WO2022016681A1

WO2022016681A1 - Laser desorption ionization method based on optical fiber conduction

Info

Publication number: WO2022016681A1
Application number: PCT/CN2020/113967
Authority: WO
Inventors: 欧阳钢锋; 徐剑桥; 胡庆坤
Original assignee: 中山大学
Priority date: 2020-07-20
Filing date: 2020-09-08
Publication date: 2022-01-27
Also published as: CN111834193B; CN111834193A

Abstract

A laser desorption ionization method based on optical fiber (3) conduction. The method comprises the following steps: S1, etching the end portion of an optical fiber (3) with hydrofluoric acid; S2, coating the etched portion of the optical fiber (3) with a solid-phase micro-extraction coating (4); S3, extracting a target analyte (5) from a sample to be detected by using the optical fiber (3), such that the target analyte (5) is adsorbed onto the solid-phase micro-extraction coating (4); S4, a laser system emitting a laser and coupling the laser into the optical fiber (3), such that the laser can be emitted to the solid-phase micro-extraction coating (4) through the optical fiber (3); and S5, after step S4, the laser being absorbed by the solid-phase micro-extraction coating (4), such that molecules of the target analyte (5) absorbed onto the solid-phase micro-extraction coating (4) are ionized, and then separated from the solid-phase micro-extraction coating (4). The method can achieve high-throughput ionization and improve the excitation efficiency, and can also remarkably reduce the background interference during small molecule detection and improve the detection sensitivity.

Description

Laser Analytical Ionization Method Based on Fiber Conduction

technical field

The invention relates to the technical field of laser analysis, and more particularly, to a laser analysis ionization method based on optical fiber conduction.

Background technique

The existing laser ionization method is matrix-assisted laser desorption ionization (MALDI), which has been widely used in the analysis and detection of biological macromolecules. It will be interfered by matrix molecules in the analysis of small molecule compounds; also, this technology is limited by the size of the laser spot, only the analyte in the laser spot will be excited, so its sensitivity is limited; The unavoidable human error in the sample spotting process causes the short-cut state difference between the target analyte and the matrix, which makes the signal deviation between multiple targets larger, and has greater limitations in quantitative detection.

The Chinese patent document with publication number CN111092359A discloses a laser system for matrix-assisted laser desorption ionization time-of-flight mass spectrometer, which solves the scattering phenomenon of single-mode pulsed light generated by solid-state lasers in multi-mode fibers, and achieves improved performance. The purpose of sample ionization effects in matrix-assisted laser desorption ionization time-of-flight mass spectrometry.

However, the above scheme is to apply laser light from the surface of the substrate to achieve molecular ionization, so that it can only excite the target molecules and substrates in the laser spot, resulting in low excitation efficiency.

SUMMARY OF THE INVENTION

The purpose of the present invention is to overcome the deficiency of low excitation efficiency, and provide a laser analytical ionization method based on optical fiber conduction, which can realize high-throughput ionization and improve excitation efficiency; detection sensitivity.

In order to solve the above-mentioned technical problems, the technical scheme adopted in the present invention is:

Provided is a laser desorption ionization method based on optical fiber conduction, comprising an optical fiber, a laser system, and a sample to be tested, and the method includes the following steps:

S1. Etch the end of the optical fiber with hydrofluoric acid;

S2. After step S1, apply a solid-phase microextraction coating on the etched position of the optical fiber;

S3. after step S2, use the optical fiber to extract the target analyte in the sample to be tested, so that the target analyte is adsorbed on the solid phase microextraction coating;

S4. After step S3, the laser system emits laser light, and couples the laser light into the optical fiber, so that the laser light can be emitted to the solid phase microextraction coating through the optical fiber;

S5. After step S4, the laser light is absorbed by the solid phase microextraction coating, so that the molecules of the target analyte attached to the solid phase microextraction coating are ionized, and then detached from the solid phase microextraction coating. Extraction coating.

The invention is a laser analytical ionization method based on optical fiber conduction. By coating the solid-phase micro-extraction coating, it can achieve high enrichment ability for target analyte molecules, and also has high laser absorption ability and photoelectric conversion efficiency. The laser ionization process of the target analyte molecules, and at the same time, the coating itself will not be detached by the laser excitation, so the background interference in the detection of small molecules can be significantly reduced. The method can realize the simultaneous laser ionization process of the entire coating, realize high-throughput ionization, and improve detection sensitivity. In addition, the solid phase microextraction coating has good stability and low damage rate, and can be reused in multiple continuous analysis processes, so the reproducibility of its analysis and detection is good, which is conducive to quantitative detection.

Further, the optical fiber includes a coating layer, an outer coating layer, and a fiber core that are sequentially arranged from outside to inside.

Further, the step S1 specifically includes the following steps:

S11. Peel off the coating at the end of the optical fiber to expose the outer coating;

S12. After step S11, the outer cladding is immersed in a hydrofluoric acid aqueous solution and left to stand, so that the fiber core is exposed.

Further, in step S2, the solid phase microextraction coating is any one or more of high molecular polymers, porous organic polymers, carbon materials, or metal oxide particles.

Further, in step S2, the coating is applied at the etched position of the optical fiber by any one of the in-situ growth method, the chemical bonding method, the sol-gel method, or the dip coating method.

Further, in step S3, when the optical fiber is used to extract the target analyte in the sample to be tested, the target analyte in the sample to be tested is extracted by headspace extraction or immersion extraction.

Further, in step S4, the laser system includes a laser generator and a laser coupling device, and the laser light emitted by the laser generator is coupled into the optical fiber through the laser coupling device, so that the laser light is transmitted at the fiber core, Then exit to the solid phase microextraction coating.

Further, the laser coupling device includes a three-dimensional base and a convex lens arranged on the three-dimensional base.

Further, the step S4 specifically includes the following steps:

S41. Fix the unetched end of the optical fiber on the three-dimensional base;

S42. The laser generator emits laser light, and gathers the laser light through the convex lens to form a laser spot;

S43. Align the fiber core with the laser by adjusting the three-dimensional base, and make the laser spot size close to or equal to the diameter of the fiber core.

Further, after step S5, the mass detection of the ionized target analyte is performed by using a time-of-flight mass spectrometer to achieve qualitative and quantitative detection of the target analyte.

Compared with the prior art, the beneficial effects of the present invention are:

(1) By coating the solid-phase microextraction coating, it can achieve high enrichment ability for the target analyte molecules, as well as high laser absorption ability and photoelectric conversion efficiency, so as to realize the laser ionization process of the target analyte molecules, At the same time, the coating itself will not be detached by laser excitation, so the background interference in the detection of small molecules can be significantly reduced.

(3) The solid phase microextraction coating has good stability and low damage rate, and can be reused in multiple continuous analysis processes, so the reproducibility of its analysis and detection is good, which is conducive to quantitative detection.

(4) The present invention can realize the simultaneous laser ionization process of the entire coating, realize high-throughput ionization, and improve detection sensitivity.

Description of drawings

FIG. 1 is a flow chart of the laser analytical ionization method based on optical fiber conduction according to the present invention.

FIG. 2 is a schematic structural diagram of the optical fiber conduction-based laser analytical ionization method of the present invention.

FIG. 3 is a schematic structural diagram of an optical fiber obtained after step S2 of the laser analytical ionization method based on optical fiber conduction according to the present invention.

FIG. 4 is a schematic structural diagram of a laser system and an optical fiber part of the present invention.

The icon marks are explained as follows:

1-laser generator, 2-laser coupling device, 21-three-dimensional base, 22-convex lens, 3-fiber, 31-coating, 32-cladding, 33-core, 4-SPE coating , 5-target analyte.

detailed description

The present invention will be further described below in conjunction with specific embodiments. Among them, the accompanying drawings are only used for exemplary description, and they are only schematic diagrams, not physical drawings, and should not be construed as restrictions on this patent; in order to better illustrate the embodiments of the present invention, some parts of the accompanying drawings will be omitted, The enlargement or reduction does not represent the size of the actual product; it is understandable to those skilled in the art that some well-known structures and their descriptions in the accompanying drawings may be omitted.

The same or similar numbers in the drawings of the embodiments of the present invention correspond to the same or similar components; in the description of the present invention, it should be understood that if there are terms “upper”, “lower”, “left” and “right” The orientation or positional relationship indicated by etc. is based on the orientation or positional relationship shown in the accompanying drawings, which is only for the convenience of describing the present invention and simplifying the description, rather than indicating or implying that the indicated device or element must have a specific orientation, a specific orientation, and a specific orientation. Orientation structure and operation, so the terms describing the positional relationship in the accompanying drawings are only used for exemplary illustration, and should not be construed as a limitation on the present patent. For those of ordinary skill in the art, the specific meanings of the above terms can be understood according to specific situations.

Example 1

As shown in FIGS. 1 to 4 , a first embodiment of a laser analytical ionization method based on optical fiber conduction of the present invention includes an optical fiber 3, a laser system, and a sample to be tested. The method includes the following steps:

S1. Pretreatment of the optical fiber: The end of the optical fiber 3 is etched with hydrofluoric acid. Wherein, the optical fiber 3 includes a coating layer 31, an outer layer 32, and a fiber core 33 sequentially arranged from outside to inside. Step S1 specifically includes the following steps:

S11. Peel off the coating layer 31 at one end of the optical fiber 3 with a length of 1-1.5 cm to expose the outer cladding 32; in this embodiment, peel off the coating layer 31 at the one end of the optical fiber 3 with a length of 1 cm.

S12. After step S11, fix the optical fiber 3 on the stage, and then immerse the exposed outer cladding 32 in a hydrofluoric acid aqueous solution to stand, so that the outer cladding 32 is removed and the core 33 is exposed. Wherein, when selecting the hydrofluoric acid with a purity of 48%-51%, it needs to be diluted, and by adding equal volume of 10ml of deionized water and 10ml of hydrofluoric acid dilution in a polytetrafluoroethylene container, an aqueous solution of hydrofluoric acid is obtained; The outer layer 32 can be removed by standing in the hydrofluoric acid aqueous solution for 3 hours.

The optical fiber 3 in this embodiment is selected from FOPC-SMA905-1000/1035/1400 from Feibot.

S2. Coating coating: after step S1, coating the solid phase microextraction coating 4 on the etched position of the optical fiber 3, that is, coating the solid phase microextraction coating 4 on the exposed position of the fiber core 33.

In step S2, the solid phase microextraction coating 4 is any one or more of high molecular polymers, porous organic polymers, carbon materials, or metal oxide particles. Among them, the high molecular polymer can be selected from polydimethylsiloxane (PDMS), polyaniline (PANI), etc.; the porous organic polymer can be selected from metal organic framework (MOF), covalent organic polymer framework (COF), etc.; The carbon material can be selected from graphene, graphene oxide, mesoporous carbon, etc.; the metal oxide particle can be selected from titanium dioxide. It should be noted that the material selection of the solid phase microextraction coating 4 includes but is not limited to the materials listed above, and the selection of high-performance materials with high enrichment ability for the target analyte 5, high laser absorption ability and photoelectric conversion rate. material.

In step S2, coating is carried out on the etched part of the optical fiber 3, that is, the exposed part of the core 33, by any one of the in-situ growth method, the chemical bonding method, the sol-gel method, or the dip coating method. cover. The coated optical fiber 3 is shown in FIG. 3 . When a high molecular polymer or a porous organic polymer is selected as the solid-phase microextraction coating 4, any one of the above methods can be used to coat the coating; when a carbon material or metal oxide particles and their composite materials are selected as the When the solid-phase microextraction coating 4 is selected, or when any of the macromolecular polymers, porous organic polymers, carbon materials, and metal oxide particles are selected as the solid-phase microextraction coating 4, the in-situ growth method can be used. , sol-gel method, or dip coating method to apply the coating. It should be noted that the coating method of the solid phase microextraction coating 4 includes but is not limited to the methods listed above, and a method that can coat the solid phase microextraction coating 4 on the optical fiber 3 may be selected. It should be noted that the thickness of the solid phase microextraction coating 4 coated on the fiber core 33 can be adjusted according to actual needs.

S3. Extraction: After step S2, the optical fiber 3 is used to extract the target analyte 5 in the sample to be tested, so that the target analyte 5 is adsorbed on the solid phase microextraction coating 4. The target analyte 5 in the sample to be tested can be extracted by headspace extraction or immersion extraction. The extraction method, extraction time, extraction temperature and other conditions are selected according to the material of the solid-phase microextraction coating 4 and the target analyte 5, which can greatly improve the detection sensitivity. The samples to be tested can be environmental water samples, urine, serum and the like.

For example, when the volatile benzene series BTEX in environmental water samples is selected as the target analyte5, headspace extraction can be used, and the polydimethylsiloxane/titania composite material can be used as the solid phase microextraction coating4 . Polydimethylsiloxane has strong adsorption capacity and is a commonly used solid-phase microextraction probe coating on the market. Titanium dioxide has good photoelectric conversion efficiency, which can improve the ionization efficiency of the coating to target molecules; Dip coating can be used to prepare the probe coating for coating application.

For another example, when selecting persistent organic pollutants such as non-volatile polycyclic aromatic hydrocarbons (PAHs) or polychlorinated biphenyls (PCBs) in environmental water samples or urine as target analytes5, immersion extraction can be used, and metal organic framework materials can be used. ZIF-8, etc. are used as solid-phase microextraction coatings 4. In-situ growth method or chemical bonding method can be used during coating coating, and organic monomers are first fixed by functional group modification, and then metal-organic frameworks are self-assembled. material grows. Metal-organic framework materials have a large specific surface area, so they have a strong adsorption capacity, and also have metal element sites, and have a strong photoelectric conversion ability.

S4. Laser transmission: after step S3, the laser system emits laser light and couples the laser light into the optical fiber 3, so that the laser light can be emitted to the solid phase microextraction coating 4 through the optical fiber 3. The laser system includes a laser generator 1 and a laser coupling device 2. The laser light emitted by the laser generator 1 is coupled into the optical fiber 3 through the laser coupling device 2, so that the laser light is transmitted at the fiber core 33, and then exits to the solid-phase microextraction coating Level 4.

The laser coupling device 2 includes a three-dimensional base 21 and a convex lens 22 disposed on the three-dimensional base 21 . As shown in Figure 4, step S4 specifically includes the following steps:

S41. Fix the unetched end of the optical fiber 3 on the three-dimensional base 21;

S42. The laser generator 1 emits laser light, and gathers the laser light through the convex lens 22 to form a laser spot;

S43. Align the fiber core 33 with the laser by adjusting the three-dimensional base 21, and then adjust the distance between the three-dimensional base 21 and the laser generator 1 so that the laser spot size is infinitely close to or equal to the diameter of the fiber core 33.

In addition, in order to prevent the laser from hurting people, in step S41, the optical fiber 3, the laser generator 1, and the laser coupling device 2 may be shielded by a casing made of metal. In this embodiment, the laser generator 1 is an adjustable laser generator, and there is a formula:

E=hc/λ;

In the formula, E represents the generated photon energy, h represents Planck's constant, c represents the speed of light, and λ represents the laser wavelength. Since the wavelength of the laser generator 1 is adjustable, the photon energy can be adjusted by adjusting the laser wavelength; and different chemical bonds in different target analytes 5 have different bond energies, so the photon energy can be adjusted by adjusting the laser wavelength, thereby realizing the chemical bond. selective fragmentation.

S5. Ionization of the laser: after step S4, the laser is absorbed by the solid phase microextraction coating 4, and the energy is transferred to the target analyte 5, so that the target analyte 5 attached to the solid phase microextraction coating 4 is The molecules are ionized and then detached from the SPE coating 4 . However, the solid phase microextraction coating 4 itself will not be detached by laser excitation, so the background interference during the detection of small molecules can be significantly reduced.

Example 2

This embodiment is similar to Embodiment 1, the difference is that this embodiment further includes step S6: after step S5, the mass detection of the ionized target analyte 5 is performed by using a time-of-flight mass spectrometer to achieve the target analyte 5. Qualitative and quantitative detection of analyte 5.

Obviously, the above-mentioned embodiments of the present invention are only examples for clearly illustrating the present invention, and are not intended to limit the embodiments of the present invention. For those of ordinary skill in the art, changes or modifications in other different forms can also be made on the basis of the above description. There is no need and cannot be exhaustive of all implementations here. Any modifications, equivalent replacements and improvements made within the spirit and principle of the present invention shall be included within the protection scope of the claims of the present invention.

Claims

A laser analytical ionization method based on optical fiber conduction, characterized in that it comprises an optical fiber (3), a laser system, and a sample to be measured, and the method comprises the following steps:

S1. The end of the optical fiber (3) is etched with hydrofluoric acid;

S2. After step S1, a solid phase microextraction coating (4) is applied at the etching place of the optical fiber (3);

S3. After step S2, the optical fiber (3) is used to extract the target analyte (5) in the sample to be tested, so that the target analyte (5) is adsorbed on the solid phase microextraction coating (4) ;

S4. After step S3, the laser system emits laser light, and couples the laser light into the optical fiber (3), so that the laser light can be emitted to the solid phase microextraction coating (4) through the optical fiber (3);

S5. After step S4, the laser light is absorbed by the solid phase microextraction coating (4), so that the molecules of the target analyte (5) attached to the solid phase microextraction coating (4) generate ions and then detached from the solid phase microextraction coating (4).
The laser analytical ionization method based on optical fiber conduction according to claim 1, characterized in that, the optical fiber (3) comprises a coating layer (31), an outer coating (32), and a fiber core which are sequentially arranged from outside to inside (33).
The laser analytical ionization method based on optical fiber conduction according to claim 2, wherein the step S1 specifically includes the following steps:

S11. peel off the coating layer (31) at the end of the optical fiber (3), so that the outer layer (32) is exposed;

S12. After step S11, the outer cladding (32) is immersed in an aqueous solution of hydrofluoric acid and allowed to stand, so that the fiber core (33) is exposed.
The laser desorption ionization method based on optical fiber conduction according to claim 1, characterized in that, in step S2, the solid phase microextraction coating (4) is made of high molecular polymer, porous organic polymer, carbon material , or any one or more of metal oxide particles.
The laser analytical ionization method based on optical fiber conduction according to claim 1, characterized in that, in step S2, by any one of in-situ growth method, chemical bonding method, sol-gel method, or dip coating method The coating of the coating is carried out at the etching of the optical fiber (3).
The optical fiber conduction-based laser desorption ionization method according to claim 1, characterized in that, in step S3, the target analyte (5) in the sample to be tested is extracted by headspace extraction or immersion extraction.
The laser analytical ionization method based on optical fiber conduction according to claim 2, characterized in that, in step S4, the laser system comprises a laser generator (1) and a laser coupling device (2), the laser generator (1) The emitted laser light is coupled into the optical fiber (3) through a laser coupling device (2), so that the laser light is transmitted at the fiber core (33), and then exits to the solid phase microextraction coating (4) place.
The laser analytical ionization method based on optical fiber conduction according to claim 7, wherein the laser coupling device (2) comprises a three-dimensional base (21) and a convex lens (22) arranged on the three-dimensional base (21). ).
The laser analytical ionization method based on optical fiber conduction according to claim 8, wherein the step S4 specifically includes the following steps:

S41. Fix the unetched end of the optical fiber (3) on the three-dimensional base (21);

S42. The laser generator (1) emits laser light, and gathers the laser light through the convex lens (22) to form a laser spot;

S43. Align the fiber core (33) with the laser by adjusting the three-dimensional base (21), and make the laser spot size close to or equal to the diameter of the fiber core (33).
The laser desorption ionization method based on optical fiber conduction according to claim 1, characterized in that, after step S5, the mass detection of the ionized target analyte (5) is carried out by using a time-of-flight mass spectrometer to realize the analysis of the target Qualitative and quantitative detection of compound (5).