阅读说明：本技术 一种基于3d打印的解吸电喷雾离子化装置 (Desorption electric spray ionization device based on 3D printing ) 是由 钱翔 刘继琳 霍新明 余泉 倪凯 王晓浩 于 2021-08-25 设计创作，主要内容包括：一种基于3D打印的解吸电喷雾离子化装置,包括3D打印成型的解吸电喷雾离子化一体结构,所述解吸电喷雾离子化一体结构内部形成有电喷雾入射流道、解吸离子收集流道以及样片插入槽,所述样片插入槽与所述电喷雾入射流道和所述解吸离子收集流道相连通,所述电喷雾入射流道用于接入电喷雾源,所述解吸离子收集流道用于连接到质谱仪进样口,所述样片插入槽用于插入载有待测样品的样片。该解吸电喷雾离子化装置能够减少搭建时的空间参数调整,使用方便快捷,提高质谱分析效率和信号质量。(The utility model provides a desorption electrospray ionization device based on 3D prints, prints fashioned desorption electrospray ionization body structure including 3D, desorption electrospray ionization body structure inside is formed with electrospray incident flow channel, desorption ion collection runner and sample piece insertion groove, the sample piece insertion groove with electrospray incident flow channel with desorption ion collection runner is linked together, electrospray incident flow channel is used for inserting the electrospray source, desorption ion collection runner is used for being connected to the mass spectrograph inlet, the sample piece insertion groove is used for inserting the sample piece that carries the sample that awaits measuring. The desorption electrospray ionization device can reduce the adjustment of space parameters during construction, is convenient and quick to use, and improves the mass spectrometry efficiency and the signal quality.)

1. The utility model provides a desorption electrospray ionization device based on 3D prints, its characterized in that, prints fashioned desorption electrospray ionization body structure including 3D, desorption electrospray ionization body structure inside is formed with electrospray incident flow channel, desorption ion collection runner and sample wafer insertion groove, the sample wafer insertion groove with electrospray incident flow channel with desorption ion collection runner is linked together, electrospray incident flow channel is used for inserting the electrospray source, desorption ion collection runner is used for being connected to the mass spectrometer introduction port, sample wafer insertion groove is used for inserting the sample wafer that carries the sample that awaits measuring.

2. The desorption electrospray ionization apparatus according to claim 1, wherein said electrospray incidence channel comprises a first aperture portion adjacent to an electrospray source, a second aperture portion communicating with said sample insertion slot, and a portion having a gradually decreasing aperture diameter connecting between said first aperture portion and said second aperture portion, said first aperture portion having an aperture diameter larger than that of said second aperture portion.

3. The desorption electrospray ionization apparatus of claim 2, wherein said tapered portion of pore size is tapered.

4. The desorption electrospray ionization apparatus of claim 1, wherein said desorption ion collection flow channel comprises a first aperture portion communicating with said sample insertion slot, a second aperture portion connected to said mass spectrometer sample inlet, and a gradually decreasing aperture portion connected between said first aperture portion and said second aperture portion, said first aperture portion having a larger aperture diameter than said second aperture portion.

5. The desorption electrospray ionization apparatus of claim 4, wherein said tapered portion of pore size is tapered.

6. The desorption electrospray ionization apparatus according to any one of claims 1 to 5, wherein the desorption electrospray ionization integrated structure has a cylindrical shape as a whole, the desorption ion collection flow channel is disposed along an axial direction of the cylindrical shape, the sample insertion slot penetrates both sides of the cylindrical shape and has an angle with the desorption ion collection flow channel, and the electrospray incidence flow channel extends obliquely downward from an upper portion of the cylindrical shape and has an angle with the sample insertion slot.

7. The desorption electrospray ionization apparatus according to claim 6, wherein a projection is integrally formed on the upper surface of said cylinder, said electrospray ionization channel obliquely passes through said projection into said cylinder, preferably said projection has a triangular cross section along the direction of said electrospray ionization channel.

8. The desorption electrospray ionization device according to any one of claims 1 to 7, wherein said electrospray is a single electrospray ionization deviceAn incident angle alpha formed between the mist incident flow channel and the sample insertion slot is 50 degrees, a collection angle beta formed between the desorbed ion collection flow channel and the sample insertion slot is 10 degrees, and a distance d from a spray tip of the electrospray incident flow channel to the sample insertion slot₁3-5mm, the distance d from the center of the mass spectrum inlet of the desorbed ion collecting flow channel to the sample insertion groove₂Is 1-2 mm.

9. The desorption electrospray ionization apparatus of claim 8, wherein the spray voltage is controlled to 5kV, the solvent flow rate of the spray is controlled to 5 μ l/min, and the pressure of the auxiliary gas is controlled to 8-10 bar.

10. The desorption electrospray ionization apparatus according to any one of claims 1 to 7, wherein said desorption electrospray ionization unitary structure is printed by Stereolithography (SL), multi-nozzle molding (MJM) or Fused Deposition Molding (FDM).

Technical Field

The invention relates to the field of mass spectrometry, in particular to a desorption electrospray ionization device based on 3D printing.

Background

Mass spectrometers are widely used in chemical and biological analysis, and can achieve highly specific recognition and highly sensitive quantification of analytes. Desorption electrospray ionization (DESI) is one of the common open ionization technologies, and can be used for directly detecting and analyzing a sample or substances on the surface of the sample without or with little sample pretreatment, so that the advantages of high sensitivity and the like of a mass spectrometer are maintained, and the advantages of convenience, rapidness, high throughput and the like are realized. Desorption electrospray ionization (DESI) technology was originally proposed by cookies et al, which is based on electrospray ionization, whereby charged droplets are used as energy and charge transfer carriers, which are ejected by an auxiliary gas stream onto a solid surface to desorb analytes from the surface into the droplets. With solvent evaporation and coulomb explosion, the analyte forms gaseous ions that enter the mass spectrum in an open environment. The spray solvent not only can be used as an ionizing reagent, but also can be used as a reaction reagent, after the spray solvent is sprayed on the surface of a sample, a specific compound is formed with an analyte instantly, and then the specific compound enters mass spectrometry. Conventional DESI is influenced by a number of factors, all of which affect ionization efficiency, including spray performance level parameters, spatial parameters, sample support matrix surface parameters, and the like. The sprayability level parameters are mainly determined by the liquid flow rate, the gas flow rate and the applied high pressure. As shown in FIG. 1, the spatial parameters include an incident angle α and a collection angle β, and a distance d from the spray tip to the sample surface₁Mass spectrum inlet center to sample surface distance d₂. The DESI device needs to carry out meticulous, stable adjustment to spraying parameter, space parameter etc. needs two accurate platforms at least to carry out the adjustment of spraying position, angle and the placing of sample, and whole consuming time and inefficiency.

It is to be noted that the information disclosed in the above background section is only for understanding the background of the present application and thus may include information that does not constitute prior art known to a person of ordinary skill in the art.

Disclosure of Invention

The main purpose of the invention is to overcome the defects of the background technology, and provide a desorption electrospray ionization device based on 3D printing, which reduces parameter adjustment during device construction, is convenient and quick to use, and improves mass spectrometry efficiency and signal quality.

In order to achieve the purpose, the invention adopts the following technical scheme:

the utility model provides a desorption electrospray ionization device based on 3D prints, prints fashioned desorption electrospray ionization body structure including 3D, desorption electrospray ionization body structure inside is formed with electrospray incident flow channel, desorption ion collection runner and sample piece insertion groove, the sample piece insertion groove with electrospray incident flow channel with desorption ion collection runner is linked together, electrospray incident flow channel is used for inserting the electrospray source, desorption ion collection runner is used for being connected to the mass spectrograph inlet, the sample piece insertion groove is used for inserting the sample piece that carries the sample that awaits measuring.

Further:

the electrospray incidence flow channel comprises a first aperture part close to an electrospray source, a second aperture part communicated with the sample insertion groove and a part with gradually reduced aperture connected between the first aperture part and the second aperture part, wherein the aperture of the first aperture part is larger than that of the second aperture part.

The portion of the bore that tapers is tapered.

The desorbed ion collection flow channel comprises a first aperture part communicated with the sample insertion groove, a second aperture part connected to the sample injection port of the mass spectrometer and a part connected between the first aperture part and the second aperture part and having gradually reduced aperture, wherein the aperture of the first aperture part is larger than that of the second aperture part.

The portion of the bore that tapers is tapered.

The desorption electrospray ionization integrated structure is integrally cylindrical, the desorption ion collection flow channel is arranged along the axial direction of the cylinder, the sample piece insertion groove penetrates through two sides of the cylinder and forms an included angle with the desorption ion collection flow channel, and the electrospray incidence flow channel extends from the upper part of the cylinder to the oblique lower part and forms an included angle with the sample piece insertion groove.

The upper surface of the cylinder is integrally formed with a protrusion, the electrospray incidence flow channel obliquely passes through the protrusion to enter the cylinder, and preferably, the cross section of the protrusion along the direction of the electrospray incidence flow channel is triangular.

An incident angle alpha formed between the electrospray incident flow channel and the sample insertion slot is 50 degrees, a collection angle beta formed between the desorbed ion collection flow channel and the sample insertion slot is 10 degrees, and a distance d from a spray tip of the electrospray incident flow channel to the sample insertion slot₁3-5mm, the distance d from the center of the mass spectrum inlet of the desorbed ion collecting flow channel to the sample insertion groove₂Is 1-2 mm.

The spraying voltage is controlled to be 5kV, the flow rate of the sprayed solvent is controlled to be 5 mul/min, and the pressure of the auxiliary gas is controlled to be 8-10 bar.

The desorption electrospray ionization integrated structure is printed and formed by a stereolithography technology (SL), a multi-nozzle forming technology (MJM) or a fused deposition forming technology (FDM).

The invention has the following beneficial effects:

the invention provides a desorption electrospray ionization device based on 3D printing, which is characterized in that an electrospray incidence flow channel, a desorption ion collection flow channel and a sample piece insertion groove which are communicated with each other are formed in a desorption electrospray ionization integrated structure formed by 3D printing, an electrospray source is connected to the electrospray incidence flow channel, a mass spectrometer sample inlet is connected to the desorption ion collection flow channel, and a sample piece loaded with a sample to be detected is inserted into the sample piece insertion groove.

The desorption electrospray ionization device based on 3D printing integrates the spray, the surface of the sample and the mass spectrum inlet into a whole and has a fixed spatial relationship, and the configuration can avoid the loss of signals and is beneficial to reducing the interference of the miscellaneous peaks in the background. Space parameters are optimized in advance, and the DESI device generated by combining a convenient and fast 3D printing technology is reduced in adjustment of a plurality of parameters compared with the traditional DESI device, is highly integrated, is beneficial to miniaturization and is suitable for field mass spectrum detection. When the desorption electrospray ionization device with fixed spatial parameters is used, the desorption electrospray ionization device is assembled on a sample inlet of a mass spectrometer, a glass slide can be used for coating a sample sheet insertion groove of the sample insertion device, point sample introduction or line sample introduction is carried out, mass spectrometry is realized, and the desorption electrospray ionization device can achieve the same effect as a traditional built DESI device and is more convenient and faster.

Drawings

Fig. 1 is a schematic diagram of a basic structure of a conventional desorption electrospray ionization apparatus.

Fig. 2 is a schematic perspective view of a desorption electrospray ionization apparatus according to an embodiment of the present invention.

FIG. 3 is a schematic cross-sectional view of a desorption electrospray ionization apparatus according to an embodiment of the present invention.

FIG. 4 is a schematic diagram of a desorption electrospray ionization apparatus according to an embodiment of the present invention.

FIG. 5 is a sample drawing of an embodiment of the present invention.

FIG. 6 is a mass spectrum of a sample injected by a desorption electrospray ionization device according to an embodiment of the present invention.

FIG. 7 is a mass spectrum of a sample injected using a conventional desorption electrospray ionization apparatus.

Detailed Description

The embodiments of the present invention will be described in detail below. It should be emphasized that the following description is merely exemplary in nature and is not intended to limit the scope of the invention or its application.

It will be understood that when an element is referred to as being "secured to" or "disposed on" another element, it can be directly on the other element or be indirectly on the other element. When an element is referred to as being "connected to" another element, it can be directly connected to the other element or be indirectly connected to the other element. In addition, the connection may be for either a fixed or coupled or communicating function.

It is to be understood that the terms "length," "width," "upper," "lower," "front," "rear," "left," "right," "vertical," "horizontal," "top," "bottom," "inner," "outer," and the like are used in an orientation or positional relationship indicated in the drawings for convenience in describing the embodiments of the present invention and to simplify the description, and are not intended to indicate or imply that the referenced device or element must have a particular orientation, be constructed in a particular orientation, and be in any way limiting of the present invention.

Furthermore, the terms "first", "second" and "first" are used for descriptive purposes only and are not to be construed as indicating or implying relative importance or implicitly indicating the number of technical features indicated. Thus, a feature defined as "first" or "second" may explicitly or implicitly include one or more of that feature. In the description of the embodiments of the present invention, "a plurality" means two or more unless specifically limited otherwise.

Referring to fig. 2 to 5, a desorption electrospray ionization device based on 3D printing comprises a desorption electrospray ionization integrated structure 1 formed by 3D printing, an electrospray incidence flow channel 2, a desorption ion collection flow channel 3 and a sample piece insertion groove 4 are formed in the desorption electrospray ionization integrated structure 1, the sample piece insertion groove 4 is communicated with the electrospray incidence flow channel 2 and the desorption ion collection flow channel 3, the electrospray incidence flow channel 2 is used for being connected to an electrospray source, the desorption ion collection flow channel 3 is used for being connected to a mass spectrometer sample inlet, and the sample piece insertion groove 4 is used for being inserted with a sample piece loaded with a sample to be detected.

Referring to fig. 3, in a preferred embodiment, the electrospray incidence channel 2 includes a first aperture portion adjacent to an electrospray source, a second aperture portion communicating with the sample insertion slot 4, and a portion connecting between the first aperture portion and the second aperture portion and having a gradually decreasing aperture, wherein the aperture of the first aperture portion is larger than that of the second aperture portion. In a more preferred embodiment, the portion of the bore that tapers is tapered.

Referring to fig. 3, in a preferred embodiment, the desorbed ion collection flow channel 3 includes a first aperture portion communicating with the sample insertion slot 4, a second aperture portion connected to the mass spectrometer sample inlet, and a gradually decreasing aperture portion connected between the first aperture portion and the second aperture portion, the first aperture portion having a larger aperture than the second aperture portion. In a more preferred embodiment, the portion of the bore that tapers is tapered.

Referring to fig. 3, in a preferred embodiment, the desorption electrospray ionization integrated structure 1 is a cylinder, the desorption ion collection flow channel 3 is disposed along an axial direction of the cylinder, the sample insertion groove 4 penetrates through two sides of the cylinder and forms an included angle with the desorption ion collection flow channel 3, and the electrospray incidence flow channel 2 extends from an upper portion of the cylinder to an obliquely lower direction and forms an included angle with the sample insertion groove 4.

Referring to fig. 2 to 3, in a more preferred embodiment, a protrusion 5 is integrally formed on an upper surface of the cylinder, the electrospray injection channel 2 obliquely passes through the protrusion 5 into the cylinder, and preferably, a cross section of the protrusion 5 along the direction of the electrospray injection channel 2 is triangular.

In a particularly preferred embodiment, the electrospray incidence channel 2 forms an incidence angle α of 50 ° with the sample insertion slot 4, the desorbed ion collection channel 3 forms a collection angle β of 10 ° with the sample insertion slot 4, and the distance d from the spray tip a of the electrospray incidence channel 2 to the sample insertion slot 4₁3-5mm, the distance d from the mass spectrum inlet center B of the desorbed ion collecting flow channel 3 to the sample insertion groove 4₂Is 1-2 mm.

In a preferred embodiment, the diameter of the mass spectrometer inlet of the desorbing ion collection flow channel 3 is established in accordance with an LCQ Fleet ion trap mass spectrometer.

In a particularly preferred embodiment, the spray voltage is controlled at 5kV, the solvent flow rate of the spray is controlled at 5. mu.l/min, and the pressure of the auxiliary gas is controlled at 8-10 bar.

In different embodiments, the desorption electrospray ionization integrated structure 1 can be printed and formed by a Stereolithography (SL), multi-nozzle molding (MJM) or Fused Deposition Modeling (FDM) process.

The desorption electrospray ionization device based on 3D printing in the embodiment of the invention integrates the spray, the sample surface and the mass spectrum inlet into a whole and has a fixed spatial relationship, and the configuration can avoid the loss of signals and is beneficial to reducing the interference of the mixed peaks in the background. Space parameters are optimized in advance, and the DESI device generated by combining a convenient and fast 3D printing technology reduces the adjustment of a plurality of parameters such as a spraying position, a related angle and a sample placing position compared with the traditional DESI device, is highly integrated, is beneficial to miniaturization, and is suitable for field mass spectrometry. When the desorption electrospray ionization device with fixed spatial parameters is used, the desorption electrospray ionization device is assembled on a sample inlet of a mass spectrometer, a glass slide can be used for coating a sample sheet insertion groove 4 of the sample insertion device, point sample introduction or line sample introduction is carried out, mass spectrometry is realized, and the desorption electrospray ionization device can achieve the same effect as a traditional DESI device and is more convenient and faster.

Specific embodiments of the present invention are further described below.

Common 3D printing methods such as Stereolithography (SL), multi-nozzle molding (MJM), Fused Deposition Modeling (FDM), etc. may be used. Stereolithography (SL) builds a 3D object layer by photopolymerizing the precursor resin collected in a vat using selective exposure, projecting each layer as an image obtained by digitally segmenting the 3D object into slices. The desorption electrospray ionization device of the embodiment is processed by a 3D printing method of a stereolithography technology.

Figure 2 shows the overall appearance of a desorption electrospray ionization device, which can be connected to a mass spectrometer, mated to the sample inlet of the mass spectrometer through a DESI 3.2mm diameter orifice.

The internal flow channel of the desorption electrospray ionization device is shown in FIG. 3, the sprayer, the sample surface and the mass spectrum inlet have a fixed spatial relationship, the incident angle alpha, the collection angle beta and the distance d from the spray tip A to the sample surface₁In the mass spectrometer inletDistance d from center B to surface of sample₂The parameters have been optimized and fixed to certain values according to earlier experiments. Preferred dimensional and spray parameters are shown in table 1.

TABLE 1 Desorption electrospray ionization apparatus space parameters and spray parameters

Spatial parameters		Parameters of spraying
				α	50°	Spray voltage	5kV
β	10°	Flow rate of solvent	5μl/min
				d1	3-5mm	Pressure of nitrogen	8-10bar
d2	1-2mm

The desorption electrospray ionization device is used for carrying out mass spectrometer sample injection after desorption electrospray ionization, can detect compounds including nonpolar micromolecules (such as alkaloid, micromolecule medicines and the like) and polar macromolecules (such as polypeptide and protein), can realize direct mass spectrometry analysis on a complete tissue sample, and can finish accurate detection and analysis on peptide, protein, lipid, medicines, metabolites and the like on the premise of not homogenizing and extracting.

Fig. 4 shows a DESI physical map after 3D printing. The sample injection mode can be point sample injection or line sample injection of the sample on the desorption glass slide. One surface of the used glass slide is a frosted surface, a cotton swab is soaked in a sample solution with a certain concentration, the frosted surface of the glass slide is coated for multiple times, and after the sample is dried in the air, the glass slide is inserted into a DESI structure for sample injection, as shown in figure 5.

Testing the effects

A10 PPM rhodamine B sample is smeared on a glass slide, the glass slide is inserted into the desorption electrospray ionization device to carry out desorption electrospray ionization sample injection to obtain a mass spectrogram shown in a figure 6, and compared with a mass spectrogram obtained by traditional DESI source desorption shown in a figure 7, mass spectrum signals of the embodiment of the invention are not lost, and the interference of peaks in the background is reduced.

The background of the present invention may contain background information related to the problem or environment of the present invention and does not necessarily describe the prior art. Accordingly, the inclusion in the background section is not an admission of prior art by the applicant.

The foregoing is a more detailed description of the invention in connection with specific/preferred embodiments and is not intended to limit the practice of the invention to those descriptions. It will be apparent to those skilled in the art that various substitutions and modifications can be made to the described embodiments without departing from the spirit of the invention, and these substitutions and modifications should be considered to fall within the scope of the invention. In the description herein, references to the description of the term "one embodiment," "some embodiments," "preferred embodiments," "an example," "a specific example," or "some examples" or the like are intended to mean that a particular feature, structure, material, or characteristic described in connection with the embodiment or example is included in at least one embodiment or example of the invention. In this specification, the schematic representations of the terms used above are not necessarily intended to refer to the same embodiment or example. Furthermore, the particular features, structures, materials, or characteristics described may be combined in any suitable manner in any one or more embodiments or examples. Various embodiments or examples and features of various embodiments or examples described in this specification can be combined and combined by one skilled in the art without contradiction. Although embodiments of the present invention and their advantages have been described in detail, it should be understood that various changes, substitutions and alterations can be made herein without departing from the scope of the claims.