ION SOURCE FOR INDUCTIVELY COUPLED PLASMA MASS SPECTROMETRY

Abstract

An ICP source (100) for generating ions using an inductively coupled plasma is configured to be coupled to a mass spectrometer (200). The sample is introduced into the plasma along a downwards-pointing vertical direction (G) under the action of gravity. In this manner, the sample can reach the plasma regardless of its condition, e.g., regardless of droplet or particle size. Transport efficiencies of up to 100% can be achieved. The ICP source can be supplied with a continuous stream comprising the sample.

Claims

1. An ICP source for generating ions from a sample using an inductively coupled plasma, the ICP source being configured to be coupled to a mass spectrometer, wherein the ICP source is configured to allow introduction of the sample into the plasma along a downwards-pointing vertical direction.

2. The ICP source of claim 1, wherein the ICP source is configured to allow ions to be extracted from the plasma along the downwards-pointing vertical direction.

3. The ICP source of claim 1, comprising a plasma torch, the plasma torch comprising an injector tube defining a longitudinal axis that is oriented vertically, the injector tube having an upper end configured to receive the sample and a lower end configured to introduce the sample into the plasma.

4. The ICP source of claim 3, comprising a metallic cooling plate that at least partially surrounds the plasma torch to protect components of the ICP source above the cooling plate from heat caused by sustaining the plasma.

5. The ICP source of claim 4, comprising a cooling system for actively cooling the metallic cooling plate by a forced flow of a cooling fluid, through the metallic cooling plate or through a component that is connected to the metallic cooling plate.

6. The ICP source of claim 1, comprising an electromagnetic coupling element for sustaining the plasma by inductive coupling, the coupling element defining a longitudinal axis, wherein the longitudinal axis is oriented vertically.

7. An ionization system comprising: an aerosolization device for aerosolizing a sample; and an ICP source for generating ions from the aerosolized sample using an inductively coupled plasma, wherein the ICP source is configured to be coupled to a mass spectrometer, wherein the ICP source is configured to allow introduction of the aerosolized sample into the plasma along a downwards-pointing vertical direction, and wherein the ICP source is coupled to the aerosolization device in such a manner that the aerosolized sample is transferred from the aerosolization device to the ICP source along the downwards-pointing vertical direction.

8. The ionization system of claim 7, wherein the aerosolization device comprises: a droplet dispenser and a vertically oriented falling tube coupled to the droplet dispenser, the falling tube allowing droplets created by the droplet dispenser to be transported downwards under the action of gravity, an outlet of the falling tube being connected to an inlet of the ICP source in such a manner that the aerosolized sample that exits the falling tube is transferred from the falling tube to the ICP source along the downwards-pointing vertical direction; or a nebulizer for aerosolizing the sample and a spray chamber coupled to the nebulizer, the spray chamber having a downwards-pointing outlet, the outlet of the spray chamber being connected to an inlet of the ICP source in such a manner that the aerosolized sample is transferred from the spray chamber to the ICP source along the downwards-pointing vertical direction; or a laser ablation cell, the laser ablation cell having a downwards-pointing outlet, the outlet of the laser ablation cell being connected to an inlet of the ICP source in such a manner that the aerosolized sample is transferred from the laser ablation cell to the ICP source along the downwards-pointing vertical direction.

9. An ionization system comprising: a flow cytometer and/or a cell sorter; and an ICP source of for generating ions from a sample using an inductively coupled plasma, the ICP source being configured to be coupled to a mass spectrometer, wherein the ICP source is configured to allow introduction of the sample into the plasma along a downwards-pointing vertical direction, and wherein the ICP source is coupled to the flow cytometer or cell sorter in such a manner that the sample is transferred from the flow cytometer or cell sorter to the ICP source along a downwards-pointing vertical direction.

10. The ionization system of claim 9, comprising a correlator configured to receive flow cytometry information from the flow cytometer and mass spectrometry information from a mass spectrometer coupled to the ICP source and to correlate the flow cytometry information with the mass spectrometry information to obtain combined flow cytometry and mass spectrometry information for individual cells or particles.

11. An ionization system comprising: a continuous-flow sample supply system; a sample introduction system; and an ICP source for generating ions from a sample using an inductively coupled plasma, the ICP source being configured to be coupled to a mass spectrometer, wherein the ICP source is configured to allow introduction of the sample into the plasma along a downwards-pointing vertical direction, wherein the sample introduction system is coupled to the continuous-flow sample supply system in such a manner that a continuous sample stream comprising the sample is transferred from the continuous-flow sample supply system to the sample introduction system, and wherein the sample introduction system is configured to introduce the sample into the ICP source along the downwards-pointing vertical direction.

12. The ionization system of claim 11, wherein the continuous-flow sample supply system comprises a continuous-flow sample pretreatment device having an inlet configured to receive a continuous inflowing stream comprising the sample and having an outlet configured to provide a continuous outflowing stream comprising the sample, at least a portion of the continuous outflowing stream forming the continuous sample stream, the continuous-flow sample pretreatment device (610) being configured to subject the continuous inflowing stream to at least one operation of analysis and/or modification of its composition.

13. The ionization system of claim 12, wherein the continuous-flow sample pretreatment device comprises a separation device configured to separate chemical species or particulate matter, in particular, cells, in the continuous inflowing stream and to elute the chemical species or the particulate matter after separation in the continuous outflowing stream.

14. The ionization system of claim 12, wherein the ionization system comprises a correlator configured to receive analytical information from the continuous-flow sample pretreatment device and mass spectrometry information from a mass spectrometer coupled to the ICP source and to correlate the analytical information with the mass spectrometry information.

15. The ionization system of claim 12, wherein the continuous-flow sample supply system comprises a flow-splitting device for continuously splitting the continuous outflowing stream into the continuous sample stream and a residual stream.

16. An ICP-MS system comprising: an ICP source for generating ions from a sample using an inductively coupled plasma, wherein the ICP source is configured to allow introduction of the sample into the plasma along a downwards-pointing vertical direction; and a mass spectrometer coupled to the ICP source for receiving said ions from the ICP source.

17. A method of mass spectrometry comprising: sustaining a plasma using an ICP source; introducing a sample into the plasma so as to generate ions from the sample; and analyzing a mass-to-charge spectrum of ions that have been extracted from the plasma, using a mass spectrometer that is coupled to the ICP source, wherein the sample is introduced into the plasma along a downwards-pointing vertical direction.

18. The method of claim 17, wherein the ions are extracted from the plasma along the downwards-pointing vertical direction.

19. The method of claim 17, further comprising: aerosolizing the sample using an aerosolization device; and transferring the aerosolized sample from the aerosolization device to the ICP source along the downwards-pointing vertical direction.

20. The method of claim 19, comprising: aerosolizing the sample using a droplet generator, passing the aerosolized sample through a vertically oriented falling tube along the downwards-pointing vertical direction, and introducing the aerosolized sample into an inlet of the ICP source along the downwards-pointing vertical direction; or aerosolizing the sample using a nebulizer, passing the aerosolized sample through a spray chamber, the spray chamber having a downwards-pointing outlet, and introducing the aerosolized sample into an inlet of the ICP source along the downwards-pointing vertical direction; or aerosolizing the sample using a laser ablation cell, the laser ablation cell having a downwards-pointing outlet, and transferring the aerosolized sample from the outlet of the laser ablation cell to the plasma along the downwards-pointing vertical direction.

21. The method of claim 17, comprising: analyzing at least one property of the sample using a flow cytometer and/or sorting sample droplets according to at least one property using a cell sorter; and transferring the sample from the flow cytometer or cell sorter into the ICP source along the downwards-pointing vertical direction.

22. The method of claim 17, comprising: continuously supplying a continuous sample stream comprising the sample from a continuous-flow sample supply system to a sample introduction system, wherein the sample is introduced into the plasma along the downwards-pointing vertical direction by the sample introduction system.

23. The method of claim 22, wherein the continuous-flow sample supply system comprises a continuous-flow sample pretreatment device having an inlet and an outlet, and wherein the method comprises: receiving at the inlet a continuous inflowing stream comprising the sample; subjecting the continuous inflowing stream to at least one operation of analysis and/or modification of its composition in the continuous-flow sample pretreatment device; providing at the outlet a continuous outflowing stream comprising the sample; and causing at least a portion of the continuous outflowing stream to form the continuous sample stream.

24. The method of claim 23, wherein the continuous-flow sample pretreatment device comprises a separation device and wherein the method comprises: separating chemical species or particulate matter, in particular, cells, in the continuous inflowing stream and eluting the chemical species or the particulate matter after separation in the continuous outflowing stream, using the separation device.

25. The method of claim 23, further comprising: continuously splitting the continuous outflowing stream into the continuous sample stream and a residual stream.

26. The ionization system of claim 12, wherein the separation device a chromatography device, an electrophoresis device or a cell sorter.

27. The method of claim 24, wherein the separation device a chromatography device, an electrophoresis device or a cell sorter.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0078] Preferred embodiments of the invention are described in the following with reference to the drawings, which are for the purpose of illustrating the present preferred embodiments of the invention and not for the purpose of limiting the same. In the drawings,

[0079] FIG. 1 shows a schematic sketch of an ICP-MS system according to an embodiment of the present invention;

[0080] FIG. 2 shows an enlarged view of a portion of the ICP-MS system of FIG. 1 together with a highly schematic sketch of a cell sorter based on flow cytometry;

[0081] FIG. 3 shows a top view of the cooling plate of the ICP source in FIG. 1;

[0082] FIG. 4 shows a plasma torch configured as a direct injection nebulizer;

[0083] FIG. 5 shows a plasma torch coupled to a falling tube;

[0084] FIG. 6 shows a plasma torch coupled to a total consumption sample introduction system;

[0085] FIG. 7 shows a plasma torch coupled to a laser ablation cell according to a first embodiment;

[0086] FIG. 8 shows a plasma torch coupled to a laser ablation cell according to a second embodiment;

[0087] FIG. 9 shows a TOF mass spectrometer suitable to be coupled to the ICP source in FIG. 1;

[0088] FIG. 10 shows a MICAP source according to an embodiment of the present invention;

[0089] FIG. 11 shows a time-resolved ICP-MS peak trace of monodisperse droplets containing .sup.133Cs;

[0090] FIG. 12 shows a time-resolved ICP-MS peak trace of monodisperse droplets containing .sup.232Th;

[0091] FIG. 13 shows a calibration curve illustrating the dependency of the ion signal on analyte mass for droplets comprising .sup.133Cs;

[0092] FIG. 14 shows a calibration curve illustrating the dependency of the ion signal on analyte mass for droplets comprising .sup.232Th;

[0093] FIG. 15 shows a time-resolved ICP-MS peak trace for a Cd-enriched Chinese Hamster Ovary (CHO) cells suspension in phosphate-buffered saline;

[0094] FIG. 16 shows a time-resolved ICP-MS peak trace for a Pb-enriched Chinese Hamster Ovary (CHO) cells suspension in water; and

[0095] FIG. 17 shows an enlarged view of a portion of the ICP-MS system of FIG. 1 together with a highly schematic sketch of a sample pretreatment system, a flow-splitting device and a sample introduction system.

DESCRIPTION OF PREFERRED EMBODIMENTS

[0096] FIG. 1 illustrates, in a highly schematic manner, an ICP-MS system according to an exemplary embodiment of the present invention. The ICP-MS system comprises an ICP source 100 for generating an argon plasma and a mass spectrometer 200 coupled to an outlet end of the ICP source.

[0097] In the present example, the ICP source 100 comprises an RF generator 110 mounted on an elevator 150 so as to be adjustable in height h relative to the mass spectrometer 200. The RF generator 110 feeds an alternating current in a frequency range of typically 10 to 100 MHz, e.g. at 27 MHz or 40 MHz, to a resonant circuit comprising a capacitor 112 and an induction coil 115. The capacitor 112 and one end of the induction coil 115 are electrically connected via a vertical metal bar 113 and via a horizontal metal bar 114 preferably made of a highly conductive metal like copper, silver or gold, supported by a PTFE support 116. Likewise, the other end of the induction coil 115 is electrically connected to the RF generator via another horizontal metal bar 114 and another vertical metal bar 113. By using the horizontal metal bars 114, it becomes possible to place the induction coil 115 in a location that is at a sufficiently large lateral distance from the RF generator 110 so as to arrange a mass spectrometer 200 below the induction coil 115 without interfering with the RF generator 110. A typical length of the horizontal metal bears 114 is 10 to 50 cm, in particular, about 20 cm.

[0098] The ICP source 100 further comprises a torch box 120. The torch box 120 comprises a housing made of an electrically conducting metal in order to electromagnetically shield its interior. A plasma torch 130, which will be described in more detail below in conjunction with FIG. 2, is arranged in the torch box 120 together with the induction coil 115, the horizontal metal bars 114 and the vertical metal bars 113. The induction coil 115 surrounds a lower portion of the plasma torch 130. Above the induction coil 115, a horizontal cooling plate 140 is arranged. The cooling plate 140 is supported in the torch box 120 by two vertical, fluid-cooled metal panels 141 (cooled, e.g., by water or by a cooling liquid like a mixture of ethylene glycol and water). The cooling plate 140 protects the components in the torch box 120 that are arranged above the induction coil 115 from convective heat generated during operation of the ICP source. A ventilation grid 121 allows gases and heat to escape from the torch box 120.

[0099] At its outlet end 122, the torch box 120 is open towards the bottom and forms an extraction opening for interfacing the ICP source 100 to the mass spectrometer 200. The mass spectrometer comprises a vacuum interface 210 that will be explained in more detail below in conjunction with FIG. 2, followed by an ion optics unit 215, an inlet baffle 220, a quadrupole mass analyzer 230, an exit baffle 240, and a detector 250. A mechanical pump 261 evacuates the region of the vacuum interface 210. Turbo-molecular pumps 262 evacuate the region of the ion optics unit 215, mass analyzer 230 and detector 250. The setup of such a type of mass spectrometer is well known in the art; however, usually the extraction of ions from the ion source occurs horizontally, whereas the axis of ion extraction in the setup of FIG. 1 is oriented vertically downwards.

[0100] FIG. 2 illustrates the plasma torch 130 and the interface 210 to the mass spectrometer 200 in more detail. The plasma torch 130 is constructed in a manner well known in the art. It comprises three concentric tubes 131, 132, 133. A flow of a gas (typically argon) for forming the plasma is passed between the outer tube 133 and the middle tube 132 at a flow rate of typically 12 to 17 l/min. A second gas flow is passed between the intermediate tube 132 and the central tube 131 at a flow rate of 1 l/min and is used to sustain the plasma and adjust the position of the base of the plasma relative to the end of these tubes. The central tube 131, often called the injector tube, is employed for feeding the sample to the plasma.

[0101] The plasma torch 130 is positioned centrally in the induction coil 115. When RF power is applied to the induction coil 115, an intense electromagnetic field is created inside the induction coil 115. A high-voltage spark is used to ionize a fraction of gas inside the induction coil 115, and by acceleration of electrons and ions through the RF electromagnetic field a plasma can be sustained. The coupling between the coil and the plasma is inductive, i.e., energy transfer occurs predominantly by the magnetic field produced by the oscillating current in the induction coil, and only to a small extent by electric field gradient along the induction coil.

[0102] The sample is introduced into the plasma through the central tube (injector tube) 131 under the action of gravity. The plasma is sufficiently hot to progressively evaporate the sample, dissociate the sample, and ionize the elements contained in the sample.

[0103] The interface 210 to the mass spectrometer 200 is formed between a first baffle 211 that comprises a small opening in a so-called sampler cone 212 and a second baffle 213 that comprises a small opening in a so-called skimmer cone 214. A mechanical pump is connected to evacuate the interspace between the first and second baffles 211, 213. Ions that have passed both the sampler cone 212 and the skimmer cone 214 enter a space at high vacuum and are focused by an ion optics unit 215 into the mass analyzer.

[0104] FIG. 2 further schematically illustrates how the ICP-MS system of the present invention can be coupled to an electrostatic cell sorter 320, which in turn is coupled to a flow cytometer 310. Such a combination of a flow cytometer cooperating with a cell sorter is known in the art as a fluorescent-activated cell sorter. In the flow cytometer 310, a cell suspension 311 is fed to a nozzle 312. Droplets containing single cells are created by the nozzle 312. Each droplet is interrogated by one or more laser beams created by one or more lasers 313. Light along the direction of illumination as well as fluorescent light emitted by the droplet is detected by an optical detection system 314 and analyzed by an analyzer 315. Depending on the result of the analysis, the analyzer 315 applies a positive or negative charge to the nozzle tip or to a charging electrode so as to apply a charge of predefined sign to the droplet before it is discharged from the nozzle. In the cell sorter 320, the droplets are deflected according to their charge state by deflection plates 321 to which a DC voltage is applied. Depending on their charge state, droplets either end up in collection containers 322 or in a sample inlet 323. From the sample inlet 323, the droplets are transferred downwards directly into the injector tube 131 of the plasma torch 130, where they fall down vertically under the action of gravity.

[0105] The cell sorter 320 can also be omitted, and droplets that exit the flow cytometer 310 can be directly introduced into the plasma by placing the inlet of the ICP source directly under the output nozzle of the flow cytometer. No additional nebulization system is needed, and a transport efficiency of 100% can be obtained.

[0106] Regardless of whether the droplets are sorted or not, the results obtained from the flow cytometer 310 can be correlated with the results from the mass spectrometer 200 for each individual droplet. By combining flow cytometry with mass spectrometry in the presently proposed configuration, the number of cellular parameters that can be quantified simultaneously is increased when compared to flow cytometry alone or to mass spectrometry alone. To this end, the analyzer 315 can be configured to carry out correlations between flow cytometry and mass spectrometry results, or a separate correlator can be provided.

[0107] FIG. 3 illustrates the cooling plate 140 and the vertical metal panels 141 in greater detail. The cooling plate 140 has a cutout 142 for accommodating the plasma torch when the cooling plate is installed. The vertical panels are provided with a plurality of channels or bores 143, which extend in-plane within each of the panels, for passing a cooling fluid like cool air or water through the bores in order to actively cool the cooling plate.

[0108] FIG. 4 illustrates a variant in which the plasma torch 130′ is configured as a so-called direct injection high-efficiency nebulizer (DIHEN), which enables direct sample introduction into the plasma without the need of a separate aerosolization device. A high-efficiency nebulizer 134 replaces the injector tube in the plasma torch 130′. Thereby the sample can be directly introduced into the plasma without the need of prior aerosolization. 100% transport efficiency is thereby obtained. Such a direct injection nebulizer is known per se (A. Montaser, “Inductively Coupled Plasma Mass Spectrometry”, Wiley-VCH: Washington D.C., 1998). However, normally it is operated in a horizontal configuration, whereas in the present invention the direct injection nebulizer is operated in a vertical configuration.

[0109] FIGS. 5 to 8 illustrate four examples of aerosolization devices coupled to the plasma torch 130 of the ICP source shown in FIG. 1. These Figures are schematic, and relative dimensions of the components shown in these Figures are not to scale.

[0110] In FIG. 5, a droplet delivery and low-temperature desolvation system 410 is illustrated. A droplet dispenser 411 is connected to a flow adapter 412 that sits on top of a so-called falling tube 413. The falling tube 413 is a 40 cm long stainless steel tube with an inner diameter of 4 mm. A mixture of argon and helium is used to desolvate the droplets inside the falling tube 413. The desolvation of the droplets leads to reduced local cooling of the plasma. For more details, reference is made to S. Gschwind et al., “Capabilities of inductively coupled plasma mass spectrometry for the detection of nanoparticles carried by monodisperse microdroplets”, J. Anal. At. Spectrom., 2011, 26, 1166-1174, DOI: 0.1039/C0JA00249F. Whereas in the prior art the aerosolized sample that leaves the falling tube 413 is transported horizontally to the ICP source using a carrier gas flow, in the present example the aerosolized sample is directly introduced into the injector tube 131 of the plasma torch along the downward direction, without requiring an additional carrier gas flow. In this manner, all sample droplets or particles that leave the falling tube 413 will reach the plasma, independently of their size, and independently of the gas flow rate.

[0111] In FIG. 6, aerosolization is carried out by a so-called total consumption sample introduction system 420. A low flow nebulizer 421, usually operated at a liquid flow rate of less than 10 μL/min, is coupled to a small volume spray chamber 422, which forces the droplets generated by the nebulizer 421 down along its central axis and prevents the droplets from sticking to the walls of the spray chamber 422. The spray chamber 422 is open at its bottom to form an outlet. The outlet is directly coupled to the injector tube 131 of the plasma torch 130.

[0112] In FIG. 7, a solid sample 432 is aerosolized in a laser ablation cell 430 using a laser 431. The laser 431 shines an intense pulsed laser beam onto the rear side of the sample 432, which faces away from the ICP source. The induced shock wave leads to an ejection of sample material, which falls down into the injector tube 131 of the plasma torch 130 (“rear side ablation”).

[0113] FIG. 8 illustrates aerosolization using a laser ablation cell 440 according to U.S. Pat. No. 9,922,811 B2. A laser 441 shines laser onto a surface of a solid sample 442, causing sample material to be ablated. The ablated material enters a flow channel 443, from where it is directly transferred downwards into the injector tube 131 of the plasma torch 130. For more details of the laser ablation cell 440 and its mode of operation, reference is made to U.S. Pat. No. 9,922,811 B2. Whereas in the prior art the flow channel 443 is oriented horizontally and the laser beam impinges onto the sample surface vertically, in the present example the flow channel 443 is oriented vertically, and the laser beam is oriented horizontally.

[0114] The presently proposed ICP source can be used with any type and configuration of mass spectrometer. For instance, FIG. 9 illustrates a TOF mass spectrometer 200′ that can be used in conjunction with the ICP source shown in FIGS. 1 and 2. The interface 210 is constructed in the same manner as in FIGS. 1 and 2. Ions extracted from the ICP source through the interface 210 are passed through a notch filter 260 and an extractor 270 into a TOF mass analyzer 280. Any other type and configuration of mass spectrometer can be employed. For instance, a quadrupole mass spectrometer, sector field mass spectrometer or an ion trap mass spectrometer can be used instead. If required, electrostatic mirrors and/or bending magnets can be used to deflect the ions into the mass spectrometer.

[0115] FIG. 10 illustrates a microwave inductively coupled atmospheric-pressure plasma (MICAP) source 500 that is configured for vertical sample introduction. The MICAP source comprises an RF generator (microwave generator) 510 in the form of a magnetron. A fan 511 provides cooling for the magnetron 510. An antenna 512 couples the microwave field into the interior of the torch box 520. An annular dielectric resonator 515 is immersed in the microwave field. The resonator exhibits a bulk polarization current around the ring, which oscillates with the microwaves' frequency. A plasma torch 530 is arranged above the resonator 515. The plasma torch 530 is constructed in the same manner as the plasma torch 130 that has been described in conjunction with FIG. 2. Nitrogen gas is passed into the region of the center of the resonator 530. A nitrogen plasma is sustained by the electromagnetic field in the center of the resonator 515 by inductive coupling. For details, reference is made to US 2016/0025656 A1 and to M. Schild et al., “Replacing the Argon ICP: Nitrogen Microwave Inductively Coupled Atmospheric-Pressure Plasma (MICAP) for Mass Spectrometry”, Anal. Chem. 2018, 90(22), 13443-13450, DOI: 10.1021/acs.analchem.8b03251. Whereas in the prior art the plasma torch of the MICAP source is oriented horizontally, in the present example the plasma torch 530 is oriented vertically, allowing introduction of the sample through the central tube 531 along the direction of the gravity vector.

[0116] FIGS. 11 to 16 illustrate experimental results that have been obtained with a setup as illustrated in FIG. 1.

[0117] FIGS. 11 and 12 show time-resolved ICP-MS peak traces of monodisperse droplets containing .sup.133Cs (FIG. 11) and .sup.232Th (FIG. 12). Droplets of 66 μm diameter were generated at 20 Hz from a solution comprising 20 ppb each of both .sup.133Cs and .sup.232Th, using a droplet generator. All the dispensed droplets arrived in the plasma and were successfully detected by ICP-MS. It is noted that .sup.133Cs possesses an ionization energy of 3.89 eV and .sup.232Th an ionization energy of 6.31 eV. These results prove that the ICP-MS system of the present invention can readily achieve 100% transport efficiency.

[0118] FIGS. 13 and 14 show diagrams illustrating the dependency of the ion signal on analyte mass for droplets containing .sup.133Cs (FIG. 11) and .sup.232Th (FIG. 12). These results were obtained by investigating monodisperse droplets having different analyte concentrations as follows: 2 ppb (leftmost data point), 5 ppb, 10 ppb and 20 ppb (rightmost data point), for both .sup.133Cs and .sup.232Th. Both diagrams exhibit a linear relationship between analyte mass and ion signal, indicating complete desolvation, vaporization, dissociation and ionization of the droplets using the vertical plasma configuration of the present invention.

[0119] FIG. 15 shows a time-resolved ICP-MS peak trace for a Cd-enriched Chinese Hamster Ovary (CHO) cell suspension in phosphate-buffered saline. FIG. 16 shows a time-resolved ICP-MS peak trace for a Pb-enriched Chinese Hamster Ovary (CHO) cells suspension in water. These traces illustrate that cells can be successfully introduced into the plasma using the vertical configuration of the present invention. Since a transport efficiency of 100% is expected, it is believed that “missing” peaks are due to droplets that did not contain cells. On the other hand, it cannot be excluded that other droplets contained multiple cells.

[0120] FIG. 17 schematically illustrates the coupling of an ICP-MS system according to an embodiment of the present invention to a continuous sample supply system comprising a sample pretreatment device 610. The sample pretreatment device 610 may be a separation device, for instance, a chromatography device such as a HPLC or GC device or an electrophoresis device such as a CE device. In other embodiments, the sample pretreatment device may be any other device that subjects an inflowing fluid stream that comprises the sample to some kind of analysis or treatment.

[0121] The sample pretreatment device 610 has an inlet 611 and an outlet 612. It receives at its inlet 611 a continuous inflowing fluid stream F.sub.in. At its outlet 612, it provides a continuous outflowing fluid stream F.sub.out. If the sample pretreatment device 610 is a separation device, the outflowing fluid stream F.sub.out may comprise a temporally varying composition, and the separation device may be configured to determine information about this composition, as it is well known in the art.

[0122] A flow-splitting device 620 is coupled to the output of the sample pretreatment device 610. The flow-splitting device 620 splits the continuous outflowing fluid stream F.sub.out into a sample stream F.sub.sample and a residual fluid stream F.sub.res. The flow rate of the sample stream F.sub.sample may be much smaller than the flow rate of the residual fluid stream F.sub.res. Apart from the different flow rates, the compositions of these two fluid streams may be identical.

[0123] The sample stream F.sub.sample enters a sample introduction system, which in the present example is configured as a droplet delivery and desolvation system as discussed above in conjunction with FIG. 5. However, any other sample introduction system that enables the introduction of a small continuous flow of fluid sample into the plasma of the ICP source may be employed. In particular, the sample introduction system may be a total consumption system, as in FIG. 6, or it may comprise the nebulizer of a DIHEN, as in FIG. 4. The sample introduction system may be integrated with the ICP source to form a single unit.

[0124] The flow-splitting device 620 is provided because flow rates at the outlet of some sample pretreatment devices, in particular separation devices like HPLC devices, are typically much larger than the flow rate that is required by the sample introduction system (e.g., between 0.1 and 10 μl/min using a droplet generation device at a rate of 1000 Hz). For some other sample pretreatment devices, e.g., some CE devices, the flow-splitting device 620 may not be required and can be left away.

[0125] The sample introduction system is arranged above the ICP source in such a manner that the sample is introduced into the ICP source along the downwards-pointing vertical direction G (i.e., along the direction of gravity).

[0126] A correlator 630 receives separation information about the various fractions that exit the sample pretreatment device 610. It further receives mass information about the mass distributions in the fractions from the mass spectrometer that is coupled to the ICP source. It correlates the separation information with the mass information as it is well known in the art, e.g., in the form of LC/MS, GC/MS or CE/MS information.

[0127] Many modifications are possible without leaving the scope of the present invention. In particular, other types of ICP source than the two types discussed above can be employed. The sample can be split up into small droplets or particles in other manners than discussed above. Any type and orientation of mass spectrometer can be employed.

LIST OF REFERENCE SIGNS

[0128] 100 ICP source [0129] 110 RF generator [0130] 112 plate capacitor [0131] 113 vertical metal bar [0132] 114 horizontal metal bar [0133] 115 induction coil [0134] 116 PTFE support [0135] 120 torch box [0136] 121 ventilation grid [0137] 122 outlet end [0138] 130, 130′ plasma torch [0139] 131 central tube (injector tube) [0140] 132 middle tube [0141] 133 outer tube [0142] 134 nebulizer [0143] 140 cooling plate [0144] 141 vertical panel [0145] 142 cutout [0146] 143 bore [0147] 150 elevator [0148] 200 quadrupole mass spectrometer [0149] 200′ TOF mass spectrometer [0150] 210 interface [0151] 211 first baffle [0152] 212 sampler cone [0153] 213 second baffle [0154] 214 skimmer cone [0155] 215 ion optics unit [0156] 220 inlet baffle [0157] 230 quadrupole mass analyzer [0158] 240 outlet baffle [0159] 250 detector [0160] 260 notch filter [0161] 270 extractor [0162] 280 TOF mass analyzer [0163] 261 mechanical pump [0164] 262 turbomolecular pump [0165] 310 flow cytometer [0166] 311 slurry [0167] 312 nozzle [0168] 313 laser [0169] 314 detection system [0170] 315 analyzer [0171] 320 cell sorter [0172] 321 deflection plate [0173] 322 collection container [0174] 323 sample inlet [0175] 410 droplet delivery and desolvation system [0176] 411 droplet dispenser [0177] 412 flow adapter [0178] 413 falling tube [0179] 420 total consumption sample introduction system [0180] 421 nebulizer [0181] 422 spray chamber [0182] 430 laser ablation cell [0183] 431 laser [0184] 432 sample [0185] 440 laser ablation cell [0186] 441 laser [0187] 442 sample [0188] 443 flow channel [0189] 500 MICAP source [0190] 510 RF generator (magnetron) [0191] 511 fan [0192] 512 antenna [0193] 515 resonator [0194] 520 torch box [0195] 530 plasma torch [0196] 531 injector tube [0197] 610 sample pretreatment device [0198] 611 inlet [0199] 612 outlet [0200] 620 flow-splitting device [0201] h height [0202] G direction of gravity [0203] F.sub.in inflowing stream [0204] F.sub.out outflowing stream [0205] F.sub.sample sample stream [0206] F.sub.res residual stream