FIELD OF INVENTION

[1] The present invention generally relates to ICP-MS and particularly to a method for ion generation for ICP-MS.

BACKGROUND

[2] Inductively coupled plasma mass spectrometry (ICP-MS) is a type of mass spectrometry that uses an Inductively coupled plasma (ICP) to ionize the sample. The plasma in ICP has a high temperature (5000-10000 K), which atomizes, ionizes, and excites the constituents of any sample. This process results in the formation of numerous excited species in the plasma, including atomic and polyatomic ions and meta-stable atoms and molecules. This system is a highly efficient ion source since it can produce metallic cations and to some extent non-metallic cations. It can detect different isotopes of the same element, which makes it a versatile tool in isotopic labeling.

[3] In general, the ICP has a poor efficiency in generating atomic anions at a significant level. Generation of a high yield of negative ions has been a challenging endeavor in ICP-MS. Production of negative ions is necessary to obtain a complete profile of the sample (for example nutrition elements in the human body such as Phosphorous (P), Sulfur (S), Chlorine (Cl) and Iodine (I)). Current ICP-MS systems are unable to generate and detect these elements to a significant level; since they cannot ionize these species efficiently.

[4] Argon (Ar) is commonly used in ICP-MS (other gases, such as helium, are also used but are less common). An Ar plasma produces a high number of Ar meta-stable neutrals (Ar ^* ) and Ar metastable ions (Ar* ⁺ ) in addition to other cations. Ar* and Ar* ⁺ entering the mass spectrometer are known to cause negative effects. Therefore, reduction of Ar ^* and Ar ^*+ significantly improves the performance of ICP-MS devices.

[5] Mass spectrometers normally operate under vacuum, while the ions are created in atmospheric pressures. There are different pressure regions in the MS system, varying from atmospheric level to the vacuum. Due to the high flow of gas through the entrance aperture (orifice) of the MS, all the constituents of the plasma may enter the MS. Subsequently, charge separation occurs downstream of the entrance aperture where momentum of the flow becomes less, and electrostatic fields become the dominant force affecting the ions. Therefore, current ICP-MS systems typically use various forms of ion deflectors to separate the sample ions from the rest of the species and prevent meta stables, neutrals, and photons from entering the mass analyzer.

[6] FIG. 1 shows a prior mass spectrometer that operates under different pressure regions. The inductively-coupled plasma (ICP) ion source 100 works at the atmospheric pressure, and the mass spectrometer 190 works in vacuum. The analytes are typically injected into the ion source in the form of an aqueous solution to be ionized by the intense heat of the plasma. As the ions 105 are generated inside the plasma, they go through an orifice (aperture) 115 and expand into a lower pressure region 116. They may then enter a first skimmers 151 and expand into a lower pressure region 117. The expansion process may continue through another skimmer 152 to even lower pressures 118.

[7] In most mass spectrometers, some device is used to remove all unwanted species and prevent them from entering the later stages of the MS. These devices mainly use an ion deflector, which comes in a variety of different types. An ion deflector only deflects the ions and allows them to enter the mass analyzer. All other neutral species, including the photons generated by the plasma, are unaffected by the ion deflected and are evacuated or collide with the walls of the deflector, making sure they do not enter the subsequent stages of MS. For example, the ions may go through an ion guide 161 and a lens 171 while the pressure is gradually decreased until a low pressure 119 is reached before entering the last stage of the mass spectrometer 190. Different systems may have different number of stages, skimmer and ions guides. A set of vacuum pumps control the pressure in different stages.

[8] The devices that are typically used to prevent the unwanted species from entering the MS are complicated and expensive. All of these devices use some form of electric/magnetic field to manipulate the ions. This necessitates extensive electronic circuit design which adds to the cost and complexity of the system. More importantly, a significant portion of the desired ions are lost in the process along with the unwanted species due to the inefficiencies associated with these devices. BRIEF SUMMARY OF THE INVENTION

[9] A new ICP-MS ion transfer method is disclosed capable of generating and transporting high yields of positive and negative ions, with the ability of quenching undesirable meta stable ions and neutrals while using the existing ICP torch. This system and method do not use any electrostatic deflector, ion guide, or similar types of deflectors as commonly used in conventional mass spectrometers to eliminate the unwanted species and photons. A mechanism utilizing free electrons and meta-stable neutrals (Ar ^* for example) is used to form high yields of negatively charged elements (which are stable in negative ionic form) which are originally atomized within the plasma. This can be achieved farther away from the plasma source where the pressure is lower than atmosphere, the temperature is cold enough, and negative ions are stable.

[10] The present device and method generate a high number of negative ions. Negative analytes can be produced at various pressure regions of the MS when anions, free electrons, and meta-stables (originally present in the plasma) react with an appropriate catalyst dopant or directly with the analyte itself.

[11] The present system and method comprise of the following novel processes:

• Adding the right dopant in various pressure regions of the mass spectrometer interface, where reaction time is suitable for gas-phase ion/molecular reaction to occur.

• Introducing dopants or analyte in the provided RF confinement fields for generating a high yield of negative ions in various pressure regions of mass spectrometer.

• Introducing the right quenching gas at various pressure regions for quenching unwanted meta-stable neutrals. Quenching the meta-stable plasma gas ions/neutrals before entering the mass analyzer is an enormous improvement. The right quenching gas can quench all of the unwanted metastable neutrals, which is an important advancement.

[12] The present system utilizes a mechanism for the generation of negative ions which can work with any other plasma gases, i.e., He, Ne and di-atomic and tri-atomic molecular gases. A new means for introducing analytes or sample to be analyzed by the mass spectrometer is introduced through inlet ports (at various pressure stages of the MS) other than through the injector tube of the ICP torch.

[13] In the present system, the negative ions are formed after the source (the ICP), and in later stages of the MS where the pressure is lower than atmosphere. For example, in a low-pressure cavity between the sampler cone and skimmer cone; that is within the sampling interface. None of the previous ICP-MS systems were able to form or detect negative ions.

[14] In the present system, the flow is bent from the sampler orifice to the skimmer (i.e., a flow driven cavity). This is a new method of blocking photons (due to the off-axis design) and meta-stable argon species in ICP-MS. In addition, in the present system, meta-stable species are eliminated and are used to form negative ions “at the same time”.

BRIEF DESCRIPTION OF THE DRAWINGS

[15] Embodiments herein will hereinafter be described in conjunction with the appended drawings provided to illustrate and not to limit the scope of the claims, wherein like designations denote like elements, and in which:

FIG. 1 shows a prior art ICP-MS system.

FIG. 2 shows the first embodiment of the present system with dopant introduction in the cavity and two skimmers.

FIG. 3 shows the second embodiment of the present system with dopant introduction in the cavity, one skimmer, and one RF-only ion guide after the skimmer.

FIG. 4 shows the third embodiment of the present system with dopant introduction in the cavity and two RF-only ion guides.

FIG. 5 shows the fourth embodiment of the present system with dopant introduction in the second pressure region of the MS within the first ion guide.

FIG. 6 shows the fifth embodiment of the present system with dopant introduction in the third pressure region of the MS within the second ion guide. FIG. 7 shows the sixth embodiment of the present system with dopant introduction in the fourth pressure region of the MS within the third ion guide.

FIG. 8 shows the seventh embodiment of the present system with dopant introduction in the first pumping region the MS that has two skimmers.

FIG. 9 shows the eights embodiment of the present system with dopant introduction in the first pumping region of the MS that has one skimmer and one ion guide.

FIG. 10A shows image of the present device in operation.

FIG. 10B shows image of the present device in operation.

FIG. 10C shows image of the present device in operation.

DETAILED DESCRIPTION

[16] FIG. 2 shows the main elements of the present system. The system comprises of a section for the introduction of a dopant or analyte into the sample chamber prior to entrance to the MS and after the ionization source.

[17] A cavity (chamber) 220, which is field-free, is configured to receive charged species and transport them purely by momentum of the background gas to the MS. This field-free cavity does not use any electrostatic or other electric or magnetic fields for ion separation, as commonly used in ion deflectors. It is mainly a flow driven cavity. The pressure inside the cavity is lower than atmosphere. This is another innovative aspect of the present invention. The pressure inside the cavity is determined by the size of the sample

[18] All species (positive, negative and meta-stable ions, neutrals, free electrons, and photons) generated from the ICP torch 200 will enter the cavity 220, having walls, from a first inlet 203. One or multiple inlets 210 are provided for introducing an appropriate dopant 201 or analyte 202 of interest at various pressure regions. Proper dopant can react with interference ions and meta-stable neutrals/ions in any pressure region provided. An off-axis exit 230 (in which the axis of the system 207 is not aligned with the axis 203a of the inlet 203) at the cavity allows the mixture in the cavity to leave the cavity as they flow with the fluid flow while blocking the photons (which can generate signal noise if they reach the detector) from entering the MS as they collide with the walls of the cavity 220. In the first embodiment of the present system, a dual-skimmer (FIG. 2) 250 and 260 followed by an ion guide 280 allow to pressure drop from the pressure inside the cavity 211 to lower pressures in different pressure stages, 212, 213, 214, and 215. The dimensions of the cavity are configured to allow for proper mixing and reaction times of the dopant with the species. A lens 270 at the exit of the ion guide 280 allows species on the vicinity of the system axis 207 to enter the MS 290.

[19] FIG. 3 shows the second embodiment of the same invention that uses one skimmer 350 and an ion guide 380. Since after the first skimmer 350, the momentum of the flow is reduced, and the electrostatic forces become dominant, species start to diverge from the central axis. Therefore, an ion guide 381 with upstream and downstream lenses 370 and 270, respectively, are used as a more effective way in controlling the ions and focusing their flow around the central axis. An RF-only ion guide is used for this purpose. The most probable charge separation region is mainly on the central axis 307 is in the ion guide 380, where single polarity charged species pass. Complete charge separation occurs in the RF ion guide region 307 of 381 . Electrons become unstable due to RF. Single polarity ions, meta-stable neutrals and ions are formed.

[20] FIG. 4 shows a third embodiment of the same invention, in which two ion-guides 481 and 482 separated by a lens 470 are used successively instead of the two skimmers of the first embodiment. The most probable charge separation region is around the central axis 407 of the system and in the second ion guide 482. Single polarity charged species pass through this region. Another RF-only ion guide 483 separated from the second ion guide 482 with a lens 472 is used for complete charge separation. In this ion guide 483, electron become unstable due to RF and single polarity ions, meta-stable neutrals and ions are formed and go through lens 473 to enter the MS.

[21] The dopant addition is the critical aspect of quenching the metastables. Metastable ions and neutrals are formed inside the plasma. Neutrals are more troublesome because they do not have a charge and they cannot be filtered with the mass analyzer or the ion guide. Although most of these metastable are formed inside the plasma, some of them can also be formed in later stages of the mass spectrometer. For example, with Ar as the main plasma gas, neutral meta-stable Ar (Ar ^* ) can be formed by the following reactions:

Ar ^*+ + Ar ® Ar ^* + Ar ⁺ M ⁺ + Ar ® Ar ^* + M + e ^_

H ^* + Ar ® Ar ^* + H

[22] A metastable argon ion reacts with an argon atom, which is neutral, and turns it into a metastable, while itself going back to the ground state. Or if a molecule or an ion M ⁺ , which has a higher ionization potential than the metastable energy of argon, collide with the argon atom it can form a metastable argon atom and the species itself becomes neutralized and one electron is released in the process. Or if another metastable atom H ^* with a higher metastable energy than that of argon collides with an Ar atom, it can form a metastable argon while the atom itself relaxes to the ground state. In addition, other reactions can occur at the later stages of the mass spectrometer to form metastable argon atoms.

[23] In the present system and method, a quenching mechanism is used for quenching meta stable neutrals and ions, as destruction of Ar ^* is desirable and beneficial for the MS. The process that is used in the present system to neutralize the species is penning ionization. Penning ionization is known to be a very effective ionization process in which the excess energy of a meta-stable dissipates into the reacting partner, causing the reactant to be ionized, if the ionization energy of reactant is less than the meta-stable energy of the plasma gas. For example, Ar ^* ground state is a doublet with energies of 11 .4 and 11.6 eV. Any reactant X with an ionization energy lower than this will be readily ionized:

Ar ^* + X ® X ⁺ + Ar + e ^_

[24] Table 1 provides a list of suitable compounds with ionization energy less than that of Ar ^* (i.e., <11 .4 eV). These compounds can be used to quench the energy of Ar ^* and become ionized themselves. Any of these compounds can be introduced in various pressure regions, which result in transfer of energy from Ar ^* and ionization of the compound itself. Subsequently, these ionized compounds can easily be filtered by MS. The same scheme can be used to eliminate interference ions from ions of interest, for example, it can be used to remove the interference of ArO ⁺ on Fe ⁺ . Table 1 - List of some suitable compounds with ionization energy less than that of Ar*

Mechanism for generation of negative ions

[25] In an Ar plasma, these are the predominantly generated compounds:

Inside the plasma, there are Argon ions, Argon metastable ions, the metastable neutrals, fast electrons, and slow electrons.

Ar ^± Ar* ¹ , Ar*, fast free e-, slow free e-

[26] Mechanism of production of negative ions in an Ar discharge can be through the following routes:

Case-1 : A molecule or ion is negatively ionized by electron attachment. The resulting negative ion then reacts with the analyte of interest (An) and turns it into a negative ion by way of electron transfer.

Electron attachment Electron transfer

M + e- slow - M- + An - ^► An-

Case-2: A metastable neutral argon atom reacts with a dopant with an ionization energy less than 11.4 eV. The metastable energy of argon atom is dissipated into the dopant molecule and ionize it, while the argon atom itself relaxes into ground state. A free electron will also be released in this reaction which can ionize an analyte (An) through electron attachment. Chemi-ionization Electron attachment

Ar ^* + Dop Dop ⁺ + Ar + e- + An - _► Arr

11.4 eV Ionization energy <11 4 eV

Case-3: A free slow electron form in previous stages can directly ionize an analyte through electron attachment.

Electron attachment e- slow + An - An-

Case-4: a negative ion collides with an analyte and, provided that the electron affinity of the analyte is higher, it will capture that electron from the negative ion and becomes negatively charged itself.

Electron transfer

A + An - An-

EA(A) < EA(An)

EA: electron affinity

[27] All of the reactions mentioned above can be used to form negative ions. Formation of negative ions inside the cavity

[28] The following cases may occur when a dopant is added inside the cavity. Case-1 : Formation of negative analyte ion (An-) via direct electron attachment:

. , Electron attachment

An + e- slow - An-

Case-2: Formation of negative analyte ion via introduction of a proper dopant:

Dop + e- slow - _► Dop- + An - An- + Dop

Ar ^* + Dop Dop ⁺ + e- + An An ^_

These reactions might proceed downstream in any pressure regions.

[29] FIG. 5 shows another embodiment of the present invention, the system has first 511 , 2d 512, 3 ^rd 513, 4 ^th 514, and fifth 515 pressure regions. The dopant 530 is added in the second pressure region 512, in which the pressure is controlled by a pump 522. In this case, electrons are still present in this region due to high flow of gas from the cavity. The following cases may occur. Case-1 : Formation of negative analyte ion via direct electron attachment Electron attachment

An + e- ^slow - _► A _A n-

Case-2: Formation of negative analyte ion via introduction of a proper dopant

Dop + e- slow Dop- + An An- + Dop

Ar ^* + Dop Dop ⁺ + e- + An An-

These reactions might proceed downstream in any pressure regions.

[30] FIG. 6 shows another embodiment of the present invention, in which the dopant 530 is added in the third pressure region 513, and negative ions are generated in that region.

• Electrons are no longer present in this region.

• Formation of negative analyte ion via introduction of a proper dopant can occur:

Ar ^* + Dop - _► Dop ⁺ + e- + An - An-

• These reactions might proceed downstream in any pressure regions.

[31] In the third pressure region of the mass spectrometer, electrons are mostly lost because of collision with other heavier species or various walls of the orifices and MS. Therefore, there are no free electrons in these regions. Then, dopant can be introduced and through ionization of the dopant, negative ions are formed.

[32] FIG. 7 shows another embodiment of the same invention, in which the introduction of the dopant 530 and formation of negative ions is in the fourth pressure region 514.

• Electrons are no longer present in this region

• Formation of negative analyte ion via introduction of a proper dopant can occur:

Ar ^* + Dop - Dop ⁺ + e- + An - _► Am

[33] FIG. 8 illustrates another embodiment of the present invention, in which introduction of dopant 530 or analyte is in the first pumping region 512 of the MS that has two skimmers 851, 852. The species then enter the ion guide 880 followed by a lens 871 [34] And FIG. 9 illustrates another embodiment of the present invention, in which introduction of dopant 530 or analyte is in the first pumping region 512 of the MS that has one skimmer 951 and one ion-guide 961. A second ion guide 962 separated from the first one with a lens 971 receives species and provides ions to the MS through lens 972.

[35] In all these systems, the dopant is selected to have an ionization energy lower than the energy of the meta-stable neutrals. Therefore, the energy of the meta-stable neutrals is dissipated into the molecules of the dopant to quench the meta-stable neutrals and to generate dopant ions and free electrons in any of the pressure stages of the system. The free electrons ionize the analytes through electron attachment to form negative analyte ions in any of the pressure stages of the system. A molecule or ion is negatively ionized by electron attachment, then transfers the electron to the analytes through electron transfer to form negative analyte ions in any of the pressure stages of the system. The dopant molecule is negatively ionized by electron attachment, then transfers the electron to the analytes through electron transfer to form negative analyte ions in any of the pressure stages of the system. In this system, the meta-stable neutrals are quenched generating high yields of negative ions for inductively coupled mass spectrometer (ICP- MS).

[36] The background gas and analytes are injected into the ICP torch to form a plasma comprising of positive and negative ions, meta-stable ions and neutrals, and molecules of the background gas, and free electrons. The plasma enters into the cavity that sustained at a pressure lower than atmosphere. A dopant is also injected into the cavity and is mixed with the plasma to quench meta-stable neutrals and form a mixture. Then the mixture is directed out of the cavity by the momentum of the background gas towards a mass spectrometer for analysis. As noted the background gas can be helium (He), nitrogen (IS ), argon (Ar), oxygen (O2), hydrogen (H2), air, water vapor or a combination thereof. The dopant is selected such that it has an ionization energy lower than the meta stable energy of the meta-stable neutrals. For example for Ar meta-stable neutrals, dopants comprise of Butenal, Butene, Butyne, Allene, Acetone, Propene, Hexyne, Ammonia, Pentyne, Hexane, Methylene, Ethylene, Hexane, Formic acid, or a combination thereof react with and quench Ar meta-stable neutrals and become ionized themselves. [37] FIG. 10A shows and embodiment of the present invention in which an argon ICP torch is placed in front of the sampler orifice which is coupled with an off-axis cavity. The ions generated by the argon plasma are sucked into the sampler orifice and flow through the cavity which is maintained at a lower pressure than atmosphere. The cavity also has a separate inlet to introduce a dopant or other types of analytes. FIG. 10B shows the exit of the cavity at the second stage of the MS. All the ion and neutral species are seen to flow out of the cavity and move toward the skimmer orifice to go into the third stage of the MS. The pink light emission is mainly due to the metastable Ar species. FIG. 10C shows a similar case with acetone vapor being injected into the cavity. It can be seen that the metastable species are significantly quenched as manifested by the change of color of the light emitted from the beam.