EP1444048A1

EP1444048A1 - Focussed electrospray device

Info

Publication number: EP1444048A1
Application number: EP02803023A
Authority: EP
Inventors: Heike Klesper; Gregor FUSSHÖLLER
Original assignee: Carbotec Gesellschaft fur Instrumentelle Analytik Mbh
Current assignee: Carbotec Gesellschaft fur Instrumentelle Analytik Mbh
Priority date: 2001-11-14
Filing date: 2002-11-14
Publication date: 2004-08-11
Also published as: WO2003041869A1; DE20210784U1

Abstract

The invention relates to a device for the spraying of electrically charged fluids, a device for generation of an ion cloud with an aperture within the ion cloud and application of said devices in mass spectrometry. The aim of the invention is to produce a comparatively very fine electrospray with a spray cone having a comparatively small apex angle, in order to improve sensitivity on application in mass spectrometry. Said aim is achieved, whereby a charged fluid (1) is sprayed through an electric field to give an electrospray (5), the electrospray is diverted, or restricted in the extent thereof by means of a gas flow (2) or several gas flows, whereby the spraying point is not affected by the gas stream (2) the gas stream being thus not involved in the generation of the electrospray.

Description

Fused electrospray device

Description:

The invention relates to a device for spraying electrically charged liquids and uses of the device, for example in liquid analysis or mass spectrometry,

Devices for spraying and methods for liquid analysis are known for example from DE 1 00 07 498.7, DE 101 25 849.6 and DE 1 01 34 427.9. In electrospray devices, a liquid, e.g. a substance is placed in a suitable solvent at potential opposite a counter electrode and atomized. The solvent evaporates from the resulting charged drops and ions are released.These ions can be transferred to an analyzer and detected there or the sprayed substance reaches e.g. as a coating on a target.

Liquids can be atomized purely electrostatically, or also electrostatically and pneumatically atomized by gas (pneumatically assisted electrospray),

In the electrostatic electrospray device, the sample solution is sprayed only electrostatically. The solvent evaporates from the charged droplets formed and ions are released. Some of these ions pass through the inlet of the mass spectrometer and can be detected. The more ions are formed from the sample solution and the more of the ions formed reach the mass spectrometer, the higher the sensitivity of the analysis.

With the pneumatically assisted electrospray, the sample solution is not only atomized electrostatically. Although the solution is at electrical potential, it is also atomized by a gas stream; Exemplary embodiments are shown in US Patent 4,861,988. The gas stream flows around and along the tip or capillary from which the liquid is to be sprayed, and tears the liquid away from this spray point. The resulting drops are larger than with pure electrospray and therefore it takes longer to get out of these larger charged drops Ions are released. For this reason, the distance between the mass spectrometer inlet and the spraying point should be chosen larger in this case compared to the pure electrospray method. The sensitivity of detection can deteriorate compared to pure electrospray.

Another problem with both methods arises from the fact that the charged drops formed diverge from one another due to their Coulomb repulsion and a spray cone is formed. The larger the ratio of charge to drop volume, the greater the opening angle of the cone.

With the pneumatically assisted electrospray, the gas stream used for atomization envelops the cloud of drops of the same name and counteracts the dropping of the drops apart.The opening angle of the spray cone is therefore smaller (and due to the lower ratio of charge to drop volume) than with the pure one Electrospray, since the distance to the mass spectrometer inlet is larger, however, this does not lead to a higher density of released ions in front of the mass spectrometer inlet and thus to a higher detection sensitivity,

The aim is therefore to reduce the opening angle of the spray cone and still generate drops as small as possible with a high charge-to-drop volume ratio, from which ions are released after the shortest possible flight distance, i.e. the advantages of the above-mentioned methods get and avoid the associated disadvantages. ^• To solve the problem regarding the opening angle of the spray cone, an enveloping gas flow for the spray has already been provided If a spray cone is enveloped by a gas stream, it is restricted in its attempt to drift apart. This effect is stronger the higher the gas velocity. This increases the density of charged drops and thus of the ions released from them in comparison to a freely sprayed spray cone. With such systems, a slightly higher signal intensity can be achieved for low gas velocities in electrospray mass spectrometry (in which there is still no pneumatic atomization of the liquid). Exemplary embodiments can be found in: US Pat. No. 5,349, 1,866,

The disadvantage here is that the gas velocity is limited, since the enveloping gas flow additionally causes pneumatic atomization of the liquid at higher gas velocities; there is therefore a disadvantageous tearing off of the drops from the

Spraying points. There is therefore pneumatically assisted electrospray with the associated disadvantages mentioned above.

In a further method to reduce the spreading apart of the spray cone, the procedure is as follows, a spray is surrounded by closely adjacent sprays of the same name, the droplet clouds of the same name repel each other, a spray cone, which is surrounded by such droplet clouds of the same name surrounded is limited in its striving to strive apart. However, such a device is susceptible to interference,

In particular, if one of the enveloping sprays fails, the enveloped spray cone deflects in this direction.This reduces the density of charged drops and ions in the spray cone and changes its position, so that it no longer hits the inlet of the mass spectrometer and the signal as precisely adjusted in advance gets smaller or disappears, explanations can be found in: H. Klesper, G, Klesper, G. Fusshoeller, Proc. 48th Conf, on Mass Spectrometry and Allied Topics, Long Beach, CA, June 1 1-15, (2000); M. Wilm, J. Käst, Proc, 48th Conf, on Mass Spectrometry and Allied Topics, Long Beach, CA, June 1 1 -1 5, (2000); GA Schultz, TN Corso, SJ Prosser, Proc, 49th Conf. on Mass Spectrometry and Allied Topics, Chicago, IL, May 27-31, (2001); K. Tang, Y, Lin, D, W, Matson, T, Kim, RD Smith, Proc, on 49th Conf, on Mass Spectrometry and Allied Topics, Chicago, IL, May 27-31, (2001) AJ, Rulison, RC, Flagan, Rev, Be. Instum. 64 (3), (1 993), 683-686

The object of the invention is to provide an electrospray device, for example for mass spectrometry, in which, as in the prior art mentioned at the outset, a comparatively very fine electrospray is generated with a spray cone with a comparatively small opening angle, for example when used in mass spectrometry compared to the prior art technology to improve sensitivity,

The object of the invention is achieved by a device with the features of the first claim. Advantageous refinements result from the subclaims.

The device according to the invention for spraying electrically charged liquids has at least one tip or capillary from which the charged liquid is sprayed,

The liquid that is atomized is electrically charged. This

Liquid can, for example, be sufficiently electrically charged by itself.

Means can also be used to charge the liquid (e.g. by ionizing radiation), i.e. means to change the electrical potential of the liquid, as a result of which the liquid is electrically charged. The number of positive or negative electrical

So charge carriers are changed by these means

The means for changing the electrical potential of the liquid in the aforementioned manner are, for example Electrode that the liquid is directed past. The liquid is charged electrochemically by the aforementioned means. This works particularly well, for example, when a polar liquid is used. Polar liquids (e.g. water, methanol, acetonitrile, etc.) are suitable, for example salt or sugar solutions. An aqueous solution with proteins dissolved in it is another example of a polar and therefore well-suited solution. Non-polar liquids such as benzene, hexane or toluene are less suitable.

If the supply of the liquid, for example a capillary, is not conductive, the contacting can be realized by a metal contact which is immersed in the liquid. If, for example, the feed means are coated in a conductive or conductive manner, the contact can take place directly via the contacting of the feed means.

There must be such a contact between the electrode and the liquid that a charge exchange can take place in order to bring the liquid to potential,

Means are also provided for generating an electric field for the spraying of the charged liquid. One or more counter electrodes are provided, for example a conductive plate, which is mounted insulated from the charged liquid to be sprayed. The counter electrode is usually located in front of the inlet of a possibly downstream mass spectrometer or is the surface to be sprayed itself. However, other parts of the device which are arranged closer to the tip or capillary can act as counter electrode with a corresponding charge, for example one surrounding the device Casing. By

Applying a voltage, this counter electrode is brought to a potential that differs from that of the charged liquid, this potential difference forms an electric field between the two, which acts on the liquid, the strength of this field is sufficient to the surface tension of the liquid to break up, the liquid is sprayed in particular from the tip or capillaries on which it was before the spraying. The resulting charged droplets are attracted to the electrode or electrodes.

The droplets are detached in particular at the points where the electric field has a high electrical flux density. This is particularly the case at the points where the charged liquid converges in an almost punctiform manner before detaching, which is the case at the tips or capillaries ,

When applying the potential between the counter electrode and the liquid, avoid creating an excessive electrical flux density. This can occur at the tips and lead to an undesirable gas discharge. It can be left to the person skilled in the art to adjust the electric field accordingly so that this phenomenon does not occur,

The supply of the liquid to the point or points from which spraying can take place in different ways and the way is also not essential for the invention. The liquid can be supplied, for example, by pumps or by capillary forces. It can be supplied from chromatographic systems such as LC (liquid chromatogtaphy), HPLC (high performance liquid chromatography), CE (capillary electrophoresis) or directly (e.g. via a syringe feed). If several tips or capillaries are provided from which the liquid is sprayed, supplied liquids can be sprayed with higher flow rates,

Means are also provided for generating one or more gas streams. The composition of the gas streams is not essential for the process, use of compressed air, nitrogen, carbon dioxide, sulfur hexafluoride and noble gases and mixtures of these gases are possible, In an advantageous embodiment of the device according to the invention, the gas stream or the gas streams consist of gases which have a high gas discharge resistance. Examples of gases with higher gas discharge resistance than nitrogen are sulfur hexafluoride, oxygen, octafluorocyclobutane and decafluoro-n-butane, as well as other perfluorinated aliphatics into consideration. Mixtures of these gases with one another and / or with other gases, such as air, nitrogen, noble gases, can also be used advantageously,

Through the use of such gases or gas mixtures for the gas flow or the gas flows, the occurrence of undesired gas discharges at the point (s) from which spraying takes place is reduced. This has an advantageous effect on efficient electrostatic atomization of the liquid and thus on the Signal intensity in the mass spectrometry. In addition, higher potential differences can be used without causing gas discharges, which in turn increases the efficient atomization and thus the signal intensity.

For example, in mass spectrometry, the use of the device according to the invention with pure sulfur hexafluoride or mixtures of sulfur hexafluoride and air or nitrogen as a gas stream / gas streams increases the signal intensity regardless of the solvent composition. This increase in signal intensity in mass spectrometry is particularly pronounced if the solution to be sprayed has a high water content (e.g., 95-1 00%) or if a negative electrospray is used (instead of positively charged drops or ions, negatively charged drops or ions are generated; the

Potentials on the liquid and counter electrode then have the opposite sign as in the positive electrospray),

In the prior art, it is difficult both in the case of positive and in the case of negative electrospray to make solutions with approximately 100% water content accessible to the mass spectrometric analysis, since disruptive gas discharges occur. This also has a disadvantageous effect if the solution to be analyzed comes from a chromatographic separation is supplied, in which the solvent gradient (continuous change of

Solvent mixture) is at times almost 100% water, in such cases, mass spectrometric analysis using electrospray has been difficult so far, In the state of the art, the occurrence of undesired gas discharges is very pronounced for negative electrospray, so far the mass spectrometric analysis of solutions with a high water content with negative electrospray has been possible, if at all, only with extremely low signal intensities. For the same reasons, coupling has also hitherto been possible hardly carried out negative electrospray with chromatographic separation methods, especially if solvent gradients (continuous change of the solvent mixture) with water components are used,

When using the device according to the invention with sulfur hexafluoride or mixtures of sulfur hexafluoride with air or nitrogen as the gas stream / gas streams, on the other hand, analyte solutions with a very high water content (e.g. 100% or 95%) can be analyzed with both negative and positive electrospray with high signal intensities.

Therefore, with the device according to the invention there is a coupling with chromatographic for both positive and negative electrospray

Separation methods with very good signal intensities in the

To implement mass spectrometry advantageously, even if at times very high water proportions in the solvent gradients used

(e.g. 95% -] 00%) occur

The device according to the invention makes it possible to analyze classes of substances which have hitherto been difficult to analyze with electrospray.

Mass spectrometry were accessible, e.g. Oligonucleotides that can only be detected with negative electrospray and are often present in solutions with a high water content. Such substance classes can be used with the device according to the invention in electrospray

Mass spectrometry now also in combination with chromatographic

Separation methods are analyzed,

The gas flow (gas flows) is directed on the one hand so that the sprayed

Liquid, i.e. the one formed during electrical spraying

Droplets are captured and the droplet spray from the gas stream

/ is carried along. On the other hand, when aligning the gas stream or gas streams, it is essential that the gas stream or gas streams are not Spraying points, such as tips and capillaries, i.e. the sprayed liquid is only recorded after spraying,

With the first measure, the gas flow acts specifically on the shape and direction of the spray. The spray is aimed towards the

The gas flow is directed, for example, if there is a spray cone without a gas flow, the gas flow or the gas flows are oriented so that the opening angle of the spray cone is reduced. The respective gas flow is oriented so that the spray is detected if there are still droplets, If the liquid in the droplets has already evaporated, there is a current of ions which is difficult or impossible to control by the gas flow,

The fact that the spraying point or points are not detected means that the charged liquid is not torn off by a gas flow, in particular a high flow velocity, which flows past the liquid from the outside, as is done in the pneumatically assisted electrospray process. This prevents this that relatively large droplets with an uneven size distribution and a low charge are formed. When used in the

Mass spectrometry increases the signal intensity, the signal-to-noise ratio, and also reduces the fluctuation of the ion signal, which leads to improved reproducibility of the measurement results.

In particular - this is how it prevents the spray from entering

Downstream of the mass spectrometer is the disadvantage that the distance between the mass spectrometer inlet and the spraying point has to be increased, since it takes longer for ions to be released from these larger charged drops. Otherwise the detection sensitivity deteriorates,

In contrast to the prior art, which is known from the publication US Pat. No. 5,349,186, it is impossible for the gas flow to capture the liquid before spraying. In this prior art, tubes with a diameter of approximately 1 mm are provided. This Tubes are arranged in a ring around a liquid-carrying capillary. The tubes directly adjoin the capillary by means of which the electrospray is generated. The capillary from which the electrospray detaches extends beyond the ends of the tubes from which the enveloping gas flow emerges. This arrangement means that the gas stream that emerges from the tubes hits the electrospray directly,

In the device according to the invention, the gas flow is arranged in such a way that the tip or capillary from which spraying is arranged is next to the gas flow, but in so doing protrudes only insignificantly beyond the area from which the gas flow separates from the device the distance between the electrospray and the area from which the gas flow separates is chosen such that this ensures that the gas flow never strikes the points from which spraying takes place.

The outlet opening of the gas stream or the outlet openings of the gas streams are advantageously arranged around the tip or capillary, from which the charged liquid is sprayed. This means that the electrospray first forms in a known manner in an area in which there is no gas flow, i.e. in the non-flow area between the outlet opening or the outlet openings. In the case of a gas flow, there is a non-flow area within the outlet opening, in which one or more tips or capillaries, from which is sprayed, are arranged. It is again essential that the gas flow or flows are directed in such a way that the liquid is sprayed by the respective gas flow and the spraying points are not already detected.

The arrangement of the outlet opening (s) around the tip (-n) or capillary (-n) ensures that gas flow acts on the electrospray formed from the liquid from several sides. The gas flows or the gas flow thus have a concentrating effect on the electrospray, lying For example, if there is a spray cone in front of a gas stream, the opening angle of this spray cone is reduced. In this way, it is possible to supply considerably more ions to a possibly subsequent mass spectrometer. The sensitivity is increased accordingly.

Therefore, the alignment of the gas stream or the gas streams depends on the one hand that they do not detect the spraying point, on the other hand they record the sprayed liquid at all in order to be able to act as a bundle.Therefore, it may be sufficient for several gas flows in a special case that these are directed slightly apart to bundle the electrospray in the flowless space created in this way. Stronger bundling is achieved if the gas flows are arranged parallel to one another as far as possible or if a gas flow is in the form of a lateral surface of a cylinder.

In the case of several gas streams, the lateral influence on the electrospray can also be varied, for example, by different flow velocities.

In the device according to the invention, the

Outlet opening of the gas stream or the outlet openings of the gas streams arranged in a ring around the tip or capillary from which the charged liquid is sprayed. The annular outlet opening creates an annular gas stream, for example the means for generating a gas stream have a circular slot as the outlet opening, For this purpose, for example, a centrally introduced body can be provided in a capillary opening from which the gas stream exits, the gas stream exiting from the remaining gap between the capillary and the body. Furthermore, means are provided, for example, which generate a plurality of gas flows arranged in a ring. For example, there are several tubes arranged in a ring, from which a corresponding number of gas flows emerge. The tip (s) or Kαpillαre (s), from which the charged liquid is sprayed, are arranged within the flowless area in the annular gas stream or the gas streams arranged in the ring. For example, the tip or capillary is largely arranged in the center of the flowless area.

Due to the ring-shaped arrangement around the point or places from which spraying takes place, the gas flow or the gas flows act on all sides and particularly evenly on the electrospray. The spray cone which is actually drifting apart is enveloped evenly and the drifting apart is contained,

It is again essential that the gas flows or the gas flow do not act on the place or places from which the liquid is sprayed.These act only where the electrospray has already arisen and then have a concentrating, limiting effect on it succeeds so that initially the electrospray can form without being disturbed by the gas flow, the enveloping gas flow only causes a subsequent constriction of the electrospray, accordingly the ions hit the entrance of a possibly provided mass spectrometer, the sensitivity is increased accordingly.

In a further advantageous embodiment of the invention, a plurality of annular, concentric outlet openings for gas streams are provided. As a result, for example, a second gas stream surrounds a first gas stream in a ring. By this arrangement of the outlet openings and so that the gas streams impact, the gas flows to the electrospray with the distance from the center of the outlet openings can be varied and the focusing are adjusted particularly ^"efficient. Further effects this arrangement is that the inner gas flow through the respective outer gas stream is shielded from the surrounding still air. Turbulence and turbulence due to the large differences in speed between gas flow and the surrounding environment can be avoided in the inner gas flow. The outer gas flow thus has the effect that the difference in speed between the surroundings of the inner gas flow and the inner gas flow itself is reduced, if not completely eliminated. To prevent turbulence, it may therefore be sufficient for the outer gas stream to emerge with a lower flow than the inner gas stream.

On the other hand, the further enveloping gas stream with higher

Speeds are operated. In one embodiment, the speeds are typically over 80 m / s. B. from 100 m / s. It is thereby achieved that the outer gas stream with respect to the respective spraying point has an increased flow velocity compared to the inner gas stream and thus the bundling effect of the

Gas flows with the distance increases. In the case of more than two annular, concentrically surrounding gas streams, these can be staggered with an outwardly increasing flow velocity.

As an alternative to the above embodiment, a gas stream can be provided which already has a flow profile in the outlet area, which has an increasing or decreasing flow velocity with increasing distance from the spraying point,

In an advantageous embodiment of the invention, the outlet opening of the gas stream is shaped or arranged in such a way that the gas stream or the gas streams is or are oriented conically, focusing on one point, i.e. the gas streams intersect at one point or the gas stream is constricted at one point It is only necessary to ensure that the flow-free cone thus obtained runs in such a way that it does not cover the area in which the electrospray is formed. Focusing is further improved by the alignment of the gas stream or gas streams achieved in this way. The sensitivity in mass spectrometry is correspondingly improved in order to obtain a correspondingly shaped gas stream obtained, for example, the outlet opening of the gas stream can be shaped or angled accordingly, for example, if tubes are used as outlet openings, these can be conically oriented in relation to one another,

In a further embodiment of the invention, means are advantageously provided with which the gas stream or the gas streams are advantageously heated. This accelerates the evaporation of the drops. For this reason, the distance between a possibly downstream mass spectrometer inlet and the spray point can be chosen to be smaller. In addition to the advantageous smaller dimensions in connection with a mass spectrometer, the sensitivity can be increased further, because then the ions get into the mass spectrometer more concentrated due to the greater proximity to the spray point. The way in which the gas stream is heated is not essential, one is special A simple possibility is to pass the gas flow through a tube in which there is a wire that is heated by passing through current. Typical dimensions are approximately 1.5 m tube length with an inner diameter of approximately 1 mm, approximately 1 , 5 m wire length at a

Wire diameter of 0.15 mm (tungsten wire) proven. As materials come for the tube come e.g. PEEK, fluoropolymers, glass and various other insulators that can be used up to approx. 1 50 ° C are heat stable.

If the device according to the invention succeeds, an unheated one

Gas flow an increase in sensitivity or the intensity by a factor of 5 compared to the prior art mentioned above, however, with a heated gas flow and a concomitant reduction in the above-mentioned distance

Increasing the intensity or improving the sensitivity by one

Factor 9 reached, in both cases the gas velocity is approx. 80 m / s.

In the device according to the invention, the means for generating one or more gas flows are such that the gas flow in the outlet area is at least 20 m / s. In the prior art, as known from US-5,349, 1 86, it is necessary to i Limit gas speed to a maximum of 6.5 m / s. Otherwise, the gas flow causes the liquid to be atomized pneumatically at higher gas speeds, i.e. the drops are torn off from the points from which the electrospray is detached or the spray conditions are disrupted. In contrast, the device according to the invention allows higher gas speeds, in particular at least 20 m / s. The rule is: the higher the gas speed, the better the focusing, provided that there is no pneumatic atomization. Consequently, the measure mentioned increases the sensitivity in the case of downstream analysis,

In the device according to the invention, an outlet opening for an auxiliary gas flow is advantageously provided in the area between the gas flow and the tip or capillary. Will the

If the gas velocity is increased too much, a vacuum is created in the area between the tip / capillary and the gas flow or the gas flows, which can then have a disadvantageous pneumatic atomizing or otherwise disruptive effect. To avoid liquid tearing off, the auxiliary gas flow is provided, which over the outlet opening can be introduced within the space mentioned above. In one embodiment of the invention, for example, an annular gas outlet area is provided for the auxiliary gas flow, which is located between the annular gas outlet area and the locations from which spraying takes place. The auxiliary gas flow is introduced via this additional gas outlet area. However, this happens at such a low speed that it only counteracts the formation of a negative pressure and does not negatively influence the formation of an electrospray. The speed is typically a few m / s, the width of the annular gap in the gas outlet area. for the auxiliary gas flow is typically 0.1 mm. In one embodiment of the invention, this annular gap directly adjoins the capillary, from the capillary opening or tip of which the liquid is sprayed. With regard to the annular gas outlet area provided in this embodiment, stands for the actual gas flow this additional ring-shaped exit area for the auxiliary gas flow typically emerges by approx. 0.1 5 mm to 0.4 mm.

In the device according to the invention the is also advantageous

Provide a tear-off edge for the outlet opening of the respective gas flow. The tear-off edge causes the gas flow to be detached sharply from the gas outlet opening in comparison, widening of the gas flow and its speed profile, and turbulence and turbulence to the side of the center of the gas flow are reduced. To achieve this tear-off edge, cutouts can be provided in the device,

In the device according to the invention, the tip or capillary is also advantageously arranged in a recess in the device. This allows a flowless area to be produced particularly well, in order to avoid according to the invention that liquid is torn off from the spraying point,

Furthermore, the tip or capillary, from which the charged liquid is sprayed, stands out from adjacent areas of the device. For example, it is a projecting capillary opening. This prevents the liquid, which for example emerges from the opening of the capillary, from wetting adjacent areas. The formation of a fine electrospray is otherwise hindered, the limitation remains the objective not to let the point or places from which the charged liquid is sprayed protrude so far that they are caught by the gas stream or the gas streams or one of the gas flows generated negative pressure acts on the site or sites and the liquid to be sprayed. How far the location or locations may protrude depends on how large the distance to the gas flow or gas flows is selected. Because this distance is in the interest a strong bundling of the electrospray is to be minimized, the extent of the protrusion must also be minimized. Accordingly, it can be left to the person skilled in the art to set the optimum dimensions on the basis of a few experiments within the technically feasible limits.

In practice, it has been shown in any case that with the current processing and manufacturing technology and the associated dimensioning, a protrusion of 0.15 mm to 0.25 mm is sufficient to ensure the creation of an electrospray on the one hand and to ensure this on the other to ensure that a gas stream surrounding at a distance of 0.3 mm to 0.45 mm does not strike the spraying point directly and therefore destructively. New processing methods would have to be used to achieve even smaller dimensions. In particular, micromechanical processing methods would have to be used. For cost reasons, these have not yet been carried out, as they would not currently be economically viable. If larger quantities were realized in practice than before, micromechanical machining methods would become economical. Under these circumstances, smaller dimensions could certainly be achieved in practice,

In the prior art, the diameter of the enveloping gas flow at the gas outlet is 1.2 cm

Diameter typically 0.9 mm. In the prior art, the liquid-supplying capillary protrudes typically by 3 cm compared to the tubes from which the enveloping gas stream emerges and by 1.5 cm from the above-mentioned gas outlet the point from which the spray is carried out, for example a liquid-carrying capillary, only typically protrudes by 0.3 mm from the ring-shaped gas outlet. Thus, the capillary or point from which the electrospray comes off and the means from which are located the enveloping gas stream emerges, almost on one level. In the prior art, as described in US Pat. No. 5,349,186 is known, the liquid-supplying capillary is finally in a tube with an inner diameter of 1.2 cm. The air flow thus directly captures the outlet opening of the liquid-supplying capillary.

This is not the case with the invention. For example, in one embodiment, in addition to the liquid-supplying capillary, a cylindrical body is also provided, which typically has an outer diameter of 0.6 mm. The inner diameter of the capillary is typically 10 μm to 50 μm, particularly preferably 40 up to 50 μm. This ensures that there is a distance between the gas outlet and the area from which the electrospray separates, in particular the two measures relating to the provision of a distance between the area where the electrospray forms and the points from which the enveloping gas flow separates and the fact that the capillary practically does not protrude from the gas outlet brings about a significant improvement in sensitivity compared to the prior art mentioned at the outset while maintaining the fine atomization desired,

In a further embodiment, which has a liquid-supplying capillary, the end of the capillary is advantageously pointed or beveled. As a result, the area from which the electrospray detaches is further reduced. A correspondingly improved electrospray succeeds.

In a further embodiment of the invention, spacers are provided which bring about the exact centering of the capillary within the gas outlet opening in the means for generating the gas flow, for example flexible wires which are welded to the cylindrical body or the capillary or are otherwise fastened thereto

Fibers or webs made of glass, metals and various plastics, as

/ Further spacers are possible, flexible wires or fibers or webs made of glass, metals and various plastics - which are attached to the means for generating the gas flow, Due to the exact centering, a particularly good encapsulation of the

Sprays achieved by the gas flow and thus the sensitivity in the

Significantly increased compared to the state of the art.

For precise centering, tubes can be provided which are arranged in a ring around the capillary, tip, from which the electrospray emerges. These tubes are adjacent to the capillary or tip, they also represent the spacer from the means from which the enveloping gas stream emerges. A gas stream or an auxiliary gas stream can escape from these tubes in order to avoid turbulence or a vacuum which is destructive could affect the formation of the electrospray.

With appropriate dimensioning and arrangement, the tubes arranged in a ring around the capillary or tip can also be used to generate the supplying gas flow, this is only a question of dimensioning and arrangement, so it is important that compared to the State of the art the capillary or tip is essentially in one plane with the other gas outlets,

In a further advantageous embodiment of the invention, the means for generating an electric field have an electrode which is arranged essentially in a ring and / or disk shape around the outlet opening of the gas stream. The electrode is located, for example, in a ring around the gas stream, or this electrode is disc-shaped with the gas outlet opening as the center,

This electrode can be used depending on the

Potential differences. act as a counter electrode or as a repelling electrode on the charged droplets of the sprayed liquid,

If the electrode is repulsive, the focusing is additionally improved. A distinction must be made: the potential difference that is necessary for spraying the liquid and which between the Liquid and a counter electrode (eg in front of the mass spectrometer inlet) and the potential difference, which exists between the above-mentioned repulsive electrode and the charged liquid. The potentials of the liquid and the repellent electrode must be of the same name, but not of the same height, in order to have a repellent effect on the liquid or on the liquid spray that is produced. The repelling electrode must be electrically isolated from the liquid.

Since charges of the same name repel each other, the charged drops are increasingly pushed away by the charge of the same name of the repelling electrode,

With an essentially annular or disc-shaped shape and corresponding arrangement of the repelling electrode around the gas flow, the repulsion acts on several sides and evenly on the charged sprayed liquid, the opening angle of the spray cone becomes smaller, and the density of charged particles becomes higher and the detection sensitivity of a possibly connected mass spectrometer increased.

The effect can be influenced on the one hand by the applied potential as well as by the arrangement: the greater the spatial extent of this repelling electrode, and the closer it is to the charged drops in the spray cone, the stronger this effect.

The higher the potential that is present at the repelling counter electrode, the stronger the compacting (focusing) effect on the spray cone. These potentials can even be higher than the potential at the liquid to be sprayed. It is to be avoided here that the potential difference between the liquid and the repellent electrode becomes larger than the difference between the liquid and the counter electrode, since otherwise the repellent electrode becomes the counter electrode. For clarification, examples of favorable potentials of liquid and repellent electrode are given below:

Liquid repellent electrode on the sprayer + 6.5 kV + 5.5 kV

+ 5.5 kV + 5.0 kV

+ 5.5 kV + 7.0 kV

+ 7.0 kV + 7.0 kV

+ 6.0 kV + 7.0 kV

Such field focusing easily leads to signal increases of more than factor 5 in mass spectrometry. Together with gas focusing, an increase in the signal intensity of approx. 20 can be achieved.

The repelling electrode can be brought to the desired repelling potential with a voltage supply. Another possibility is to gradually bring them to the same potential by hitting, charged drops of the sprayed liquid. In the latter procedure, it can consist not only of conductive materials but also of insulating materials. The power supply can thus be dispensed with and the device becomes cheaper, if the repelling electrode charges itself independently due to impinging charged droplets, it does not have to be made of metal, it can then also be made of a dielectric material, the device can be manufactured correspondingly more variably and individual needs are addressed,

On the one hand, the larger the repelling electrode, the better the focusing by the repelling electrode, on the other hand, a large-area electrode surrounding the gas stream, possibly also enveloping, tends to prevent the inflow of air into the vacuum region behind and around the gas stream, this can due to the resulting turbulence, the Spray point or places is disadvantageously detected by the gas flow, which is to be prevented according to the invention.

For this purpose, the repelling counter electrode has different embodiments of the repelling electrode provided with openings, which are optimized with regard to the above-mentioned fluidic problems as well as the course of the electric field, for example it is provided with rods arranged in a ring around the gas flow, whereby the closer the rods are to electrospray, the more repellent and therefore focusing, in a further embodiment the electrode has a spiral shape, being arranged in the spiral direction around the gas flow. Furthermore, an enveloping and charged tube can be provided as a repelling electrode the tube can in turn serve as a gas supply,

It can be left to the person skilled in the art to achieve a particularly good embodiment in accordance with the above-mentioned requirements. Only a few attempts are necessary for this,

In a further embodiment of the invention, the repulsive

Electrode of the same name but with lower potential than at the

When the liquid is applied, the repelling electrode has less focus on the spray cone, but there are other advantages:

Because the focus of the spray cone is less strong, its spatial extension remains greater and the adjustment of the spray cone to the mass spectrometer inlet (= MS inlet) is easier,

In addition, the repelling electrode can be brought to the same potential as the MS inlet or the attracting electrode in front of the MS inlet. This can be done particularly easily, for example, by an electrically conductive one

/ Connection to the MS inlet or the attracting electrode in front of the MS inlet This saves a voltage source and the construction is thus cheaper. In addition, accidental contact between the spray device and the MS inlet or the attracting electrode in front of the MS inlet does not lead to voltage flashovers. This increases occupational safety.

For clarification, examples of cheap ones are given below

Potentials at the repelling electrode and the liquid to be sprayed at liquid flow rates from approx. 1 00 nl / min to 1 000 nl / min:

Liquid repellent electrode on sprayer + 2.5 kV + 200 V

+ 2.8 kV + 450 V

+ 3.0 kV + 700 V

In a further advantageous embodiment of the invention, the repelling electrode described, the liquid to be sprayed and the means which provide for a distance between the gas outlet and the area from which the electrospray is detached have the same but not necessarily the same potential.

If the repelling electrode, the liquid to be sprayed and the means which provide a distance between the gas outlet and the area from which the electrospray separates are electrically conductively connected to one another, they can be brought to the same name with just one voltage source , It will be in this

Design requires only one voltage source, the device is simplified and therefore cheaper,

In this embodiment, the areas of the spray device that are very close to the area from which the electrospray detaches are at the same electrical potential as the liquid. This leads, in particular, to the spraying of difficultly volatile solutions (e.g. solutions with a high water content) particularly efficient release of ions from the spray.

In this embodiment, for example, the repelling electrode and the means that provide a distance between the gas outlet and the area from which the electrospray is detached can be made of conductive materials. The form of the repelling electrode comes in the embodiments described above consideration It can be left to the person skilled in the art to achieve a particularly good embodiment in accordance with the above-mentioned requirements. Only a few attempts are necessary for this,

For clarification, examples of cheap ones are given below

Potentials on the repelling electrode, liquid to be sprayed and on the means that provide a distance between the gas outlet and the area from which the electrospray separates are mentioned: 2.5 kV to 6.0 kV for liquid flow rates of approx. 1 00 nl / min to 1 000 nl / min

In a further advantageous embodiment of the invention, the repelling electrode, the liquid to be sprayed and the means which provide a distance between the gas outlet and the region from which the electrospray is detached are partially or completely electrically insulated from one another. In this way, they can be brought to electrical potentials of the same name, but not necessarily the same, independently of one another.

In a further advantageous embodiment of the invention, the said electrode takes on the function of a counterelectrode, so that the device can be operated independently of the more distant counterelectrode and the device does not have to be aligned with this, this has a favorable effect on the spray conditions more distant counter electrode must, if they even still be present, need only abut or a low potential, to direct the ions formed in the desired direction, a farther from the ^{'Versprühstelle} or bodies distant counter electrode which the charged drops in the gas flow direction pulls, can even be omitted,

The electrohydrodynamic spraying takes place as usual, for example in the direction of flow of the liquid out of the supplying capillary, since this counter-electrode is usually arranged on the side away from the gas flow or the spraying direction, corresponding to the repelling electrode mentioned above, without the gas flow the charged drops formed along the Field lines to the rear of this counterelectrode, which is located relatively close be performed and there would be an extreme increase in the spray cone angle.

Without gas flow, this would result in the ion density in front of the mass spectrometer inlet becoming lower compared to one

Counter electrode which is in the spraying direction, In addition, the drops that strike the nearby counter electrode can form a conductive liquid film, which can lead to a short circuit between the liquid to be sprayed and the nearby counter electrode, this would reduce the potential difference and the electrospray skip,

If a gas flow is used, this can be avoided. This detects the charged drops of the liquid spray and thus prevents them from hitting the nearby electrode. A short circuit between the liquid and the nearby counter electrode is avoided. It also ensures that the angle is reduced Effect on the spray cone that the spray cone is steered in the desired direction with only a small opening angle.

If the gas stream is additionally heated, it supports the release of ions from the drops, so that the device can be brought closer to the mass spectrometer inlet.

The closely located counterelectrode has a small spatial expansion compared to the repelling electrode, since with an increasing spatial expansion more and more droplets of the sprayed liquid would follow along the field lines, which necessitates a stronger gas flow. In this case, an annular, closely arranged counter electrode is suitable is as a plate-shaped electrode as preferred as the repelling electrode. ^"

The described combination of closely arranged counter electrode and angle-reducing, direction-influencing and heatable Gas current leads to significant increases in the ion density upstream of the mass spectrometer inlet and thus to significant increases in the signal intensity (factor 1 0),

The mass spectrometer then does not have to be such that it acts as a counter electrode. The gas flow ensures that the droplets or the electrospray nevertheless reach the mass spectrometer,

In this embodiment, only one voltage source is required. The device is simplified and therefore cheaper. In addition, the speed of the drops is slowed down. This allows the size of the device to be reduced. Also in this way it can be achieved that the droplets or the spray reach the mass spectrometer at a point in time at which the spray has not yet expanded significantly. This can also bring about an improvement in sensitivity compared to the prior art mentioned at the outset.

If the device according to the claims is to be used in another area, ie not in mass spectrometry, it can be advantageous to use the closely arranged counterelectrode and to dispense with a more distant counterelectrode which pulls the drops in the gas flow direction. In this way, for example, non-conductive surfaces can be coated. The enveloping gas stream then ensures that the loaded particles hit the desired surface,

In one embodiment of the invention, care must then be taken to ensure that the charge that strikes the non-conductive surface is removed. In this way, it is continuously ensured that droplets or the spray hits the desired surface. Otherwise it will

Performances finally stopped due to the increasing cargo of the same name. In a further advantageous embodiment of the invention, the means for generating an electric field have one or more peaks for corona discharges. For example, the electrode is provided with one or more tips, which have been electrochemically etched out, for example, or the free ends of an electrode provided with rods are pointed for this purpose. If there is a sufficient potential difference, one or more corona discharges burn at the tips. This easily generates a few μA of charged Corona products. The resulting space charge repels the particles of the spray cone with the same name more strongly than the charged electrodes. When the tips and thus the corona charge clouds are arranged around the gas flow or the tip (s) or capillary (s), a particularly strong compression is achieved and the spray cone is focused, since the resulting corona products and those caused by the electrospray generated drops / ions are charged with the same name, the different charge clouds do not mix. Also, due to the same charge, reactions between the charged corona products and the released ions cannot occur. It is therefore advantageous to only increase the sensitivity. If the ion distribution is measured across the gas flow in such a system, the result is a “W-shaped spatial distribution of the ion density: on the outside, a very high ion density (corona products) is measured, on the way to the center the ion density drops to almost 0 (area , in which corona products and electrospray ions repel each other), only to rise again towards the center in the center of the gas flow (electrospray products).

The device also advantageously has a mass spectrometer in order to be able to carry out mass spectrometric analyzes with high detection sensitivity. For this purpose, for example, the gas stream with the droplets located further forward to the spray point and further back with the ions located therein aims at the inlet of the mass spectrometer, In the aforementioned embodiment, the mass spectrometer can be closer to earth potential than the charged droplets. However, practical circumstances are also of interest, in which the situation is reversed. The mass spectrometer is then further away from the earth potential compared to the charged droplets.If the mass spectrometer is, for example, -5 KV, the liquid is typically 1 KV, the repelling electrode is then typically 0 KV, so the potential differences are suitable coordinated. This example shows that it does not matter that a mass spectrometer used must be closer to earth potential compared to electrospray.

In a further embodiment of the invention, the main direction of the electrospray points in a direction that leads past the input of the mass spectrometer. The main direction is understood to mean the central axis of the spray, in which the spray expands.This direction is basically the same as the direction of the gas flow.If the charged droplets fly past the entrance of the mass spectrometer, only ions get into it due to the electrical charge

Mass spectrometer due to the attractive charge, In this way it is ensured that the input of the mass spectrometer is less contaminated and the signal-to-noise ratio is improved. Nevertheless, the intensity or sensitivity is increased compared to the prior art, because of this is carried that the ions fly past the entrance in a very concentrated manner,

In a further embodiment of the invention, the main direction of the electrospray has a location next to the entrance of the

Mass spectrometers, low-charged and / or large drops fly due to their greater inertia compared to small drops and

Ions to a location next to the mass spectrometer input, which means that the input of the mass spectrometer is less contaminated, As already stated above, the supply of the liquid to the point or the points from which spraying can take place in different ways and the way is also not essential for the invention. The devices described can be used at different flow rates , With small ones

Flow rates will be the diameter of the fluid delivery means, e.g. Capillary, adapted so that there is a stable, pure electrospray, The devices described can be used for flow rates from a few nano-liters per minute to approx. 10 μ-liters per minute, the exact upper limit represents the flow rate, which can no longer be sprayed in a pure electrospay (depending on the solvent used, among other things). If higher flow rates are to be sprayed (this would be difficult with pure electropspray) or if a device with a wide variety of flow rates is to be used, the excess part of the liquid can be separated off before being fed to the point or the points from which spraying takes place.

The liquid-carrying capillary can be coaxially encased by an additional capillary through which another liquid is supplied, when the liquids emerge from the inner and outer liquid-carrying capillaries, the liquids mix, this can be advantageous if, e.g. for larger capillary diameters and / or high water contents (e.g. when combining the spray devices according to the invention with a chromatographic separation method), for high water contents and larger ones

Capillary diameters pure electrospray is becoming increasingly difficult. If you increase the proportion of organic solvent (methanol or other suitable solvents) in the analyte solution shortly before spraying, this can possibly more easily sprayed through pure electropsray (sheath liquid),

In a further embodiment, such high flow velocities, for example approx. 200 m / s, of the gas flow or the gas flows are provided in the device that the turbulences and / or turbulences occurring around the gas flow reach the tip (s). or Kαpillαre (n) act and cause pneumatic atomization there. As a result, the signal intensity is increased by a factor of 3 compared to known pneumatic electrospray processes. An increase is achieved in particular in combination with a heated gas stream and an additional electrode attached close to the tip or capillary.

All of the aforementioned measures can be applied individually in order to achieve the desired effects or the disclosed effects. If the measures are applied in combination, the effects combine accordingly,

The invention furthermore relates to a device for generating an ion cloud, which has an aperture arranged in the ion cloud. The ion cloud is generated, for example, by an electrospray device according to the configurations described above or according to the prior art. Furthermore, the ion cloud can be determined by API (atmospheric pressure ionization) methods such as (micro, nano) electrospray, pneumatically assisted electrospray, atmospheric pressure chemical ionization or by atmospheric pressure photo ionization.

The aperture alone or in combination with the above-mentioned measures produces a comparatively very fine ion cloud or electrospray with a spray cone with a comparatively small opening angle, in order to improve sensitivity, for example when used in mass spectrometry, compared to the prior art mentioned.

If the aperture is used in combination with the above-mentioned measures, this also contributes to the constriction and focusing of the ion cloud or electrospray and thus increases the sensitivity of a mass spectrometer which may be connected downstream. The diaphragm has a hole which is arranged, for example, in front of the inlet opening of a mass spectrometer. The aperture loads in one Embodiment by the impinging ions of the spray to such an extent that it has a repulsive and thus compressing effect on the spray cone of the same name, which is aimed at the diaphragm and the possibly downstream mass spectrometer inlet,

In an alternative embodiment to this, means can be provided to bring the diaphragm to an electrical potential in such a way that the diaphragm emits a field which has a repelling effect on the ion cloud, the potential or the field being set such that, due to the repulsion, the one that passes but the ion cloud is focused

Passage of the ions is not prevented due to excessive rejection.

In this way, more charged ions get into the area behind the diaphragm, i.e. possibly into the mass spectrometer instead of one

To hit the counter electrode and discharge there. The aperture achieves focusing regardless of which of the above-mentioned methods is used to generate the ion cloud. The signal intensity with a downstream mass spectrometer can easily be increased by a factor of 2 compared to the prior art,

The panel is preferably made of an insulating and chemical-resistant material with a relatively high dielectric strength, e.g. PEEK, Teflon, silicon carbide, the resistance to chemicals makes the panel universally applicable, the insulating property enables the panel to be applied to conductive materials without any charge flowing off can and the focusing effect is lost, the diaphragm can be made of conductive material (eg metal) in a further embodiment. In this case, the screen is attached in an electrically insulating manner, it can be brought to potential by charged droplets or ions hitting it, or means, for example a voltage source, can be provided to bring the screen to potential. If the orifice is arranged upstream of a mass spectrometer inlet, the hole in the orifice is positioned as symmetrically and concentrically as possible with respect to the inlet in order to ensure effective ion throughput through the orifice into the mass spectrometer. If the ion throughput is viewed by the device behind the orifice in or in the mass spectrometer arranged counterelectrode causes, the hole of the diaphragm must be dimensioned so that the refractive focusing effect of the diaphragm does not prevent the passage of the ions, because the ions cannot perceive the field behind the counterelectrode, if this is the case

Select the radius of the hole accordingly larger. On the other hand, the radius must not be too large, since otherwise the focusing effect is absent. The expert is able to set an optimal radius of the hole after a few attempts.

If the device has a gas stream, such as the electrospray devices according to the invention, this can be used to drive the ions through the hole in the screen. Since the throughput of the ions through the orifice supports the gas flow or even, if there is no counter electrode on or in the mass spectrometer, solely by the gas flow and possibly. only in combination with a light drawing field, the radius of the hole must be dimensioned differently compared to the case described above. The dimensions of the aperture also depend on the mass spectrometer which may be connected downstream,

In the device according to the invention for producing an ion spray, the screen advantageously has at least one opening for a gas stream, for example nitrogen. These are, for example, a plurality of openings arranged in a star shape in the hole in the screen, from which gas flows out toward the center of the hole in the screen. The gas flow serves to prevent drops from the existing spray from passing through the screen, as can be the case, for example, with the electrospray devices. It takes advantage of that Allowing drops to be deflected more easily by the gas flow than ions. With the mass spectrometer connected downstream, the droplets do not get into the outlet,

It also prevents solvent vapors from getting into the mass spectrometer that may be connected downstream, where they may deteriorate the measurement result due to condensation products,

-

The diaphragm of the device also advantageously has means for heating the gas flow. For example, this is a resistance wire arranged in the orifice for heating the gas flowing past.Thanks to the heated gas flow thus achieved, the drops of the spray can be prevented particularly well from passing through the orifice and penetrating into the mass spectrometer, since the liquid in the drops acts upon it of the heated gas flow evaporates and consequently at most the ions released from the drops can pass through the aperture.

Examples of dimensions and materials used in the different embodiments.

The constructions mentioned should consist of materials that are resistant to the liquids used. The following are examples of materials and dimensions:

Liquid supplying capillaries

• rjFused silica with polyimide outer coating; 1D: 40 μm, OD: 1 05 μm; ID; 50 µm, OD: 1 50 µm; ID: 1 60 µm, OD: 230 µm; ID: 1 50, OD: 360 µm; ID 20 µm, OD: 90 µm; ID: 20 µm, OD: 1 50 µm; ID: 1 5μm,

OD 90μm, ID: 1 Oμm, OD: 1 50μm _r ^•

• rjStainless-steel capillaries; ID: 1 30 μm, OD: 260 μm

Plastic capillaries e.g. Made of fluoropolymers, polyethylene, polypropylene with comparable dimensions / as with fused silica and stainless steel

Cylindrical bodies around the capillary as a spacer; QPEEK body: ID: 1 25 μm, OD: 625 μm, ID: 1 80 μm, OD; 625 μm, ID:

455 μm OD: 625 μm

• QTeflon or fluoropolymers; ID; 500 µm; OD: 1, 6 mm • stainless steel or other metals: ID; 260 µm; OD: 520 μm

• fused silica or, glass or ceramic: ID: 1 50 μm; OD: 360 µm, ID: 1 80 µm;

OD: 600 µm; ID: 400 μm, OD: 600 μm

Enveloping tube for the gas flow

Q (with different shape of the additional electrode)

• jMetals (stainless steel, brass, tungsten, precious metals, etc.)

• Q plastics (PEEK, Teflon, fluoropolymers, polyimide, etc.)

• Glass, ceramics, fused silica

Spacers:

• Metallic wires or capillaries (e.g. iron, stainless steel, tungsten, platinum, platinum / iridium)

• D plastic fibers or capillaries (fluoropolymers, PEEK, polymimide, polyethylene, polypropylene)

• Glass or ceramic fibers and glass or ceramic capillaries

The figures are described below: FIG. 1 shows a perspective side view of an embodiment of part of the invention. FIG. 2 is a perspective side view of a further embodiment with an opening for an auxiliary gas flow.

FIG. 3 is the top view belonging to FIG. 2. FIG. 4 shows a sectional view of a further embodiment with several capillaries and openings for auxiliary gas flows. Figure 5 is the pe ^{'rspektivische} detail view of part of the embodiment shown in Figure 4, the figures όa to 6c show longitudinal sections of different embodiments having different recesses and separation edges for the gas stream, the figures 6d and 6e show two further embodiment in a sectional view where the

Outlet openings are shaped in order to obtain a gas stream focused on a point, FIG. 1 5 shows different ways of centering the spacer and thus the spraying point in the gas outlet opening, FIG. 1 6 shows different embodiments which can have the end of the liquid-carrying capillaries. FIG. 7a is a perspective view of a further embodiment with two concentrically arranged gas flows, FIG. 7b shows the sectional view associated with FIG. / a, FIG. 8a shows a sectional view of a further embodiment, wherein several annularly arranged tubes are provided as gas outlet openings. FIGS. 8b and 8c show longitudinal sections of two more belonging to FIG. 8a

Embodiments. FIGS. 9a-9j show further embodiments, different electrodes being arranged around the spraying points, FIGS. 10 and 1 2 show intensity spectra of the device according to the invention, FIGS. 1 1 and 1 3 show the respectively associated intensity spectra recorded with a device according to the prior art Technology, FIGS. 1 7 and 1 9 show intensity _{spectra of the} device according to the invention when using SF _ό as a gas stream, FIGS. 1 8 and 20 show the respectively associated intensity spectra recorded with a device according to the prior art, FIGS. 1 4 a, 1 4 b and 1 4 c show an embodiment of the diaphragm according to the invention,

In the embodiment according to the perspective view in FIG. 1, a capillary 3 is provided, via which a charged liquid 1

Capillary opening 8 is supplied, from which it is sprayed into an electrospray 5 by an electric field. Furthermore, a tube 6 surrounding the capillary 3 is provided, via which a gas stream 2 is supplied in the direction marked by arrows, on the imaginary tube axis the capillary 3 arranged centrally. The

Capillary 3 is surrounded by a cylindrical body 4 in such a way that there is an annular outlet opening 7 between the cylindrical body 4 and the tube 6 for the gas stream 2, due to the arrangement of the capillary 3 and the cylindrical body 4 acting as a spacer, and their dimensions the gas stream 2 is directed past the capillary 3. The area marked with 9 and lying approximately between the dotted lines therefore has no gas flow. This ensures that the capillary opening 8 and the liquid 1 located there are not captured by the gas stream 2. Because of the annular outlet opening 7 with the one arranged in the center

Capillary 3, the gas droplet 2 also emerges in a ring and surrounds the electrospray 5 in an evenly enveloping manner. As a result, the electrospray 5 is only laterally sprayed on all sides by the gas stream 2 detected and the otherwise widening spray cone of electrospray 5 is contained or focused,

The further embodiment shown in FIG. 2 also has a capillary 1 3 to the opening 1 2 of which a charged liquid is supplied and sprayed. Furthermore, a tube 1 5 is provided which surrounds the capillary 1 3. The capillary 1 3 in turn is located centrally in a tubular body 10. An annular gap 1 1 is left between the capillary 1 3 and the tubular body 1 0, through which an auxiliary gas flow is supplied the capillary 1 3 avoided, via the gap 1 4 lying between the tubular body 1 0 and the tube 1 5, a gas stream is fed in the direction of the arrows, due to the arrangement of the capillary 1 3 and the tubular body 4 acting as a spacer and their The gas flow is dimensioned past the capillary 1 3. The area around the capillary opening 1 2 therefore has no gas flow. This ensures that the capillary opening 1 2 and the liquid located there are not captured by the gas flow, due to the annular outlet opening 1 4 with the capillary 1 arranged in the center 3, the gas stream also emerges in a ring and surrounds the electrospray uniformly, so that the electrospray is only caught on all sides later after spraying but on all sides by the gas stream and the otherwise widening spray cone of the electrospray is contained or focused, FIG. 3 is for Clarification of the associated top view,

FIG. 4 shows a section of a further embodiment. In contrast to FIG. 2 or 3, this has several (seven) capillaries 42, to the opening 41 of which a charged liquid is supplied and sprayed.

Due to the large number of capillaries 42, liquid can be sprayed at a higher inflow rate. Furthermore, a tube 45 is provided which surrounds the capillaries 42. Each capillary 42 'is surrounded by a cylindrical body 46, which in turn is located in a tubular body 44, between the cylindrical ones Bodies 46 themselves as well as those between the bodies 46 and the tubular body 44 are left outlet openings 40 for an auxiliary gas flow, via which an auxiliary gas flow is supplied.This avoids a possible negative pressure in the area around the capillaries 42, the cylindrical bodies 46 prevent that the auxiliary gas flow rests directly on the capillaries 42 in order to ensure that liquid 41 is not pneumatically torn from the auxiliary gas flow from the capillary opening. A gas stream is supplied via the annular gap 47 lying between the tubular body 44 and the tube 45. Due to the

The arrangement of the capillaries 42 and of the tubular body 44 functioning as a spacer and their dimensioning, the gas flow is directed past the capillaries 42. The area around the respective capillary opening 41 therefore has no gas flow. This ensures that the capillary opening 41 and the liquid located there are not caught by the gas stream. Due to the annular outlet opening 47 with the capillaries 42 arranged therein, the gas stream also emerges in a ring and surrounds the electrospray in a uniform envelope. As a result, the electrospray is only caught on all sides later by the gas stream after spraying, and the otherwise widening spray cone of the electrospray is contained or focused,

In FIG. 5, an associated detailed view is shown in perspective form for clarification. The surrounding tube 45 is missing here. Several (seven) capillaries 42 are provided, to the opening 41 of which a charged liquid is supplied and each sprayed to an electrospray 53, because With the large number of capillaries 42, liquid can be sprayed at a higher inflow rate. Furthermore, a tube 45 is provided, which surrounds the capillaries 42. Each capillary 42 is surrounded by a cylindrical body 46, which in turn is located in a tubular body 44, between the cylindrical bodies 46 themselves and between the bodies 46 and tubular bodies 44 are left outlet openings 40 for an auxiliary gas stream 52, via which an auxiliary gas stream 52 is supplied Any negative pressure in the area around the capillaries 42 is avoided. The cylindrical bodies 46 prevent the auxiliary gas flow 52 from being in direct contact with the capillaries 42, in order to ensure that liquid 41 is not pneumatically torn from the capillary opening by the auxiliary gas flow 52, so that the tubular body 44 (and between a gas stream 51 is fed to the surrounding tube wall (not shown). Due to the arrangement of the capillaries 42 and the tubular body 44 acting as a spacer and their dimensions, the gas stream 51 is directed past the capillaries 42, the area around the respective capillary opening 41 therefore has no gas flow. It is thus ensured that the capillary opening 41 and the liquid located there are not captured by the gas flow 51. Due to the annular outlet opening 47 with the capillaries 42 arranged therein, the gas stream 51 also emerges in a ring and surrounds the electrospray 53 in an evenly enveloping manner. As a result, the electrospray 53 is only laterally detected on all sides by the gas stream 53 after spraying and otherwise widening Spray cone of electrospray 53 is contained or focused.

FIG. 6 a shows a longitudinal section through an embodiment of the invention. A capillary 61 is provided via which a charged liquid is supplied to the capillary opening 61, from which it is sprayed into an electrospray by an electric field. A tube 64 surrounding the capillary 61 is also provided, via which a gas stream is supplied in the direction marked by arrows.

On the imaginary tube axis, the capillary 61 is located centrally, the capillary 61 is surrounded with a cylindrical body 62, is that an annular From ^'opening 63 is obtained for the gas flow, due to the arrangement of the capillary 61 and acting as spacers cylindrical body 62 and its dimensioning, the gas flow is directed past the capillary 61, around the point marked 65 and between the two The area lying in dotted lines therefore has no gas flow. This ensures that the capillary opening 61 and the liquid located there are not captured by the gas flow. Due to the annular outlet opening 63 with the capillary 61 arranged in the center, the gas flow also emerges in a ring and surrounds the electrospray formed at the capillary opening in an even envelope. As a result, the electrospray is only caught on all sides later by the gas flow after the spraying, and the otherwise widening spray cone of the electrospray is contained or focused.

The embodiments shown in FIGS. 6b and 6c differ from those in FIG. 6a in that recesses 67 are provided and one tear-off edge 66 is provided. The tear-off edge 66 causes the gas flow to be detached sharply from the gas outlet opening in comparison. Widening of the gas flow and its velocity profile, as well as turbulence and turbulence, penetrate less into the area marked with 65 and lying between the dotted lines and thus cannot lead to pneumatic tearing off of the liquid from the capillary 61. The arrangement of the respective capillary 61 in the recess 67 creates a flowless region 65 around the capillary 61 in a particularly effective manner, in order to avoid according to the invention that liquid is torn off from the spraying point.

FIGS. 6 d and 6 e show embodiments in which the discharge opening 68 of the gas in the surrounding pipe 64 and / or on the cylindrical body 62 serving as a spacer is molded accordingly in order to cause the enveloping gas flow to focus on a point 69 is, and this results in a conical flowless region 65, the electrospray is more strongly focused compared to a tubular gas flow due to the conically tapering gas flow. FIG. 1 5 shows different ways of centering the cylindrical body 64 serving as a spacer and thus the spray point 61 in the gas outlet opening 68. The wires, fibers and webs used for this purpose as a spacer 21 1 between the cylindrical body 62 serving as a spacer and the means for generating a gas flow, which can be a tube 64, for example, can be made from a wide variety of materials. The wires used as a spacer 21 1 , Fiber and webs can be attached both to the cylindrical body 62 and to the means for generating the gas stream 64,

FIG. 1 6 shows different shapes for the end of the liquid-carrying capillaries 61, from which the liquid is detached,

FIG. 7a shows an embodiment with a plurality of concentrically arranged, annular outlet openings 79, 78 for a plurality of gas streams 76a and 76b,

A capillary 72 is also provided, to the opening 77 of which a charged liquid is fed and sprayed into an electrospray 71. Furthermore, a tube 75 is provided which surrounds the capillary 72. The capillary 72 itself is located centrally in a cylindrical body 73. The cylindrical body 73 is arranged in a tubular body 74 such that an annular gap 78 remains as an outlet opening between the two , via which a gas stream 76 b is fed in the direction marked by arrows. The tubular body 73 is in turn arranged in the tube 75 such that an annular gap 79 remains as an outlet opening between the two, through which a gas stream 76 b is supplied in the direction marked by arrows. It is hereby achieved that the outer gas flow 76 a with respect to the capillary 72 has a different flow rate compared to the inner gas flow 76 b and thus the bundling effect of the gas flows changes with the distance. Figure 7 b is the associated sectional view.

/ Figure 8a is the sectional view of another embodiment of the

Invention. For precise centering, tubes 82 are provided, which are arranged in a ring around the capillary 81, from which the Electrospray emerges. These tubes 82 adjoin the cylindrical body 83 surrounding the capillary 81. They also provide the spacer to the tube from which the enveloping gas stream exits. A gas stream or an auxiliary gas stream can emerge from these tubes 82 in order to avoid turbulence or a vacuum which could have a destructive effect on the formation of the electrospray, the figures 8b and 8c show different embodiments of the tubes 82 in a sectional view,

FIGS. 9a to 9j show further embodiments, different electrodes being arranged around the capillary 92, which electrodes can be both attractively and repulsively charged with respect to the liquid. In each case 91 is the electrospray, the enveloping gas stream or its annular outlet opening is designated 93, the capillary 92 is surrounded by a cylindrical body 98 which causes an orientation of the gas stream that a flowless area around the capillary 92 or its outlet opening In FIG. 9 a, the tube 94 represents the electrode. This configuration is preferred if this electrode is to act as a counter electrode with respect to the liquid, that is to say it is attractive to the liquid,

By contrast, FIG. 9b shows a further embodiment in which a disk-shaped electrode 96 is provided on the tube and around the capillary.

FIG. 9c shows a further embodiment, in which rods 96 which protrude from a plate represent the electrode. The plate can vary in diameter or can be omitted accordingly. The plate can be perforated so that air or gas can flow through these openings from the rear, in order to possibly cause negative pressure effects and the associated turbulence

To reduce focus gas

/

^" FIG. 9 d shows a further embodiment, a spiral 97 which protrudes from a plate represents the additional electrode, the plate can vary in diameter or can be omitted, the plate can be perforated so that air or gas can flow from behind through these openings, in order to reduce any negative pressure effects which may occur and the associated turbulence caused by the focusing gas,

An enveloping net or grid (without drawing) has a comparable effect,

FIG. 9 e shows a pot-shaped electrode as a further embodiment, which can be designed in one or more parts. FIG. 9 f shows the sectional view according to the section line drawn in FIG. 9 e and marked with I, FIG. 9 g shows the sectional view according to the section line drawn in FIG. 9e and marked with II, the pot has protruding portions 101 surrounding the capillary 92 and a disk-shaped portion

Bottom 100, on the one hand there is an annular outlet opening 93 for the gas flow in the disk-shaped bottom 100, the gas flow points in the direction marked with arrows in FIG these breakthroughs can flow to possibly occurring

To reduce negative pressure effects and the associated turbulence caused by the focusing gas. However, the shape of the openings 99 is not essential for achieving the desired effect.

The ^' - Figure 9 h shows another pot-shaped electrode, which can be designed in one or more parts. FIG. 9 i shows the sectional view according to the sectional line drawn in FIG. 9 h and marked with I, FIG. 9 j shows the sectional view according to the sectional line drawn in FIG. 9 h and marked with II, the pot protrudes the capillary 92 in a ring shape surrounding sections 1 01 and a disc-shaped bottom 1 00, there on the one hand an annular outlet opening 93 for the gas flow in the disc-shaped

/ Floor 1 00 provided. The gas flow points in the direction marked by arrows in FIG. 9 f. Circular openings 102 are provided in the sleeve and / or plate for air or gas to pass through them Breakthroughs can flow in order to reduce any negative pressure effects and the associated turbulence caused by the focusing gas. The shape of the openings 1 02 is, however, not essential for achieving the desired effect.

Figures 1 0 to 1 3 show increases in the signal intensity and thus in the signal-to-noise ratio, which were achieved by using the spray device described compared to conventional spray 0 devices. The spectra were on the same device under otherwise the same conditions added.

FIGS. 1 0 and 1 1 make it possible to compare the signal intensities in mass spectrometry between the spray devices according to the invention and conventional spray devices

Figure 1 0: spray device according to the invention signal intensity: 0, 1 3x1 0 ^"7 0 [5-leucine] enkephalin (mass = 555.6 Da)

1 0 \ + (- 5) mol / l in 50/50 MeOH / H \ - (2) 0 + 1% acetic acid flow rate = 500 nl / min

Figure 1 1: conventional spray device 5 signal intensity; 0.1 xl O ^"8

[5-leucine] enkephalin (mass = 555.6 Da)

1 0 \ + (-5) mol / l in 50/50 MeOH / H \ - (2) 0 + 1% acetic acid flow rate = 500 nl / min

Figures 1 2 and 1 3 also enable the comparison of the signal intensities in mass spectrometry between the spray devices according to the invention and conventional spray devices

3.5 Figure 1 2: Spray device according to the invention Signal intensity: 1 00% = 0, 1 1 3x1 0 ^"7 Horse Heart Myoglobin (mass = 1 6952 Da) 1 0 ^{" 5} mol / l in 50/50 MeOH / H20 + 1% acetic acid • flow rate = 500 nl / min

Figure 1 3: conventional spray device signal intensity: 1 00% = 0, 1 1 x1 0 ^"8 Horse Heart Myoglobin (mass = 1 6952 Da) TO ^'5 mol / l in 50/50 MeOH / H20 + 1% acetic acid flow rate = 500 nl / min

FIGS. 1 7 and 1 8 enable the comparison of the signal intensities in mass spectrometry in the case of positive electrospray between the spray devices according to the invention with SF ₆ as a gas stream and conventional spray devices,

Figure 1 7: Spray device according to the invention with SF ₆ m as a gas stream positive electrospray signal intensity: 34300 cps

[5-leucine] enkephalin (mass = 555.6 Da)

1 pmol / μl in 95: 5 H ₂ 0 / acetonitrile + 0.1% formic acid flow rate = 500 nl / min

Figure 1 8: conventional spray device positive electrospray

Signal intensity: 1 41 0 cps

[5-leucine] enkephalin (mass = 555.6 Da)

FIGS. 19 and 20 enable the comparison of the signal intensities in mass spectrometry in the case of negative electrospray between the spray devices according to the invention with SF ₆ as a gas stream and conventional spray devices,

/ Figure 1 9: Spray device according to the invention with SF _ό as a gas flow negative electrospray

Signal intensity: 1 6900 cps

[5-leucine] enkephalin (mass = 555.6 Da) 1 pmol / μl in 95: 5 H ₂ 0 / acetonitrile + 0.1% formic acid flow rate = 500 nl / min

Figure 20; conventional spray device negative electrospray

Signal intensity: 1 2 cps

[5-leucine] enkephalin (mass = 555.6 Da)

2.5 pmol / μl in 95: 5 H ₂ 0 / acetonitrile 4- 0.1% formic acid flow rate = 500 nl / min

Figure 1 4 a shows an embodiment of the panel according to the invention in supervision. 1 b is the sectional view of the diaphragm along the section line drawn in FIG. 1 4 a and marked with I, FIG. 1 c shows the rear view of the diaphragm body designated by 201 in FIG. 14 a,

The diaphragm body 201, here a disc made of PEEK with a diameter of 45 mm, is provided with a hole, here with a diameter of 8 mm, the diaphragm body is shaped like a pot and has projecting annular sections, the body is perpendicular to an imaginary one, through the hole going axis rotationally symmetrical, so as to generate a similarly designed electric field in the charged state, which acts accordingly focusing on the ion cloud that approaches the hole and passes through the hole, the aperture is provided with channels 204 for one or more gas flows,

Figure 1 4 b shows a sectional view of the diaphragm body, wherein this is made of several parts. To cover the gas channels 204 milled into the recesses in the diaphragm body, for example with dimensions of 0.6 x 0.6 mm, a cover 205 is made, for example, of 100 μm thick peek film provided. Alternatively, the panel body 201 can be designed in one piece and the cover _. 205 are omitted, in particular if the channels 204 can be drilled in the diaphragm body and therefore do not require a cover. The arrow labeled 206 indicates the direction in which the ion cloud passes the diaphragm, Figure 1 4c shows the rear view of the body designated 201. The channels 207 for the gas flow 208 are shown. In this case, outlet openings are provided all around the hole 202 in order to allow the gas flow to exit there and thus to detect the droplets approaching and / or passing the hole from the emerging star-shaped gas flows on all sides, if possible, The gas streams are interconnected by annular channels 207 in the diaphragm body 201. Furthermore, the gas stream is heated by a resistance wire 209 provided in the channels with electrical contacting 21 0 provided therefor.

In a preferred embodiment, the device for spraying electrically charged liquids has a spacer 4 between the tip or capillary 3 and means for generating a gas stream 7

Embodiment, a cylindrical body can be provided, which ensures a distance between the annular outlet opening 7 for the gas and the tip or capillary 3. This structural design is intended to ensure that the tip or capillary 3 or the spraying point is not caught by the gas flow. This desired effect occurs when the distance between the spray point 3 and the outlet opening 7 is chosen to be sufficiently large. A distance of at least 200 to 300 μm regularly proves to be sufficient,

The spacer 4 between the tip or capillary (3) or

The spray point and means for generating a gas stream 7 preferably have a tear-off edge for the gas stream so that it does not catch the spray point. In the case of a cylindrical body 4, this is achieved by an approximately right angle at the corresponding transition between the cylinder jacket surface and the corresponding head surface.

The cylindrical body 4 functioning as a spacer preferably has a diameter of at least 600 μm in order to provide the required distance from a capillary, In a further embodiment of the device for spraying electrically charged liquids, the tip or capillary 3 or the spraying point (s) protrude from the spacer. This ensures that the liquid leaves the tip or capillary 3. What is important is a certain spatial separation between the spraying point and the spacer, which can alternatively be provided by an annular recess between the spacer and the tip or capillary.

Claims

Expectations:

, Device for spraying electrically charged liquids, having at least one tip or a capillary (3) from which the charged liquid is sprayed, with means for generating an electric field for spraying the electrically charged liquid, with means for generating at least one gas stream (2), which is directed so that the tip or capillary (3) is not caught by the gas stream (2).

2. Device for spraying electrically charged liquids according to the preceding claim, wherein the outlet opening (7) of the gas stream (2) or the outlet openings of the gas streams are arranged around the tip or capillary (3),

3. Device for spraying electrically charged liquids according to the preceding claim, wherein the outlet opening (7) of the gas stream (2) or the outlet openings of the gas streams are arranged in a ring around the tip or capillary (3)

4. Device for spraying electrically charged liquids according to one of the preceding claims, wherein a plurality of outlet openings (78, 79) of the gas streams are arranged in a ring and concentrically around the tip or the capillary (72),

5. Device for spraying electrically charged liquids according to one of the preceding claims, wherein the outlet opening (63) of the gas stream is shaped (68) or arranged in such a way that the gas stream or the gas streams is conically oriented, focusing on a point (69) or are, , Device for spraying electrically charged liquids according to one of the preceding claims, wherein means for heating the gas flow or the gas flows are provided.

, Device for spraying electrically charged liquids according to one of the preceding claims, the means for generating one or more gas flows being such that the gas flow in the outlet area is at least 20 m / s,

, Device for spraying electrically charged liquids according to one of the preceding claims, with an outlet opening (1 1, 40) for an auxiliary gas flow in the area between the gas flow and in each case the tip or capillary (13, 46),

, Device for spraying electrically charged liquids according to one of the preceding claims, wherein the gas in one or more gas streams consists of nitrogen, sulfur hexafluoride, air or mixtures thereof,

0, device for spraying electrically charged liquids according to one of the preceding claims, wherein the outlet opening has a tear-off edge (66),

1, device for spraying electrically charged liquids according to one of the preceding claims, wherein the tip or capillary (61) is arranged in a recess of the device (67).

2. Device for spraying electrically charged liquids according to one of the preceding claims, the tip or capillary (61) projecting from adjacent regions of the device (62),

3, device for spraying electrically charged liquids according to one of the preceding claims, wherein the means for Generating an electric field have an electrode (94, 95, 96, 97, 1 00, 1 01) which is arranged essentially in a ring and / or in a disc shape around the outlet opening of the gas stream (93).

, Device for spraying electrically charged liquids according to one of the preceding claims, wherein the means for generating an electric field comprise one or more peaks for corona discharges.

, Device for spraying electrically charged liquids according to one of the preceding claims, with a mass spectrometer,

Spraying device according to the preceding claim, wherein the gas flow is not aligned with the input of the mass spectrometer.

, Device for spraying electrically charged liquids according to one of the preceding claims with a spacer (4) between the tip or capillary (3) and means for generating a gas flow (7), a spacer in particular being provided as a cylindrical body which has a distance between an annular outlet opening (7) for the gas and a capillary (3),

, Device for spraying electrically charged liquids according to one of the preceding claims, with a spacer (4) between the tip or capillary (3) and means for generating a gas flow (7), the spacer having a tear-off edge for the gas flow, which in particular by is formed at a right angle

, Device for spraying electrically charged liquids according to one of the preceding claims with a spacer (4) between the tip or capillary (3) and means for generating a gas flow (7), which has a distance of at least 200 μm, preferably at least 300 μm, between an annular outlet opening (7) for the gas and the capillary (3) generated,

20, device for spraying electrically charged liquids according to one of the preceding claims with a spacer (4) between the tip or capillary (3) and means for generating a gas flow (7), the tip or capillary (3) protruding from the spacer .

21. Device for generating an ion cloud, with an aperture (201, 203, 205) arranged in the ion cloud.

22. Device for generating an ion cloud according to the preceding claim, wherein the diaphragm (201, 203, 205) made of an insulating and / or chemical-resistant material.

23, Device for generating an ion cloud according to one of the two preceding claims, wherein at least one opening for a gas stream is arranged in the hole (202) of the diaphragm (201, 203, 205).

24. Device for generating an ion cloud according to the preceding claim, wherein means for heating (209) the gas stream are provided,

25, Use of the device according to one of the preceding claims in mass spectrometry.