Mass spectrum Lamannite combined substrate and preparation method thereof

Abstract

The invention discloses a mass spectrum Lamannite combined substrate and a preparation method, relates to the technical field of analysis and detection, and provides a difunctional substrate which can support electrospray ionization mass spectrometry detection and surface enhanced Raman detection at the same time, does not interfere with each other and is suitable for on-site rapid operation. The substrate comprises a substrate film and at least one directional liquid transmission channel positioned on the surface of the substrate film, and a Raman detection area and a mass spectrum detection area are arranged in the channel; the mass spectrometry detection area is arranged at the tail end of the channel, the tail end is of a pointed structure, and a substrate film at the tail end comprises a metal conductive layer; the Raman detection area is arranged at any position, which is not overlapped with the mass spectrum detection area, in the channel, and a metal nanostructure is arranged on a substrate film of the Raman detection area and is used for realizing surface-enhanced Raman detection; after the liquid sample flows through the Raman detection area, the Raman detection device performs Raman detection on the liquid sample, and when the liquid sample flows to the mass spectrum detection area, the mass spectrum detection device performs mass spectrum detection on the liquid sample.

Description

Technical Field

[0001] This application relates to the field of analytical detection technology, and in particular to a mass spectrometry La Mans application substrate and its preparation method. Background Technology

[0002] Raman spectroscopy and mass spectrometry are commonly used analytical techniques because they can provide molecular vibrational and mass-to-charge ratio information. Since Raman spectroscopy and mass spectrometry are significantly complementary in terms of information dimensions—Raman spectroscopy provides molecular vibrational fingerprints for structural screening, while mass spectrometry provides mass-to-charge ratio and fragmentation information for structural confirmation—combining the two on the same platform can significantly improve the accuracy and reliability of detecting complex samples.

[0003] Currently, paper-based materials are commonly used as sample carriers when combining paper spray mass spectrometry with surface-enhanced Raman scattering (SERS) detection. However, the inherent properties of paper-based materials, such as their liquid absorption, non-uniform fiber structure, and uncontrollable liquid diffusion, lead to random sample migration paths, unstable spraying processes, and large fluctuations in ionization efficiency. Furthermore, paper-based materials are difficult to support precisely morphologically controllable metal nanostructures, resulting in limited enhancement effects and poor reproducibility when used as SERS substrates. Moreover, the spraying region and SERS detection region in paper spraying are usually not clearly delineated on the same substrate, causing interference between the two detection modes and preventing true synergistic dual-modal co-operation. In summary, a dual-functional substrate that can simultaneously support electrospray mass spectrometry and surface-enhanced Raman detection without interference and suitable for rapid on-site operation is still lacking. Summary of the Invention

[0004] This application provides a dual-function substrate for mass spectrometry and Raman spectroscopy, and its preparation method. This substrate can simultaneously support electrospray mass spectrometry detection and surface-enhanced Raman detection without interference between the two, and is suitable for rapid on-site operation.

[0005] To achieve the above objectives, this application adopts the following technical solution: In a first aspect, this application provides a mass spectrometry Raman-compatible substrate, the substrate comprising: a base membrane and at least one directional liquid transport channel located on the surface of the base membrane, wherein the directional liquid transport channel is provided with a Raman detection region and a mass spectrometry detection region, and the directional liquid transport channel is used to guide the liquid sample to be detected to achieve directional migration; The mass spectrometry detection region is located at the end of the directional liquid transport channel. The end of the directional liquid transport channel corresponding to the mass spectrometry detection region is a pointed structure, and the base film at the end of the directional liquid transport channel includes a metal conductive layer. The Raman detection region is located at any position in the directional liquid transport channel that does not overlap with the mass spectrometry detection region. A metal nanostructure is disposed on the base film corresponding to the Raman detection region to achieve surface-enhanced Raman detection. The liquid sample undergoes directional migration in the directional liquid transport channel. After the liquid sample flows through the Raman detection region, the Raman detection device performs Raman detection on the liquid sample in the Raman detection region. When the liquid sample flows to the mass spectrometry detection region, the mass spectrometry detection device performs mass spectrometry detection on the liquid sample.

[0006] As one possible implementation, the Raman detection region and the mass spectrometry detection region are located in the same directional liquid transport channel; or, the Raman detection region and the mass spectrometry detection region are located in different directional liquid transport channels.

[0007] As one possible implementation, the directional liquid transport channel includes any one or more of the following: a groove structure channel, a periodic asymmetric ridge-valley structure channel, and a surface wettability gradient structure channel.

[0008] As one possible implementation, the area of ​​the Raman detection region is 0.05-100 mm²; The metal nanostructure is made of gold and / or silver, or the metal nanostructure is made of a core-shell structure, multilayer structure or composite structure composed of gold and silver. The morphologies of the metal nanostructures include: metal nanofilm structures, nanoisland structures, nanoparticle stacking structures, nanocolumn structures, and periodic array structures. The thickness of the metal nanostructure ranges from 2 nm to 200 nm.

[0009] As one possible implementation, the pointed structure is a structure formed by sharpening the end of any directional liquid transport channel. The sharpening process can form a single-tip, double-tip, or multi-tip array structure, wherein the tip angle ranges from 5° to 70°. The metallic conductive layer is made of gold and / or platinum; When the liquid sample flows to the pointed structure at the end of the directional liquid transport channel, it forms an electrospray under the action of an applied electric field.

[0010] As one possible implementation, the base film is made of polymer materials, glass materials, silicon-based materials, metal materials, or metal composite materials.

[0011] A second aspect of this application provides a method for preparing a mass spectrometry-Latmann compatible substrate. This method is used to prepare the mass spectrometry-Latmann compatible substrate described in the first aspect of this application. The method includes: At least one directional liquid transport channel is formed on the surface of the basement membrane, the directional liquid transport channel being used to guide the liquid sample to be detected to achieve directional migration; A Raman detection region and a mass spectrometry detection region are provided in the directional liquid transport channel, wherein the mass spectrometry detection region is located at the end of the directional liquid transport channel, and the Raman detection region is located at any position in the directional liquid transport channel that does not overlap with the mass spectrometry detection region; Using the first processing method, the end of the directional liquid transport channel corresponding to the mass spectrometry detection region is processed into a pointed structure, and a metal conductive layer is formed on the base film at the end of the directional liquid transport channel; Using a second processing method, a metal nanostructure is formed on the base film corresponding to the Raman detection region; The liquid sample undergoes directional migration in the directional liquid transport channel. After the liquid sample flows through the Raman detection region, the Raman detection device performs Raman detection on the sample in the Raman detection region. When the liquid sample flows to the mass spectrometry detection region, the mass spectrometry detection device performs mass spectrometry detection on the liquid sample.

[0012] As one possible implementation, forming at least one directional liquid transport channel on the surface of the basement membrane includes: At least one directional liquid transport channel is formed on the surface of the substrate film by means of molding, etching, laser processing or photopolymerization printing.

[0013] As one possible implementation, the first processing method includes: laser cutting, physical shaping, micro-milling, and chemical etching.

[0014] As one possible implementation method, the second processing method includes: magnetron sputtering, evaporation, annealing and reconstruction, nanoparticle self-assembly, template-assisted deposition, photolithography and etching.

[0015] The beneficial effects of the technical solutions provided in this application include at least the following: The mass spectrometry-Raman composite substrate provided in this application includes: a base membrane and at least one directional liquid transport channel located on the surface of the base membrane. The directional liquid transport channel has a Raman detection region and a mass spectrometry detection region. The directional liquid transport channel guides the liquid sample to be detected to achieve directional migration. The mass spectrometry detection region is located at the end of the directional liquid transport channel, and the end of the directional liquid transport channel corresponding to the mass spectrometry detection region has a pointed structure. A metal conductive layer is included on the base membrane at the end of the directional liquid transport channel. The Raman detection region is located at any position in the directional liquid transport channel that does not overlap with the mass spectrometry detection region. A metal nanostructure is provided on the base membrane corresponding to the Raman detection region to achieve surface-enhanced Raman detection. The liquid sample achieves directional migration in the directional liquid transport channel. After the liquid sample flows through the Raman detection region, the Raman detection device performs Raman detection on the liquid sample in the Raman detection region. When the liquid sample flows to the mass spectrometry detection region, the mass spectrometry detection device performs mass spectrometry detection on the liquid sample.

[0016] The mass spectrometry-Raman combined substrate provided in this application has Raman detection region and mass spectrometry detection region respectively set on a single substrate membrane, and the liquid sample is connected and migrated between the detection regions through a directional liquid transport channel. The Raman detection region and the mass spectrometry detection region are spatially independent and functionally separated, structurally avoiding the problems of contamination, abnormal background signal, and decreased instrument stability caused by the entry of active metal nanostructures into the mass spectrometry system via electrospraying in surface-enhanced Raman scattering detection in the prior art. This improves the reliability of dual-modal detection and the safety of instrument use.

[0017] Meanwhile, this application constructs a directional liquid transport channel with directional liquid migration on the base membrane, enabling the liquid sample to stably migrate from its starting position along a preset direction and flow through or be split to reach the Raman detection region and the mass spectrometry detection region, respectively. Compared to the existing paper-based materials that rely on random capillary diffusion for liquid diffusion, this application significantly improves the controllability of the liquid sample migration path, residence position, and effective volume, thereby enhancing the consistency and repeatability of the Raman detection and electrospray mass spectrometry detection processes.

[0018] Furthermore, compared to existing technologies that use flexible paper-based materials as carriers and rely on manual cutting to form the spray tip, the base film used in this application can be made of materials with high mechanical strength and structural stability. This makes the spray tip less prone to bending, deformation, or positional drift under the influence of an electric field and solvent wetting conditions. As a result, the spray position and geometry exhibit good stability and repeatability, the spray initiation conditions are more consistent, the electrospray ionization process is more stable, and ion signal fluctuations are effectively reduced. Simultaneously, the tipped spray structure has good durability and reusability, making it suitable for multiple tests and continuous operation, which is beneficial for improving the reliability and practicality of rapid on-site testing and long-term applications.

[0019] Secondly, this application constructs a Raman detection region at a predetermined location on the base film, and a metal nanostructure layer can be formed within this region using various mature processes, thus confining the Raman enhancement interface to the designated area. Compared to the existing paper-based SERS where metal nanoparticles are randomly distributed on the paper fiber surface, this application is beneficial for improving the spatial uniformity and detection reproducibility of the Raman signal, thereby enhancing the reliability of Raman detection in qualitative and quantitative analysis.

[0020] Furthermore, this application enables Raman detection and mass spectrometry detection to be performed separately or in combination by controlling the migration path of the liquid sample in the directional liquid transport channel, thereby acquiring multidimensional spectroscopic information of the same sample on the same substrate. This reduces the need for sample aliquoting and repeated sampling, lowers the sample volume, and simplifies the operation process. Attached Figure Description

[0021] Figure 1 A schematic diagram of a mass spectrometry La Mans application substrate provided in this application embodiment. Figure 1 ; Figure 2 A schematic diagram of a mass spectrometry La Mans application substrate provided in this application embodiment. Figure 2 ; Figure 3 A schematic diagram of a mass spectrometry La Mans application substrate provided in this application embodiment. Figure 3 ; Figure 4 A schematic diagram of a mass spectrometry La Mans application substrate provided in this application embodiment. Figure 4 ; Figure 5 A schematic diagram of a mass spectrometry La Mans application substrate provided in this application embodiment. Figure 5 ; Figure 6 A flowchart illustrating a method for preparing a mass spectrometry La Mans-compatible substrate is provided in this application embodiment; Figure 7 A scanning electron microscope for Raman detection region provided in this application embodiment Figure 1 ; Figure 8 A Raman shift spectrum for the detection of a rhodamine sample is provided in an embodiment of this application; Figure 9 A mass spectrum for the detection of rhodamine in a sample provided in an embodiment of this application; Figure 10 A scanning electron microscope for Raman detection region provided in this application embodiment Figure 2 ; Figure 11 A Raman shift spectrum for 4-MBA sample detection provided in this application embodiment; Figure 12 This is a mass spectrum for detecting a 4-MBA sample, provided as an embodiment of this application. Detailed Implementation

[0022] The technical solutions of the embodiments of this application will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of this application, and not all embodiments. Based on the embodiments of this application, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of this application.

[0023] Hereinafter, the terms "first" and "second" are used for descriptive purposes only and should not be construed as indicating or implying relative importance or implicitly specifying the number of indicated technical features. Thus, a feature defined as "first" or "second" may explicitly or implicitly include one or more of that feature. In the description of embodiments of this disclosure, unless otherwise stated, "a plurality of" means two or more.

[0024] In addition, the use of “based on” or “according to” implies openness and inclusivity, because processes, steps, calculations or other actions “based on” or “according to” one or more conditions or values ​​can in practice be based on additional conditions or values ​​beyond those conditions.

[0025] Raman spectroscopy and mass spectrometry are commonly used analytical techniques because they can provide information on molecular vibrations and mass-to-charge ratios. Raman spectroscopy offers advantages such as fast detection speed, small sample volume, no need for complex pretreatment, and non-destructive analysis; however, its resolution is limited when analyzing isomers with highly similar chemical structures and weakly Raman-active substances, and it is easily affected by fluorescence background interference. Surface-enhanced Raman scattering (SERS) technology can significantly enhance Raman signal intensity by generating a strong local electromagnetic field on the surface of metal nanostructures, thereby improving detection sensitivity. However, the detection performance of SERS is highly dependent on the morphology, stability, and batch-to-batch homogeneity of the substrate nanostructure, making it challenging to obtain enhancement effects with high repeatability and reliability. Mass spectrometry, as another Class A confirmatory technique, has extremely high sensitivity, selectivity, and structural resolution capabilities, making it an important method for confirmatory analysis of complex chemical substances. However, traditional electrospray ionization usually relies on large mass spectrometers and stable electric field conditions, imposing strict requirements on the spray interface morphology, sample morphology, and pretreatment process, limiting its application in rapid on-site analysis scenarios.

[0026] Because Raman spectroscopy and mass spectrometry are significantly complementary in terms of information dimensions—Raman spectroscopy provides molecular vibrational fingerprints for structural screening, while mass spectrometry provides mass-to-charge ratio and fragmentation information for structural confirmation—combining them on the same platform can significantly improve the accuracy and reliability of detecting complex samples. For homologues, isomers, and synthetic drug derivatives with extremely similar structures, relying solely on a single detection technique is often insufficient for effective differentiation. Dual-modal detection can compensate for the shortcomings of each technique, achieving more comprehensive analytical results. Therefore, constructing a dual-modal analysis system capable of simultaneously performing Raman and mass spectrometry detection in a portable device is of great significance for rapid on-site detection.

[0027] Current technologies attempt to combine paper spray mass spectrometry with SERS detection, but they have the following drawbacks: 1. In existing paper spray mass spectrometry techniques, spraying typically relies on manually cutting ordinary paper-based materials to form a tip structure to achieve electrospray ionization. However, the paper-based material itself is soft and has a random fiber distribution, making it difficult to maintain consistent tip angle, tip radius, and effective spray position during manual cutting. These factors can lead to fluctuations in the concentration of the electric field and the liquid supply state, resulting in inconsistent spray initiation voltage, unstable spray morphology, and large fluctuations in ion signal intensity. Furthermore, in practice, the paper spray tip is prone to bending, deformation, or positional drift under solvent wetting or high voltage, further reducing spray stability and repeatability.

[0028] 2. Existing paper-based coupling schemes mainly rely on the random capillary action of the paper itself for liquid diffusion. The migration path, distribution position and volume of the sample reaching the detection area on the paper substrate are difficult to control precisely, which can easily lead to non-uniform SERS signals or unstable spray ionization.

[0029] 3. Limited uniformity and reproducibility of SERS signals. Paper-based SERS is usually loaded with metal nanoparticles through impregnation, spraying, or printing. The distribution of nanostructures is greatly affected by the randomness of paper fibers, which easily leads to uneven distribution of "hot spots" and insufficient spatial consistency of Raman signals, affecting quantitative and comparative analysis.

[0030] 4. Potential mutual interference issues in the SERS-MS coupling process. In existing paper-based SERS-MS coupling techniques, paper-based SERS is typically achieved by loading gold, silver, or other metal nanoparticles or nanostructure layers onto the surface of paper fibers through methods such as impregnation, spraying, or printing. However, during subsequent paper spray mass spectrometry analysis, the spraying process, under the influence of a high electric field and solvent, carries some metal nanoparticles or their aggregates into the electrospray gas phase system. Once these metal nanoparticles enter the mass spectrometry ion transport channel, they may deposit or contaminate the sampling cone, ion guiding structure, or ion optical elements, causing abnormal background signals, decreased ion transport efficiency, and even potential damage to the long-term stable operation of the detector and vacuum system. Therefore, existing technologies lack effective physical isolation or functional separation mechanisms between the active metal layer of the SERS and the mass spectrometry ionization process.

[0031] To address the problems of structural instability, uncontrollable sample transport, poor detection repeatability, and mutual interference between two modes in existing paper-based SERS and paper spray mass spectrometry technologies, this application aims to solve the following technical problems.

[0032] First, in response to the problems of existing paper spray mass spectrometry relying on the manual cutting of flexible paper substrates to form spray tips, resulting in uncontrollable tip geometry, inconsistent spray initiation conditions, and large fluctuations in ion signals, this application aims to solve how to construct a mass spectrometry spray structure with a clear geometry and stable spray position on a substrate.

[0033] This application aims to provide a tipped spray structure integrally formed from the end of a base membrane. Through the structural design of the number of spray tips, the range of tip angles, and the conductivity of the tip surface, the liquid sample can stably and repeatedly generate an electrospray ionization process under the action of an external electric field, thereby reducing the spray uncertainty caused by manual cutting or material flexibility.

[0034] Secondly, in view of the problem that existing paper-based coupling schemes mainly rely on random capillary action of paper fibers for liquid diffusion, sample migration path and distribution volume are difficult to control, resulting in non-uniform SERS signals or unstable spray ionization, this application needs to provide a sample transport method with a clear liquid migration direction and controllable transport path, so as to realize the directional migration, sequential arrival or diversion of liquid samples to different detection areas on the same substrate, thereby improving the controllability and repeatability of the detection process.

[0035] Furthermore, in response to the problems of the distribution of metal nanoparticles in existing paper-based SERS substrates being greatly affected by the randomness of paper fibers, uneven distribution of local "hot spots," and insufficient spatial consistency and reproducibility of Raman signals, this application aims to construct a stable and repeatable Raman detection interface that can form within a specified region, thereby improving the reliability of SERS detection and making it more suitable for qualitative and quantitative analysis scenarios.

[0036] Furthermore, in the existing technology, SERS active metal nanoparticles may enter the mass spectrometry system during paper spraying, causing contamination of ion elements, abnormal background signals, and decreased instrument stability. This application aims to solve the problem of physical and functional isolation between SERS detection and mass spectrometry ionization to avoid the adverse effects of metal nanoparticles entering the mass spectrometry system. In summary, this application aims to provide a dual-modal detection substrate and its preparation method that enables directional transport of liquid samples on a single substrate, allows for spatial independence and non-interference between the Raman and mass spectrometry detection regions, and simultaneously ensures detection stability, repeatability, and instrument safety. This aims to overcome the aforementioned shortcomings of existing technologies in the field of Raman-mass spectrometry coupling. The specific solution is as follows.

[0037] This application provides a mass spectrometry La Mans-compatible substrate, such as... Figure 1 As shown, the substrate includes: a base membrane and at least one directional liquid transport channel located on the surface of the base membrane. The directional liquid transport channel is provided with a Raman detection region and a mass spectrometry detection region. The directional liquid transport channel is used to guide the liquid sample to be detected to achieve directional migration. The mass spectrometry detection region is located at the end of the directional liquid transport channel. The end of the directional liquid transport channel corresponding to the mass spectrometry detection region is a pointed structure, and the base film at the end of the directional liquid transport channel includes a metal conductive layer. The Raman detection region is located at any position in the directional liquid transport channel that does not overlap with the mass spectrometry detection region. A metal nanostructure is disposed on the base film corresponding to the Raman detection region to achieve surface-enhanced Raman detection. The liquid sample undergoes directional migration in the directional liquid transport channel. After the liquid sample flows through the Raman detection region, the Raman detection device performs Raman detection on the liquid sample in the Raman detection region. When the liquid sample flows to the mass spectrometry detection region, the mass spectrometry detection device performs mass spectrometry detection on the liquid sample.

[0038] Optionally, the directional liquid transport channel includes any one or more of the following: a groove structure channel, a periodic asymmetric ridge-valley structure channel, and a surface wettability gradient structure channel.

[0039] The liquid sample to be tested includes a liquid containing the target analyte, and the liquid is selected from methanol, acetonitrile, ethyl acetate, water or a mixture thereof.

[0040] like Figure 2 As shown, the mass spectrometry Raman-compatible substrate provided in this application is illustrated using a directional liquid transport channel with a four-line groove structure as an example, including: a substrate membrane, directional liquid transport channels, a Raman detection region, and a mass spectrometry detection region. Among them, Figure 2 The black area in the image represents the Raman detection area. Figure 2 The tip region at the end of the directional liquid transport channel is the mass spectrometry detection region.

[0041] like Figure 3 As shown, the mass spectrometry Lahm-Mall substrate provided in this application is illustrated using four periodic asymmetric ridge-valley structured directional liquid transport channels as an example. Figure 3 The four ridge-valley structures within are directional fluid transport channels. Figure 3 The black area in the image represents the Raman detection area. Figure 3 The tip region at the end of the directional liquid transport channel is the mass spectrometry detection region.

[0042] Optionally, the base membrane, which serves as the main body supporting various functional structures, can be made of polymer materials, glass materials, silicon-based materials, metal sheets, or their composite materials. It possesses certain mechanical strength and structural stability to meet the usage requirements in liquid sample transport and electrospray ionization processes.

[0043] A directional liquid transport channel is provided along the length direction on the surface of the base membrane. For example... Figure 1 and 2 As shown, multiple directional liquid transport channels are arranged along a preset direction. Each directional liquid transport channel has a distinct directional characteristic, enabling the liquid sample to migrate only along the set direction under the combined effects of capillary action and surface energy differences, thereby achieving directional transport of the liquid sample. Through this directional liquid transport channel, the liquid sample can stably migrate from the initial position of the substrate to the downstream functional area, avoiding random diffusion.

[0044] The mass spectrometry detection region is located at the end of the directional liquid transport channel, while the Raman detection region is located at any position within the directional liquid transport channel that does not overlap with the mass spectrometry detection region; that is, the Raman detection region is located between the beginning and end of the directional liquid transport channel. When a liquid sample migrates to this region under the guidance of the directional liquid transport channel, Raman spectroscopy or surface-enhanced Raman scattering can be performed within this region.

[0045] In a preferred embodiment, the Raman detection region is a surface-enhanced Raman scattering (SERS) detection region, and a metal nanostructure is disposed on the base film corresponding to the Raman detection region to enhance the Raman scattering signal of the analyte molecule. The metal nanostructure layer may be composed of gold, silver, or their alloys, and may exhibit a nano-island structure, a nanoparticle stacked structure, a nanocolumn structure, or a periodic array structure. The metal nanostructure layer is limited to the Raman detection region and does not extend into the mass spectrometry detection region or other regions of the directional liquid transport channel, thereby avoiding interference with subsequent electrospray mass spectrometry detection.

[0046] The mass spectrometry detection region is integrally formed into a pointed spray structure at the end of the base membrane. When a liquid sample continues to migrate to this region along the directional liquid transport channel, a stable electrospray is formed at the tip under the action of an applied electric field, achieving ionization of the liquid sample and enabling its collection and analysis by the mass spectrometer. The pointed spray structure has a well-defined geometric morphology; its tip can be a single tip, a double tip, or a multi-tip array, and the tip angle range is limited to enhance the electric field concentration effect and improve the consistency of spray initiation conditions. A conductive metal layer is disposed on the surface of the pointed structure to improve electrical conductivity and electrospray ionization efficiency, making the spray process more stable and continuous.

[0047] Through the above structural design, this application realizes the process of liquid sample moving from the starting position to the Raman detection region and the mass spectrometry detection region sequentially or selectively on a single substrate, so that Raman detection and electrospray mass spectrometry detection are spatially independent and functionally complementary, thereby realizing the acquisition of dual-modal spectroscopic information.

[0048] Optional, as the first implementation method, such as Figure 4 As shown, if a directional liquid transport channel is included on the surface of the base membrane, the Raman detection region is disposed between the start and end of the directional liquid transport channel, and the mass spectrometry detection region is disposed at the end of the directional liquid transport channel; the liquid sample flows in from the start of the liquid transport channel, passes through the Raman detection region, and then flows to the mass spectrometry detection region.

[0049] Optionally, as a second implementation method, such as Figure 5As shown, if the basement membrane surface includes multiple directional liquid transport channels, the Raman detection region and the mass spectrometry detection region can be respectively set in different directional liquid transport channels. After the liquid sample is split into multiple portions, the multiple liquid samples flow into each directional liquid transport channel from the beginning end to the end end of each directional liquid transport channel.

[0050] Optionally, as a third implementation method, such as Figure 2 As shown, if the basement membrane surface includes multiple directional liquid transport channels, the Raman detection region and the mass spectrometry detection region can be set in the same directional liquid transport channel. After the liquid sample is split into multiple portions, the multiple liquid samples flow into each directional liquid transport channel from the beginning end to the end end of each directional liquid transport channel.

[0051] Based on the above three implementation methods, it can be understood that there can be one or more directional liquid transport channels on the basement membrane. If there is only one directional liquid transport channel, a Raman detection region can be set between the start and end of the directional liquid transport channel, and a mass spectrometry detection region can be set at the end of the directional liquid transport channel.

[0052] If there are multiple directional liquid transport channels, the Raman detection region and the mass spectrometry detection region can be set on one directional liquid transport channel, or the Raman detection region and the mass spectrometry detection region can be distributed on different directional liquid transport channels. The number, position or arrangement of the Raman detection region and the mass spectrometry detection region in this application can be flexibly set or selected according to the detection requirements to achieve single-mode detection or dual-mode joint detection. This application does not impose specific limitations on this.

[0053] Optionally, the area of ​​the Raman detection region is 0.05-100 mm²; the Raman detection region includes a conventional Raman detection region and a surface-enhanced Raman detection region; if the Raman detection region is a surface-enhanced Raman detection region, then the base film corresponding to the Raman detection region also includes a layer of metal nanostructures; The metal nanostructure is made of gold and / or silver, or the metal nanostructure is made of a core-shell structure, multilayer structure or composite structure composed of gold and silver. The morphology of the metal nanostructures includes: metal nanofilm structures, nanoisland structures, nanoparticle stacking structures, nanocolumn structures, and periodic array structures; the thickness of the metal nanostructures ranges from 2 nm to 200 nm.

[0054] The metal nanostructure layer of this application is limited to the Raman detection region and does not extend to the mass spectrometry detection region or other regions of the directional liquid transport channel, thereby avoiding interference with subsequent electrospray mass spectrometry detection.

[0055] Optionally, the end of the directional liquid transport channel corresponding to the mass spectrometry detection region is processed into a pointed structure, and the base film at the end of the directional liquid transport channel includes a metal conductive layer. When the liquid sample flows to the pointed structure at the end of the directional liquid transport channel, it forms an electrospray under the action of an external electric field; the pointed structure is a structure formed by sharpening the end of any directional liquid transport channel, and the sharpening method can form a single-tip, double-tip or multi-tip array structure, wherein the tip angle range is 5°-70°; The conductive metal layer is made of gold and / or platinum and is used to improve the conductivity and electrospray ionization efficiency of the spray region, thereby enhancing the stability and repeatability of mass spectrometry detection.

[0056] This application also provides a method for preparing a mass spectrometry La Mans-compatible substrate, used to prepare the mass spectrometry La Mans-compatible substrate described in this application embodiment, such as... Figure 6 As shown, the method includes the following steps: Step 101: Form at least one directional liquid transport channel on the surface of the basement membrane, wherein the directional liquid transport channel is used to guide the liquid sample to be detected to achieve directional migration; Step 102: Set a Raman detection region and a mass spectrometry detection region in the directional liquid transport channel, wherein the mass spectrometry detection region is set at the end of the directional liquid transport channel, and the Raman detection region is set at any position in the directional liquid transport channel that does not overlap with the mass spectrometry detection region; Step 103: Using the first processing method, the end of the directional liquid transport channel corresponding to the mass spectrometry detection area is processed into a pointed structure, and a metal conductive layer is formed on the base film at the end of the directional liquid transport channel; Step 104: Using the second processing method, a metal nanostructure is formed on the base film corresponding to the Raman detection area; Step 105: The liquid sample undergoes directional migration in the directional liquid transport channel. After the liquid sample flows through the Raman detection area, the Raman detection device performs Raman detection on the sample in the Raman detection area. When the liquid sample flows to the mass spectrometry detection area, the mass spectrometry detection device performs mass spectrometry detection on the liquid sample.

[0057] Optionally, forming at least one directional liquid transport channel on the surface of the substrate film includes forming at least one directional liquid transport channel on the surface of the substrate film by means of molding, etching, laser processing or photopolymerization printing.

[0058] Optionally, the first processing method includes: laser cutting, physical shaping, micro-milling, and chemical etching.

[0059] Optionally, the second processing method includes: magnetron sputtering, vapor deposition, annealing reconstruction, nanoparticle self-assembly, template-assisted deposition, photolithography, and etching.

[0060] During the detection process, the liquid sample to be tested is added to the initiating end of the basement membrane. Guided by the directional liquid transport channel, the liquid sample migrates from the initiating end along a preset direction on the substrate surface. When the liquid sample migrates to the Raman detection region, the Raman spectrum or surface-enhanced Raman scattering spectrum of the sample is acquired in this region, enabling rapid screening or preliminary identification of the target analyte. Subsequently, the liquid sample can continue to migrate along the directional liquid transport channel or be split in the multi-channel structure and enter the mass spectrometry detection region. An external voltage is applied to the pointed spray structure in the mass spectrometry detection region, causing the liquid sample to undergo electrospray ionization, and the mass spectrometry device acquires the mass spectrometry data, enabling confirmatory analysis of the target analyte.

[0061] The method for preparing a mass spectrometry-La Manson composite substrate provided in the above embodiments is further illustrated in this application. The following embodiments describe the technical solutions of this application in more detail. These embodiments are for illustrative purposes only, as various modifications and variations within the scope of the disclosure of this application will be apparent to those skilled in the art. The reagents and raw materials used in the embodiments are commercially available or synthesized using conventional methods and can be used directly without further processing. Similarly, the instruments and apparatus used in the embodiments are commercially available.

[0062] Example 1: 1. Preparation of La Man Mass Spectrometry Components S1. Preparation of a basement membrane with directional liquid transport channels.

[0063] Polymethyl methacrylate (PMMA) film was selected as the substrate material. A linear trench structure distributed along a predetermined direction was formed on the surface of the PMMA film using laser etching, thereby obtaining a substrate film with linear trenches providing directional liquid transport channels. This linear trench structure can guide the liquid sample to migrate directionally along the trench direction under the combined effects of surface tension and wetting differences, such as... Figure 2 As shown.

[0064] S2. Construction of the Raman detection region.

[0065] A Raman detection region is constructed at a predetermined location on the basement membrane surface obtained in step S1. In this embodiment, the Raman detection region is a surface-enhanced Raman scattering detection region. Specifically, the basement membrane is first subjected to surface cleaning treatment. The surface of the basement membrane is ultrasonically cleaned sequentially with anhydrous ethanol and alkaline solution to remove surface organic contaminants and weakly attached impurities. Then, it is thoroughly rinsed with deionized water and allowed to air dry. The cleaned basement membrane is placed in a clean petri dish, and a mixed solution of chloroauric acid and a reducing agent is added to the basement membrane at the Raman detection region location. The solution is then incubated at 40°C for several hours to allow gold ions to be reduced in situ on the PP surface to generate gold nanoparticles, which then self-assemble to form a dense and uniformly distributed layer of gold nanoparticles. After natural cooling and drying, a gold nanoparticle-modified Raman detection region is obtained in the predetermined region to enhance the Raman scattering signal. The scanning electron microscope image of the Raman detection region prepared by the above process is shown below. Figure 7 As shown.

[0066] S3. Advanced processing of the mass spectrometry detection area.

[0067] The ends of the basement membrane are sharpened to form a mass spectrometry detection region. In this embodiment, a UV picosecond laser is used to precisely cut the ends of the linear grooves, forming a tip structure for electrospray ionization at the ends of the basement membrane. Three tips are used, each integrally formed, with an included angle of 60°. The multiple tips are parallel and aligned towards the front end of the basement membrane, with their central axes parallel to the sampling cone of the mass spectrometer to improve ion transport and collection efficiency.

[0068] S4. Deposition of conductive layer A conductive metal layer is deposited on the surface of the tipped structure obtained in step S3 to improve the electrospray ionization efficiency. In this embodiment, a magnetic sputtering method is used to deposit a conductive gold layer of a certain thickness on the surface of the tip region, so that the mass spectrometry detection region has good conductivity and stable spray performance.

[0069] After preparing the mass spectrometry La Manz-compatible substrate, the substrate-based detection applications are as follows: S1. The mass spectrometry Raman composite substrate is placed within the detection range of the Raman spectrometer and the mass spectrometer, wherein the detection range of the Raman spectrometer corresponds to the Raman detection region, and the detection range of the mass spectrometer corresponds to the mass spectrometry detection region; S2. A liquid sample to be detected, consisting of a 10 ppm rhodamine methanol solution, is dropped onto the starting end of the basement membrane. Guided by the linear groove structure on the basement membrane surface, the liquid sample migrates directionally from its starting position to the Raman detection region under the mediation of surface tension. Raman spectroscopy measurements are then performed on the liquid sample. Figure 8As shown, a clear Raman shift spectrum of the Rhodamine methanol solution can be obtained using the Raman detection region, and its characteristic Raman scattering peaks are clearly distinguishable, reflecting the molecular vibrational information of the target substance. S3 Subsequently, the liquid sample continues to migrate to the mass spectrometry detection region, where a high voltage is applied to cause electrospray ionization of the liquid sample, and the corresponding mass spectrometry data is acquired; such as Figure 9 As shown, the mass spectrum of the rhodamine methanol solution can be obtained using the mass spectrometry detection region, reflecting the mass-to-charge ratio information of the target substance; S4. By jointly analyzing the Raman spectroscopy data and mass spectrometry data obtained above, qualitative identification and quantitative analysis of target substances in the liquid sample to be tested can be achieved.

[0070] Example 2: 1. Preparation of La Man Mass Spectrometry Components S1. Preparation of a basement membrane with directional liquid transport channels A flat polypropylene (PP) film is provided as the base film material. The PP film is heated to its melting and softening temperature, which is 130°C. A mold for forming a periodic ridge-valley structure is pressed onto its surface and held under a pressure of 35 kPa for 10 seconds to replicate the periodic ridge-valley structure onto the PP film surface. After printing, the PP film and the mold are cooled to room temperature together. After the PP film has cooled and regained its hardness, it is separated from the mold to obtain a base film with a periodic ridge-valley structure on its surface. The periodic ridge-valley structure can guide the liquid sample to migrate directionally along a predetermined direction under the combined action of surface energy difference and capillary action, such as... Figure 3 As shown.

[0071] S2. Construction of the Raman detection region A Raman detection region is constructed at a predetermined location on the base membrane obtained in step S1. Specifically, the base membrane surface is first cleaned sequentially with ethanol and alkaline solution to remove surface organic contaminants, followed by rinsing with deionized water and air drying. Then, the base membrane is placed in a clean petri dish, and a certain volume of gold nanoparticle solution with a predetermined concentration (50-100 nm in diameter) is added to the Raman detection region. After standing at room temperature for 12 hours to allow the solvent to evaporate naturally, the gold nanoparticles self-assemble or uniformly distribute on the PP surface, forming a dense nanoparticle layer, thus constructing the Raman detection region for surface-enhanced Raman scattering detection. The scanning electron microscope image of the Raman detection region prepared by the above process is shown below. Figure 10 As shown.

[0072] S3. Advanced processing of the mass spectrometry detection area The end of the basement membrane is processed to form a mass spectrometry detection region. Specifically, this includes: cutting the end of the periodic ridge-valley structure with an ultraviolet picosecond laser; forming multiple integrated tip structures, in this embodiment there are 3 tips; the included angle of the tips is 60°, and the direction of the multiple tips is towards focusing, with their focusing axis aligned with the sampling cone of the mass spectrometer.

[0073] S4. Deposition of conductive layer Depositing a metallic conductive layer on the surface of the tipped structure specifically includes: sputtering a metallic gold conductive layer of a certain thickness on the surface of the tip region using a magnetron sputtering method.

[0074] After preparing the mass spectrometry La Manz-compatible substrate, the substrate-based detection applications are as follows: The mass spectrometry Raman composite substrate is placed within the detection range of both the Raman spectrometer and the mass spectrometer, wherein the detection range of the Raman spectrometer corresponds to the Raman detection region, and the detection range of the mass spectrometer corresponds to the mass spectrometry detection region. A liquid sample to be tested, which is a 1 ppm 4-mercaptobenzoic acid (4-MBA) methanol solution, is dropped onto the starting end of the basement membrane. Guided by the periodic ridge-valley structure, the liquid sample migrates directionally from its initial position on the substrate to the Raman detection region under the mediation of surface tension, and Raman spectroscopy measurements are performed on this region; Figure 11 As shown, the Raman shift spectrum of the 4-MBA methanol solution can be obtained using the Raman detection region, and its characteristic Raman scattering peaks are clearly visible, indicating that the substrate has good surface-enhanced Raman detection performance. Subsequently, the liquid sample continues to migrate to the mass spectrometry detection region, where a high voltage is applied to the multi-tip structure to cause electrospray ionization of the liquid sample, and corresponding mass spectrometry data are acquired; such as Figure 12 As shown, a mass spectrum of a 4-MBA methanol solution can be obtained using the mass spectrometry detection region. By jointly analyzing the obtained Raman spectroscopy data and mass spectrometry data, qualitative identification and quantitative analysis of target substances in the liquid sample to be tested can be achieved.

[0075] The mass spectrometry-Raman combined substrate provided in this application has Raman detection region and mass spectrometry detection region respectively set on a single substrate membrane, and the liquid sample is connected and migrated between the detection regions through a directional liquid transport channel. The Raman detection region and the mass spectrometry detection region are spatially independent and functionally separated, structurally avoiding the problems of contamination, abnormal background signal, and decreased instrument stability caused by the entry of active metal nanostructures into the mass spectrometry system via electrospraying in surface-enhanced Raman scattering detection in the prior art. This improves the reliability of dual-modal detection and the safety of instrument use.

[0076] Meanwhile, this application constructs a directional liquid transport channel with directional liquid migration on the base membrane, enabling the liquid sample to stably migrate from its starting position along a preset direction and flow through or be split to reach the Raman detection region and the mass spectrometry detection region, respectively. Compared to the existing paper-based materials that rely on random capillary diffusion for liquid diffusion, this application significantly improves the controllability of the liquid sample migration path, residence position, and effective volume, thereby enhancing the consistency and repeatability of the Raman detection and electrospray mass spectrometry detection processes.

[0077] Furthermore, compared to existing technologies that use flexible paper-based materials as carriers and rely on manual cutting to form the spray tip, the base film used in this application can be made of materials with high mechanical strength and structural stability. This makes the spray tip less prone to bending, deformation, or positional drift under the influence of an electric field and solvent wetting conditions. As a result, the spray position and geometry exhibit good stability and repeatability, the spray initiation conditions are more consistent, the electrospray ionization process is more stable, and ion signal fluctuations are effectively reduced. Simultaneously, the tipped spray structure has good durability and reusability, making it suitable for multiple tests and continuous operation, which is beneficial for improving the reliability and practicality of rapid on-site testing and long-term applications.

[0078] Secondly, this application constructs a Raman detection region at a predetermined location on the base film, and a metal nanostructure layer can be formed within this region using various mature processes, thus confining the Raman enhancement interface to the designated area. Compared to the existing paper-based SERS where metal nanoparticles are randomly distributed on the paper fiber surface, this application is beneficial for improving the spatial uniformity and detection reproducibility of the Raman signal, thereby enhancing the reliability of Raman detection in qualitative and quantitative analysis.

[0079] Furthermore, this application enables Raman detection and mass spectrometry detection to be performed separately or in combination by controlling the migration path of the liquid sample in the directional liquid transport channel, thereby acquiring multidimensional spectroscopic information of the same sample on the same substrate. This reduces the need for sample aliquoting and repeated sampling, lowers the sample volume, and simplifies the operation process.

[0080] The technical features of the above embodiments can be combined in any way. For the sake of brevity, not all possible combinations of the technical features in the above embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0081] The above embodiments merely illustrate several implementation methods of this application, and while the descriptions are relatively specific and detailed, they should not be construed as limiting the scope of the invention patent. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of this application, and these all fall within the protection scope of this application. Therefore, the protection scope of this patent application should be determined by the appended claims.

Claims

1. A mass spectrometry La Mans-compatible substrate, characterized in that, The substrate includes: a base membrane and at least one directional liquid transport channel located on the surface of the base membrane, wherein the directional liquid transport channel is provided with a Raman detection region and a mass spectrometry detection region, and the directional liquid transport channel is used to guide the liquid sample to be detected to achieve directional migration; The mass spectrometry detection region is located at the end of the directional liquid transport channel. The end of the directional liquid transport channel corresponding to the mass spectrometry detection region is a pointed structure, and the base film at the end of the directional liquid transport channel includes a metal conductive layer. The Raman detection region is located at any position in the directional liquid transport channel that does not overlap with the mass spectrometry detection region. A metal nanostructure is disposed on the base film corresponding to the Raman detection region to achieve surface-enhanced Raman detection. The liquid sample undergoes directional migration in the directional liquid transport channel. After the liquid sample flows through the Raman detection region, the Raman detection device performs Raman detection on the liquid sample in the Raman detection region. When the liquid sample flows to the mass spectrometry detection region, the mass spectrometry detection device performs mass spectrometry detection on the liquid sample.

2. The substrate according to claim 1, characterized in that, The Raman detection region and the mass spectrometry detection region are located in the same directional liquid transport channel; or, the Raman detection region and the mass spectrometry detection region are located in different directional liquid transport channels.

3. The substrate according to claim 1, characterized in that, The directional liquid transport channel includes any one or more of the following: groove structure channel, periodic asymmetric ridge-valley structure channel, and surface wettability gradient structure channel.

4. The substrate according to claim 1, characterized in that, The area of ​​the Raman detection region is 0.05-100 mm²; The metal nanostructure is made of gold and / or silver, or the metal nanostructure is made of a core-shell structure, multilayer structure or composite structure composed of gold and silver. The morphologies of the metal nanostructures include: metal nanofilm structures, nanoisland structures, nanoparticle stacking structures, nanocolumn structures, and periodic array structures. The thickness of the metal nanostructure ranges from 2 nm to 200 nm.

5. The substrate according to claim 1, characterized in that, The pointed structure is a structure formed by sharpening the end of any directional liquid transport channel. The sharpening process can form a single-tip, double-tip, or multi-tip array structure, wherein the tip angle ranges from 5° to 70°. The metallic conductive layer is made of gold and / or platinum; When the liquid sample flows to the pointed structure at the end of the directional liquid transport channel, it forms an electrospray under the action of an applied electric field.

6. The substrate according to claim 1, characterized in that, The base film is made of polymer materials, glass materials, silicon-based materials, metal materials, or metal composite materials.

7. A method for preparing a mass spectrometry La Mans-compatible substrate, characterized in that, The method for preparing the mass spectrometry La Mans composite substrate according to any one of claims 1-6 comprises: At least one directional liquid transport channel is formed on the surface of the basement membrane, the directional liquid transport channel being used to guide the liquid sample to be detected to achieve directional migration; A Raman detection region and a mass spectrometry detection region are provided in the directional liquid transport channel, wherein the mass spectrometry detection region is located at the end of the directional liquid transport channel, and the Raman detection region is located at any position in the directional liquid transport channel that does not overlap with the mass spectrometry detection region; Using the first processing method, the end of the directional liquid transport channel corresponding to the mass spectrometry detection region is processed into a pointed structure, and a metal conductive layer is formed on the base film at the end of the directional liquid transport channel; Using a second processing method, a metal nanostructure is formed on the base film corresponding to the Raman detection region; The liquid sample undergoes directional migration in the directional liquid transport channel. After the liquid sample flows through the Raman detection region, the Raman detection device performs Raman detection on the sample in the Raman detection region. When the liquid sample flows to the mass spectrometry detection region, the mass spectrometry detection device performs mass spectrometry detection on the liquid sample.

8. The method according to claim 7, characterized in that, The formation of at least one directional liquid transport channel on the surface of the basement membrane includes: At least one directional liquid transport channel is formed on the surface of the substrate film by means of molding, etching, laser processing or photopolymerization printing.

9. The method according to claim 7, characterized in that, The first processing method includes: laser cutting, physical shaping, micro-milling and chemical etching.

10. The method according to claim 7, characterized in that, The second processing method includes: magnetron sputtering, vapor deposition, annealing and reconstruction, nanoparticle self-assembly, template-assisted deposition, photolithography and etching.

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