[go: up one dir, main page]
More Web Proxy on the site http://driver.im/

WO2020085757A1 - Microbeads and preparation method therefor - Google Patents

Microbeads and preparation method therefor Download PDF

Info

Publication number
WO2020085757A1
WO2020085757A1 PCT/KR2019/013875 KR2019013875W WO2020085757A1 WO 2020085757 A1 WO2020085757 A1 WO 2020085757A1 KR 2019013875 W KR2019013875 W KR 2019013875W WO 2020085757 A1 WO2020085757 A1 WO 2020085757A1
Authority
WO
WIPO (PCT)
Prior art keywords
microbead
microbeads
sample
acid
present
Prior art date
Application number
PCT/KR2019/013875
Other languages
French (fr)
Korean (ko)
Inventor
박병현
김병현
한수연
Original Assignee
주식회사 엘지화학
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from KR1020190130775A external-priority patent/KR102451333B1/en
Application filed by 주식회사 엘지화학 filed Critical 주식회사 엘지화학
Priority to US16/979,730 priority Critical patent/US20210041332A1/en
Priority to JP2020543975A priority patent/JP7048023B2/en
Priority to CN201980014541.0A priority patent/CN111757849B/en
Priority to EP19875170.3A priority patent/EP3741724B1/en
Publication of WO2020085757A1 publication Critical patent/WO2020085757A1/en

Links

Images

Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • C—CHEMISTRY; METALLURGY
    • C01—INORGANIC CHEMISTRY
    • C01B—NON-METALLIC ELEMENTS; COMPOUNDS THEREOF; METALLOIDS OR COMPOUNDS THEREOF NOT COVERED BY SUBCLASS C01C
    • C01B33/00—Silicon; Compounds thereof
    • C01B33/113—Silicon oxides; Hydrates thereof
    • C01B33/12—Silica; Hydrates thereof, e.g. lepidoic silicic acid
    • C01B33/18—Preparation of finely divided silica neither in sol nor in gel form; After-treatment thereof

Definitions

  • the present invention relates to microbeads capable of adjusting the pH of a sample, and relates to a microbead capable of easily adjusting the pH of a sample by passing the sample through a microbead controlled to a desired pH.
  • a value obtained by adding an acid or base solution to a sample is measured with a pH meter or a pH paper sensor, and the above-described operation is performed until the desired pH value is reached to optimize the pH.
  • the present invention provides microbeads in which Si-OH groups on a microbead surface are adsorbed by a pair acid and a pair base by electrostatic interaction.
  • the microbead may be used for controlling the pH value of the sample.
  • the microbead may have a specific pH selected from pH 1 to 13.
  • the microbeads may be silica-based glass microbeads.
  • the average diameter of the microbeads may be 100 to 300um.
  • It provides a method of preparing a microbead whose pH is controlled by volatilizing a solvent.
  • the step of volatilizing the solvent may be performed under 40 to 70 °C and inert gas atmosphere.
  • the inert gas may include one or more selected from the group consisting of nitrogen, argon and helium.
  • the present invention can save time and money because it is possible to adjust the sample to the desired pH through a simple and easy method without requiring an automatic device such as an additional valve system to adjust the pH. It can be usefully applied to the field.
  • FIG. 1 is a schematic diagram schematically illustrating the appearance of a microbead.
  • FIG. 2 is a schematic diagram of an apparatus according to an embodiment of the present invention.
  • Figure 3 is a graph showing the relationship between the deviation and microbead pH according to the results.
  • bearing as used herein may be used interchangeably with “beads”, unless otherwise specified. Further, unless otherwise specified, a singular expression of a term can be understood as a meaning including plural expressions of the term, and a plural expression of a term is understood as a meaning including a singular expression of the term. Can be.
  • the expression “to” is used as an expression including the corresponding numerical value. Specifically, for example, the expression “1 to 2” means not only to include 1 and 2, but also to include both numbers between 1 and 2.
  • microbeads according to embodiments of the present invention and a method of manufacturing the same will be described in more detail.
  • the present invention comprises the steps of adsorbing the conjugate acid and conjugate base component to the microbead by supporting microbeads in a buffer solution containing the conjugate acid and conjugate base;
  • It provides a method of preparing a microbead whose pH is controlled by volatilizing a solvent.
  • the sample can be adjusted to the desired pH by passing the sample through the microbeads prepared as described above.
  • the sample may be, for example, a neutral sample, for example, a sample having a value of pH 6.8 to 7.9, for example, pH 7.
  • the step of volatilizing the solvent may be performed under an inert gas atmosphere at 40 to 70 ° C, for example, 50 ° C.
  • the inert gas may include, for example, one or more selected from the group consisting of nitrogen, argon and helium, and for example, nitrogen gas (N 2 ) may be used.
  • nitrogen gas N 2
  • purging the inert gas as described above it is possible to volatilize the solvent under reduced pressure.
  • the solvent may be included without particular limitation as long as it is a solution capable of dissolving each substance well according to the type of the conjugate acid and the conjugate base, for example, distilled water, deionized water, and the like.
  • the buffer solution may have a specific pH selected from pH 1 to 13, and the microbeads may be controlled to have a specific pH selected from pH 1 to 13 according to each buffer solution.
  • the microbeads are supported on a buffer solution having a specific pH selected from a range of pH 1 to 13 to control the pH to be the same or similar to or close to the buffer solution.
  • the microbeads may include, for example, silica-based microbeads, and specifically, may include, for example, silica-based glass microbeads.
  • Microbeads may be present with a good salt coating on the surface during the manufacturing process, and Si-OH groups on the surface can be easily eluted with the salt coated on the microbead surface when the sample passes through the microbead.
  • the pair acid and the pair base may be eluted when the sample passes through the beads because the pair acid and the pair base contained in the buffer solution are adsorbed by electrostatic interaction on the Si-OH group on the microbead surface.
  • the microbead used in the present invention can serve as a carrier for the buffer solution in this way, and any component in the buffer solution can be used without particular limitation as long as it is well adsorbed.
  • any component in the buffer solution can be used without particular limitation as long as it is well adsorbed.
  • the average diameter of the microbead is not particularly limited, and may be, for example, 100 to 300um, for example, 150 to 210um. As described above, a schematic diagram of the microbead whose pH is controlled is shown in FIG. 1.
  • the buffer solution may be prepared for each target pH concentration using the conjugate acid and conjugate base compound reagents shown in Table 1.
  • the desired pH buffer solution can be prepared by adjusting the ratio of the base and acid.
  • K a is an acid dissociation constant
  • [HA] is the acid concentration
  • [A-] is the conjugate base concentration
  • [H +] is the hydrogen ion concentration
  • the buffer solution above pH 0 and below pH 14 or corresponding to pH 1 to pH 13 is a reagent combination of weak acid / strong acid, acid / base, acid / base, weak base / strong base, salt / base.
  • a buffer solution having various pH values can be prepared through an acid / base reagent combination and a composition ratio thereof, but for example, in the case of a weak acid / strong acid reagent combination, an acidic buffer solution of pH 2 to pH 4 can be used. It can be mainly used to prepare, and in the case of a combination of weak base / strong base reagent, it can be mainly used to prepare a basic buffer solution of pH 9 to pH 11.
  • all the components in the buffer solution can be adsorbed to the microbeads, wherein the pH of the microbeads depends on the composition ratio of all components of the substance except the solvent component in each pH buffer solution, for example, the composition ratio of the compound shown in Table 1. Can be determined. When the sample passes through the prepared microbeads, salts adsorbed on the microbeads are eluted to change the pH of the sample and through this, the sample having a desired pH can be adjusted.
  • potassium hydrogen phthalate in the case of potassium hydrogen phthalate / hydrochloric acid, potassium hydrogen phthalate is used as a weak acid, hydrochloric acid is used as a strong acid, and potassium hydrogen phthalate comes out according to the amount of hydrochloric acid, a strong acid.
  • the concentration of the hydrogen ion and the concentration of the counter base can be determined to adjust the pH.
  • the apparatus including the microbead according to the present invention may include an inlet 10 through which a sample is injected, a channel 20 through which pH adjustment of the injected sample is made, and an outlet 30 through which a pH-adjusted sample is discharged. It is shown in Figure 2 as an example.
  • a device capable of controlling multiple pHs of a sample by providing a plurality of devices as shown in FIG. 2 and filling each channel with microbeads having different pHs.
  • a sample may be injected into one integrated injection unit, and the injected sample is simultaneously adjusted to a desired pH by a pH-controlled microbead included in each channel through a plurality of channels, respectively. It can be discharged through the outlet.
  • a pH-controlled microbead included in each channel through a plurality of channels, respectively. It can be discharged through the outlet.
  • Buffer solutions of pH 1 to 13 were prepared as shown in Table 2.
  • pH-controlled microbeads 200 mg of silica-based glass microbeads (average particle size 150 to 210 um) were incubated in 5 mL of each buffer solution according to the above preparation example. Then, the solvent components were volatilized under a nitrogen gas (N 2 ) atmosphere to prepare microbeads having respective pH concentrations. Examples and comparative examples were prepared by varying the temperature at the time of volatilization of the solvent component. Specifically, Comparative Example 1 was prepared at room temperature, Example 1 at 50 ° C, and Comparative Example 2 at 90 ° C.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Inorganic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Solid-Sorbent Or Filter-Aiding Compositions (AREA)

Abstract

The present invention relates to microbeads capable of controlling the pH of a sample. The present invention can control the pH of a sample to be equal, similar or close to a target pH without an automated device and the like such as an additional valve system for controlling pH, and thus could be readily applied to fields requiring pH control.

Description

마이크로비드 및 그 제조방법Microbead and its manufacturing method
본 발명은 시료의 pH 조절이 가능한 마이크로비드(microbeads)에 관한 것으로서, 목적으로 하는 pH로 제어된 마이크로비드에 시료를 통과시킴으로써 시료의 pH를 용이하게 조절할 수 있는 마이크로비드에 관한 것이다.The present invention relates to microbeads capable of adjusting the pH of a sample, and relates to a microbead capable of easily adjusting the pH of a sample by passing the sample through a microbead controlled to a desired pH.
일반적으로, pH 조절을 위해서는 산 혹은 염기 용액을 시료에 가하여 얻어지는 값을 pH 미터 혹은 pH 종이 센서로 측정하며 원하는 pH 값에 도달할 때까지 이와 같은 작업을 수행하여 pH를 최적화시키는 과정을 수행한다.In general, in order to adjust the pH, a value obtained by adding an acid or base solution to a sample is measured with a pH meter or a pH paper sensor, and the above-described operation is performed until the desired pH value is reached to optimize the pH.
하지만, 종래의 이러한 일련의 최적화 과정은 노동집약적이며 많은 시간이 소요된다는 단점을 가지므로 비경제적이다. 또한, 종래의 pH 자동 제어 시스템의 경우 산이나 염기를 연속적으로 첨가하여 시료의 pH를 전기화학적 시스템을 통하여 실시간으로 관찰하는 과정을 밸브 시스템 등을 이용하여 자동화시키는데 많은 시간과 비용이 필요하다.However, this series of optimization processes in the related art is not economical because it has a disadvantage of being labor intensive and time consuming. In addition, in the case of the conventional pH automatic control system, a lot of time and cost are required to automate the process of observing the pH of a sample in real time through an electrochemical system by continuously adding an acid or a base using a valve system or the like.
따라서, 간단하고 경제적인 방법으로 pH를 조절할 수 있는 물질 및 방법이 필요하다.Therefore, there is a need for materials and methods that can adjust the pH in a simple and economical way.
본 발명의 목적은 간편하고 신속하게 시료를 원하는 특정 pH로 조절할 수 있는 마이크로비드를 제공하는 것이다.It is an object of the present invention to provide a microbead that can conveniently and quickly adjust a sample to a desired specific pH.
상기 과제를 해결하기 위하여 본 발명은 마이크로비드 표면의 Si-OH기에 짝산 및 짝염기가 정전기적 상호작용으로 흡착된 마이크로비드를 제공한다.In order to solve the above problems, the present invention provides microbeads in which Si-OH groups on a microbead surface are adsorbed by a pair acid and a pair base by electrostatic interaction.
상기 마이크로비드는 시료의 pH 값을 제어하기 위한 용도로 사용될 수 있다.The microbead may be used for controlling the pH value of the sample.
일구현예에 따르면, 상기 마이크로비드는 pH 1 내지 13에서 선택되는 특정 pH를 가질 수 있다.According to one embodiment, the microbead may have a specific pH selected from pH 1 to 13.
일구현예에 따르면, 상기 마이크로비드는 실리카계 유리 마이크로비드일 수 있다.According to one embodiment, the microbeads may be silica-based glass microbeads.
일구현예에 따르면, 상기 마이크로비드의 평균 직경은 100 내지 300um일 수 있다.According to one embodiment, the average diameter of the microbeads may be 100 to 300um.
본 발명의 다른 구현예에 따르면, 상기한 바와 같은 마이크로비드를 제조하는 방법으로,According to another embodiment of the present invention, a method for manufacturing a microbead as described above,
짝산 및 짝염기를 포함하는 완충 용액에 마이크로비드를 담지시켜 짝산 및 짝염기 성분을 마이크로비드에 흡착시키는 단계; 및Adsorbing the conjugate acid and the conjugate base component to the microbead by supporting the microbead in a buffer solution containing the conjugate acid and conjugate base; And
용매를 휘발시켜 pH가 제어된 마이크로비드를 제조하는 방법을 제공한다.It provides a method of preparing a microbead whose pH is controlled by volatilizing a solvent.
일구현예에 따르면, 상기 용매를 휘발시키는 단계는 40 내지 70℃ 및 불활성 기체 분위기 하에서 진행될 수 있다.According to one embodiment, the step of volatilizing the solvent may be performed under 40 to 70 ℃ and inert gas atmosphere.
또한, 상기 불활성 기체는 질소, 아르곤 및 헬륨으로 이루어지는 군으로부터 선택되는 하나 이상을 포함할 수 있다.In addition, the inert gas may include one or more selected from the group consisting of nitrogen, argon and helium.
본 발명의 다른 구현예에 따르면, 상기와 같은 마이크로비드를 포함하는, 시료의 pH 값을 제어하기 위한 장치를 제공할 수 있다.According to another embodiment of the present invention, it is possible to provide an apparatus for controlling the pH value of a sample, including the microbeads as described above.
본 발명의 또 다른 구현예에 따르면, 상기와 같은 마이크로비드를 포함하는, 시료의 pH 값을 제어하기 위한 pH 조절 시스템을 제공할 수 있다.According to another embodiment of the present invention, it is possible to provide a pH control system for controlling the pH value of a sample, including the microbeads as described above.
기타 본 발명의 구현예들의 구체적인 사항은 이하의 상세한 설명에 포함되어 있다.Other specific details of the embodiments of the present invention are included in the following detailed description.
본 발명은 pH의 조절을 위하여 추가의 밸브 시스템과 같은 자동화 장치 등을 필요로 하지 않으면서, 시료를 간단하고 용이한 방법을 통하여 목적으로 하는 pH로 조절할 수 있으므로 시간 및 비용을 절약할 수 있어 다양한 분야에 유용하게 적용할 수 있다.The present invention can save time and money because it is possible to adjust the sample to the desired pH through a simple and easy method without requiring an automatic device such as an additional valve system to adjust the pH. It can be usefully applied to the field.
도 1은 마이크로비드의 모습을 도식화한 모식도이다.1 is a schematic diagram schematically illustrating the appearance of a microbead.
도 2는 본 발명의 일실시예에 따른 장치의 개략도이다.2 is a schematic diagram of an apparatus according to an embodiment of the present invention.
도 3은 결과값에 따른 편차와 마이크로비드 pH의 관계를 나타낸 그래프이다.Figure 3 is a graph showing the relationship between the deviation and microbead pH according to the results.
본 발명은 다양한 변환을 가할 수 있고 여러 가지 실시예를 가질 수 있는 바, 특정 실시예를 도면에 예시하고 상세하게 설명하고자 한다. 그러나, 이는 본 발명을 특정한 실시 형태에 대해 한정하려는 것이 아니며, 본 발명의 사상 및 기술 범위에 포함되는 모든 변환, 균등물 내지 대체물을 포함하는 것으로 이해되어야 한다. 본 발명을 설명함에 있어서 관련된 공지 기술에 대한 구체적인 설명이 본 발명의 요지를 흐릴 수 있다고 판단되는 경우 그 상세한 설명을 생략한다.The present invention can be applied to a variety of transformations and may have various embodiments, and specific embodiments will be illustrated in the drawings and described in detail. However, this is not intended to limit the present invention to specific embodiments, and should be understood to include all conversions, equivalents, and substitutes included in the spirit and scope of the present invention. In the description of the present invention, when it is determined that a detailed description of known technologies related to the present invention may obscure the subject matter of the present invention, the detailed description will be omitted.
본 명세서에 사용된 용어 "비드(bead)"는 특별한 언급이 없는 한, "비즈(beads)"와 혼용하여 사용할 수 있다. 또한, 특별한 언급이 없는 한, 어떤 용어의 단수의 표현은 그 용어의 복수의 표현을 포함하는 의미로 이해될 수 있고, 어떤 용어의 복수의 표현은 그 용어의 단수의 표현을 포함하는 의미로 이해될 수 있다.The term "bead" as used herein may be used interchangeably with "beads", unless otherwise specified. Further, unless otherwise specified, a singular expression of a term can be understood as a meaning including plural expressions of the term, and a plural expression of a term is understood as a meaning including a singular expression of the term. Can be.
본 명세서 내에서 특별한 언급이 없는 한, "내지"라는 표현은 해당 수치를 포함하는 표현으로 사용된다. 구체적으로 예를 들면, "1 내지 2"라는 표현은 1 및 2를 포함할 뿐만 아니라 1과 2 사이의 수치를 모두 포함하는 것을 의미한다.Unless otherwise specified in this specification, the expression "to" is used as an expression including the corresponding numerical value. Specifically, for example, the expression "1 to 2" means not only to include 1 and 2, but also to include both numbers between 1 and 2.
이하, 본 발명의 구현예에 따른 마이크로비드(microbeads) 및 그 제조방법에 대하여 보다 상세하게 설명한다.Hereinafter, microbeads according to embodiments of the present invention and a method of manufacturing the same will be described in more detail.
본 발명은 짝산 및 짝염기를 포함하는 완충 용액에 마이크로비드(microbeads)를 담지시켜 짝산 및 짝염기 성분을 마이크로비드에 흡착시키는 단계; 및The present invention comprises the steps of adsorbing the conjugate acid and conjugate base component to the microbead by supporting microbeads in a buffer solution containing the conjugate acid and conjugate base; And
용매를 휘발시켜 pH가 제어된 마이크로비드를 제조하는 방법을 제공한다.It provides a method of preparing a microbead whose pH is controlled by volatilizing a solvent.
상기와 같이 제조된 마이크로비드에 시료를 통과시킴으로써 목적으로 하는 pH로 시료를 조절할 수 있다.The sample can be adjusted to the desired pH by passing the sample through the microbeads prepared as described above.
일구현예에 따르면, 상기 시료는 예를 들어 중성의 시료일 수 있고, 예를 들면, pH6.8 내지 7.9, 예를 들면 pH 7의 값을 가지는 시료일 수 있다.According to one embodiment, the sample may be, for example, a neutral sample, for example, a sample having a value of pH 6.8 to 7.9, for example, pH 7.
일구현예에 따르면, 상기 용매를 휘발시키는 단계는 40 내지 70℃, 예를 들어 50℃에서 불활성 기체 분위기 하에 진행될 수 있다. 불활성 기체로는 예를 들면, 질소, 아르곤 및 헬륨으로 이루어지는 군으로부터 선택되는 하나 이상을 포함할 수 있고, 예를 들면 질소 기체(N 2)를 사용할 수 있다. 또한, 상기와 같은 불활성 기체 퍼지 시 감압 하에 용매의 휘발이 가능하다.According to one embodiment, the step of volatilizing the solvent may be performed under an inert gas atmosphere at 40 to 70 ° C, for example, 50 ° C. The inert gas may include, for example, one or more selected from the group consisting of nitrogen, argon and helium, and for example, nitrogen gas (N 2 ) may be used. In addition, when purging the inert gas as described above, it is possible to volatilize the solvent under reduced pressure.
일구현예에 따르면, 상기 용매는 짝산 및 짝염기의 종류에 따라 각 물질을 잘 용해 시킬 수 있는 용액이라면 특별히 제한되지 않고 포함할 수 있으며, 예를 들면 증류수, 탈이온수 등을 포함할 수 있다.According to one embodiment, the solvent may be included without particular limitation as long as it is a solution capable of dissolving each substance well according to the type of the conjugate acid and the conjugate base, for example, distilled water, deionized water, and the like.
일구현예에 따르면, 완충 용액은 pH 1 내지 13에서 선택되는 특정 pH를 가질 수 있고, 상기 마이크로비드는 각각의 완충 용액에 따라, pH 1 내지 13에서 선택되는 특정 pH를 가지는 것으로 제어될 수 있다. 구체적으로, pH 1 내지 13 범위 중 선택되는 특정 pH를 가지는 완충 용액에 마이크로비드를 담지시켜 상기 완충 용액과 동일 내지 유사 또는 근접한 pH를 가지도록 제어할 수 있다.According to one embodiment, the buffer solution may have a specific pH selected from pH 1 to 13, and the microbeads may be controlled to have a specific pH selected from pH 1 to 13 according to each buffer solution. . Specifically, the microbeads are supported on a buffer solution having a specific pH selected from a range of pH 1 to 13 to control the pH to be the same or similar to or close to the buffer solution.
일구현예에 따르면, 상기 마이크로비드는 예를 들면 실리카(silica)계 마이크로비드를 포함할 수 있고, 구체적으로 예를 들면, 실리카계 유리(glass) 마이크로비드를 포함할 수 있다. 마이크로비드는 제조 과정에서 표면에 염(salt)이 양호하게 코팅되어 존재할 수 있고, 시료가 마이크로비드를 통과할 때 마이크로비드 표면에 코팅된 염이 시료에 잘 용리될 수 있도록 표면에 Si-OH기를 가질 수 있다. 즉, 마이크로비드 표면의 Si-OH기에 상기 완충 용액이 포함하는 짝산 및 짝염기가 정전기적 상호작용으로 흡착되어 시료가 비즈를 통과할 때 짝산 및 짝염기가 용리될 수 있다. 본 발명에 사용되는 마이크로비드는 이와 같이 완충 용액의 담지체로서의 역할을 할 수 있고, 완충 용액 내의 모든 성분이 잘 흡착되는 것이라면 특별히 제한되지 않고 사용할 수 있다. 다공성의 구조를 가지는 경우, 표면적이 넓기 때문에 더욱 큰 용량의 시료 pH 조절에 용이할 수 있다. 또한, 마이크로비드의 평균 직경은 특별히 제한되지 않으며, 예를 들면, 100 내지 300um, 예를 들면 150 내지 210um일 수 있다. 상기한 바와 같이, pH가 제어된 마이크로비드의 모식도를 도 1에 나타내었다.According to one embodiment, the microbeads may include, for example, silica-based microbeads, and specifically, may include, for example, silica-based glass microbeads. Microbeads may be present with a good salt coating on the surface during the manufacturing process, and Si-OH groups on the surface can be easily eluted with the salt coated on the microbead surface when the sample passes through the microbead. Can have That is, the pair acid and the pair base may be eluted when the sample passes through the beads because the pair acid and the pair base contained in the buffer solution are adsorbed by electrostatic interaction on the Si-OH group on the microbead surface. The microbead used in the present invention can serve as a carrier for the buffer solution in this way, and any component in the buffer solution can be used without particular limitation as long as it is well adsorbed. In the case of having a porous structure, since the surface area is large, it may be easy to adjust the pH of the sample in a larger capacity. In addition, the average diameter of the microbead is not particularly limited, and may be, for example, 100 to 300um, for example, 150 to 210um. As described above, a schematic diagram of the microbead whose pH is controlled is shown in FIG. 1.
일구현예에 따르면, 상기 완충 용액은 표 1과 같은 짝산 및 짝염기 화합물 시약을 사용하여 목적으로 하는 각각의 pH 농도 별로 제조할 수 있다.According to one embodiment, the buffer solution may be prepared for each target pH concentration using the conjugate acid and conjugate base compound reagents shown in Table 1.
Figure PCTKR2019013875-appb-img-000001
Figure PCTKR2019013875-appb-img-000001
보다 구체적으로는, 다음 수학식 1의 헨더슨-하셀바흐 식(Henderson-Hasselbach equation)에 따라 짝염기 및 산의 비율을 조절하여 원하는 pH 완충 용액을 제조할 수 있다.More specifically, according to the Henderson-Hasselbach equation of the following Equation 1, the desired pH buffer solution can be prepared by adjusting the ratio of the base and acid.
[수학식 1][Equation 1]
Figure PCTKR2019013875-appb-img-000002
Figure PCTKR2019013875-appb-img-000002
상기 식에서, K a는 산 해리 상수(acid dissociation constant)이고, [HA]는 산의 농도, [A-]는 짝염기의 농도, [H+]는 수소 이온 농도이다.In the above formula, K a is an acid dissociation constant, [HA] is the acid concentration, [A-] is the conjugate base concentration, and [H +] is the hydrogen ion concentration.
부연하면, pH 0 초과 pH 14 미만 또는 pH 1 내지 pH 13에 해당되는 완충 용액은 약산/강산, 산/염기, 산/짝염기, 약염기/강염기, 염(salt)/염기의 시약(reagent) 조합을 통해 제조할 수 있다. 대체적으로, 산/염기 시약 조합 및 그에 따른 조성비를 통해, 다양한 pH 값을 갖는 완충용액을 제조할 수 있지만, 예를 들면, 약산/강산 시약 조합의 경우, pH 2 내지 pH 4의 산성 완충 용액을 제조하는데 주로 사용될 수 있고, 약염기/강염기 시약의 조합의 경우 pH 9 내지 pH 11의 염기성 완충 용액을 제조하는데 주로 사용될 수 있다.Incidentally, the buffer solution above pH 0 and below pH 14 or corresponding to pH 1 to pH 13 is a reagent combination of weak acid / strong acid, acid / base, acid / base, weak base / strong base, salt / base. Can be manufactured through. Generally, a buffer solution having various pH values can be prepared through an acid / base reagent combination and a composition ratio thereof, but for example, in the case of a weak acid / strong acid reagent combination, an acidic buffer solution of pH 2 to pH 4 can be used. It can be mainly used to prepare, and in the case of a combination of weak base / strong base reagent, it can be mainly used to prepare a basic buffer solution of pH 9 to pH 11.
또한, 마이크로비드에는 완충 용액 내 모든 성분들이 흡착될 수 있으며, 이때 각각의 pH 완충 용액에서 용매성분을 제외한 물질의 모든 성분들의 조성비, 예를 들면 표 1과 같은 화합물의 조성비에 따라 마이크로비드의 pH가 결정될 수 있다. 이렇게 제조된 마이크로비드에 시료가 통과하는 경우 마이크로비드에 흡착되어 있던 염들이 용리되어 시료의 pH가 변하게 되고 이를 통하여 원하는 pH를 가지는 시료로 조절할 수 있다.In addition, all the components in the buffer solution can be adsorbed to the microbeads, wherein the pH of the microbeads depends on the composition ratio of all components of the substance except the solvent component in each pH buffer solution, for example, the composition ratio of the compound shown in Table 1. Can be determined. When the sample passes through the prepared microbeads, salts adsorbed on the microbeads are eluted to change the pH of the sample and through this, the sample having a desired pH can be adjusted.
예를 들면, 표 1에서, 프탈산수소칼륨(potassium hydrogen phthalate)/염산(hydrochloric acid)의 경우, 프탈산수소칼륨은 약산으로, 염산은 강산으로 사용되고, 강산인 염산의 첨가량에 따라 프탈산수소칼륨에서 나오는 수소 이온 농도와 짝염기의 농도가 결정되어 pH를 조절할 수 있다.For example, in Table 1, in the case of potassium hydrogen phthalate / hydrochloric acid, potassium hydrogen phthalate is used as a weak acid, hydrochloric acid is used as a strong acid, and potassium hydrogen phthalate comes out according to the amount of hydrochloric acid, a strong acid. The concentration of the hydrogen ion and the concentration of the counter base can be determined to adjust the pH.
본 발명의 다른 구현예에 따르면, 상기와 같은 마이크로비드를 포함하는 장치를 제공함으로써 시료의 pH를 더욱 간편하고 경제적으로 조절할 수 있다. 본 발명에 따른 마이크로비드를 포함하는 장치는 시료가 주입되는 주입구(10), 주입된 시료의 pH 조절이 이루어지는 채널(20), pH 조절이 이루어진 시료의 배출이 이루어지는 출구(30)를 구비할 수 있으며, 도 2에 예시로서 나타내었다. 또한, 예를 들면, 도 2와 같은 장치를 복수개 구비하고, 각각의 채널이 다른 pH를 가지는 마이크로비드로 채워짐으로써 시료의 다중 pH 조절이 가능한 장치를 제공할 수 있다. 구체적으로 예를 들면, 하나의 통합 주입부로 시료가 주입될 수 있고, 주입된 시료는 동시에 복수 개의 채널을 각각 통과하여 각각의 채널 내에 포함된 pH-제어된 마이크로비드에 의하여 원하는 pH로 조절되어 각각의 배출구로 배출될 수 있다. 이러한 장치를 사용하면 시료의 pH를 동시에 다중으로 조절할 수 있으므로 시간과 노력을 단축시킬 수 있어 보다 효율적이다.According to another embodiment of the present invention, it is possible to more conveniently and economically adjust the pH of the sample by providing the device including the microbeads as described above. The apparatus including the microbead according to the present invention may include an inlet 10 through which a sample is injected, a channel 20 through which pH adjustment of the injected sample is made, and an outlet 30 through which a pH-adjusted sample is discharged. It is shown in Figure 2 as an example. In addition, for example, it is possible to provide a device capable of controlling multiple pHs of a sample by providing a plurality of devices as shown in FIG. 2 and filling each channel with microbeads having different pHs. Specifically, for example, a sample may be injected into one integrated injection unit, and the injected sample is simultaneously adjusted to a desired pH by a pH-controlled microbead included in each channel through a plurality of channels, respectively. It can be discharged through the outlet. Using such a device, it is possible to simultaneously adjust the pH of a sample multiple times, thereby reducing time and effort, which is more efficient.
또한, 다른 구현예에 따르면, 상기와 같은 원리를 적용한 pH 조절 시스템을 제공할 수 있다.In addition, according to another embodiment, it is possible to provide a pH control system to which the above principles are applied.
이하, 본 발명이 속하는 기술 분야에서 통상의 지식을 가진 자가 용이하게 실시할 수 있도록 본 발명의 실시예에 대하여 상세히 설명한다. 그러나 본 발명은 여러 가지 상이한 형태로 구현될 수 있으며 여기에서 설명하는 실시예에 한정되지 않는다.Hereinafter, embodiments of the present invention will be described in detail so that those skilled in the art to which the present invention pertains can easily practice. However, the present invention can be implemented in many different forms and is not limited to the embodiments described herein.
제조예: 완충 용액 제조Preparation Example: Preparation of buffer solution
pH 1 내지 13의 완충 용액을 표 2와 같이 제조하였다.Buffer solutions of pH 1 to 13 were prepared as shown in Table 2.
Figure PCTKR2019013875-appb-img-000003
Figure PCTKR2019013875-appb-img-000003
실시예 및 비교예Examples and comparative examples
pH-제어된 마이크로비드를 제조하기 위하여, 상기 제조예에 따른 각각의 완충 용액 5mL에 실리카계 유리 마이크로비드(평균 입경 150~210um) 200mg을 인큐베이션(incubation)시켰다. 그 후 용매 성분을 질소 가스(N 2) 분위기 하에서 휘발시켜 각각의 pH 농도를 가지는 마이크로비드를 제조하였다. 용매 성분을 휘발시킬 때의 온도를 달리하여 실시예 및 비교예를 제조하였으며, 구체적으로 비교예 1은 상온, 실시예 1은 50℃ 및 비교예 2는 90℃에서 제조하였다.In order to prepare pH-controlled microbeads, 200 mg of silica-based glass microbeads (average particle size 150 to 210 um) were incubated in 5 mL of each buffer solution according to the above preparation example. Then, the solvent components were volatilized under a nitrogen gas (N 2 ) atmosphere to prepare microbeads having respective pH concentrations. Examples and comparative examples were prepared by varying the temperature at the time of volatilization of the solvent component. Specifically, Comparative Example 1 was prepared at room temperature, Example 1 at 50 ° C, and Comparative Example 2 at 90 ° C.
실험예Experimental example
기준이 되는 표준 용액으로서 pH 4, 6, 9 및 10의 시료를 사용하여 pH 측정 기기(S220 SevenCompact tm pH/Ion, METTLER TOLEDO)의 pH를 보정한 후, 시료의 pH를 측정하였다. 시료 2mL을 각각의 pH-제어된 마이크로비드에 통과시킨 후, 시료의 pH를 측정하였다. 그 결과를 표 3에 나타내었다.After the pH of the pH measuring device (S220 SevenCompact tm pH / Ion, METTLER TOLEDO) was corrected using samples of pH 4, 6, 9, and 10 as standard solutions, the pH of the samples was measured. After passing 2 mL of the sample through each pH-controlled microbead, the pH of the sample was measured. Table 3 shows the results.
Figure PCTKR2019013875-appb-img-000004
Figure PCTKR2019013875-appb-img-000004
표 3에 따른 결과를 도 3에 나타내었다. 표 3 및 도 3에 나타난 바와 같이, 제조 과정에서 온도의 변화에 따른 각각의 마이크로비드를 사용한 결과에 차이가 있는 것을 알 수 있다. 구체적으로, 실시예 1에 따른 비즈를 사용한 경우 시료의 pH 편차가 가장 적게 나타남을 확인할 수 있고, 반면 비교예 1 및 2에 따른 비즈를 사용한 경우 편차가 크게 증가하는 것을 알 수 있다.The results according to Table 3 are shown in FIG. 3. As shown in Table 3 and Figure 3, it can be seen that there is a difference in the result of using each microbead according to a change in temperature in the manufacturing process. Specifically, when using the beads according to Example 1, it can be seen that the pH deviation of the sample is the smallest, whereas when using the beads according to Comparative Examples 1 and 2, it can be seen that the deviation is greatly increased.
이상으로 본 발명 내용의 특정한 부분을 상세히 기술한 바, 당업계의 통상의 지식을 가진 자에게 있어서, 이러한 구체적 기술은 단지 바람직한 실시 양태일 뿐이며, 이에 의해 본 발명의 범위가 제한되는 것이 아닌 점은 명백할 것이다. 따라서 본 발명의 실질적인 범위는 첨부된 청구항들과 그것들의 등가물에 의하여 정의된다고 할 것이다.The specific parts of the present invention have been described in detail above. For those skilled in the art, this specific technology is only a preferred embodiment, and it is obvious that the scope of the present invention is not limited thereby. something to do. Therefore, the substantial scope of the present invention will be defined by the appended claims and their equivalents.

Claims (10)

  1. 마이크로비드 표면의 Si-OH기에 짝산 및 짝염기가 정전기적 상호작용으로 흡착된 마이크로비드.Microbeads in which Si-OH groups on a microbead surface are adsorbed by a pair acid and a base by electrostatic interaction.
  2. 제1항에 있어서,According to claim 1,
    상기 마이크로비드가 시료의 pH 값을 제어하기 위한 것인, 마이크로비드.The microbead is to control the pH value of the sample, the microbead.
  3. 제1항에 있어서,According to claim 1,
    상기 마이크로비드가 pH 1 내지 13에서 선택되는 특정 pH를 가지는 것인, 마이크로비드.The microbeads will have a specific pH selected from pH 1 to 13.
  4. 제1항에 있어서,According to claim 1,
    상기 마이크로비드가 실리카계 유리 마이크로비드인 것인, 마이크로비드.Microbeads, wherein the microbeads are silica-based glass microbeads.
  5. 제1항에 있어서,According to claim 1,
    상기 마이크로비드의 평균 직경이 100 내지 300um인 것인, 마이크로비드.The average diameter of the microbeads is 100 to 300um, microbeads.
  6. 제1항의 마이크로비드를 제조하는 방법으로,A method for manufacturing the microbead of claim 1,
    짝산 및 짝염기를 포함하는 완충 용액에 마이크로비드를 담지시켜 짝산 및 짝염기 성분을 마이크로비드에 흡착시키는 단계; 및Adsorbing the conjugate acid and the conjugate base component to the microbead by supporting the microbead in a buffer solution containing the conjugate acid and conjugate base; And
    용매를 휘발시켜 pH가 제어된 마이크로비드를 제조하는 방법.A method of preparing a microbead whose pH is controlled by volatilizing a solvent.
  7. 제6항에 있어서,The method of claim 6,
    상기 용매를 휘발시키는 단계가 40 내지 70℃ 및 불활성 기체 분위기 하에서 진행되는 것인, 마이크로비드 제조방법.The step of volatilizing the solvent is to proceed under 40 to 70 ℃ and inert gas atmosphere, microbead manufacturing method.
  8. 제7항에 있어서,The method of claim 7,
    상기 불활성 기체가 질소, 아르곤 및 헬륨으로 이루어지는 군으로부터 선택되는 하나 이상을 포함하는 것인, 마이크로비드 제조방법.The inert gas is nitrogen, argon and helium containing one or more selected from the group consisting of helium, microbead manufacturing method.
  9. 제1항에 따른 마이크로비드를 포함하는, 시료의 pH 값을 제어하기 위한 장치.Apparatus for controlling the pH value of a sample, comprising the microbead according to claim 1.
  10. 제1항에 따른 마이크로비드를 포함하는, 시료의 pH 값을 제어하기 위한 pH 조절 시스템.A pH control system for controlling the pH value of a sample, comprising the microbead according to claim 1.
PCT/KR2019/013875 2018-10-22 2019-10-22 Microbeads and preparation method therefor WO2020085757A1 (en)

Priority Applications (4)

Application Number Priority Date Filing Date Title
US16/979,730 US20210041332A1 (en) 2018-10-22 2019-10-22 Microbeads and Preparation Method Therefor
JP2020543975A JP7048023B2 (en) 2018-10-22 2019-10-22 Microbeads and their manufacturing methods
CN201980014541.0A CN111757849B (en) 2018-10-22 2019-10-22 Microbeads and method for producing same
EP19875170.3A EP3741724B1 (en) 2018-10-22 2019-10-22 Microbeads and preparation method therefor

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
KR10-2018-0125755 2018-10-22
KR20180125755 2018-10-22
KR10-2019-0130775 2019-10-21
KR1020190130775A KR102451333B1 (en) 2018-10-22 2019-10-21 Microbeads and preparation method thereof

Publications (1)

Publication Number Publication Date
WO2020085757A1 true WO2020085757A1 (en) 2020-04-30

Family

ID=70331581

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/KR2019/013875 WO2020085757A1 (en) 2018-10-22 2019-10-22 Microbeads and preparation method therefor

Country Status (1)

Country Link
WO (1) WO2020085757A1 (en)

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2008514425A (en) * 2004-10-01 2008-05-08 フェノメネクス インコーポレイテッド PH stable chromatographic media using templated multilayer organic / inorganic graffiti
JP2008521980A (en) * 2004-12-01 2008-06-26 ワッカー ケミー アクチエンゲゼルシャフト Metal oxide with permanent positive surface charge over a wide range of pH
JP2015078105A (en) * 2013-10-18 2015-04-23 新日鉄住金マテリアルズ株式会社 Spherical amorphous silica particle, manufacturing method therefor and resin composition containing the same
WO2017208501A1 (en) * 2016-05-30 2017-12-07 日本軽金属株式会社 Surface-modified sodium hypochlorite pentahydrate crystal, and method for producing same
JP2018076218A (en) * 2017-01-06 2018-05-17 エム・テクニック株式会社 Method for producing color characteristic-controlled silicon compound-coated oxide particles

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2008514425A (en) * 2004-10-01 2008-05-08 フェノメネクス インコーポレイテッド PH stable chromatographic media using templated multilayer organic / inorganic graffiti
JP2008521980A (en) * 2004-12-01 2008-06-26 ワッカー ケミー アクチエンゲゼルシャフト Metal oxide with permanent positive surface charge over a wide range of pH
JP2015078105A (en) * 2013-10-18 2015-04-23 新日鉄住金マテリアルズ株式会社 Spherical amorphous silica particle, manufacturing method therefor and resin composition containing the same
WO2017208501A1 (en) * 2016-05-30 2017-12-07 日本軽金属株式会社 Surface-modified sodium hypochlorite pentahydrate crystal, and method for producing same
JP2018076218A (en) * 2017-01-06 2018-05-17 エム・テクニック株式会社 Method for producing color characteristic-controlled silicon compound-coated oxide particles

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See also references of EP3741724A4 *

Similar Documents

Publication Publication Date Title
Barbosa et al. Retention behaviour of quinolone derivatives in high-performance liquid chromatography: Effect of pH and evaluation of ionization constants
WO2019196233A1 (en) Method for measuring contents of various endocrine disruptors in estuary sediment
CN106053622B (en) The liquid chromatography tandom mass spectrometry determination method of 18 kind of half volatile organic compounds in water
WO2020085757A1 (en) Microbeads and preparation method therefor
CN109342624A (en) The method that Solid Phase Extraction pre-treatment combination LC-MS technology detects 15 kinds of antibiotic in aquaculture system simultaneously
KR20070011572A (en) Methods and systems for detection, identification and quantitation of macrolides and their impurities
Jimbo et al. Passive transport of ionic drugs through membranes with pH-dependent fixed charges
CN107247094A (en) A kind of assay method for being applied to passive type air clearing product to TVOC clean-up effects
Zheng et al. Fully-automated SPE coupled to UHPLC-MS/MS method for multiresidue analysis of 26 trace antibiotics in environmental waters: SPE optimization and method validation
Ammann Arsenic speciation by gradient anion exchange narrow bore ion chromatography and high resolution inductively coupled plasma mass spectrometry detection
CN113533569B (en) Method for detecting related substances in antibacterial eye drops
Salem et al. Simultaneous determination of omeprazole, tinidazole and clarithromycin in bulk powder and Helicure® tablets by HPLC
KR20200045425A (en) Microbeads and preparation method thereof
CN111562330A (en) Method for measuring pyridine content in industrial wastewater
CN111220722B (en) Method for simultaneously determining 8 p-hydroxybenzoate compounds in soil
CN111693622B (en) Tobramycin raw material and related preparation impurity mass spectrum analysis method
KR20070011580A (en) Methods and systems for detection of macrolides
CN111751482B (en) Method for synchronously detecting residual quantity of various antibiotics in pig-raising wastewater
WO2020046027A1 (en) Device comprising microbeads capable of adjusting ph of sample
CN114577931A (en) Solid phase extraction-ultra high performance liquid chromatography-tandem mass spectrometry rapid determination method of antibiotics in sewage
CN114236022A (en) Method for detecting kanamycin content in fermentation liquor by pre-column derivatization-HPLC
CN118050228B (en) Method for directly detecting glyphosate in water
Tarbuck et al. Estimation of the progress of Streptomyces clavuligerus fermentations for improved on-line control of antibiotic production
CN111024870A (en) Method for detecting neomycin sulfate component and related substances
Guaratini et al. Cathodic stripping voltammetric detection and determination at a hanging mercury-drop electrode of dye contaminants in purified biomaterials: study of the human serum albumin and reactive dye 120 system

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 19875170

Country of ref document: EP

Kind code of ref document: A1

ENP Entry into the national phase

Ref document number: 2020543975

Country of ref document: JP

Kind code of ref document: A

ENP Entry into the national phase

Ref document number: 2019875170

Country of ref document: EP

Effective date: 20200818

NENP Non-entry into the national phase

Ref country code: DE