GB2472894A - Method and apparatus for the transfer of charged droplets along a path - Google Patents

Abstract

The invention relates to guiding charged droplets 2 along a defined path, for example from the spray capillary 1 of an electrospray ion source at atmospheric pressure to the inlet capillary 7 of the vacuum system of an ion mobility or mass spectrometer. This is achieved by providing a focusing pseudopotential distribution generated by applying an audio frequency AC voltage to the electrodes 4 of a guiding device 3. The droplets 2 can be driven along the droplet guide 3 by a gas flow 5, an axial electric field or a combination of both, and can be manipulated in different ways, for example evaporated down to a desired size. The ability to guide the droplets also makes it possible to install a segmented inlet capillary 7, 9 with intermediate pumping, which allows pumping capacity to be saved.

Description

Method and apparatus for the transfer of charged droplets along a path [1] The invention relates to the guiding of charged droplets along a defined path, e.g. from a droplet source to a droplet sink.

[2] The generation of ions of heavy analyte molecules with molecular weights of several hundred to many thousand daltons in an electrospray ion source is very well known. The ability to ionize macromolecules, which cannot be vaporized thermally, is extremely important; John Bennett Fenn was awarded a part of the 2002 Nobel Prize for Chemistry for the development of the electrospray ion source toward the end of the 1980s.

[3] A high voltage of several kilovolts is applied to a pointed spray capillary containing spray liquid with dissolved analyte molecules in order to generate an extremely strong electric field around the tip. This polarizes the surface of the spray liquid in the open tip and highly charges it; the electric tractive force creates a so-called "Taylor cone" on the surface of the liquid, and the electric drawing field draws a fine jet of liquid out of the tip of the cone. This jet is intrinsically unstable due to its high surface charge, which opposes the surface tension: it disintegrates by constriction into minute, highly charged droplets with diameters in the order of a hundred nanometres to a few micrometers.

[4] The size of the droplets depends on the aperture at the tip of the spray capillary and the electric field generated around the tip. So-called nanoelectrospray ionization uses apertures of around 2 to 3 micrometers, which require only voltages below one kilovolt for the spraying; droplets of 100 to nanometres in diameter are then generated at flow rates of a few tens to a maximum of one thousand nanoliters per minute. For normal electrospraying with one to a few thousand microlitres per minute, apertures of around ten to thirty micrometers diameter are used with spray voltages of three to five kilovolts, and droplet diameters of one to two micrometers are produced, which thus have a volume more than a thousand times larger than that of the nanospray droplets.

Droplets with a diameter of around one micrometer carry about 50,000 elementary charges. The decomposition of the jet of liquid into droplets can be assisted by a focused jet of a spray gas, which is blown in around the tip of the capillary by a concentric spray gas capillary. This causes the jet of droplets to be guided in a somewhat more focused way, although the droplets are created with greater diameter variance.

[51 The droplets subsequently evaporate in a hot drying gas, a process whereby it is usually only the neutral solvent molecules which vaporize initially. This causes the charge density on the surface to increase continuously. If the charge density on the surface becomes so large that the Coulomb repulsion exceeds the force of the cohesive surface tension ("Rayleigh limit"), small droplets start to split off The unstable surface brings about random oscillations of the fluid on the surface, and these random motions in turn cause smaller droplets to separate off, causing the charges of both droplets to fall below the Rayleigh limit again. Smaller droplets which split off have a much higher charge in relation to their mass, if only because the total charge qR of a droplet at the Rayleigh limit is proportional to the root of the third power of the diameter d, (q Jd3). Droplets which have split off can thus carry away only two per cent of the mass, but fifteen per cent of the charge, for example. The droplets generated, both large and small, have a mass-to-charge ratio above the Rayleigh limit, however, and can thus vaporize further.

[6] Different-sized droplets with charge densities at the respective Rayleigh limit show different magnitudes of their electric mobilities 1u = vIE (v = velocity) when they are pulled through gas by electric fields of field strength E. Slow motions of the droplets without eddying are subject to Stokes' law, exhibiting a friction proportional to the diameter d and the velocity v of the droplets.

The electric mobility 1u is therefore proportional to Id, and is thus, surprisingly, higher for larger droplets than for smaller ones. Rapid motions with turbulent eddying are subject to Newtonian friction, proportional to the cross-section d2 and the square of the velocity v2. Under these conditions, which usually do not, however, apply to spray droplets and their velocities in drying gases, the electric mobility 1u is proportional to the inverse root K2 of the field strength E and the inverse fourth root d4 of the diameter d.

[7] All droplets, large and small, continue to vaporize, small droplets vaporizing faster and faster due to the fact that the coordination number of their surface molecules gets ever smaller, causing the vapour pressure to increase, until the splitting off and vaporization processes end relatively rapidly in the complete drying of a droplet, and it is primarily only multiply charged ions of the analyte molecules contained in the droplet which remain. In the last phase, protonated water molecules may also vaporize. The analyte ions thus formed are generally only surrounded by a somewhat more strongly bound sheath of one to two molecular layers of solvent molecules, usually water molecules.

118] As already indicated above, there are in principle two different types of electrospraying, which are also used in different ways: nanoelectrospraying (nanospraying for short) with very small droplets, which are usually sprayed directly into the inlet capillary leading to the ion analyzer, and normal electrospraying: (microspraying for short) which vaporizes the droplets in free air and draws only the resulting analyte ions into the inlet capillary.

[9] Nanospraying generates very small droplets with approximately equal diameters in the order of around 100 to 200 nanometres, which are sprayed directly into the inlet capillary. The droplets are drawn into the inlet capillary by a specially introduced transport gas, usually nitrogen at a temperature which can be adjusted between room temperature and 300 degrees Celsius, and are accelerated there in the transport gas flow. They then vaporize slowly in the inlet capillary, supported by the ever decreasing pressure, but remain as droplets for a long time. The advantage of introducing droplets into the inlet capillary is that gas-dynamic focusing can be used to guide the droplets through the capillary with very low losses. In the inlet capillary, brief boundary turbulences give way to a stable laminar flow of the transport gas with parabolic velocity profile: fastest in the centre, resting at the wall. The droplets are entrained by this fast gas stream with parabolic velocity profile, which flows around them, and are held in the axis of the capillary. If they swerve to the side, they get into a region where they are in a gas stream which flows at different speeds on either side; the Bernoulli effect then drives them back toward the axis with a lift similar to that of an airplane wing.

[10] The greater the velocity difference between gas and droplets, the stronger this "Bernoulli focusing", because the lift is proportional to the difference between the squares of the velocities on either side of the droplet. Since the gas flows faster and faster toward the end of the inlet capillary, the droplets can never achieve the velocity of the gas; this focusing effect is thus maintained until the droplets are completely vaporized or have left the capillary. An opposing electric field in the inlet capillary enhances this focusing effect further because it decelerates the droplets and prevents them assuming the velocity of the gas. It is still unclear whether larger analyte ions are also subject to this Bernoulli focusing if they are decelerated by an opposing field, and whether this focusing can be effective against the repulsion by the space charge prevailing in the axis.

[11] Nanospraying requires very good adjustment of the spray capillary tips with respect to the aperture of the inlet capillary. Since the spray capillaries have to be replaced frequently, the ion sources are usually equipped with microscopes or microcameras for aligning the tips. This requirement to carefully adjust the spray capillary tips is one of the disadvantages of nanospraying, in addition to the low flow rate.

[12] With normal electrospraying (microspraying), on the other hand, the droplets are completely vaporized outside the inlet capillary, thus releasing the analyte ions. These analyte ions generally still have a solvate layer. Only these analyte ions are brought to the entrance aperture of the inlet capillary. The analyte ions lose their solvate layer on their way through the inlet capillary into the vacuum system, a process which is assisted by the heating caused by the hot transport gas and the decreasing pressure along the inlet capillary. The objective is to draw as many of these analyte ions as possible with the hot transport gas into the admission aperture of the inlet capillary, but this only succeeds to a very limited extent due to the large volume in which the analyte ions are produced. In general, microspraying feeds far less than one percent of the sprayed analyte molecules into the ion analyzer in ionized form.

[13] In both cases, the inlet capillary guides the charged analyte molecules, either in the form of charged droplets or in the form of solvated analyte ions, into the vacuum system of the ion analyzer operating in a vacuum, which can be a mass spectrometer or an ion mobility spectrometer, for example. In the vacuum system, the analyte ions can be captured by a so-called ion funnel, for example, then separated from the accompanying transport gas and introduced into the ion analyzer via further ion guides and pumping stages. The analyte ions of the desired type are analyzed in the ion analyzer. A single inlet capillary can be used to introduce the analyte ions into the vacuum; it is also possible to bundle several inlet capillaries together in order to introduce the analyte ions into the vacuum. This bundle of inlet capillaries shall be included here when the term "inlet capillary" is used.

[14] Most of the analyte ions are multiply charged. However, the number of charges for ions of a single substance varies greatly, and the average number of charges increases roughly in proportion to the mass of the analyte ions. For heavy ions, the mass-to-charge ratios m/z (m = mass; z = number of excess elementary charges of the ion) have a wide distribution from about m/z = 700 daltons up to about m/z = 1,600 daltons with a maximum at around m/z = 1,200 daltons. The heavy molecules of albumin (m 66 kDa) thus carry a 50-fold charge on average, while light molecules with molecular weights below m = 2 kDa are predominantly singly charged. The distribution of the charges can be affected by the composition of the solvent, the spraying processes and the processes with which the ions are guided through gases.

[15] Since the droplets of the spray jet from the spray capillary are all very highly charged, with 50,000 elementary charges for one droplet with a diameter of one micrometer, for example, they repel each other very strongly. This causes the jet of spray droplets which are accelerated in the electric field to broaden to a cloud with a pronounced funnel shape immediately after the droplets have been formed. With nanoelectrospraying, the broadening is limited by the transport gas with which the cloud of droplets is drawn into the inlet capillary and which entrains the droplets and accelerates them. With normal electrospraying, the volume of the gas containing the analyte ions after the liquid has vaporized from the droplets is considerably large. It is difficult to draw a large number of analyte ions from this large volume into the inlet capillary. A focused jet of spray gas, which can be heated up to around 150°C, can be introduced concentrically around the spray capillary to reduce this volume in radial direction; the spray droplets are then accelerated even more, however. This produces a very elongated ion formation volume of moderate width, but in which many fast, unvaporized droplets are flying through the cloud of analyte ions.

[16] Thus an elongated and moderately wide volume with analyte ions is produced by application of a spray gas. The ions are usually extracted more or less perpendicularly and fed to the inlet capillary. This is successful for only a small fraction of the analyte ions, however, because only analyte ions from a small section of the length and width of this ion formation volume reach the inlet capillary. More analyte ions can be extracted if the ion formation volume can be better focused in radial direction. This can be achieved by additionally blowing in a "super hot" sheath gas at a temperature of about 3 00°C around the hot spray gas. This causes a "thermal focusing" of the droplets; the utilization of the analyte ions is better and the sensitivity of the method is greater.

[17] Although normal electrospraying ionizes practically all analyte molecules if the droplets are completely vaporized, the yield of ions introduced into the analyzer is very small, despite all these improvements. Nevertheless, normal electrospraying is now widespread, because it can be easily coupled to the normal flow rates of analytical liquid chromatography (HPLC). Nano-electrospraying, in contrast, provides a very high yield of analyte ions, but it cannot be coupled with liquid chromatography without an unfavourable splitting of the flow of liquid because even so-called nano-HPLC has flow rates which are far above those which nanospraying can cope with.

The unfavourable splitting of the liquid flow cancels out the favourable ion yield, however.

Attempts to inject larger droplets, which are produced at slightly higher flow rates with slightly larger spray tip aperture diameters, directly into the inlet capillary have so far been unsuccessful.

[18] The objective of the invention is to transfer charged droplets with low losses along a specified path, e.g., from a droplet source to a droplet sink, such as a gas-aspirating capillary. It is advanta-geous here if the droplets can be manipulated during the transfer, e.g. vaporized down to a desired size.

[19] The invention uses the pseudopotential of a special guiding device to introduce the cloud of charged droplets of a droplet source finely focused into a droplet sink. The guiding device can be a multipole rod system, or a stack of diaphragms, or another pattern of electrodes around the path, just like the well-known RF guide systems for ions in high and medium vacua. It operates, however, at much higher pressure, for example up to atmospheric pressure, but at much lower frequencies, typically at audio frequencies, for charged particles of greater mass. The guiding device for the droplets is also termed "droplet guide" below. The best and strongest focusing is achieved by an alternating field having the cross-section of a quadrupole, a so-called "two

dimensional quadrupole field".

[20] Accordingly, in a first aspect of the invention, there is provided a method for the transfer of charged droplets along a path, which method comprises providing a guiding device comprising a plurality of electrodes disposed around the path, and generating a radial pseudopotential distribution to keep the the droplets radially on their path, by providing AC voltages on the electrodes of the guiding device.

[21] Within the guiding device, the charged droplets can be moved in the axial direction by a gas flow, an axial electric field, an electric travelling field or by a combination of these. Droplets of different size can be moved in different ways due to their different mobilities. For instance, large droplets can be held back until evaporated down to a desired size.

[22] The invention may explained by way of example using a special electrospray device as source of the charged droplets and an inlet capillary as a sink. In this special electrospray device, the spray droplets from the spray capillary should not be evaporated before they enter the inlet capillary.

The cloud of droplets should be fed into the entrance aperture of the inlet capillary as completely as possible, finely focused by the pseudopotentials of the guiding device. The inlet capillary acts as the droplet sink, similar to the process used currently for nanospraying, but with much higher flow rates in the spray capillary. As has already been explained in the introduction, it is advantageous to introduce droplets into the inlet capillary because they are guided through the capillary with low losses by Bernoulli focusing. Spray capillaries with liquid flow up to a few hundred microlitres per minute can be used. The droplets must be evaporated down to a small size to be accepted by the inlet capillary in high numbers. They should not, however, completely evaporate before being introduced into the inlet capillary.

[23] The different mobilities of the spray droplets of different sizes can be used for this almost complete evaporation of the droplets. In order to introduce only relatively small droplets, preferably all of the same size and preferably only 50 to 200 nanometres or so in diameter, larger droplets have to be kept longer within the drying gas of the droplet guide than smaller ones. This is achieved by generating a flow of a hot drying gas and an opposing electric field in the droplet guide in such a way that small droplets move faster, and larger droplets move more slowly or not at all, toward the inlet capillary. Gas flow and axial electric field may have favourably tailored profiles. If the droplets move relatively slowly through a moving drying gas, the mobility of droplets at the Rayleigh limit is proportional to the root of the diameter, and thus higher for larger droplets than for small droplets, an effect which can be utilized. The droplets retained longer in the droplet guide thus have more time to vaporize. But the final evaporation of the spray droplets must only occur after they have left the droplet guide, i.e. in the inlet capillary at the earliest, because the analyte ions would immediately be attracted by the electrodes of the droplet guide until they hit the electrodes and are discharged.

[24] The alternating electric field in the droplet guide already helps to deform larger droplets by shaking motions and thus make them unstable so that they experience a perturbation of the spherically symmetrical charge distribution and are thus torn into smaller droplets. If larger droplets do not already decompose in the alternating electric field, their vaporization can be increased by irradiation with infrared light or microwaves. Nebulization by ultrasound is also possible.

[25] After the droplets have been introduced into the inlet capillary, gas-dynamic focusing (Bernoulli focusing) acts to keep them on the axis of the inlet capillary for as long as possible. To achieve this, premature complete evaporation of the droplets must be prevented. The evaporation can be controlled by selecting the size of the droplets introduced and by controlling the humidity of the transport gas. The focusing can particularly be enhanced by an opposing electric field in the inlet capillary.

[26] The invention also offers the possibility of segmenting the inlet capillary into two or more segments so that a large proportion of the inflowing transport gas can be evacuated with small pumps at relatively high pressure. According to the invention, the droplets are guided between the segments by means of droplet guides, for example small quadrupole rod systems, from the last segment (as droplet source) to the aperture of the next segment of the inlet capillary (as droplet sink). In each case, new transport gas with the desired temperature and humidity can also be fed in for the next segment, in order to completely evaporate the droplets in the last segment, for example. Segmented inlet capillaries make it possible to select capillaries with larger internal diameters and therefore higher gas throughput, which also means that more droplets can be transported.

[27] If droplets are introduced into a first stage of the vacuum system, they can be completely evaporated there, but they can also be made to burst into smaller droplets or even into analyte ions by impacting on hot surfaces, for example.

[28] Applying the invention to electrospray devices makes it possible to introduce an extraordinarily large number of ionized analyte molecules into the vacuum system of the ion analyzer, even at flow rates in the spray capillary of up to a few hundred microlitres. Analyte molecules in far lower concentrations can therefore be detected; the sensitivity of ion analyzers equipped in this way increases by one order of magnitude at least. The new type of electro spray ion source can be coupled particularly well with nano-liquid chromatographs, and also with chip-based separating systems.

[29] Figure 1 is a schematic representation of an electrospray ion source according to this invention. A jet (2) of fine droplets is drawn from the spray capillary (1) by a voltage of a few kilovolts. The droplets are held on axis in a tubular droplet guide (3), which has an electrode pattern (4) inside for generating a two-dimensional quadrupole AC field, and are guided to the entrance of the inlet capillary (7). The forward propulsion is effected by a balance between a stream of hot drying gas (5) and an opposing electric drawing field generated by voltages applied to the electrode pattern.

The profile of the stream of drying gas (5) and the profile of the axial DC field are adjusted in such a way that larger droplets are kept back until evaporation and splitting have made them sufficiently small so that only small droplets of roughly equal size are introduced into the inlet capillary (7). A temperature-and humidity-controlled transport gas (6) is introduced around the inlet capillary (7) and drawn in by the inlet capillary (7), together with the droplets. -The inlet capillary (7) is segmented within an intermediate pump station (10) with pump (11), the charged droplets (2) being transferred by a quadrupole rod system (8) according to the invention into the second segment (9) of the inlet capillary. A suitable temperature-und humidity-controlled transport gas can again be added (12). The droplets now vaporize either while still in the inlet capillary (9) or afterwards in a first vacuum stage of the ion analyzer.

[30] Figure 2 represents a schematic array of a tubular droplet guide, only two of the four sides being shown, however. Wire-shaped electrodes (33, 34) are embedded in the ceramic main bodies, of which only the main bodies (31) and (32) are visible here; with appropriate AC and DC voltages, the pattern of these electrodes can generate a quadrupolar alternating field in radial and a DC electric field profile in axial direction. The ceramic bodies can be equipped with apertures (35) for

the introduction and removal of gases.

[31] Figure 3 shows one of these ceramic main bodies (32) in cross-section with a wire loop inserted (34). Electric circuits with electronic components (36) can be mounted on the back of the main body (32) in order to supply the wire loops (34) with the required voltages.

[32] Figure 4 shows a slightly different embodiment of an electrospray ion source according to this invention, wherein the tubular droplet guide (3, 4) is replaced by a quadrupole rod system, whose two pole rods (14) and (15) are visible in the illustration. Within the quadrupole rod system there is a thin-walled tube (16) made from a dielectric that is a very poor electrical conductor, which allows the AC field of the rod system to penetrate. In this weakly conducting tube, a voltage drop can be generated, against which the stream of drying gas drives the droplets to the inlet capillary.

[33] Quite generally, the invention makes it possible to radially compress a cloud of charged droplets from a droplet source to form ajet of droplets by means of a guiding device with audio-frequency alternating voltages applied to suitably formed electrodes, and to guide the droplets along a predefined path to a droplet sink. The term "droplet source" means the same as in normal usage, i.e. the appearance of droplets at one point of a defined observation region; the term "droplet sink" means the disappearance at a different point in the region observed. The compression of the cloud is based on the effect of inhomogeneous alternating fields on the droplets; this effect is known for ions in a vacuum and is explained there by so-called "pseudopotentials", which are known to the person skilled in the art and are not further explained here. The strongest "compression" ofajet of droplets, simply termed "focusing" below, is generated by a two-dimensional quadrupole field; two-dimensional higher-order multipole fields, such as hexapole or

octopole fields, exert a slightly weaker effect.

[34] The storage of charged particles in inhomogeneous alternating fields, just as in Paul ion traps, with audio frequencies at atmospheric pressure has been known for 50 years and is also used in some technical fields, for example to determine the size of charged aerosol or dust particles. It is therefore surprising that this type of particle storage and guidance has not yet been used for the guiding of charged droplets in electrospray devices.

[35] In the interior of the guiding device, the droplets can be moved in the axial direction by the friction in a gas flow, by axial electric fields, by a travelling electric field with travelling potential minima or a combination of these.

[36] This invention makes it possible, for example, to design an electrospray device in which the spray droplets are introduced -as finely focused as possible and preferably with uniform size -centrally into the entrance aperture of an inlet capillary leading to the ion analyzer, a procedure similar to that used up to now in nanospraying, but with higher flow rates of up to a few hundred microlitres per minute.

[37] A favourable embodiment for such an electro spray device is illustrated schematically in Figure 1.

The spray capillary (1) has an aperture with a diameter of between five and ten micrometers. A voltage of between two and four kilovolts with respect to the average voltage on the electrodes (4) of the droplet guide (3) is applied to the spray capillary. At optimum operation, the spray capillary feeds a liquid stream of around 10 microlitres per minute to the spray tip, preferably from a nano-HPLC. The liquid, usually water mixed with some organic solvents such as aceto-nitrile, contains the analyte molecules in solution. A sequence of droplets (2) is drawn out of this liquid by the electric drawing field, forming a Taylor cone in the process. Pseudopotentials of the guiding device (3, 4) focus the cloud of droplets into a fine jet (2).

[38] The guiding device can in principle be designed as a multipole rod system, as a stack of ring diaphragms, or as one of the many other known forms of RF ion guide, as are used for the guiding of ions in high and medium vacua. Those skilled in the art are familiar with these ion guides. For charged particles of larger mass, these guide systems can operate at far higher pressure, here at atmospheric pressure. The alternating voltages used must then have much lower frequencies, however. To guide the highly charged droplets, the guide system can be operated with alternating voltages of between 20 and 3,000 volts in the audio frequency range between 20 and 20,000 hertz.

[39] In Figure 1, a tube (3) is used as the droplet guide. This tube has an electrode pattern (4) on the inside to generate a two-dimensional quadrupole AC field and also an axial DC field of arbitrary field strength profile. The tube can have a diameter of ten millimetres and a length of ten centimetres, for example. Figure 2 shows a schematic representation of two of the four sides of such a droplet guide. Wire-shaped electrodes (33) and (34) are embedded in four ceramic main bodies, of which only two, (31) and (32), are depicted here. These electrodes can generate a quadrupole AC field in radial direction and a DC electric field profile in the axial direction when suitable AC and DC voltages are applied. The quadrupole alternating field forms a strictly quadrupolar field in the centre, but one which is distorted toward the outside. The voltages can be generated by voltage dividers of a printed circuit on the back of the ceramic main bodies, as depicted schematically in Figure 3. Alternating voltages of a few hundred volts with frequencies roughly between 2 and 10 kilohertz are preferably used for focusing the droplets. -In order to prevent the droplets getting too close to the wires, adjacent wires can carry alternating voltages of the same phase, but different amplitudes; this generates a strongly repelling pseudopotential close to the wires, which repels the droplets. -It is also possible to coat the insulating surfaces between the wires with a high-resistance layer in order to discharge the charges of any impacting droplets.

Alternatively, the wires can be replaced by flat metal strips which cover a large part of the surface.

The metal strips can even overlap without touching to completely cover the insulating base.

[40] The tube (3) of the droplet guide is equipped with gas feeds and gas exits at the ends. One gas feed supplies the preferably heated drying gas (5); this gas flows in the direction against the axial electric drawing field. A second gas feed supplies the transport gas (6), which is injected at a point further along the tube and is drawn in almost completely by the inlet capillary (7). The temperature and humidity of this transport gas (6) can be controlled independently of the drying gas (5) in order to leave the droplets in the inlet capillary (7) unevapourated for as long as wanted.

[41] The tube (3) of the droplet guide is aligned once very accurately with respect to the aperture and the axis of the inlet capillary when the ion source is assembled. This means there is no need for the user to subsequently repeat the alignment, as is the case with nanospraying.

[42] Since it is advantageous to introduce only very small droplets preferably of equal size into the inlet capillary (7), the different mobilities of different-sized spray droplets can be used to keep back larger droplets with higher mobility in the droplet guide until they have evaporated or split to form smaller droplets. This requires the generation of a forward propulsion for the droplets in the droplet guide (3, 4) which transports smaller droplets faster through the droplet guide, larger droplets, in contrast, more slowly or not at all. Such a differentiating forward propulsion can be generated by an axial electric field and a counterfiowing drying gas (5). A calculation of Reynolds numbers for droplets shows that the droplets move strictly in the region of Stokes friction. When Stokes friction occurs, the mobility of droplets at the Rayleigh limit is proportional to the square root of the diameter d, and hence higher for larger droplets than for smaller droplets. When the magnitude of the gas flow and the axial voltage profile are set correctly, the larger droplets can be retained longer in the droplet guide (3, 4) and have more time to vaporize. The voltage profile may be tailored to exhibit a non-linear field strength, weak at the entrance and high at the exit of the droplet guide. The size of the droplets introduced into the inlet capillary is determined by the setting of the field strength at the end of the droplet guide and the setting of the flow of the drying gas (5). Advantageous diameters are between 20 and 200 nanometres, most favourable at around nanometres; field strength at the end of the droplet guide and drying gas flow are best adjusted by optimizing the analytical sensitivity, i.e. by maximizing the ion current when a liquid with a constant analyte concentration is supplied.

[43] The voltage and frequency of the audio-frequency alternating voltage on the electrodes can also be selected so that the heavier droplets vaporize faster due to the shaking movement in the alternating electric field, and particularly break up faster into smaller droplets as a result of the deformation thus caused. Since larger droplets possess a smaller m/z than smaller droplets, the space charge drives them further away from the axis of the guiding device than smaller droplets, i.e. they are subject to a stronger alternating field. If the larger droplets are positioned sufficiently far away from the axis, they are also not driven so strongly against the axial field by the flow of the drying gas, which has a parabolic velocity distribution, and are thus held back.

[44] The lower the frequency of the alternating voltage, the greater the shaking movement of these droplets; the preferred vaporization of larger droplets can thus be controlled to a certain extent by the choice of frequency. The choice of voltage determines the diameter of the cloud, and the choice of frequency determines the amplitude of the shaking motion. The two parameters are not independent of each other, however: a higher frequency must be compensated by a voltage which increases as the square if the diameter of the cloud is to stay the same. Advantageous conditions exist in the region of five to ten kilohertz at voltages up to several thousand volts.

[45] The vaporization of the droplets in the droplet guide can also be supported by further measures, such as infrared radiation, ultrasound or microwaves. These measures are not shown in Figure 1.

It is expedient here to adjust the wavelength of the infrared light according to the solvent sprayed -water, for example -in order to achieve high absorption.

[46] After the droplets have been introduced into the inlet capillary, gas-dynamic focusing (Bernoulli focusing) keeps them on the axis of the inlet capillary. The principle of this focusing was described in detail in the introduction. If this focusing is to be maintained over a long part of the inlet capillary (7), premature evaporation of the droplets must be prevented by selecting the size of the droplets introduced and by controlling the humidity of the transport gas (6) which flows into the inlet capillary (7). The focusing can particularly be enhanced by an opposing electric field in the inlet capillary. This reduces the velocity of the droplets with respect to the gas, and the focusing Bernoulli lift for the droplets toward the axis of the inlet capillary increases.

[47] It has been shown to be expedient to coat the inner surface of the inlet capillary (7) with a high-resistance layer in order to discharge impacting droplets or ions and thus prevent an accumulation of charges. This layer also helps to form an uniform opposing electric field. Techniques for the production of high-resistance layers in glass capillaries are known.

[48] This invention can also be applied to divide the inlet capillary into two or more segments, in order to pump off most of the inflowing transport gas with small pumps at relatively high pressure.

Figure 1 shows a schematic representation of such an intermediate pumping station (10) with a pump (11). Within the intermediate pumping station (10) the inlet capillary is divided into the segments (7) and (9); the droplets emerging from the segment (7) are guided via a droplet guide (8) according to the invention to the entrance of the next segment (9) of the inlet capillary and collected in the aperture of the inlet capillary (9). The droplet guide (8) here has the form of a very small quadrupole rod system. Since the pressure of the gas is lower here and the velocity of the droplets high, high alternating voltage frequencies and low alternating voltages must be used.

A relatively small pump (11) can be used because the transport gas can be pumped away at sig-nificantly higher pressure than at the end of a single stage embodiment of the inlet capillary (7).

[49] In this intermediate pumping station (10), new transport gas (12) with desired temperature and humidity can also be fed in for the next segment (9), in order to completely evaporate the droplets in segment (9), for example. The inlet capillary is not limited to two segments, more are also possible. The segmented inlet capillary makes it possible to save pump capacities, on the one hand, and also to select higher gas throughputs by using capillaries which have larger internal diameters in individual segments, which means that more droplets can be transported.

[50] The invention leads to electrospray devices which introduce extraordinarily high numbers of ionized analyte molecules into the vacuum system of the ion analyzer, even at flow rates in the spray capillary up to a few hundred microlitres. These new types of electro spray ion source can be coupled well with nano-liquid chromatographs, and also with chip-based separation systems, without having to split the flow of liquid.

[51] In a slightly different type of embodiment of an electrospray device, which is based on this invention, a tube made of a dielectric that is a very poor conductor ("leaky dielectric") can be used within a quadrupole rod system, as is depicted in Figure 4. The alternating electric field is weakened only slightly as it passes through the dielectric and generates the focusing; on the other hand, a voltage drop at the poorly conducting dielectric can generate the axial DC field, against which the flow of the drying gas pushes the droplets to the inlet capillary. The spray capillary sprays directly into this tube if the spray capillary is set at a potential which differs from the potential of the poorly conducting dielectric by a few kilovolts. In order to vary the ratio of flow strength and electric field along the axis, a slightly conical tube of poorly conducting dielectric material can be used, for example.

[52] There are further embodiments for the droplet guides of the invention, and also many embodiments of ion guides with and without axial forward propulsion of the ions by axial electric fields. Axial fields can be generated by segmented quadrupole rod systems or by quadrupole rod systems with non-conducting high-resistance coatings, for example. Ion guides with forward propulsion are also known in the form of diaphragm stacks. Helically wound high-resistance wires can also be used. All these forms can be used according to the invention in electrospray devices.

Claims (21)

1. Claims 1. A method for the transfer of charged droplets along a path, which method comprises providing a guiding device comprising a plurality of electrodes disposed around the path, and generating a radial pseudopotential distribution to keep the the droplets radially on their path, by providing AC voltages on the electrodes of the guiding device.
2. 2. A method according to Claim 1, wherein the guiding device comprises a multipole rod system, or a stack of apertured diaphragms.
3. 3. A method according to Claim 1 or Claim 2, wherein the charged droplets are transferred along the path from a droplet source to a droplet sink.
4. 4. A method according to any one of Claims ito 3, including generating a gas flow profile and an electric field profile along the path in the guiding device, whereby the transfer velocity of the droplets is dependent on their mobility.
5. 5. A method according to Claim 4, wherein the direction and profile of the electric field and the direction and profile of the gas flow in the guiding device are such that larger droplets with higher mobility remain longer in the guiding device than smaller droplets.
6. 6. A method according to Claim 5, wherein the gas of the flow is heated and the droplets are kept evaporating within the gas flow for as long as all droplets exit the droplet guide with roughly the same diameter.
7. 7. A method according to any one of Claims ito 6, wherein the electrodes of the guiding device are configured to generate a two-dimensional quadrupole alternating field.
8. 8. A method according to any one of Claims ito 7, wherein the pseudopotential is generated by an alternating voltage in the range 20 and 20,000 hertz with a voltage of from 20 to 3,000 volts at the electrodes of the guiding device.
9. 9. A method according to any one of Claims ito 8, wherein the frequency and amplitude of the AC voltage at the guiding device are such that the droplets of the droplet mixture are subject to a shaking motion, causing the larger droplets to vaporize and disintegrate faster than the smaller droplets.
10. 10. A method according to any one of Claims ito 9, wherein the droplets in the droplet guide are irradiated with infrared light, ultrasound or microwaves.
11. 11. Method according to any one of the Claims 1 to 10, wherein the charged droplets are transferred from an electrospray ion source to a gas-aspirating inlet capillary leading to an ion analyzer operating in a vacuum.
12. 12. A device for transferring charged droplets along a path, having a droplet guide comprising electrodes which can generate a two-dimensional multipole field in the axis of the guiding device, and an audio AC voltage generator for supplying AC voltages to the electrodes.
13. 13. A device according to Claim 12, wherein the droplet guide comprises electrodes able togenerate a two-dimensional quadrupole field,
14. 14. A Device according to Claim 13, wherein the audio AC voltage generator is able to suppy an alternating voltage with a frequency of from 20 to 20,000 hertz and an amplitude of from 20 to 3,000 volts to the electrodes of the guiding device.
15. 15. A device according to any one of Claims 12 to 14, , wherein the guiding device comprises an insulating tube whose inner surface carries the electrodes of the guiding device.
16. 16. A device according to Claim 15, wherein the electrodes in the tube form a pattern which generates both a radial two-dimensional quadrupole alternating field and an axial DC field profile.
17. 17. A device according to any one of Claims 11 to 14, further comprising a gas supply for the gas flow through the droplet guide.
18. 18. A device according to any one of Claims 12 to 17, wherein the droplets are generated by a spray capillary of an electrospray device, and the droplets are transferred to a gas-aspirating inlet capillary leading to an ion analyzer in a vacuum.
19. 19. A device according to any one of Claims l2to 17, wherein the droplets exit a first segment of a segmented inlet capillary and are transferred by the guiding device to a next segment of the inlet capillary.
20. 20. A method for the transfer of charged droplets along a path, substantially as hereinbefore described with reference to, and as illustrated by, the accompanying drawings.
21. 21. A device for transferring charged droplets along a path, substantially as hereinbefore described with reference to, and as illustrated by, the accompanying drawings.