Spray head for electrospray ionization

Abstract

The invention relates to a spray head for electrospray ionization (ESI). The invention also relates to a method for producing a spray head according to the invention and to the use of a spray head according to the invention for electrospray ionization (ESI). The invention also relates to a chromatography column comprising a spray head according to the invention and to a device for carrying out electrospray ionization (ESI) comprising a spray head according to the invention or comprising a chromatography column according to the invention.

Description

[0001] Spray head for electrospray ionization

[0002] The present invention relates to a spray head for electrospray ionization (ESI). The present invention also relates to a method for producing a spray head according to the invention and to the use of a spray head according to the invention for electrospray ionization (ESI). The present invention also relates to a chromatography column comprising a spray head according to the invention and to a device for performing electrospray ionization (ESI) comprising a spray head according to the invention or comprising a chromatography column according to the invention.

[0003] The invention is defined in the appended claims. Preferred aspects of the present invention will become apparent from the following description, including the examples.

[0004] To the extent that certain embodiments are designated as preferred for one aspect of the invention, the corresponding statements also apply to the other aspects of the present invention, mutatis mutandis. Preferred individual features of aspects of the invention (as defined in the claims and / or disclosed in the description) can be combined with one another and are preferably combined with one another, unless otherwise apparent to the person skilled in the art from the present text.

[0005] The generation of ions of, for example, heavy analyte molecules with molecular weights ranging from a few hundred to many thousands of Daltons in an electrospray ion source is widely known. The ability to ionize very large molecules, especially those that are not thermally vaporizable, is extremely important; for the development of the electrospray ion source in the late 1980s, John Bennett Fenn was awarded the Nobel Prize in Chemistry in 2002.

[0006] For electrospray ionization (ESI), a high voltage of several kilovolts is applied to a spray nozzle, which during operation contains spray liquid or an analyte solution with dissolved analyte molecules. This creates a strong electric field around the spray nozzle outlet. This polarizes the surface of the spray liquid at the spray nozzle outlet and becomes highly charged. The electrical pulling force creates a so-called Taylor cone on the liquid surface, from whose tip a fine jet of liquid is drawn by the electric pulling field. This jet is inherently unstable due to its high surface charge, which opposes the surface tension: it breaks up into tiny, highly charged droplets with diameters on the order of a micrometer.

[0007] All droplets, large and small, continue to evaporate, with small droplets evaporating faster and faster due to their ever-decreasing coordination number of the surface molecules and the resulting increase in vapor pressure, until the separation and evaporation processes end relatively quickly in the complete drying of a droplet and only predominantly multiply charged ions of the analyte molecules contained in the droplet remain.

[0008] Electrospray ionization is a preferred method for generating analyte ions for mass spectrometry (MS) and is particularly used in the mass spectrometric analysis of large molecules (such as biomolecules) and in the case of coupling a mass spectrometric analysis with upstream liquid chromatography (LC).

[0009] In practice, so-called "pulled emitters" are often used as spray nozzles for electrospray ionization. These emitters consist of thin-walled capillaries made of quartz glass (also called fused silica or FS) that are pulled to a fine point on the outlet side. The pulled points are very thin to increase the sensitivity for electrospray ionization.

[0010] A disadvantage of using pulled emitters for electrospray ionization is that pulling the outlet to a point reduces the inner diameter of the capillary channel carrying the analyte solution toward the outlet, making pulled emitters more susceptible to clogging. The problem of the increased risk of clogging with pulled emitters is further exacerbated for pulled emitters intended for use in nano-electrospray ionization (nano-ESI), since pulled emitters for nano-ESI already inherently feature a very small inner diameter for the analyte solution channel.

[0011] An alternative to pulled emitters are spray heads for electrospray ionization, which can be attached to the end of a line carrying analyte solution, for example, to the end of a liquid chromatography (LC) column. Electrospray ionization spray heads also have (in addition to an inlet for the analyte solution) a spray nozzle, which can be obtained by methods other than pulling a glass capillary; for example, using an injection molding process or through mechanical processing steps. See, for example, document US 10,591,451 B2.

[0012] Spray heads for electrospray ionization, however, typically have the disadvantage that the outer diameter of the outlet or the tip of the spray nozzle must have a minimum size and cannot be chosen arbitrarily small. This is because, on the one hand, the channel of the spray nozzle carrying the analyte solution must also have a certain minimum inner diameter at the outlet. Additionally, the wall of the spray nozzle must have a certain minimum thickness due to the channel at the outlet for stability and manufacturing reasons. A wider outer diameter of the outlet, however, adversely affects the shape of the Taylor cone and the achievable sensitivity for electrospray ionization.

[0013] US 2004 / 0113068 A1 discloses a microfluidic chip for mass spectrometric analysis comprising an electrospray ionization tip that can taper to a pointed edge at its end. The problem with such a configuration is that the edge forming at the end of the tip is still relatively wide, and the tip has multiple edges, each of which can form a Taylor cone in an uncontrolled manner (i.e., the ultimate position and number of Taylor cones forming at the tip during electrospray ionization can be poorly predicted and controlled).

[0014] In light of the aforementioned disadvantages of the prior art, a primary object of the present invention was to provide spray heads for (nano-)electrospray ionization with which improved sensitivity for electrospray ionization can be achieved. A further object of the present invention was to provide a method for producing such spray heads.

[0015] Further objects arise from the following description and the patent claims.

[0016] The primary object of the present invention is achieved by a spray head for electrospray ionization (ESI), comprising: an inlet for fluids, in particular for liquids; and a spray nozzle comprising an outlet for fluids, in particular for liquids, and comprising a channel through which the inlet is connected to the outlet of the spray nozzle; wherein the outlet of the spray nozzle is designed and positioned such that at least a portion of the fluid emerging from the outlet flows along the outer surface of a partial section of the spray nozzle (adjoining the outlet or projecting beyond the outlet) designed as a conically tapered tip before spatially separating (separating) from the spray nozzle.

[0017] By giving the fluid emerging from the outlet of the spray nozzle the opportunity to flow along the outer surface of a section of the spray nozzle designed as a conically tapered tip before separating from the spray nozzle, the location for the formation of the Taylor cone is shifted from the outlet to this section of the spray nozzle. Since the section designed as a conically tapered tip does not necessarily have to have an internal channel, but can, for example, also have a compact structure, the thickness of the tip that can be realized for this section at the end of the section is not necessarily limited by the presence of an internal channel, but can be made significantly thinner and finer. By being able to design a significantly thinner tip for this section and shifting the location for the formation of the Taylor cone to this tip (orBy focusing the tip (to the end of this tip), the formation of a smaller Taylor cone can ultimately be achieved, thereby improving the ionization process. The tapered shape of the tip also avoids any corners and edges at the tip, where unwanted and uncontrolled ionization could otherwise occur before reaching the end of the tip. On the contrary, shaping the section in question as a tapered tip allows the targeted concentration of the location for the formation of a Taylor cone, and thus the ionization process during electrospray ionization, to precisely the end point of this tapered tip.

[0018] The section designed as a conically tapered tip is preferably made of the same material as the rest of the spray nozzle and the spray nozzle including this section is preferably made of one piece (monolithic).

[0019] The design of the sub-section described above, designed as a conically tapered tip, can be realized, for example, by positioning the outlet of the spray nozzle not (centrally) at the end of the spray nozzle, but instead (off-centrally) on the side of the spray nozzle, or in other words, at a point on the outer conical surface of the conically tapered tip. Within the scope of the invention, it is expressly pointed out that the sub-section described above and in the claims - which usually adjoins the outlet or projects beyond the outlet - along which at least a portion of the fluid emerging from the outlet flows along the surface before being separated from the spray nozzle, is to be distinguished from designs in which the outlet is located at the end of a spray nozzle and is merely designed as an oblique ground section, as for example in Fig. 16 of DE 202 10 784 U1 or in Fig.5 of US 2022 / 0328300 A1. Consequently, a spray nozzle having only one outlet with a beveled cut at its end does not, within the meaning of the invention, have a further section (usually projecting beyond the outlet) described above, along the surface of which the fluid emerging from the outlet can flow before being separated from the spray nozzle.

[0020] The difference observed during operation of a merely obliquely ground outlet at the end of a spray nozzle compared to the inventive design described above is that with a merely obliquely ground outlet at the end of a spray nozzle, the formation of the Taylor cone still occurs directly at the outlet (as shown, for example, in Fig. 5 of US 2022 / 0328300 A1), and the size of the Taylor cone in this case continues to be influenced by the dimensions of the outlet and its wall. A shift in the formation of the Taylor cone away from the outlet towards another (preferably more pointed or thinner) area of ​​the spray nozzle therefore does not occur with the outlets known from the prior art at the end of a spray nozzle with an oblique ground outlet.

[0021] As already mentioned above, the section designed as a conically tapered tip, along whose surface the fluid exiting the outlet or the analyte solution exiting the outlet flows before being separated from the spray nozzle, has a shape that tapers towards its end, preferably to a tip that is as thin as possible. A spray head according to the invention is preferred, wherein the section of the spray nozzle designed as a conically tapered tip has an outer diameter of less than 15 pm, preferably less than 10 pm, particularly preferably 5 pm or less, at its end.

[0022] Preferably, the distance between the outlet and the end of the section of the spray nozzle designed as a conically tapered tip is as small as possible in order to keep the path that a fluid emerging from the outlet has to travel to the end of the tip as short as possible. A shorter path length between the outlet and the end of the tip increases the probability that as much fluid emerging from the outlet as possible reaches the end of the tip and is available there for the electrospray ionization process. Preferably, the distance between the outlet and the end of the section of the spray nozzle designed as a conically tapered tip in the horizontal direction is less than 40 pm, more preferably less than 30 pm, most preferably less than 20 pm, in each case measured from the center point of the outlet to the center point of the end of the tip.

[0023] Within the scope of the preferred embodiment of the invention described above, the spray nozzle can also have several such sections designed as conically tapered tips, toward which the fluid emerging from the outlet can flow, so that the overall flow of fluid or analyte solution can be distributed across several such tips and thus reduced for each tip, which in turn has a positive effect on the size of the Taylor cone and the efficiency of ionization. Because each of these sections designed as conically tapered tips has a specific endpoint, the location for the formation of the Taylor cones can nevertheless be determined and controlled in a controlled manner, even when several such sections are present.

[0024] The outlet or the section adjoining the outlet and formed as a conically tapered tip is preferably shaped such that the fluid exiting the outlet or the analyte solution exiting the outlet can flow in the best possible way along the outer surface of the section of the spray nozzle adjoining the outlet and formed as a conically tapered tip.

[0025] A spray head according to the invention is preferred, wherein the section of the spray nozzle designed as a conically tapered tip has a depression (e.g. in the form of a groove) in its surface, via which the fluid emerging from the outlet can be guided in the direction of the end of the section of the spray nozzle designed as a conically tapered tip, wherein the depression (groove) preferably runs from the outlet of the spray nozzle to the end of the section of the spray nozzle designed as a conically tapered tip.

[0026] Such a depression or groove advantageously supports the transfer of the fluid emerging from the outlet or the analyte solution emerging from the outlet to the end of the section designed as a conically tapered tip and the formation of a Taylor cone at precisely this end of the tip. The depression or groove is preferably designed without sharp edges, e.g. with smooth or rounded transitions, in order to prevent uncontrolled ionization events on the path from the outlet to the tip of the spray nozzle. A spray head according to the invention is preferred, wherein the spray nozzle as a whole has an outer shape that tapers towards the outlet of the spray nozzle (at least in sections), wherein the spray nozzle preferably has an outer shape that tapers towards the outlet.

[0027] A tapered or conical shape is preferably chosen for the stability of the spray nozzle. Since it is sufficient to create the smallest possible Taylor cone if only the area of ​​the spray nozzle where the fluid or analyte solution separates from the spray nozzle and forms a Taylor cone is designed as thin and fine as possible, the other areas of the spray nozzle are preferably designed wider to increase the stability and mechanical resistance of the spray nozzle.

[0028] A spray head according to the invention is preferred, wherein the spray nozzle comprises a cylindrical section at the end of the conically tapered tip. The cylindrical section preferably has a length in the range of 50 pm to 200 pm, particularly preferably in the range of 100 pm to 200 pm. The cylindrical section further distances the liquid emerging from the outlet from the wall of the spray nozzle before it is spatially separated from the spray nozzle, while simultaneously maintaining sufficient stability for the spray nozzle.

[0029] Preferably, the spray nozzle tapers (at least in sections) with an inclination in the range of 5 to 15°, preferably with an inclination in the range of 10 to 15°. Inclinations of 15° (or even more) can be achieved primarily in those cases or areas in which the tip or the final section of the spray nozzle, designed as a conically tapered tip, has a compact structure (without an internal channel).

[0030] A spray head according to the invention is preferred, additionally comprising a protective structure for protecting the spray nozzle from mechanical damage, which protective structure extends in particular laterally of the spray nozzle, which further preferably extends laterally of the spray nozzle up to at least the height of the outlet, and which is preferably spaced from the spray nozzle.

[0031] Due to its often delicate design, the spray nozzle requires special protection. Particularly in embodiments in which the spray nozzle is made of a fragile material, such as glass, and / or the spray head is designed to be particularly fine due to its intended use for nano-ESI, the presence of a protective structure on the spray nozzle can offer protection against mechanical damage and, for example, make handling the spray head significantly easier. A spray head according to the invention is preferred, wherein the protective structure has at least the same height as the spray nozzle (i.e., the end orthe tip of the spray nozzle does not protrude beyond the protective structure) and / or the spray nozzle is at least partially surrounded by the protective structure and / or the protective structure comprises a plurality of segments which are arranged (at least partially) around the spray nozzle, wherein there is preferably a space (or gap) between each of the segments of the protective structure arranged around the spray nozzle.

[0032] A protective structure that is at least the same height as the spray nozzle serves the specific purpose of protecting the typically most sensitive front part of the spray nozzle from possible mechanical damage, or at least reducing the risk of such damage. For example, such a protective structure may, under certain circumstances, allow the spray head to be placed on a surface with the protective structure and spray nozzle facing forward without necessarily causing the tip of the spray nozzle to break off or become bent.A protective structure which has at least the same height as the spray nozzle differs from conventional protective structures known from the prior art, which (for example as disclosed in US 10,591,451 B2) are often only intended to better grip the spray head and therefore usually only extend around the spray head, but not at least to the same height as the spray nozzle or even beyond.

[0033] Since the protective structure is primarily intended to protect the spray nozzle, it is also advantageous if the spray nozzle is at least partially surrounded by the protective structure. In this context, it is not absolutely necessary for the protective structure to completely surround the sides of the spray nozzle. In most cases, a sufficient protective function is already achieved if the spray nozzle is at least partially surrounded by the protective structure, so that, for example, when gripping the spray head with tweezers, the tweezers do not come into contact with the spray nozzle, but with the protective structure that at least partially surrounds the spray nozzle. The protective structure that surrounds the spray nozzle can, for example, have holes or recesses. Additionally or alternatively, the protective structure surrounding the spray nozzle can also comprise a plurality of segments, between which there is a space or gap.

[0034] A protective structure surrounding the spray nozzle, which is not completely closed, offers the overall advantage that it can direct a gas flow towards the spray nozzle, which preferably flows coaxially to the aerosol originating from the spray nozzle and which supports the spraying process itself and / or the ionization. Such a gas flow directed towards the spray nozzle can, for example, function as a sheath gas. The generation of a gas flow at or around the spray nozzle can be achieved both by actively supplying a gas to the spray nozzle and by the suction effect emanating from a negative pressure source located near the spray head (such as an inlet to a mass analyzer located near the spray head).

[0035] For the effective inflow of gas through gaps in the protective structure toward the spray nozzle, the greatest possible distance between adjacent segments of the protective structure is advantageous. The greatest possible distance between adjacent segments of the protective structure also promotes the drainage of any liquid that may precipitate around the spray nozzle during electrospray ionization. The distance between adjacent segments of the protective structure is preferably at least one millimeter.

[0036] The inflow of a gas stream toward the spray nozzle can be further enhanced and optimized by further technical configurations of the spray head and its protective structure. In this context, a spray head according to the invention is preferred, wherein the sides of the spray head or the base body of the spray head are at least partially beveled, preferably in the areas of the spaces between segments of the protective structure arranged around the spray nozzle. Such beveling of the sides of the spray head further enhances the delivery of a gas stream to the spray nozzle.

[0037] If segments of the protective structure are arranged around the spray nozzle with spaces between the segments, connecting pieces can preferably be located between adjacent segments, which are preferably designed in a streamlined manner and by means of which a gas flow to be guided to the spray nozzle can be additionally influenced. Additionally or alternatively, the walls of segments of the protective structure arranged around the spray nozzle can also have bulges for influencing a gas flow to be guided to the spray nozzle. Preferably, one or more edges of the protective structure are rounded. Rounding the edges of the protective structure (and preferably other edges of the spray head) has the effect that any liquid or gas that comes close to the protective structure is deflected.This makes it more difficult for the analyte solution to attach to the surface and reduces the probability that uncontrolled ionization of molecules occurs at the edges of the protective structure (i.e., the edges of the protective structure serve as a starting point for the formation of further Taylor cones without any control).

[0038] Uncontrolled ionization at any point on the spray head has the disadvantage that it can result in signals that are difficult to define during further analysis of the generated ions, and it can also lead to excessive space charge in the area of ​​the spray head, which impairs the actual ionization at the spray nozzle. The rounded edges of the protective structure also ensure that any gas that is to be directed to the spray nozzle and bypasses the protective structure reaches the spray nozzle more effectively and with less turbulence.

[0039] If segments of the protective structure are arranged around the spray nozzle, the segments of the protective structure preferably taper toward the spray nozzle. Such a taper has a beneficial effect on the supply of a gas flow toward the spray nozzle and also ensures that any liquid that may separate around the spray nozzle during electrospray ionization can flow more easily out of the spray head. At the same time, this maintains a stable and resilient structure for the segments of the protective structure.

[0040] A spray head according to the invention is preferred, wherein the base of the spray head, on which one or more spray nozzles are located, is designed to slope downwards from the one or more spray nozzles toward the outer sides of the spray head. Such a slope toward the outer sides of the spray head also promotes efficient drainage of any liquid that may precipitate around the spray nozzle during electrospray ionization.

[0041] The protective structure is preferably as far apart as possible from the outlet or from the tip of the spray nozzle (preferably a distance of at least 600 μm, particularly preferably a distance of at least 800 μm) in order to minimize any contact of fluid emerging from the outlet or analyte solution emerging from the outlet with the protective structure, wherein the protective structure must of course also be designed and positioned in such a way that it can adequately protect the spray nozzle from mechanical damage. In order to reconcile both concerns, a spray head according to the invention is preferred, wherein the wall or walls of the protective structure facing the spray nozzle are tapered in the direction of the outlet and / or the tip of the spray nozzle. This results in a greater distance between the protective structure and the outlet orthe tip of the spray nozzle while maintaining the highest possible stability of the protective structure.

[0042] A spray head according to the invention is preferred, wherein the inlet and the spray nozzle of the spray head, preferably the inlet, the spray nozzle and the protective structure of the spray head, particularly preferably the entire spray head, is or are made from one piece (monolithic).

[0043] Manufacturing as many spray head components as possible from a single piece offers the significant advantage of avoiding joints that could represent weak points in the spray head's structure. Monolithic manufacturing thus increases the stability of the spray head. Furthermore, monolithic manufacturing of as many spray head components as possible simplifies the production of the spray head itself, as it eliminates the need to join the individual spray head components (which vary on a micrometer scale). Monolithic manufacturing can also significantly increase the precision of the spray head's manufacturing and dimensions, as it eliminates any undesirable misalignment when connecting individual components.

[0044] A spray head according to the invention is preferred, wherein the inlet and the spray nozzle of the spray head, preferably the inlet, the spray nozzle and the protective structure of the spray head, particularly preferably all parts of the spray head made from one piece (monolithic), very particularly preferably the entire spray head, is or are obtained by selective laser-induced etching (Selective Laser-induced Etching, SLE) or by two-photon polymerization (2PP).

[0045] Selective laser-induced etching (also known as SLE) is a two-step manufacturing process for producing complex 3D components from transparent materials such as glass or sapphire. In a first step, ultrashort-pulsed laser radiation is focused into the volume of the transparent workpiece. The pulse energy is absorbed only in the focal volume through a multiphoton process. There, the transparent material is modified without cracking, altering its chemical properties. This allows for subsequent selective chemical etching of the material. By deflecting the focus in the workpiece with a micro-scanning system, contiguous areas of the workpiece to be processed are modified.The areas modified by the focus deflection in the workpiece can be selectively removed by wet-chemical etching in a second process step. This is because the areas modified by laser radiation exhibit a sensitivity and solubility that is many times higher (for example, by a factor of 1000) than unmodified areas compared to conventional wet-chemical etching agents (such as highly concentrated KOH solution). In this way, microchannels and fine, complex structures, for example, can be realized with high precision and reproducibility in materials with high chemical and high temperature resistance, such as quartz glass.

[0046] Two-photon polymerization (2PP) is a high-precision additive manufacturing technology that enables the high-resolution 3D printing of virtually any micro-, meso-, and macroscale structure with submicrometer features and extremely high dimensional accuracy. Two-photon polymerization (also known as two-photon or multi-photon lithography or direct laser writing) utilizes the fundamental physical effect of two-photon absorption. Two-photon absorption occurs when an atom or molecule absorbs two photons simultaneously, allowing it to enter a higher energy state. The medium is typically a liquid resin, which is light-sensitive and can be cured by UV light. 2PP printing uses lower-energy light, e.g.in the near-infrared (NIR) range, which only solidifies the printing material when the molecules of the photopolymer present simultaneously absorb the energy of two photons. This mechanism is only possible in the focal volume of pulsed light, as it requires a high light intensity within a volume of the photosensitive material.

[0047] Using selective laser-induced etching (SLE) and two-photon polymerization (2PP), spray heads for (nano-)electrospray ionization can be manufactured. These can not only be produced quickly and cost-effectively, but also feature microchannels with reproducible and uniform inner diameters that are particularly suitable for nano-electrospray ionization, which are ideal for low-clogging guidance of analyte solution to the spray nozzle outlet. SLE also allows for the production of such precisely and reproducibly manufactured ESI spray heads from a thermally and chemically highly resistant material such as quartz glass.

[0048] Neither the uniformity nor the reproducibility of the channel dimensions and other dimensions of the spray heads manufactured using SLE or 2PP, and in particular of the spray nozzles thereof, can be achieved with conventional manufacturing methods used for the production of ESI spray heads.

[0049] By using SLE or 2PP for, among other things, the production of the spray nozzle of the spray head according to the invention, the spray head or the spray nozzle of the spray head is given special technical properties that cannot be achieved otherwise. For example, mechanical processing methods, particularly in the field of glass or plastics processing, cannot achieve the uniform microchannel structures that are possible with SLE or 2PP.The spray head according to the invention is already distinguished from the spray heads disclosed in US 10,591,451 B2 by the fact that only certain materials can be processed by means of SLE and 2PP - such as, for example, glass or sapphire in the case of SLE and, in the case of 2PP, liquid photopolymers that can be cured by means of 2PP, such as, for example, epoxies, hybrid polymers and hydrogels suitable for 2PP - (i.e., for example, the spray nozzle of a spray head according to the invention must necessarily consist of a material that can be processed by means of SLE or 2PP), whereas in US 10,591,451 B2 only spray heads or spray nozzles made of a material that cannot be processed by means of SLE or 2PP are disclosed.

[0050] Due to the particular precision and reproducibility associated with manufacturing using SLE or 2PP, and the simultaneous fast, simple, and cost-effective production achievable using SLE or 2PP, as many spray head components as possible are preferably obtained this way. Furthermore, manufacturing as many spray head components as possible using the same manufacturing method simultaneously offers the possibility of producing as many components as possible from a single piece, thus benefiting from the advantages of monolithic manufacturing of multiple components explained above. Monolithic manufacturing of one or more spray head components can be achieved simply and easily, both with SLE and 2PP spray head manufacturing.

[0051] A spray head according to the invention is preferred, wherein the inlet and the spray nozzle of the spray head, preferably the inlet, the spray nozzle and the protective structure of the spray head, particularly preferably all parts of the spray head manufactured from one piece (monolithic), very particularly preferably the entire spray head, consists or consist of glass, diamond, sapphire or a cured photopolymer (for example an epoxy, hybrid polymer or hydrogel), preferably of a glass selected from the group containing or consisting of quartz glass (fused silica, FS), borosilicate glass and aluminosilicate glass, particularly preferably of quartz glass. All of the aforementioned materials are advantageously predestined for the production of an ES I spray head. The use of glass and in particular quartz glass offers particular advantages due to its extremely high chemical resistance and temperature resistance.

[0052] The inlet of a spray head according to the invention is preferably designed and configured to accommodate or attach a chromatography column for liquid chromatography (LC column), particularly preferably for nano-liquid chromatography (nano-LC column). For this purpose, the spray head preferably has a recess into which the end of a (nano-)LC column can be guided to the inlet of the spray head, as far as possible while avoiding dead volume. For a permanent and secure hold between the (nano-)LC column and the spray head, the end of a (nano-)LC column is preferably fixed to the spray head according to the invention using an adhesive connection. Epoxy resin adhesives, for example, are suitable for creating the adhesive connection.

[0053] A spray head according to the invention is preferred, wherein the spray head has a recess for attaching a supply line (for example, for attaching the end of an LC column) to the inlet. The recess is typically designed such that the supply line can be inserted precisely into it and guided to the inlet. However, the recess preferably has a widening in the direction of the inlet, so that the diameter of the recess at the inlet is preferably larger than the outer diameter of the supply line to be inserted into the recess. It has been shown that such a widening of the recess in the direction of the inlet or at the inlet has an advantageous effect on the connection of the supply line to the inlet and contributes to reducing the dead volume at the connection point between the supply line and the inlet.

[0054] Preferably, the inner diameter of the spray head inlet is smaller than the inner diameter of a supply line (for example, smaller than the inner diameter of the LC column connected to the spray head), through which a fluid or analyte solution is fed into the inlet. By selecting an inlet that is smaller than the supply line, the flow rate applied to the spray head during operation can be influenced and reduced. This ultimately has advantages in terms of finer spraying of the analyte solution and ultimately has a positive effect on the sensitivity achievable with the spray head when using electrospray ionization (ESI) as an ion source for ion spectrometric investigations, in particular ion mobility analyses, mass analyses, or combined ion mobility-mass analyses.Choosing the smallest possible inner diameter for the spray nozzle inlet (and for the channel connecting the inlet to the spray nozzle outlet) also supports the smallest possible Taylor cone during electrospray ionization (ESI), which contributes to improving ionization performance. Manufacturing the inlet using SLE or 2PP offers the possibility of easily and reproducibly realizing such a smaller inner diameter of the inlet (and channel) compared to the size of the supply line. Furthermore, the inner diameter of the inlet can be easily and flexibly adapted and modified depending on the type and size of the supply line.

[0055] A spray head according to the invention is preferred, wherein the inlet of the spray head is designed such that the entry of particles into the channel that could cause a blockage of the channel connecting the inlet and outlet is prevented, while at the same time the flow of fluids or analyte solution into the channel is ensured. The inlet of the spray head therefore preferably has, for example, a sieve-like structure through which larger particles that could cause a blockage of the channel are retained. In this context, the inlet preferably has openings of different sizes (which are each smaller than the inner diameter of the channel) so that, for example, any larger particles can become trapped in the larger openings and be prevented from flowing further, while at the same time further fluid or analyte solution can enter the channel through the further, smaller openings through the inlet.Preferably, the various openings at the inlet have different shapes. In a particularly preferred embodiment, the inlet has a larger opening in its center (e.g., in the shape of a circle) to retain and trap any particles, and one or more smaller openings (e.g., in the shape of rectangles or squares) around this central opening to ensure continued flow of fluid or analyte solution in the event of the central opening becoming blocked.

[0056] A spray head according to the invention is preferred, wherein the inner diameter of the channel of the spray nozzle (through which the inlet is connected to the outlet of the spray nozzle) is substantially the same over its entire length, wherein the inner diameter of the channel of the spray nozzle over its entire length particularly preferably fluctuates only within the error tolerance customary within the scope of SLE or 2PP.

[0057] The channel encompassed by the spray nozzle, through which the inlet is connected to the outlet of the spray nozzle, can also extend over other regions of the spray head; however, within the scope of the invention, its extent can alternatively be limited solely to the area of ​​the spray nozzle. If the channel through which the inlet is connected to the outlet of the spray nozzle also extends beyond the spray nozzle, this part of the channel extending beyond the spray nozzle preferably also has largely the same inner diameter, particularly preferably an inner diameter that is the same within the error tolerance typical for SLE or 2PP, as the remaining part of the channel.

[0058] Depending on the design of the channel connecting the inlet and outlet of the spray nozzle, the inlet of the spray head intended for fluids, in particular for analyte solution, can be located either directly on the spray nozzle or at another location on the spray head.

[0059] As already noted above, the spray head according to the invention is intended for use in nano-electrospray ionization (nano-ESI) and accordingly has the usual and suitable designs and dimensions for use as an ESI spray head or nano-ESI spray head. A spray head according to the invention is preferred, wherein the outer diameter and / or the height of the spray head is in the range from 500 pm to 2000 pm, preferably in the range from 1000 pm to 1500 pm, and / or the channel through which the inlet is connected to the outlet of the spray nozzle has a length in the range from 50 pm to 2000 pm, preferably in the range from 500 pm to 1000 pm, and / or the channel through which the inlet is connected to the outlet of the spray nozzle has an inner diameter in the range from 5 pm to 50 pm, preferably in the range from 10 pm to 20 pm, particularly preferably in the range from 15 pm to 20 pm,and / or the spray nozzle has a length in the range of 100 pm to 500 pm, preferably in the range of 250 pm to 300 pm, and / or the recess for attaching a supply line to the inlet has a diameter in the range of 200 pm to 1000 pm, preferably in the range of 350 pm to 500 pm, and / or the spray nozzle at the outlet has an outer diameter in the range of 15 pm to 50 pm, preferably in the range of 20 pm to 40 pm, particularly preferably in the range of 30 pm to 40 pm.

[0060] The above preferred dimensions have proven to be particularly advantageous for a spray head according to the invention.

[0061] Within the scope of the present invention, a spray head can also have more than one spray nozzle. Therefore, a spray head according to the invention is preferred, wherein the spray head comprises more than one spray nozzle, preferably two, four, eight, or twelve spray nozzles.

[0062] The presence of multiple spray nozzles can offer various advantages. For example, the flow of fluid or analyte solution coming from a supply line can be distributed among multiple spray nozzles, so that the flow rate at the spray nozzles, particularly at the spray nozzle outlets, can be influenced and reduced compared to the flow rate at the supply line or at the spray head inlet. Implementing different flow rates at the spray head inlet and the spray nozzle outlets is advantageous because a somewhat higher flow rate is generally desired near the inlet (to minimize the effects of any dead volume present at the inlet), while a lower flow rate is generally desired at the outlets (since a lower flow rate has a positive effect on the achievable ionization rate at a spray nozzle).The presence of several spray nozzles thus makes it possible, for example, to achieve a flow of 1 pL / min at the supply line or inlet and, at the same time, a flow of 250 nL / min (in the case of 4 spray nozzles) or 100 nL / min (in the case of 10 spray nozzles) at the outlets.

[0063] The presence of several spray nozzles also enables the controlled generation of several ionization centers.

[0064] In the case of multiple spray nozzles, usually and preferably all spray nozzles are protected by the protective structure.

[0065] If there are several spray nozzles, their outlet can each be connected to an inlet for fluids or analyte solution by a separate channel. However, it is also possible for several or all spray nozzles to share a central section of a channel, which branches off on the way to the spray nozzles, and for several or all spray nozzles to be connected to a branch of this channel. If a central section of a channel branches, the branches usually have a smaller inner diameter than the central section of the channel in order to at least prevent the flow velocity from dropping too sharply. In such preferred embodiments, the central section of the channel preferably comprises a constriction and / or a sieve-like structure at at least one point, wherein the maximum extent orThe diameter of the largest opening at the constriction and / or sieve-like structure is preferably smaller than the maximum extension or the inner diameter of the branches. This prevents any blockage in one of the branches by previously retaining particles that could cause such a blockage in the central section of the channel. The constriction and / or sieve-like structure is designed (for example, by the presence of several, preferably differently sized, openings in the sieve-like structure) such that the entrapment of a particle at this constriction and / or sieve-like structure does not usually lead to a complete blockage of the central section of the channel.

[0066] In the case of multiple spray nozzles, these are preferably arranged at a largely uniform distance from one another around a central point, preferably around the center point, of the spray head. In the case of three, four, or more than four spray nozzles, these are arranged, for example, at the corners of an imaginary equilateral triangle, square, or quadrilateral. At least one segment of the protective structure is preferably also located in the center of multiple spray nozzles, in particular laterally and spaced from this arrangement of multiple spray nozzles.

[0067] In the case of multiple spray nozzles, the distance between adjacent spray nozzles is preferably in a range between 300 pm and 400 pm, measured from the respective center of the outlet of adjacent spray nozzles or measured from the respective center of the spray nozzle tip. Such a preferred distance between adjacent spray nozzles contributes to the efficient formation of a Taylor cone at the outlets or tips of the multiple spray nozzles.

[0068] If multiple spray nozzles are present, these preferably have an extended support leg at their end facing the base of the spray head, which creates space for a more flexible design of the course of the channels connecting the inlet and outlet of a spray nozzle. This makes it possible, for example, to avoid right angles in a channel guide, which require greater production effort and lead to a greater susceptibility of a channel to blockages during operation of the spray head. The reduction of the flow from the supply line or inlet to the outlet of the one or more spray nozzles can also be achieved in other ways. A spray head according to the invention is preferred, wherein the spray head has a bypass line for branching off a portion of the flow reaching the inlet of the spray head.Using such a bypass line, the flow arriving at the spray nozzle outlet can also be significantly reduced, for example, if only one spray nozzle is present. The flow diverted via the bypass line is typically not reused but instead directed into a drain or waste container.

[0069] A spray head according to the invention is also preferred, wherein the spray head or spray nozzle additionally comprises a channel for supplying solvent to the channel connecting the inlet and outlet of the spray nozzle or for supplying solvent to the outlet of the spray nozzle. In other words, the channel for supplying solvent can be connected both to the channel that connects the inlet and outlet of the spray nozzle and also end directly at the outlet of the spray nozzle, for example via a separate additional outlet. The purpose of such an additional channel for supplying solvent is, among other things, that fluids or analyte solutions which originate from liquid chromatography in particular often have a high proportion of protic solvents (such as water), which have a negative effect on ionization by means of ESI. In order to ensure the ionization of such a fluid orTo improve the ionization of such an analyte solution, an aprotic solvent (such as acetonitrile) can be added through the solvent supply channel. In this way, for example, the concentration of an analyte solution originating from liquid chromatography, which often has an aprotic solvent concentration in the range of 5-35%, can be increased to, for example, 50-70% before ionization, thereby significantly improving the ionization potential of the analyte solution.

[0070] As already explained above, a uniform inner diameter of the channel through which the inlet is connected to the outlet of the spray nozzle - in particular one that does not taper towards the outlet - can help prevent blockages. Therefore, a spray head according to the invention is preferred, wherein the channel through which the inlet is connected to the outlet of the spray nozzle has a (largely) constant inner diameter. In preferred embodiments in which the channel has a central section and several branches, the branches leading to the outlet of a spray nozzle preferably each have a (largely) constant inner diameter.

[0071] A spray head according to the invention is preferred, wherein the spray head is a spray head for nano-electrospray ionization (nano-ESI) and / or is designed and suitable for setting flow rates of less than 1000 nL / min, preferably less than 250 nL / min, particularly preferably less than 10 nL / min.

[0072] Also preferred is a spray head according to the invention, wherein the spray head is designed and suitable for setting flow rates of less than 10,000 nL / min.

[0073] Preferably, the spray head is designed and suitable for setting flow rates of less than 1000 nL / min, preferably less than 250 nL / min, particularly preferably less than 10 nL / min, depending on the spray nozzle present on the spray head.

[0074] Nano-ESI is particularly characterized by the realization of lower flow rates at the spray nozzle outlets, which can be achieved, for example, by smaller dimensions of the outlets and the one or more channels connecting the outlet to the spray head inlet, and / or by other measures, such as splitting the amount of analyte solution coming from the supply line (as explained in various ways above). The advantage of implementing nano-ESI lies in the achievement of higher sensitivity.

[0075] A spray head according to the invention is preferred, wherein the spray head additionally has a layer of a conductive material, preferably a metal layer, particularly preferably a layer comprising or consisting of gold or silver, and / or has a microstructure.

[0076] Preferably, the layer and / or microstructure mentioned is located on the outer (conical) surface of the spray nozzles of the spray head, but can also be located at other locations on the spray head and, for example, extend over the entire outer surface or the entire surface of the spray head. An additional layer of conductive material serves in particular to increase the conductivity of the spray nozzle (which, due to the preferred manufacturing method used for this purpose, is preferably made of glass or a photopolymer).

[0077] The microstructuring primarily serves to increase the hydrophobicity of the surface of the spray head, in particular the surface of the spray nozzles. Preferably, the surface of one or more spray nozzles of the spray head partially or completely has a sharkskin-like structure.

[0078] Part of the invention is also a method for producing a spray head according to the invention (as defined above and in the claims), comprising the following steps: a) producing or providing a blank or starting material for producing the spray head (or for producing the parts of the spray head made from one piece), b) processing the produced or provided blank or starting material, preferably using selective laser-induced etching (SLE) or two-photon polymerization (2PP), so that the inlet and the spray nozzle of the spray head, preferably the inlet, the spray nozzle and the protective structure of the spray head, particularly preferably all parts of the spray head to be made from one piece (monolithic), very particularly preferably the entire spray head, are obtained.

[0079] Part of the invention is also the use of a spray head according to the invention (as defined above and in the claims) for electrospray ionization (ESI), preferably for nano-electrospray ionization (nano-ESI) and / or for electrospray ionization at flow rates of less than 1000 nL / min, preferably less than 250 nL / min, particularly preferably less than 10 nL / min. After generation, the ions can be subjected to an ion spectrometric analysis method, in particular an ion mobility analysis, mass analysis, or combined ion mobility-mass analysis.

[0080] The invention also includes a chromatography column, preferably a chromatography column for liquid chromatography (LC), particularly preferably for nano-liquid chromatography (nano-LC), comprising a spray head according to the invention (as defined above and in the claims) at one end (or at the outlet) of the chromatography column. The invention also includes a device for performing electrospray ionization (ESI), preferably for performing nano-electrospray ionization (nano-ESI), comprising a spray head according to the invention (as defined above and in the claims) or comprising a chromatography column according to the invention (as defined above and in the claims).

[0081] A device according to the invention for performing electrospray ionization (ESI) is characterized (in addition to the presence of a spray head according to the invention) in particular by the fact that it comprises all the components required for performing ESI, such as a counter electrode (drawing voltage electrode). The device can be coupled to an ion spectrometric device, in particular an ion mobility analyzer, mass analyzer, or combined ion mobility-mass analyzer, for ion spectrometric analysis of the generated ions.

[0082] The invention will be explained in more detail below using exemplary embodiments and the accompanying drawings. The exemplary embodiments provided below are intended to describe and explain the invention in more detail without limiting its scope.

[0083] The elements in the accompanying drawings are not necessarily drawn to scale, but are primarily intended to illustrate (largely schematically) the principles of the invention. In the drawings, corresponding elements are designated by like reference numerals throughout the different views.

[0084] They show:

[0085] Figure 1: Illustration of a spray head according to the invention.

[0086] Figure 2: Representation of a cross-section of the spray head shown in Figure 1.

[0087] Figure 3: Front view of the cross-sectional drawing from Figure 2.

[0088] Figure 4: Enlarged view of the end of the spray nozzle of the spray head shown in Figure 1.

[0089] Figure 5: Representation of a cross-section of the spray nozzle shown in Figure 4.

[0090] Figure 6: Enlarged view of the inlet of the spray head shown in Figure 1. Figure 1 shows an example of a spray head 30 according to the invention, comprising an inlet for analyte solution 31 (see Figure 1, not visible in Figure 1) and a spray nozzle 32. The spray nozzle 32 has an outlet for analyte solution 321 and a channel 322 through which the inlet 31 of the spray head is connected to the outlet 321 (see Figure 1, the channel 322 is not visible in Figure 1). The spray nozzle 32 has an outer conical shape and tapers to a tip towards the outlet 321.

[0091] In the spray head 30 shown in Figure 1, the outlet 321 of the spray nozzle 32 is not located at the end of the spray nozzle 32, in other words, not at the cone tip or not at the location of the smallest diameter. Instead, the outlet 321 is positioned and configured such that at least a portion of the analyte solution exiting the outlet 321 flows along the outer surface of a partial section 323 of the spray nozzle 32, which adjoins the outlet 321 or protrudes beyond the outlet 321 and is designed as a conically tapered tip, to the end of the tip before being separated from the spray nozzle 32. Because the outlet 321 is not located at the tip of the spray nozzle 32, the conically tapered tip of the spray nozzle 32 can be manufactured more compact (without an internal channel) and thinner.As a result, a very small outer diameter of 5 pm can be realized for the tip end of the spray nozzle 32 shown in Figure 1, which brings with it the advantages described above with regard to the formation of a smaller Taylor cone at the tip and the improved ionization.

[0092] The spray head 30 shown in Figure 1 also includes a protective structure 33 to protect the spray nozzle 32 from mechanical damage. The protective structure 33 consists of a total of four individual segments arranged around the spray nozzle 32. Between the individual segments of the protective structure 33 there are gaps which (despite the height of the protective structure 33) allow the supply of a gas flow toward the spray nozzle 32 and its tip.

[0093] The protective structure 33 has rounded edges. This reduces the likelihood of unwanted ionization regions forming at the edges of the protective structure 33. Furthermore, the rounding of the edges of the protective structure 33 minimizes the occurrence of any turbulence during the inflow of gas through the gaps of the protective structure 33.

[0094] The inner walls of the segments of the protective structure 33 taper towards the tip of the spray nozzle 32, thereby creating a greater distance between the tip of the spray nozzle 32 and the protective structure 33 and at the same time maintaining the stability of the protective structure 33 and sufficient protection of the spray nozzle 32 by the protective structure 33.

[0095] In the spray head 30 shown in Figure 1, the outer wall of the spray head 30 is also flattened at those points where the gaps of the protective structure 33 are located. This further facilitates the supply of a gas stream toward the spray nozzle 32.

[0096] Figure 2 shows a cross-section of the spray head 30 shown in Figure 1. The cross-section provides a view of the channel 322, through which the inlet 31 of the spray head 30 is connected to the outlet 321 of the spray nozzle 32. The channel 322 is a microchannel with an inner diameter of 15 μm. The channel 322 has a uniform inner diameter over its entire length and thus, for example, does not taper toward the outlet 321.

[0097] Figure 2 also shows a recess 34 located in the lower portion of the spray head 30, which allows for easy and safe attachment of a supply line, such as an LC column (not shown), to the inlet 31 of the spray head 30.

[0098] Figure 3 shows a front view of the cross-sectional drawing from Figure 2, from which it is clearly visible that the protective structure 33 is designed higher than the spray nozzle 32 and ends only a little above the tip of the spray nozzle 32. As a result, the protective structure 33 provides a protective effect against mechanical damage, particularly for the upper part and the tip of the spray nozzle 32.

[0099] The cross-sectional drawings of the spray head 30 shown in Figure 1, shown in Figures 2 and 3, also allow the positioning and design of the outlet 321 of the spray nozzle 32 to be illustrated even better.

[0100] In the cross-sectional drawings of the spray head 30 shown in Figure 1, shown in Figures 2 and 3, it can also be seen that its recess 34 for attaching a supply line to the inlet 31 of the spray head 30 has a widening both in the lower area and in the upper area (in the area of ​​the inlet 31). The widening 341 in the lower area of ​​the recess 34 allows easier insertion of a supply line into the recess 34, and the widening 342 in the area of ​​the inlet 31 allows somewhat more play and flexibility when adjusting and attaching a supply line to the inlet 31, whereby an improved connection between the supply line and the inlet 31 with less dead volume can be achieved. Figure 4 shows an enlarged view of the end of the spray nozzle 32 of the spray head 30 shown in Figure 1. Figure 5 shows a cross-section of this enlargement.This also makes it clear that the partial section 323 of the spray nozzle 32, which adjoins the outlet 321 and is designed as a conically tapered tip, has a recess in its surface, via which the analyte solution emerging from the outlet 321 can be guided towards the end of the partial section 323 of the spray nozzle, which is designed as a conically tapered tip.

[0101] From the cross-sectional drawings shown in Figures 2 and 3, it can also be seen that the spray head 30 shown here has a sieve-like structure 35 at its inlet 31, which is intended to prevent the penetration of particles into the channel 322 connecting the inlet 31 and the outlet 321 of the spray nozzle 32, which particles could cause a blockage in the channel 322. Figure 6 shows an enlarged cross-sectional view of this sieve-like structure 35. The sieve-like structure 35 is designed such that it has a round opening in the center, from which several rectangular openings, each smaller in area (with a length of the two long sides of the rectangles of 5 μm each), branch off. The diameter of the round opening of the sieve-like structure 35 is smaller than the inner diameter of the channel 322 adjoining the sieve-like structure 35.The rectangular openings of the sieve-like structure 35 also each have a taper in depth, which extends over a length of 20 pm and via which the sieve-like structure 35, with its various openings, is adapted downstream to the size of the inner diameter of the channel 322 adjoining the sieve-like structure 35. The presence of such a sieve-like structure 35 has proven particularly advantageous for preventing blockages in the channel 322 of the spray head 30.

[0102] The spray head 30 shown in Figures 1 to 6 has preferred dimensions for a spray head according to the invention, which can be summarized as follows:

[0103] Height of spray head 30: 1000 pm;

[0104] Diameter of the spray head 30: 1500 pm;

[0105] Total height of recess 34: 300 pm;

[0106] Height of the widening 341 of the recess 34 in the lower area: 25 pm;

[0107] Height of the widening 342 of the recess 34 in the upper area: 40 pm;

[0108] Diameter of the recess 34 in the middle: 370 pm; widest diameter of the recess 34 in the lower area: 350 pm; widest diameter of the recess 34 in the upper area: 320 pm;

[0109] Height of spray nozzle 32: 550 pm; height of protective structure 33: 600 pm.

[0110] Of course, a spray head according to the invention can also have other dimensions suitable for suitability as an ESI spray head, in particular for suitability as a nano-ESI spray head.

[0111] The spray head 30 shown in Figures 1 to 6 is made entirely from a single piece of quartz glass and by means of SLE.

[0112] List of reference symbols:

[0113] 30 spray heads

[0114] 31 Inlet for fluids or analyte solution

[0115] 32 spray nozzle

[0116] 33 Protective structure to protect the spray nozzle

[0117] 34 Recess for attaching a supply line to the inlet of the spray head

[0118] 35 sieve-like structure at the inlet of the spray head

[0119] 321 Spray nozzle outlet

[0120] 322 Channel through which the inlet of the spray head is connected to the outlet of the spray nozzle

[0121] 323 Part of the spray nozzle adjoining the outlet or projecting beyond the outlet and designed as a conically tapered tip, over the outer surface of which at least a part of the analyte solution emerging from the outlet can flow to the end of the tip

[0122] 341 Widening in the lower area of ​​the recess

[0123] 342 Widening of the recess towards the inlet of the spray head

Claims

Patent claims:

1. A spray head for electrospray ionization, comprising: an inlet for fluids; and a spray nozzle comprising an outlet for fluids and comprising a channel through which the inlet is connected to the outlet of the spray nozzle; wherein the outlet of the spray nozzle is configured and positioned such that at least a portion of the fluid exiting the outlet flows along the outer surface of a portion of the spray nozzle configured as a tapered tip before spatially separating from the spray nozzle.

2. Spray head according to claim 1, wherein the section of the spray nozzle formed as a conically tapered tip has at its end an outer diameter of less than 15 pm, preferably less than 10 pm, particularly preferably 5 pm or less.

3. Spray head according to one of the preceding claims, wherein the section of the spray nozzle designed as a conically tapered tip has a recess in its surface, via which the fluid emerging from the outlet can be guided towards the end of the section of the spray nozzle designed as a conically tapered tip, wherein the recess preferably runs from the outlet of the spray nozzle to the end of the section of the spray nozzle designed as a conically tapered tip.

4. Spray head according to one of the preceding claims, additionally comprising a protective structure for protecting the spray nozzle from mechanical damage.

5. Spray head according to one of the preceding claims, wherein the protective structure has at least the same height as the spray nozzle and / or the spray nozzle is at least partially surrounded by the protective structure and / or the protective structure comprises a plurality of segments which are arranged around the spray nozzle, wherein there is preferably a space between each of the segments of the protective structure arranged around the spray nozzle.

6. Spray head according to one of the preceding claims, wherein the inlet and the spray nozzle of the spray head, preferably the inlet, the spray nozzle and the protective structure of the spray head, particularly preferably the entire spray head, is or are made from one piece.

7. Spray head according to one of the preceding claims, wherein the inlet and the spray nozzle of the spray head, preferably the inlet, the spray nozzle and the protective structure of the spray head, particularly preferably all parts of the spray head made from one piece, most particularly preferably the entire spray head, is or are obtained by selective laser-induced etching or by two-photon polymerization.

8. Spray head according to one of the preceding claims, wherein the inlet and the spray nozzle of the spray head, preferably the inlet, the spray nozzle and the protective structure of the spray head, particularly preferably all parts of the spray head made from one piece, very particularly preferably the entire spray head, consists or consist of glass, diamond, sapphire or a cured photopolymer, preferably of a glass selected from the group containing or consisting of quartz glass, borosilicate glass and aluminosilicate glass, particularly preferably of quartz glass.

9. Spray head according to one of the preceding claims, wherein the spray head comprises more than one spray nozzle, preferably two, four, eight or twelve spray nozzles.

10. Spray head according to one of the preceding claims, wherein the channel through which the inlet is connected to the outlet of the spray nozzle has a constant inner diameter.

11. Spray head according to one of the preceding claims, wherein the spray head is a spray head for nano-electrospray ionization and / or is designed and suitable for setting flow rates of less than 1000 nL / min, preferably less than 250 nL / min, particularly preferably less than 10 nL / min.

12. Spray head according to one of the preceding claims, wherein the spray head additionally a layer of a conductive material, preferably a metal layer, particularly preferably a layer comprising or consisting of gold or silver, and / or a microstructure.

13. A method for producing a spray head as defined in any one of claims 1 to 12, comprising the following steps: a) producing or providing a blank or starting material for producing the spray head, b) processing the produced or provided blank or starting material, preferably using selective laser-induced etching or two-photon polymerization, so that the inlet and the spray nozzle of the spray head, preferably the inlet, the spray nozzle and the protective structure of the spray head, particularly preferably all parts of the spray head to be manufactured from one piece, very particularly preferably the entire spray head, are obtained.

14. Use of a spray head as defined in any one of claims 1 to 12 for electrospray ionization, preferably for nano-electrospray ionization and / or for electrospray ionization at flow rates of less than 1000 nL / min, preferably less than 250 nL / min, particularly preferably less than 10 nL / min.

15. Chromatography column, preferably chromatography column for liquid chromatography, particularly preferably for nano-liquid chromatography, comprising a spray head as defined in any one of claims 1 to 12 at one end of the chromatography column.

16. Apparatus for performing electrospray ionization, preferably for performing nano-electrospray ionization, comprising a spray head as defined in any one of claims 1 to 12 or comprising a chromatography column as defined in claim 15.

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