by using a standard strip and / or a standard tray prepared by a standard material composition containing nanoparticles containing quantum dots to calibrate the optical components in the bioanalysis device, the analysis accuracy of the bioanalysis device can be improved. Therefore, the present application can help provide reliable biodetection (analysis) results. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Figures 1 to 4 is a cross-sectional view showing a quantum dot-containing nanoparticle of the present application.

[0029] Figure 5 is a perspective view showing a standard strip according to the present application.

[0030] Figure 6 and Figure 7 is a flow chart showing a process of preparing a standard strip according to the present application.

[0031] Figure 8 is a perspective view showing a standard pallet according to the present application.

[0032] Fig. 9 is a schematic diagram showing standard components according to the present application.

[0033] Fig.10 is a reference diagram for explaining a process of validating a bioanalysis apparatus according to the present application.

[0034] Fig.11 2 is a reference diagram for explaining Experimental Example 1 according to the present application. DETAILED DESCRIPTION

[0035] [Best Mode]

[0036] The terms and words used in the specification and claims of this application should not be interpreted as limited to the conventional or dictionary meanings, but should be interpreted as meanings and concepts consistent with the technical idea of ​​this application, which is based on the principle that the inventor can appropriately define the concepts of the terms to describe his invention in the best way.

[0037] The present application aims to provide a standard material with improved lifetime and improved analytical accuracy of a bioanalytical device by introducing quantum dots into a standard material for verification (calibration) of a bioanalytical device, wherein the quantum dots have a small photobleaching phenomenon and are insensitive to changes in light, temperature or humidity. The present application will be described in detail with reference to the following drawings.

[0038] The present application provides a standard material composition for verifying a bioanalysis device, which includes nanoparticles containing quantum dots (hereinafter referred to as a "standard material composition"). The standard material composition according to the present application can be defined as a composition for verifying (calibrating) a bioanalysis device, so that the bioanalysis device can indicate a correct detection value (analysis value) before detecting (analyzing) a biological sample (a sample of an organism) with the bioanalysis device.

[0039] The nanoparticles containing quantum dots contained in the standard material composition according to the present application may not be particularly limited as long as they contain quantum dots. That is, the nanoparticles containing quantum dots may consist only of quantum dot particles or a combination of quantum dot particles and other components. At this time, the quantum dots in the present application are semiconductor materials and can be defined as materials in which atoms form spherical layers having about 5 to 10 layers and a radius of generally 10 nm or less, and the material exhibits a quantum confinement effect, in which the luminescence wavelength is different from the luminescence wavelength of the bulk state, because when the semiconductor material in the bulk state is reduced to a specific size or smaller, the motion properties of electrons in the semiconductor material in the bulk state are further restricted. If this quantum dot reaches an energy excitation state by receiving light from an excitation source, it can exhibit a luminescence property that automatically emits energy according to the corresponding energy band gap.

[0040] The nanoparticles containing quantum dots in the present application may specifically be quantum dot particles themselves, or Figure 1 The quantum dot-containing nanoparticle shown includes a core portion 10, a quantum dot portion 20, and a shell portion 30. The quantum dot-containing nanoparticle including the core portion 10, the quantum dot portion 20, and the shell portion 30 will be described in detail below.

[0041] The core part 10 included in the nanoparticle containing quantum dots of the present application can include organic particles or inorganic particles. Inorganic particles can specifically be one of one or more components selected from the group consisting of silicon dioxide, aluminum oxide, titanium dioxide and zinc dioxide. Because these inorganic particles have high stability, when they are applied to the core part 10, the size of the nanoparticle containing quantum dots and the size of the core part 10 can be easily controlled, and because of these, nanoparticles containing quantum dots with excellent optical properties (luminescent properties) and various particle sizes can be obtained.

[0042] The diameter of the core part 10 may be 10 to 100,000 nm, specifically 80 to 1,000 nm. Since the diameter of the core part 10 is within the above range, the processing and further post-processing of the nanoparticles containing quantum dots can be easily performed.

[0043] The quantum dot part 20 included in the quantum dot-containing nanoparticle of the present application is bonded to the surface of the core part 10, and can be used to enable the quantum dot-containing nanoparticle to exhibit optical properties. Specifically, the quantum dot part 20 can have a structure (a single quantum dot embedding layer) in which a plurality of quantum dots surround the entire surface of the core part 10. In addition, the quantum dots included in the quantum dot part 20 can form crosslinks with the silicon dioxide as a component of the shell part 30, and a structure in which the quantum dots are randomly or uniformly bonded to the silicon dioxide as a component of the shell part 30 by crosslinking can occur.

[0044] As an example, the quantum dots of the quantum dot part 20 can be uniformly dispersed and bonded to the surface of the core part 10 by a process of modifying a material having functional groups at both ends, and thereby, the quantum dot part 20 can be formed. The material having functional groups at both ends can specifically be a functional group of one or more atoms selected from the group consisting of sulfur, nitrogen and phosphorus combined at one end, and one of one or more functional groups selected from the group consisting of silane, amino, sulfone, carboxyl and hydroxyl at the other end. Specifically, the material having functional groups at both ends can be mercaptopropyltrimethoxysilane, mercaptomethyldiethoxysilane, mercaptopropylmethyldimethoxysilane or mercaptopropyltriethoxysilane.

[0045] On the one hand, the quantum dot included in the quantum dot part 20 may have a single core structure composed of a semiconductor element of the II-VI group series, a semiconductor element of the III-V group series, or a semiconductor element of the IV-IV group series, or may have a structure in which a coating is formed by coating a semiconductor element of the II-IV group series on a single core. This may also be applied to the above-mentioned quantum dot particles.

[0046] The semiconductor of the II-VI series can be a semiconductor that combines at least one IIB group element and at least one VIB group element on the periodic table. Specifically, the semiconductor of the II-VI series can be selected from CdS, CdSe, CdTe, ZnSe, ZnS, PbS, PbSe, HgS, HgSe, HgTe, CdHgTe and CdSe x Te 1-x The semiconductor of the III-V series can be specifically selected from the group consisting of GaAs, InAs and InP.

[0047] Here, in terms of luminous efficiency, it is more preferred that the quantum dot has a structure in which a coating is formed on a single core rather than a single core structure. This is because the coating acts as a passivation layer to protect the single core, thereby improving the stability of the quantum dot. Specifically, as the quantum dot, a quantum dot in which a coating made of ZnS is formed on a single core made of CdSe or CdS, or a quantum dot in which a coating made of CdSe or ZnSe is formed on a single core structure made of CdSe (type 1 quantum dot) can be used.

[0048] In addition, as the quantum dot, one in which a hydrophobic organic compound (eg, oleic acid) is coated on a quantum dot having a single core structure or one in which a coating is formed on a single core may be used.

[0049] The diameter of these quantum dots may be 1 to 50 nm, specifically 1 to 20 nm. In addition, when the quantum dot has a structure in which a coating is formed on a single core, the diameter of the single core may be 1 to 20 nm, specifically 2 to 10 nm.

[0050] The quantum dot portion 20 including quantum dots may include a plurality of quantum dot embedding layers (quantum dot coatings) 21, 22, 23, such as Figure 2 Specifically, the quantum dot portion 20 may include a first quantum dot embedding layer 21 surrounding the surface of the core portion 10, a second quantum dot embedding layer 22 surrounding the first quantum dot embedding layer 21, and a third quantum dot embedding layer 23 surrounding the second quantum dot embedding layer 22. Here, the number of quantum dot embedding layers 21, 22, and 23 is not limited to Figure 2 The number shown in , and can be adjusted according to the desired physical properties and size of the quantum dot-containing nanoparticles. In this way, when the quantum dot portion 20 includes a plurality of quantum dot embedding layers 21, 22, 23, the quantum dot-containing nanoparticles include multiple layers of multi-quantum dots, thereby exhibiting high luminous efficiency (quantum yield) and improved brightness. This leads to improved optical properties (luminescent properties) of the standard material composition according to the present application.

[0051] The shell part 30 included in the quantum dot-containing nanoparticle of the present application is combined to surround the quantum dot part 20, and may play a role in protecting the core part 10 and the quantum dot part 20. The shell part 30 may be mainly made of silicon dioxide.

[0052] The shell portion 30 may have a thickness of 1 to 1,000 nm, specifically 1 to 300 nm. Since the shell portion 30 has a thickness within the above range, the nanoparticles containing quantum dots can be prevented from becoming too heavy while protecting the core portion 10 and the quantum dot portion 20, thereby improving the applicability of the nanoparticles containing quantum dots.

[0053] like Figure 3 As shown, such a shell portion 30 may include a plurality of silica shell layers 31, 32, 33. Specifically, the shell portion 30 may include a first silica shell layer 31 surrounding the quantum dot portion 20, a second silica shell layer 32 surrounding the first silica shell layer 31, and a third silica shell layer 33 surrounding the second silica shell layer 32. Here, the number of silica shell layers 31, 32, and 33 is not limited to Figure 3 The number shown in the figure can be adjusted according to the physical properties and size of the nanoparticles containing quantum dots required. In this way, when the shell part 30 includes a plurality of silica shell layers 31, 32, 33, the coverage density of the shell part 30 becomes high to increase the stability of the nanoparticles containing quantum dots. In addition, by adjusting the number of silica shell layers 31, 32, 33, the size of the nanoparticles containing quantum dots can be freely controlled to a desired level. At this time, the size control of the nanoparticles can be achieved by controlling the thickness by adjusting the volume of the reaction material when forming the shell part 30 in addition to adjusting the number of silica shell layers 31, 32, 33 included in the shell part 30.

[0054] On the one hand, the ratio of the diameter of (a) the core portion 10 to the thickness of (b) the shell portion 30 (e.g., length ratio) can be 120 to 3: 1 to 7.5, specifically 6 to 3: 1 to 2. When the ratio of the diameter of the core portion 10 to the thickness of the shell portion 30 is within the above range, the optical properties and stability of the nanoparticles containing quantum dots can be improved.

[0055] Such quantum dot-containing nanoparticles may further include a support portion 40 that is combined with each of the core portion 10 and the shell portion 30 to support the combination of the core portion 10 and the shell portion 30. Figure 4, the quantum dot-containing nanoparticle further includes a support portion 40 having a bridge structure connecting the core portion 10 and the shell portion 30. When such a support portion 40 is further included, the binding density (crosslinking density) of the core portion 10 and the shell portion 30 increases, so that the stability of the quantum dot-containing nanoparticle is higher, and thus, a quantum dot-containing nanoparticle with excellent optical properties can be provided. This can lead to improved optical properties (luminescent properties) of the standard material composition according to the present application.

[0056] The support part 40 may be formed of a carbon support having a first functional group bonded to the core part 10 at one end and a second functional group bonded to the shell part 30 at the other end. Here, the first functional group may be selected from the group consisting of a nitro group, an imide group, an ester group, a maleimide group, an iodoacetamide group, an N-hydroxysuccinimide group, and a tosyl group. In addition, the second functional group may be selected from the group consisting of a trimethoxysilyl group, a triethoxysilyl group, a dimethoxysilyl group, a diethoxysilyl group, a methoxysilyl group, and an ethoxysilyl group.

[0057] Specifically, the carbon support can be a kind of wherein oligoethylene glycol or polyethylene glycol form main skeleton structure, wherein the first functional group is attached to one end of the main skeleton structure, and the second functional group is attached to the other end of the main skeleton structure. In addition, the carbon support can have a molecular weight of 100 to 15,000g / mol. When the carbon support has a main skeleton structure such as oligoethylene glycol or polyethylene glycol, the dispersibility in a solvent (e.g., ethanol) can be improved in the process of preparing the nanoparticle containing quantum dots, and thus, the nanoparticle containing quantum dots with improved binding density (crosslinking density) and stability can be provided.

[0058] When considering the optical properties, processability, moldability, etc. of the standard material composition, these quantum dot-containing nanoparticles can be included in the standard material composition in an amount of 1 to 80 parts by weight, specifically 1 to 40 parts by weight, based on 100 parts by weight of the standard material composition.

[0059] On the one hand, the standard material composition according to the present application may further include a binder resin, a curing agent, an additive, and a solvent to be molded into various shapes.

[0060] The binder resin further included in the standard material composition according to the present application may not be particularly limited as long as it is a resin used in the field of optical materials. Specifically, the binder resin may be one or more selected from the group consisting of acrylate-based resins, polyester-based resins, polyamide-based resins, polyimide-based resins, polycarbonate-based resins, and polysiloxane-based resins.

[0061] Such a binder resin may be included in the standard material composition in an amount of 10 to 50 parts by weight, specifically 25 to 50 parts by weight, based on 100 parts by weight of the standard material composition, when considering processability, moldability, dispersibility, etc. of the standard material composition.

[0062] The curing agent further included in the standard material composition according to the present application may not be particularly limited as long as it causes a curing reaction of the binder resin. Specifically, the curing agent may be one or more selected from the group consisting of an oxazoline-based curing agent, a polyisocyanate-based curing agent, a melamine-based curing agent, and a carbodiimide-based curing agent.

[0063] Such a curing agent may be included in the standard material composition in an amount of 1 to 10 parts by weight, specifically 1 to 5 parts by weight, based on 100 parts by weight of the standard material composition, when considering curability, workability, etc. of the standard material composition.

[0064] The additive further included in the standard material composition according to the present application may not be particularly limited as long as it is an additive used in the field of optical materials. Specifically, the additive may be one or more selected from the group consisting of an inorganic filler, a leveling agent, an anti-foaming agent, a dispersion stabilizer, a viscosity control agent, an antioxidant, and a heat stabilizer.

[0065] When considering processability, optical properties, etc. of the standard material composition, these additive resins may be included in the standard material composition in an amount of 5 to 50 parts by weight, specifically 20 to 50 parts by weight, based on 100 parts by weight of the standard material composition.

[0066] The solvent further included in the standard material composition according to the present application may not be particularly limited as long as it is a solvent used in the field of optical materials. Specifically, the solvent may be selected from an aromatic hydrocarbon-based solvent such as benzene, toluene, xylene and ethylbenzene; an aliphatic hydrocarbon-based solvent such as pentane, hexane, heptane; an alcohol-based solvent such as methanol, ethanol, propanol, isopropanol, cyclohexanol, benzyl alcohol, octanol, ethylene glycol, propylene glycol and glycerol; a ketone-based solvent such as acetone, methyl ethyl ketone, diisobutyl ketone and methyl amyl ketone; an ester-based solvent such as ethyl acetate, isopropyl acetate, butyl acetate and ethyl acetoacetate; and one or more of the group consisting of ether-based solvents such as diethyl ether, dibutyl ether, tetrahydrofuran, etc.

[0067] When considering processability, moldability, etc. of the standard material composition, these solvents may be included in the standard material composition in an amount of 1 to 50 parts by weight, specifically 10 to 20 parts by weight, based on 100 parts by weight of the standard material composition.

[0068] The above-mentioned standard material composition according to the present application can be applied to the verification (calibration) of the bioanalysis equipment through the curing and molding process according to the verification device. Specifically, the present application provides a standard strip, a standard tray or a standard component as a verification device, which will be described in detail below.

[0069] The present application provides a standard strip, which comprises one or more luminous lines formed by the above-mentioned standard material composition. Figure 5 According to the present application, the standard strip may include a strip body portion 100 and one or more luminous lines 200 .

[0070] The strip body portion 100 included in the standard strip according to the present application may be made of materials and structures commonly used in the field of biological strips.

[0071] The luminescent wire 200 included in the standard strip according to the present application is formed of the above-mentioned standard material composition, and one or more wires may be provided on the strip body portion 100. The luminescent wire 200 includes the above-mentioned nanoparticles containing quantum dots, so that the light source can emit light.

[0072] Specifically, Figure 5 As shown, the luminescent wire 200 may be provided in a plurality of ways including a first luminescent wire 201, a second luminescent wire 202, and a third luminescent wire 203, and in this case, the quantum dot concentrations between each luminescent wire may be different from each other. That is, when forming each luminescent wire, standard material compositions having different quantum dot (nanoparticles containing quantum dots) contents are respectively applied to form luminescent wires having different quantum dot concentrations. For example, the quantum dot concentration in the first luminescent wire 201 may be low (C 2 ) by setting (adjusting) the concentration (content) of the quantum dots of each standard material composition. 低 ), the quantum dot concentration in the second luminescent line 202 is higher than the quantum dot concentration in the first luminescent line 201 (C 低 <C 中 ), the quantum dot concentration in the third luminescent line 203 is higher than the quantum dot concentration in the second luminescent line 202 (C 低 <C 中 <C 高 ).

[0073] In addition, a plurality of light emitting lines 200 may be provided, and the intensity of the fluorescence signal may be different between each light emitting line 201, 202, and 203. That is, a plurality of light emitting lines 201, 202, and 203 showing different fluorescence intensities may be formed by controlling the transmission process (transmittance) of the fluorescence signal emitted from each light emitting line 201, 202, and 203.

[0074] Here, the number of the light emitting wires 200 is not limited to Figure 5The numbers shown in the table can be adjusted appropriately according to the analysis conditions.

[0075] In this way, the standard strip according to the present application has a quantum dot concentration gradient or is equipped with multiple luminous lines 201, 202 and 203 with different fluorescence signal intensities, so that the error (bias) of the analysis equipment can be more accurately corrected during the verification of the biological analysis equipment, and thereby, the analysis accuracy of the biological analysis equipment can be improved.

[0076] Such a standard strip according to the present application can be obtained by Figure 6 Or the process shown in 7 is prepared.

[0077] Specifically, Figure 6 As shown, each standard material composition having different quantum dot (or nanoparticle containing quantum dot) contents is applied (coated) on a conventional optical film (optical film) to cover the film, and then subjected to a curing treatment to prepare a plurality of QD films having a quantum dot concentration gradient (e.g., having C 低 , C 中 and C 高 Concentration), and each prepared QD film is attached to the PVC back card according to the line position of the PVC back card, and then a patterned black tape (or film) is placed and attached to the PVC back card to expose the QD film lines to prepare an uncut standard card, and then the standard card is cut into the size required to prepare the standard strip according to the present application.

[0078] In addition, if Figure 7 As shown, a QD sheet made of a standard material composition is prepared, and one surface of an optical film is patterned by a printing method to prepare a mask in which lines with different light transmittances are formed, and then the prepared QD sheet is covered with the prepared mask and cured to prepare an uncut standard card, and then the standard card is cut into a desired size to prepare a standard strip according to the present application.

[0079] Since the standard strip according to the present application contains the luminescent line 200 formed by the above-mentioned standard material composition, it can be conveniently used for verification (calibration) of biological analysis equipment, and the analysis accuracy of the biological analysis equipment can be improved. In addition, during the quality control process in the preparation process of the standard strip, photobleaching will not occur, and stable performance can be achieved even if the storage environment (shading, temperature, humidity, etc.) changes. In addition, since the standard strip is prepared using an optical film, it can be prevented from UV exposure and external contamination, so that a long service life can be ensured.

[0080] The present application provides a standard tray, the standard tray comprising a light-emitting portion formed by the above-mentioned standard material composition. Figure 8The standard tray according to the present application may include a tray body portion 300, a reference portion 400, and a light emitting portion 500. Here, the standard tray according to the present application may be a tray for mounting a biological reagent kit equipped with a biological strip.

[0081] The tray body part 300 included in the standard tray according to the present application may be made of materials and structures commonly used in the field of biological trays.

[0082] The reference part 400 included in the standard tray according to the present application is used to provide a reference point when analyzing the fluorescent signal of the light emitting part 500, and may be made of a common material.

[0083] The light emitting part 500 included in the standard tray according to the present application may be formed of the above-mentioned standard material composition to emit light through the light source. This light emitting part 500 may be formed by a process of curing the above-mentioned standard material composition into a paste state.

[0084] Since the standard tray according to the present application includes the light emitting portion 500 formed of the above-mentioned standard material composition, it can be conveniently used for verification (calibration) of a biological analysis device, and the analysis accuracy of the biological analysis device can be improved.

[0085] The present application provides a standard assembly in which the above-mentioned standard strip and standard pallet are combined. Fig. 9 The present application can provide a standard assembly, which includes a standard reagent kit equipped with the above-mentioned standard strip and the above-mentioned standard tray on which the standard reagent kit is installed. This standard assembly can be effectively used for the first and second calibrations of the bioanalysis equipment to be described later.

[0086] On the one hand, the present application provides a method for verifying a bioanalysis device using the above-mentioned standard strips and / or standard trays, and will be described in detail below. Here, the verification of the bioanalysis device according to the present application can be performed before analyzing a biological sample (e.g., an antigen, a receptor, a virus, an enzyme, an infectious immunoglobulin, a cytokine or other infectious factor) with the bioanalysis device. In addition, the fluorescence intensity of the portion other than the luminous portion 500 of the standard tray or the luminous line 200 of the standard strip is defined as a background value, and the value obtained by subtracting the background value from the fluorescence intensity value of the luminous portion 500 or the luminous line 200 in the quantitative / qualitative analysis can be used for verification and analysis.

[0087] First, a light source is irradiated to a standard tray including a light emitting portion 500 formed of the above standard material composition. In this case, the light source may be an external light source or a light source equipped in the analysis device, and its wavelength may be ultraviolet light (blue light, <420 nm).

[0088] Next, it is determined whether the fluorescence intensity value of the light emitting portion 500 emitted by the irradiation light source falls within the range of the standard fluorescence intensity value input to the optical component of the bioanalysis device. That is, the fluorescence signal emitted from the light emitting portion 500 provided in the standard tray is received by the optical component of the bioanalysis device, and it is determined by the software of the optical component whether the intensity of the received fluorescence signal falls within the range of the standard fluorescence signal intensity input (set) to the optical component. Here, the range of the standard fluorescence signal intensity value input to the optical component can be determined based on a numerical value representing the quantum yield or photoluminescence of the biological sample to be analyzed.

[0089] Next, the verification of the bioanalysis device can be performed by first correcting the range of the standard fluorescence intensity value input to the optical component, so that it can be judged that the fluorescence intensity value falls within the standard fluorescence intensity value range. Here, when it is confirmed that the fluorescence intensity value of the light-emitting portion 500 falls within the range of the standard emission intensity value input to the optical component during the judgment process, the first correction can be omitted. In addition, the first correction can be performed by applying a standard strip containing the light-emitting wire 200 instead of a standard tray containing the light-emitting portion 500.

[0090] The method for verifying the bioanalysis device according to the present application can further carry out a process of performing a secondary correction on the standard fluorescence intensity value input to the optical component by using a standard strip containing one or more luminous lines 200 formed by the above-mentioned standard material composition. That is, a light source is irradiated onto the standard strip containing one or more luminous lines 200, and it is determined whether the fluorescence intensity value of the luminous line 200 emitted by the irradiation light source falls within the first correction standard fluorescence intensity value set to the optical component of the bioanalysis device. When it does not fall within the set standard fluorescence intensity value (first correction standard fluorescence intensity value), the standard fluorescence intensity value set to the optical component of the bioanalysis device is subjected to a secondary correction.

[0091] For example, by Fig.10 The correlation coefficient (c) shown is applied to the correction to perform correction of the optical components of the bioanalysis device through the standard strip containing the luminous line 200. That is, if the standard fluorescence intensity value of the optical component input to the bioanalysis device is analyzed and formulated by a standard strip having a fluorescence intensity value prepared according to the equation Y0=a0X+b0, the equation Y1=a1X+b1 can be obtained. Here, if the correlation coefficient (c) of Y0 and Y1 is obtained and applied to Y1, the corrected equation Y1'=c(a1X+b1) can be obtained. By correcting the error (deviation) of the optical component with the corrected equation Y1'=c(a1X+b1), the present application can ensure that each bioanalysis device has the same fluorescence intensity value of the standard strip.

[0092] The first and / or second calibration in the present application is performed once every predetermined period (1 month to 6 months) so that the validation process of the bioanalysis equipment can be updated.

[0093] In this way, since the present application verifies (calibrates) the bioanalysis device through the first and / or second calibration process, the analysis error (bias) of the bioanalysis device can be further minimized, and thus, the analysis accuracy of the bioanalysis device can be improved.

[0094] The bioanalysis device in the present application is not particularly limited, as long as it is a bioanalysis device having optical components and having software programmed therein capable of analyzing fluorescence intensity values, and specifically may include a mobile phone, a bioanalyzer, etc. In addition, the error of the optical component of the bioanalysis device in the present application may refer to the error caused between the optical components (CCD, CMOS) of each bioanalysis device itself, the error caused by the operating environment of the optical component (the lighting of the surrounding environment), the error caused by the light source (UV), etc. The present application can improve the analysis accuracy of the bioanalysis device by verifying (correcting) these errors.

[0095] The present application will be described in more detail below by way of examples. However, the following examples are only used to illustrate the present application, and it is obvious to those skilled in the art that various changes and modifications may be made within the scope and range of the technical spirit of the present application, and the scope of the present application is not limited thereto.

[0096] [Example 1]

[0097] The quantum dot particles (CdSe / ZnS, 10 nm) coated with oleic acid were added to the polyester resin, aromatic hydrocarbon-based solvent and additives (anti-foaming agent, dispersion stabilizer) and mixed, and then the curing agent was added to prepare the standard material composition. At this time, the quantum dot particles were added to reach 5 parts by weight based on 100 parts by weight of the composition.

[0098] [Example 2]

[0099] A standard material composition was prepared by the same process as in Example 1, except that 10 parts by weight of quantum dot particles were added based on 100 parts by weight of the composition.

[0100] [Example 3]

[0101] A standard material composition was prepared by the same process as in Example 1, except that 20 parts by weight of quantum dot particles were added based on 100 parts by weight of the composition.

[0102] [Example 4]

[0103] 1) Preparation of nanoparticles containing quantum dots

[0104] 100 μl of 1% (v / v) mercaptopropyltrimethoxysilane (MPTMS) was added to a core part (10 mg / ml) made of silica particles having a diameter of 120 nm, and thiol groups were introduced on the surface of the silica particles by stirring at 25°C for 12 hours.

[0105] Next, 4 mg of quantum dot particles (CdSe / ZnS, 100 mg / ml) were added to the silica particles into which the thiol groups were introduced, in which the quantum dot particles were coated with oleic acid (hydrophobicity), and the quantum dot particles were bound to the thiol groups of the silica particles by vigorous stirring with a vortex. Then, 8 ml of dichloromethane, which is a hydrophobic solvent, was further added thereto, and stirred for 10 minutes to further bind the unbound quantum dot particles. Then, 100 μl of mercaptopropyltriethoxysilane (MPTES) was added thereto and stirred for 15 minutes, and then 100 μl of 25% ammonia water (NH4OH(aq)) was added as a base and stirred for 3 hours to form a quantum dot portion having a structure in which three quantum dot embedding layers were stacked.

[0106] Next, the nanoparticles in which the core part and the quantum dot part were formed were washed three times with ethanol, and then 100 μl of tetraethyl orthosilicate and 25% ammonia water were added thereto and stirred at 400 rpm for 20 hours until the shell part was formed. Thereafter, a treatment of washing with ethanol three times was performed to produce a quantum dot-containing nanoparticle 1, wherein the quantum dot-containing nanoparticle 1 comprises a silicon dioxide core part; a quantum dot part in which three quantum dot embedding layers are stacked; and a silicon dioxide shell part.

[0107] 2) Preparation of standard material composition

[0108] A standard material composition was prepared by the same process as in Example 1, except that quantum dot-containing nanoparticles 1 prepared by the above process were used instead of quantum dot particles.

[0109] [Example 5]

[0110] 1) Preparation of nanoparticles containing quantum dots

[0111] 100 μl of 1% (v / v) mercaptopropyltrimethoxysilane (MPTMS) was added to a core part (10 mg / ml) made of silica particles having a diameter of 120 nm, and thiol groups were introduced on the surface of the silica particles by stirring at 25°C for 12 hours.

[0112] Next, 4 mg of quantum dot particles (CdSe / ZnS, 100 mg / ml) were added to the silica particles into which the thiol groups were introduced, the quantum dot particles were coated with oleic acid (hydrophobic), and the quantum dot particles were bound to the thiol groups of the silica particles by vigorous stirring with a vortex. Then, 8 ml of dichloromethane, which is a hydrophobic solvent, was further added thereto, and stirred for 10 minutes to further bind the unbound quantum dot particles.

[0113] Next, 150 μl of a carbon support (molecular weight of 1000 g / mol) was added thereto and stirred for 15 minutes. The carbon support had a maleimide group and a triethoxysilyl group respectively bonded to both ends and had a polyethylene glycol main skeleton. Subsequently, 100 μl of mercaptopropyltriethoxysilane (MPTES) was added thereto and stirred for 15 minutes. Then, 100 μl of 25% ammonia water (NH4OH(aq)) as a base was added thereto and stirred for 3 hours to bond the carbon support to the surface of the core portion, thereby forming a quantum dot portion having a structure in which three quantum dot embedding layers were stacked.

[0114] Next, the nanoparticles combined with the core part, the quantum dot part and the carbon support were washed three times with ethanol, and then 100 μl of tetraethyl orthosilicate and 25% ammonia water were added thereto and stirred at 400 rpm for 20 hours to form the support part and the shell part. Thereafter, the process of washing with ethanol was performed three times to produce the nanoparticles 2 containing quantum dots, which contained a silicon dioxide core part; a quantum dot part in which three quantum dot embedding layers were stacked; a carbon support; and a silicon dioxide shell part.

[0115] 2) Preparation of standard material composition

[0116] The standard material composition was prepared by the same process as in Example 1, except that the quantum dot-containing nanoparticles 2 prepared by the above process were used instead of the quantum dot particles.

[0117] [Preparation Example 1]

[0118] From Examples 1 to 3 (applied to Figure 6A standard strip is prepared from each standard material composition prepared in the process). Specifically, each standard material composition prepared in Examples 1 to 3 is applied to an optical film (light film), covered with a cover film, and then cured to produce three QD films (8×300nm) with different quantum dot concentrations. Then, each prepared QD film is attached to the PVC back card according to the linear position of the PVC back card (60×300nm), and a patterned black tape (60×300nm) is placed and attached to the PVC back card so that the three QD film lines are exposed, thereby producing an uncut standard card. Next, the prepared standard card is cut to prepare a standard strip.

[0119] [Experimental Example 1]

[0120] After the standard strip prepared in Preparation Example 1 was installed in the biological kit, UV light was irradiated to visually check the color of the quantum dot luminescence line, and then analyzed with a biological dedicated analyzer. The results of visual confirmation and analyzer analysis are shown in Fig.11 shown.

[0121] refer to Fig.11 , only the signal of the first line A is visually confirmed, but when analyzed with the analyzer, it can be seen that lines B and C are confirmed together with line A. Using the fluorescence intensity values ​​of the three lines confirmed in this way, the verification process of the bioanalysis device according to the present application (by Fig.10 The optical components and light source of the bioanalysis equipment are calibrated using an equation correction process.

Claims

1. A standard material composition for verifying a bioanalysis device, comprising a plurality of nanoparticles containing quantum dots, wherein the nanoparticles containing quantum dots include a core portion; a quantum dot portion bound to the surface of the core portion; A shell part for protecting the core part and the quantum dot part; and a support portion bonded to each of the core portion and the shell portion to support bonding of the core portion and the shell portion, wherein the support portion is formed of a carbon support having a first functional group bonded to the core portion at one end and a second functional group bonded to the shell portion at the other end; wherein the first functional group is selected from the group consisting of a nitro group, an imide group, an ester group, a maleimide group, an iodoacetamide group, an N-hydroxysuccinimide group, and a toluenesulfonyl group; and the second functional group is selected from the group consisting of a trimethoxysilyl group, a triethoxysilyl group, a dimethoxysilyl group, a diethoxysilyl group, a methoxysilyl group, and an ethoxysilyl group; The quantum dot portion includes three stacked quantum dot embedding layers.

2. The standard material composition for verifying a bioanalysis device according to claim 1, wherein the housing portion comprises a plurality of silica shell layers.

3. The standard material composition for verifying a bioanalysis device according to claim 1, wherein the quantum dot-containing nanoparticles further comprise a supporting portion for supporting the combination of the core portion and the shell portion.

4. A standard strip comprising one or more luminescent lines formed from the standard material composition for verifying a bioanalysis device according to any one of claims 1 to 3. 5 . The standard strip according to claim 4 , wherein the plurality of luminescent lines are provided, and the concentration of quantum dots is different between the plurality of luminescent lines. The standard strip according to claim 4 , wherein the plurality of luminescent lines are provided, and the fluorescence signal intensities are different between the plurality of luminescent lines.

7. A standard tray comprising a light emitting portion formed of the standard material composition for verifying a bioanalysis device according to any one of claims 1 to 3.

8. A method for validating a bioanalytical device, comprising the steps of: irradiating a light source onto a standard tray, the standard tray comprising a light emitting portion formed of the standard material composition for verifying a bioanalysis device according to claim 1; determining whether the fluorescence intensity value of the light emitting portion emitted by the irradiated light source falls within the range of the standard fluorescence intensity value input to the optical component of the bioanalyzer; and First, the range of the standard fluorescence intensity value input to the optical component is corrected so that the fluorescence intensity value falls within the range of the standard fluorescence intensity value through the judgment.

9. The method for verifying a bioanalytical device according to claim 8 further comprises a step of performing a secondary correction on the standard fluorescence intensity value input to the optical component by means of a standard strip, wherein the standard strip comprises one or more luminescent lines formed by the standard material composition for verifying a bioanalytical device according to claim 1.

Images