WO2019129269A1 - 纸基进样装置及方法 - Google Patents

纸基进样装置及方法 Download PDF

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Publication number
WO2019129269A1
WO2019129269A1 PCT/CN2018/125474 CN2018125474W WO2019129269A1 WO 2019129269 A1 WO2019129269 A1 WO 2019129269A1 CN 2018125474 W CN2018125474 W CN 2018125474W WO 2019129269 A1 WO2019129269 A1 WO 2019129269A1
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paper
zone
filter paper
detection
sample introduction
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PCT/CN2018/125474
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English (en)
French (fr)
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闻路红
周镇宇
赵鹏
毕磊
洪欢欢
宁录胜
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宁波大学
宁波华仪宁创智能科技有限公司
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Publication of WO2019129269A1 publication Critical patent/WO2019129269A1/zh

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    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
    • H01J49/00—Particle spectrometers or separator tubes
    • H01J49/02—Details
    • H01J49/04—Arrangements for introducing or extracting samples to be analysed, e.g. vacuum locks; Arrangements for external adjustment of electron- or ion-optical components
    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
    • H01J49/00—Particle spectrometers or separator tubes
    • H01J49/02—Details
    • H01J49/04—Arrangements for introducing or extracting samples to be analysed, e.g. vacuum locks; Arrangements for external adjustment of electron- or ion-optical components
    • H01J49/0409—Sample holders or containers

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  • This invention relates to mass spectrometry, and more particularly to paper based sample introduction devices and methods.
  • the open mass spectrometry technology eliminates the need for complex sample preparation and enables in-situ, real-time, and fast ionization of samples in a very short time at atmospheric pressure. It has the advantages of portable equipment, low detection cost, and wide application range. It has broad application prospects in many fields such as food testing, drug analysis, environmental monitoring, public safety and clinical diagnosis.
  • Filter paper is used as a new type of injection method for open mass spectrometry because of its unique advantages such as low cost, portability, and functional grouping. Moreover, the use of filter paper injection method can make up for the defects of difficult analysis of biological macromolecules such as capillary tubes and glass rods, and achieve high-efficiency analysis of macromolecules such as peptides and proteins.
  • the presence of non-filter paper greatly attenuates the energy of the plasma beam ejected by the open mass spectrometer ion source, so that the ionization ability of some samples (especially small molecule samples) is weakened, resulting in a decrease in the detection signal of the sample.
  • the previous method can only use manual injection, there is a large human factor interference, and sample automation and high-throughput analysis cannot be realized.
  • the above-mentioned filter paper injection method mainly has the following defects:
  • the energy of the plasma beam emitted by the open mass spectrometer ion source is weakened, resulting in a decrease in the sample detection signal.
  • the traditional paper base adopts manual manual injection method, and there are large human factors interference, which can not achieve sample automation and high-throughput analysis.
  • the present invention provides a paper-based sample introduction device with high sensitivity, high accuracy, and high throughput analysis.
  • a paper-based sample introduction device comprising an ion source, a filter paper, and a mass spectrometry inlet; the paper-based sample introduction device further comprising:
  • Rotating platform the filter paper is disposed on the rotating platform, and is driven to rotate around a rotating shaft;
  • the filter paper has a hydrophobic region including a sample application zone, a detection zone and a connection channel, the sample application zone being at the center of the filter paper, the detection zone being at least two, and surrounding
  • the loading zone is distributed, the connecting channel is connected to the loading zone and the detecting zone; when the filter paper is rotated, a connection between the ion source and the mass spectrometry inlet passes through the detecting zone.
  • the object of the present invention is also to provide a paper-based injection method with high analysis accuracy, high-throughput analysis and high analytical sensitivity, and the object of the invention is achieved by the following technical solutions:
  • a paper-based injection method comprising the following steps:
  • the plasma emitted from the ion source acts on different detection zones, so that the sample to be tested in the detection zone is separately ionized, and the ionized sample enters the mass spectrometry inlet in a time-sharing manner.
  • the present invention has the following beneficial effects:
  • the mass spectrometry detection signal can be effectively improved, and the analysis sensitivity is improved;
  • the device is simple, easy to operate, and can improve the detection efficiency.
  • FIG. 1 is a schematic structural view of a paper-based sample introduction device according to an embodiment of the present invention
  • FIG. 2 is a schematic structural view of a filter paper according to an embodiment of the present invention.
  • Figure 3 is a mass spectrum corresponding to colistin sulfate according to Example 2 of the present invention.
  • Figure 4 is a mass spectrum corresponding to methamphetamine according to Example 3 of the present invention.
  • FIG. 1 is a schematic structural view of a paper-based sample introduction device according to Embodiment 1 of the present invention. As shown in FIG. 1, the paper-based sample introduction device includes:
  • Rotating platform the filter paper is disposed on the rotating platform, and is driven to rotate around a rotating shaft;
  • the rotating platform comprises:
  • the filter paper is disposed on the fixing frame; when the connecting line passes through the detecting area, is not blocked by the fixing frame;
  • the driving module is configured to drive the fixed frame to rotate, so that the connecting line passes through the detecting area;
  • the filter paper has a hydrophobic zone 1 and a hydrophilic zone, the hydrophilic zone comprising a sample application zone 3, a detection zone 2 and a connection channel 4, the sample application zone being at the center of the filter paper, the detection zone being at least two And surrounding the sample application area, the connection channel is connected to the sample application area and the detection area; the detection area and the sample application area are circular: the center of the detection area is on the same circle, The center of the circle is the center of the sample application zone; the diameter of the sample application zone is 2-4 mm, the diameter of the detection zone is 2-3 mm; the width of the connection channel is smaller than the detection zone and the sample application zone Diameter; when the filter paper is rotated, a line between the ion source and the mass spectrometer inlet is perpendicular to the filter paper and passes through the detection zone, the center of the detection zone being on the line.
  • the paper-based injection method of the embodiment of the present invention that is, the working process of the paper-based sample introduction device, the paper-based injection method comprises the following steps:
  • the plasma emitted from the ion source acts on different detection zones, so that the sample to be tested in the detection zone is separately ionized, and the ionized sample enters the mass spectrometry inlet in a time-sharing manner.
  • the detection area is eight, and the angle between the center of the adjacent detection area to the center of the sample application area is 45 degrees;
  • the application area is a circle having a diameter of 3 mm, and the length of the connection channel is 15mm, width is 1mm; detection area is 2mm in diameter; 15 ⁇ l of gold nanoparticle solution is added; 3 ⁇ l of sample solution is added dropwise; distance between filter paper and mass spectrometer inlet is 0.2mm, ion source nozzle and detection area
  • the center of the circle and the mass spectrometer inlet are on the same horizontal line.
  • a significant sample hydrogenation peak was observed with an intensity of 7.88e 2 and a signal-to-noise ratio of 16.3.
  • the relative standard deviation of the four measurements obtained after rotating the mobile platform was 12.52%.

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  • Chemical & Material Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Other Investigation Or Analysis Of Materials By Electrical Means (AREA)

Abstract

本发明提供了一种纸基进样装置及方法，所述纸基进样装置包括离子源、滤纸和质谱进样口；旋转平台，所述滤纸设置在所述旋转平台上，并在驱动下绕着转轴旋转；所述滤纸具有疏水区和亲水区，所述亲水区包括加样区、检测区和连接通道，所述加样区处于所述滤纸的中心，所述检测区为至少二个，并围绕所述加样区分布，所述连接通道连接所述加样区和检测区；当所述滤纸旋转时，所述离子源和质谱进样口之间的连线穿过所述检测区。本发明具有分析灵敏度高、高通量分析等优点。

Description

纸基进样装置及方法 技术领域
本发明涉及质谱分析，特别涉及纸基进样装置及方法。
背景技术
敞开式质谱分析技术无需复杂的样品前处理，能够在大气压敞开环境下，在极短时间内实现样品的原位、实时、快速离子化，具有设备便携、检测成本低、适用范围广等优点，在食品检测、药物分析、环境监测、公共安全及临床诊断等众多领域具有广阔的应用前景。
滤纸由于其成本低、易携带，且能官能团化等独特的优点，被作为一种新型的进样方式应用于敞开式质谱分析中。而且采用滤纸进样方式，可以弥补毛细管和玻璃棒等难以实现生物大分子样品分析的缺陷，实现多肽、蛋白质等大分子物质的高效分析。不过滤纸的存在会极大削弱敞开式质谱离子源所喷射等离子体束的能量，使得对部分样品(特别是小分子样品)的离子化能力减弱，从而导致样品的检测信号下降。另外，先前该方式只能采用手动进样，存在较大的人为因素干扰，无法实现样品自动化、高通量分析。
上述基于滤纸进样方式主要存在如下缺陷：
1.基于纸基进样方式会虚弱削弱敞开式质谱离子源所喷射等离子体束的能量，导致样品检测信号下降。
2.传统纸基采用人工手动进样方式，存在较大的人为因素干扰，无法实现样品自动化、高通量分析。
发明内容
为解决上述现有技术方案中的不足，本发明提供了一种分析灵敏度高、准确度高、高通量分析的纸基进样装置。
本发明的目的是通过以下技术方案实现的：
纸基进样装置，所述纸基进样装置包括离子源、滤纸和质谱进样口；所述纸基进样装置进一步包括：
旋转平台，所述滤纸设置在所述旋转平台上，并在驱动下绕着转轴旋转；
所述滤纸具有疏水区和亲水区，所述亲水区包括加样区、检测区和连接通道，所述加样区处于所述滤纸的中心，所述检测区为至少二个，并围绕所述加样区分布，所述连接通道连接所述加样区和检测区；当所述滤纸旋转时，所述离子源和质谱进样口之间的连线穿过所述检测区。
本发明的目的还在于提供了分析准确度高、高通量分析、分析灵敏度高的纸基进样方法，该发明目的是通过以下技术方案得以实现的：
纸基进样方法，所述纸基进样方法包括以下步骤：
(A1)在检测区滴加待测样品溶液，并将滤纸固定于旋转平台上，之后滤纸在驱动下绕转轴旋转；
(A2)离子源射出的等离子体作用于不同的检测区，使检测区的待测样品分别离子化，离子化的样品分时地进入质谱进样口。
与现有技术相比，本发明具有的有益效果为：
1.通过旋转平台精确控制进样，从而消除人为因素造成的干扰，提高分析准确性，实现样品的自动化和高通量分析；
2.通过在检测区添加金纳米颗粒可以有效提高质谱检测信号，提升分析灵敏度；
3.设计独特的滤纸亲水图案，通过毛细作用同时实现多个检测区纳米颗粒修饰；
4.装置简单，操作方便，可提升检测效率。
附图说明
参照附图，本发明的公开内容将变得更易理解。本领域技术人员容易理解的是：这些附图仅仅用于举例说明本发明的技术方案，而并非意在对本发明的保护范围构成限制。图中：
图1是根据本发明实施例的纸基进样装置的结构简图；
图2是根据本发明实施例的滤纸的结构简图；
图3是根据本发明实施例2的硫酸粘杆菌素对应的质谱图；
图4是根据本发明实施例3的甲基苯丙胺对应的质谱图。
具体实施方式
图1-4和以下说明描述了本发明的可选实施方式以教导本领域技术人员如何实施和再现本发明。为了教导本发明技术方案，已简化或省略了一些常规方面。本领域技术人员应该理解源自这些实施方式的变型或替换将在本发明的范围内。本领域技术人员应该理解下述特征能够以各种方式组合以形成本发明的多个变型。由此，本发明并不局限于下述可选实施方式，而仅由权利要求和它们的等同物限定。
实施例1：
图1示意性地给出了本发明实施例1的纸基进样装置的结构简图，如图1所示，所述纸基进样装置包括：
离子源、滤纸和质谱进样口；其特征在于：所述纸基进样装置进一步包括：
旋转平台，所述滤纸设置在所述旋转平台上，并在驱动下绕着转轴旋转；所述旋转平台包括：
固定框，所述滤纸设置在固定框上；在所述连线穿过所述检测区时，不受所述固定框的阻挡；
驱动模块，所述驱动模块用于驱动所述固定框旋转，使得所述连线穿过检测区；
所述滤纸具有疏水区1和亲水区，所述亲水区包括加样区3、检测区2和连接通道4，所述加样区处于所述滤纸的中心，所述检测区为至少二个，并围绕所述加样区分布，所述连接通道连接所述加样区和检测区；所述检测区和加样区为圆形：所述检测区的中心处于同一个圆上，该圆的圆心为所述加样区的圆心；所述加样区的直径为2-4mm，所述检测区的直径为2-3mm；所述连接通道的宽度小于所述检测区和加样区的直径；当所述滤纸旋转时，所述离子源和质谱进样口之间的连线垂直于所述滤纸并穿过所述检测区，所述检测区的圆心处于所述连线上。
本发明实施例的纸基进样方法，也即上述纸基进样装置的工作过程，所述纸基进样方法包括以下步骤：
(A0)在加样区滴加金纳米颗粒溶液，金纳米颗粒通过毛细作用穿过连接通道进入所述检测区；
(A1)在检测区滴加待测样品溶液，并将滤纸固定于旋转平台上，之后滤纸在驱动下绕转轴旋转；
(A2)离子源射出的等离子体作用于不同的检测区，使检测区的待测样品分别离子化，离子化的样品分时地进入质谱进样口。
实施例2：
根据本发明实施例1的纸基进样装置及方法在硫酸粘杆菌素检测中的应用例。
在该应用例中，检测区为8个，相邻检测区的中心到所述加样区的中心的连接线间的夹角为45度；加样区中心为直径4mm圆形，连接通道长度为15mm，宽度为1mm；检测区为直径为3mm圆形；滴加金纳米颗粒溶液为20μl；滴加待测样品溶液为3μl；滤纸距离质谱进样口距离为0.2mm，离子源喷嘴、检测区圆心和质谱进样口位于同一水平线上；质谱检测m/z范围设为200-1200，检测样品为10ppm硫酸粘杆菌素标准样品(溶剂为甲醇：水＝1:1混合溶液)，所对应质谱谱图如图3所示。从中可观察到1156.69(带一个电荷)和578.65(带两个电荷)两个目标信号峰，强度分别为1.85e 4和4.95e 3，信噪比为21.45和10.88。旋转移动平台后所得四次测量值相对标准偏差为7.23％。
实施例3：
根据本发明实施例1的纸基进样装置及方法在甲基苯丙胺检测中的应用例。
在该应用例中，检测区为8个，相邻检测区的中心到所述加样区的中心的连接线间的夹角为45度；加样区为直径3mm圆形，连接通道长度为15mm，宽度为1mm；检测区为直径为2mm圆形；滴加金纳米颗粒溶液为15μl；滴加待测样品溶液为3μl；滤纸距离质谱进样口距离为0.2mm，离子源喷嘴、检测区圆心和质谱进样口位于同一水平线上。质谱检测m/z范围设为60-400，检测样品为10ppb甲基苯丙胺样品(溶剂为甲醇：水＝1:1混合溶液)，所对应质谱谱图如图4所示。从中可观察到明显样品加氢峰，强度为7.88e 2，信噪比为16.3。旋转移动平台后所得四次测量值相对标准偏差为12.52％。

Claims (10)

  1. 纸基进样装置，所述纸基进样装置包括离子源、滤纸和质谱进样口；其特征在于：所述纸基进样装置进一步包括：
    旋转平台，所述滤纸设置在所述旋转平台上，并在驱动下绕着转轴旋转；
    所述滤纸具有疏水区和亲水区，所述亲水区包括加样区、检测区和连接通道，所述加样区处于所述滤纸的中心，所述检测区为至少二个，并围绕所述加样区分布，所述连接通道连接所述加样区和检测区；当所述滤纸旋转时，所述离子源和质谱进样口之间的连线穿过所述检测区。
  2. 根据权利要求1所述的纸基进样装置，其特征在于：所述检测区和加样区为圆形，所述连接通道的宽度小于所述检测区和加样区的直径。
  3. 根据权利要求2所述的纸基进样装置，其特征在于：所述检测区的中心处于同一个圆上，该圆的圆心为所述加样区的圆心。
  4. 根据权利要求2所述的纸基进样装置，其特征在于：所述加样区的直径为2-4mm，所述检测区的直径为2-3mm。
  5. 根据权利要求2所述的纸基进样装置，其特征在于：所述连线垂直于所述滤纸，且所述检测区的圆心处于所述连线上。
  6. 根据权利要求1所述的纸基进样装置，其特征在于：所述旋转平台包括：
    固定框，所述滤纸设置在固定框上；在所述连线穿过所述检测区时，不受所述固定框的阻挡；
    驱动模块，所述驱动模块用于驱动所述固定框旋转，使得所述连线穿过检测区。
  7. 根据权利要求1所述的纸基进样装置，其特征在于：相邻检测区的中心到所述加样区的中心的连接线间的夹角为45度。
  8. 根据权利要求1所述的纸基进样装置，其特征在于：所述检测区具有金纳米颗粒。
  9. 根据权利要求1-7任一所述的纸基进样装置的纸基进样方法，所述纸基进样方法包括以下步骤：
    (A1)在检测区滴加待测样品溶液，并将滤纸固定于旋转平台上，之后滤纸在驱动下绕转轴旋转；
    (A2)离子源射出的等离子体作用于不同的检测区，使检测区的待测样品分别离子化，离子化的样品分时地进入质谱进样口。
  10. 根据权利要求9所述的纸基进样方法，其特征在于：所述纸基进样方法进一步包括以下步骤：
    (A0)在加样区滴加金纳米颗粒溶液，金纳米颗粒通过连接通道进入所述检测区。
PCT/CN2018/125474 2017-12-31 2018-12-29 纸基进样装置及方法 WO2019129269A1 (zh)

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