CA2324911C - Method and apparatus for producing a discrete particle - Google Patents
Method and apparatus for producing a discrete particle Download PDFInfo
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- CA2324911C CA2324911C CA 2324911 CA2324911A CA2324911C CA 2324911 C CA2324911 C CA 2324911C CA 2324911 CA2324911 CA 2324911 CA 2324911 A CA2324911 A CA 2324911A CA 2324911 C CA2324911 C CA 2324911C
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- H—ELECTRICITY
- H01—ELECTRIC ELEMENTS
- H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
- H01J49/00—Particle spectrometers or separator tubes
- H01J49/02—Details
- H01J49/04—Arrangements for introducing or extracting samples to be analysed, e.g. vacuum locks; Arrangements for external adjustment of electron- or ion-optical components
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Abstract
A method and apparatus for producing a discrete particle for subsequent analysis (such as mass spectrometry) or manipulation is disclosed. A discrete particle is generated by a particle generator. A net charge is induced onto the particle by an induction electrode. The particle is delivered to a levitation device where it is then electrodynamically levitated. If the particle is a droplet, desolvation will occur, leading to Coloumbic fissioning of the droplet into smaller droplets. The movement of the levitated droplet(s) can be manipulated by an electrode assembly. The droplet(s), and the charge thereon, can be delivered to a mass spectrometer in one aspect of the invention, providing an ion source for mass spectrometry without the detrimental space charge effects of electrospray ionization. techniques. In another aspect of the invention, the levitated particle(s) may be deposited onto a plate for subsequent analysis by matrix assisted laser desorption and ionization mass spectrometry.
Description
METHOD AND APPARATUS FOR PRODUCING A DISCRETE
PARTICLE
Technical Field This invention pertains to the production of a discrete particle for application, for example, in the field of mass spectrometry.
Background Mass spectrometry is a technique that weighs individual molecules, thus providing valuable chemical information. A mass spectrometer operates by exerting forces on charged particles (ions) in a vacuum using magnetic and electric fields. A compound must be charged (ionized) to be analyzed in a mass spectrometer. The ions must be introduced in the gas phase into the vacuum of the mass spectrometer.
Ionizing large molecules of biological origins such as proteins, peptides and strands of DNA and RNA has proven difficult in the past since these molecules have effectively zero vapour pressure and are labile. A major thrust in mass spectrometry for some time has been the development of ionization sources for such large bio-molecules.
Electrospray ionization ("ESI") and matrix-assisted laser desorption and ionization ("MALDI") are two techniques that have been developed to ionize large bio-molecules.
ESI is a desolvation method in which a high DC electric potential is applied to a metallic capillary needle that is separated from a counter electrode held at a lower DC potential. The electric field causes a liquid (containing the analyte in solution) emerging from the capillary to be dispersed into a fine spray of millions of charged droplets. The droplets in the aerosol carry a net charge of the same polarity as the electric field. As the solvent evaporates from the droplets, the droplets decrease in size, increasing the charge concentration on the droplet surface. Eventually, a "Coulombic explosion" occurs when Coulombic repulsion overcomes a droplet's surface tension. This results in the droplet exploding, forming a series of smaller, lower charged droplets. This process of shrinking and exploding repeats until individually charged analyte ions are formed. The rate of solvent evaporation can be increased by introducing a drying gas flow counter to the current of'the sprayed ions.
Nitrogen is frequently used as the drying gas.
With evaporation of the solvent from the droplets, the cyclical process of coulomb fission and solvent evaporation ultimately leads to the deposition of net charge onto the analyte molecule (e.g. bio-molecule) in the droplet. The bio-molecule, adducted by, for example, multiple protons, is desorbed from the droplet at atmospheric pressure. A small fraction of these ions pass through an orifice into the vacuum of the mass spectrome-ter for analysis.
A disadvantage of the ESI method is that only a small fraction (0.01 % or less) of the sample material is utilized. The majority of the material emerging from the capillary ends up on the counter electrode or on the plate that has the sampling orifice. The reason for this is that the electric field that disperses the liquid solution into droplets is also responsible for causing detrimental space charge effects. Space charge effects arise because each droplet, and the resulting ions in the aerosol plume, all carry net charge of the same polarity, causing these drop-lets/ions to repel one another because of electrostatic repulsion. This causes the spray of droplets leaving the tip of the capillary to spread out into a cone having its apex at the tip of the capillary. Hence, the overall sample utilization efficiency is low in conventional ESI methods because the droplets/ions at atmospheric pressure are extremely difficult to focus through the sampling orifice. This limits the effectiveness of ESI if only a small amount of analyte is available for analysis, which is often the case in respect of bio-molecules.
PARTICLE
Technical Field This invention pertains to the production of a discrete particle for application, for example, in the field of mass spectrometry.
Background Mass spectrometry is a technique that weighs individual molecules, thus providing valuable chemical information. A mass spectrometer operates by exerting forces on charged particles (ions) in a vacuum using magnetic and electric fields. A compound must be charged (ionized) to be analyzed in a mass spectrometer. The ions must be introduced in the gas phase into the vacuum of the mass spectrometer.
Ionizing large molecules of biological origins such as proteins, peptides and strands of DNA and RNA has proven difficult in the past since these molecules have effectively zero vapour pressure and are labile. A major thrust in mass spectrometry for some time has been the development of ionization sources for such large bio-molecules.
Electrospray ionization ("ESI") and matrix-assisted laser desorption and ionization ("MALDI") are two techniques that have been developed to ionize large bio-molecules.
ESI is a desolvation method in which a high DC electric potential is applied to a metallic capillary needle that is separated from a counter electrode held at a lower DC potential. The electric field causes a liquid (containing the analyte in solution) emerging from the capillary to be dispersed into a fine spray of millions of charged droplets. The droplets in the aerosol carry a net charge of the same polarity as the electric field. As the solvent evaporates from the droplets, the droplets decrease in size, increasing the charge concentration on the droplet surface. Eventually, a "Coulombic explosion" occurs when Coulombic repulsion overcomes a droplet's surface tension. This results in the droplet exploding, forming a series of smaller, lower charged droplets. This process of shrinking and exploding repeats until individually charged analyte ions are formed. The rate of solvent evaporation can be increased by introducing a drying gas flow counter to the current of'the sprayed ions.
Nitrogen is frequently used as the drying gas.
With evaporation of the solvent from the droplets, the cyclical process of coulomb fission and solvent evaporation ultimately leads to the deposition of net charge onto the analyte molecule (e.g. bio-molecule) in the droplet. The bio-molecule, adducted by, for example, multiple protons, is desorbed from the droplet at atmospheric pressure. A small fraction of these ions pass through an orifice into the vacuum of the mass spectrome-ter for analysis.
A disadvantage of the ESI method is that only a small fraction (0.01 % or less) of the sample material is utilized. The majority of the material emerging from the capillary ends up on the counter electrode or on the plate that has the sampling orifice. The reason for this is that the electric field that disperses the liquid solution into droplets is also responsible for causing detrimental space charge effects. Space charge effects arise because each droplet, and the resulting ions in the aerosol plume, all carry net charge of the same polarity, causing these drop-lets/ions to repel one another because of electrostatic repulsion. This causes the spray of droplets leaving the tip of the capillary to spread out into a cone having its apex at the tip of the capillary. Hence, the overall sample utilization efficiency is low in conventional ESI methods because the droplets/ions at atmospheric pressure are extremely difficult to focus through the sampling orifice. This limits the effectiveness of ESI if only a small amount of analyte is available for analysis, which is often the case in respect of bio-molecules.
MALDI: involves the deposition of a sanlple, usually as a liquid, onto a flat plate ol- into recessed wells formed in a plate. A matrix of one or more compounds is also used. The matrix may be a solid or a liquid. The sample material can be deposited as a layer on top of or below the matrix or iritimately mixed with the matrix. Typically, the matrix molecules are present in the starting solution in a concentration approxi-mately 1000 times greater than the arialyte molecules. After deposition, the plate is exposed to a pulsed laser beani. The matrix absorbs the energy from the laser, causing rapid vibrational excitation and desorption of the chromophore. The matrix molecules evaporate away and the desorbed analyte molecules can be cationized by a proton or an alkali metal ion.
The ionized analyte inolecules can be analyzed using a time-of-flight ("TOF") analyzer. In such a case, the overall technique is often referred to as matrix-assisted laser desorption and ionization time-of-flight mass spectrometry ("1VIALDI-TOF-MS' ).
The need has therefore arisen for a method and apparatus for producing a source of ions, suitable for mass spectrometric analysis, from a discrete particle. The need has also arisen for improved techniques for depositing an analyte, such as a bio-molecule, onto a plate for MALDI
mass spectrometry.
Summary of Invention In accordance with one aspect of the invention, an apparatus for producing a discrete particle for subsequent analysis or manipulation is disclosed. The apparatus comprises a particle generator for generating a discrete particle; an induction electrode for inducing a net charge onto the discrete particle; and a levitation device for electrodynamically levitating the discrete particle following the induction of the net charge.
The ionized analyte inolecules can be analyzed using a time-of-flight ("TOF") analyzer. In such a case, the overall technique is often referred to as matrix-assisted laser desorption and ionization time-of-flight mass spectrometry ("1VIALDI-TOF-MS' ).
The need has therefore arisen for a method and apparatus for producing a source of ions, suitable for mass spectrometric analysis, from a discrete particle. The need has also arisen for improved techniques for depositing an analyte, such as a bio-molecule, onto a plate for MALDI
mass spectrometry.
Summary of Invention In accordance with one aspect of the invention, an apparatus for producing a discrete particle for subsequent analysis or manipulation is disclosed. The apparatus comprises a particle generator for generating a discrete particle; an induction electrode for inducing a net charge onto the discrete particle; and a levitation device for electrodynamically levitating the discrete particle following the induction of the net charge.
In one embodiment, the levitation device is an electrodynamic balance comprising a pair of separated levitation electrodes. The levitation electrodes may include a pair of first ring electrodes extending in parallel planes. Preferably a voltage difference is maintained across the first ring electrodes. For example, the voltage across the first ring electrodes may be approximately 20 V. In order to minimize convection currents, the levitation device may be substantially enclosed within a chamber.
The apparatus may also include an electrode assembly for delivering the discrete particle from the levitation device to a target remote from the levitation device. The remote target may be, for example, an orifice in communication with the vacuum chamber of an atmospheric gas sampling mass spectrometer. Alternatively, the remote target may be a substrate for deposition of the particle thereon, such as a plate suitable for matrix assisted laser desorption and ionization mass spectrometric analysis.
The electrode assembly may form part of the levitation device or it may constitute a separate component of the apparatus. In one aspect of the invention the electrode assembly is operable at atmospheric pressure and comprises a first plate electrode positioned between the particle generator and the levitation device and a second plate electrode positioned between the levitation device and the orifice.
The first plate electrode and the second plate electrode each have apertures formed therein to permit the passage of the discrete particle therethrough.
In another aspect of the invention the levitation device is located proximal to the orifice and includes the electrode assembly.
In another aspect of the invention, the electrode assembly may comprise a quadrupole electrode assembly disposed between the levitation device and the orifice.
In yet another aspect of the invention the electrode assembly niay include a stack of separated second ring electrodes disposed in parallel planes between the levitation device and the orifice. The second ring electrodes may be progressively smaller in diameter in the direction from the levitation device toward the orifice. For example, four separate second ring electrodes may be provided, each spaced approximately 3 mm apart from one another.
As will be appreciated by a person skilled in the art, the various electrode assemblies described herein may also be used if the remote target is something other than the an orifice in communication with a vacuum chamber of a mass spectrometer, such as a MALDI plate or some other substrate suitable for deposition of the discrete particle thereon.
Preferably the induction electrode is located proximal to the particle generator and a net charge is induced in the particle as it is generated by the particle generator. In one embodiment of the invention, the particle generator is a droplet generator for generating a discrete droplet comprising an analyte and solvent. The droplet generator may consist of a hollow, flat-tipped nozzle through which the discrete droplet is dispensed. The droplet is levitated in the levitation device for a sufficient period of time to allow at least partial desolvation of the droplet, thereby yielding a source of ions for mass spectrometric analysis.
As indicated above, the discrete particle may be deposited on a plate suitable for matrix assisted laser desorption and ionization mass spectrometric analysis. The plate preferably comprises a material for receiving the particle, such as a matrix coated on the plate.
The apparatus may also include an electrode assembly for delivering the discrete particle from the levitation device to a target remote from the levitation device. The remote target may be, for example, an orifice in communication with the vacuum chamber of an atmospheric gas sampling mass spectrometer. Alternatively, the remote target may be a substrate for deposition of the particle thereon, such as a plate suitable for matrix assisted laser desorption and ionization mass spectrometric analysis.
The electrode assembly may form part of the levitation device or it may constitute a separate component of the apparatus. In one aspect of the invention the electrode assembly is operable at atmospheric pressure and comprises a first plate electrode positioned between the particle generator and the levitation device and a second plate electrode positioned between the levitation device and the orifice.
The first plate electrode and the second plate electrode each have apertures formed therein to permit the passage of the discrete particle therethrough.
In another aspect of the invention the levitation device is located proximal to the orifice and includes the electrode assembly.
In another aspect of the invention, the electrode assembly may comprise a quadrupole electrode assembly disposed between the levitation device and the orifice.
In yet another aspect of the invention the electrode assembly niay include a stack of separated second ring electrodes disposed in parallel planes between the levitation device and the orifice. The second ring electrodes may be progressively smaller in diameter in the direction from the levitation device toward the orifice. For example, four separate second ring electrodes may be provided, each spaced approximately 3 mm apart from one another.
As will be appreciated by a person skilled in the art, the various electrode assemblies described herein may also be used if the remote target is something other than the an orifice in communication with a vacuum chamber of a mass spectrometer, such as a MALDI plate or some other substrate suitable for deposition of the discrete particle thereon.
Preferably the induction electrode is located proximal to the particle generator and a net charge is induced in the particle as it is generated by the particle generator. In one embodiment of the invention, the particle generator is a droplet generator for generating a discrete droplet comprising an analyte and solvent. The droplet generator may consist of a hollow, flat-tipped nozzle through which the discrete droplet is dispensed. The droplet is levitated in the levitation device for a sufficient period of time to allow at least partial desolvation of the droplet, thereby yielding a source of ions for mass spectrometric analysis.
As indicated above, the discrete particle may be deposited on a plate suitable for matrix assisted laser desorption and ionization mass spectrometric analysis. The plate preferably comprises a material for receiving the particle, such as a matrix coated on the plate.
In another embodiment of the invention Applicant's apparatus may comprise a particle generator for generating a discrete particle and a levitation device for levitating the discrete particle, wherein the discrete particle is delivered by the apparatus to a target remote from the levitation device. An electrode assembly may be employed for delivering the particle from the levitation device to the remote target as discussed above.
In another embodiment of the invention an apparatus for delivering a source of ions to a vacuum chamber of a mass spectrometer is disclosed. The apparatus includes a droplet generator for generating a single isolated droplet, the droplet comprising solvent; an induction electrode for applying a net charge onto the droplet; a levitation device for levitating the droplet for a period of time sufficient to permit desolvation of the droplet to cause the droplet to become unstable, thereby releasing ions by droplet Coulomb fission; an orifice in communication with the vacuum chamber; and an electrode assembly for delivering the ions from the levitation device to the orifice.
The Applicant's invention also includes a mass spectrometer comprising a vacuum chamber; a detector for detecting the passage of ions through the vacuum chamber; a particle generator for generating a discrete particle; an induction electrode for ionizing the particle; a levitation device for electrodynamically tevitating the discrete particle following the ionization; an orifice in communication with the vacuum chamber; and means to deliver the ionized particle from the levitation device to the orifice.
A method for producing a discrete particle for subsequent analysis or manipulation is also disclosed. The metliod comprises (a) generating a discrete particle; (b) inducing a net charge onto the discrete particle; (c) and electrodynanlically levitating the discrete particle following the induction of the net charge. In one embodiment step (c) is carried out at atmospheric pressure. The method may also include the step of delivering the discrete particle from the levitation device to a target remote from the levitation device. For example, the discrete particle may be delivered to an atmospheric gas sampling mass spectrometer or a remote substrate, such as a MALDI plate. A material, such as a matrix, may be applied to the plate for receiving the particle.
As indicated above, the discrete particle may be a discrete droplet comprising an analyte and solvent. In this case, Applicant's method may include the step of electrodynamically levitating the droplet for a period of time sufficient to permit at least partial desolvation of the discrete droplet.
The net. charge is preferably induced when the particle is generated. The particle may be levitated by applying a constant voltage difference across an electrodynamic balance. In one variant the discrete particle may be subjected to a gas while it is levitated to control the evaporation rate of the solvent.
In a further embodiment, Applicant's method includes the steps of (a) generating a discrete particle; (b) levitating the discrete particle; and (c) delivering the discrete particle to the target. As indicated above, the discrete particle may be levitated electrodynamically.
A method of mass spectrometry is also disclosed comprising:
(a) generating a discrete particle; (b) ionizing the discrete particle; (c) electrodynamically levitating the ionized discrete particle; (d) delivering the ionized discrete particle to a vacuum chamber of an atmospheric pressure gas sampling mass spectrometer; and (e) detecting the passage of the ionized discrete particle through the vacuum chamber.
In another embodiment of the invention an apparatus for delivering a source of ions to a vacuum chamber of a mass spectrometer is disclosed. The apparatus includes a droplet generator for generating a single isolated droplet, the droplet comprising solvent; an induction electrode for applying a net charge onto the droplet; a levitation device for levitating the droplet for a period of time sufficient to permit desolvation of the droplet to cause the droplet to become unstable, thereby releasing ions by droplet Coulomb fission; an orifice in communication with the vacuum chamber; and an electrode assembly for delivering the ions from the levitation device to the orifice.
The Applicant's invention also includes a mass spectrometer comprising a vacuum chamber; a detector for detecting the passage of ions through the vacuum chamber; a particle generator for generating a discrete particle; an induction electrode for ionizing the particle; a levitation device for electrodynamically tevitating the discrete particle following the ionization; an orifice in communication with the vacuum chamber; and means to deliver the ionized particle from the levitation device to the orifice.
A method for producing a discrete particle for subsequent analysis or manipulation is also disclosed. The metliod comprises (a) generating a discrete particle; (b) inducing a net charge onto the discrete particle; (c) and electrodynanlically levitating the discrete particle following the induction of the net charge. In one embodiment step (c) is carried out at atmospheric pressure. The method may also include the step of delivering the discrete particle from the levitation device to a target remote from the levitation device. For example, the discrete particle may be delivered to an atmospheric gas sampling mass spectrometer or a remote substrate, such as a MALDI plate. A material, such as a matrix, may be applied to the plate for receiving the particle.
As indicated above, the discrete particle may be a discrete droplet comprising an analyte and solvent. In this case, Applicant's method may include the step of electrodynamically levitating the droplet for a period of time sufficient to permit at least partial desolvation of the discrete droplet.
The net. charge is preferably induced when the particle is generated. The particle may be levitated by applying a constant voltage difference across an electrodynamic balance. In one variant the discrete particle may be subjected to a gas while it is levitated to control the evaporation rate of the solvent.
In a further embodiment, Applicant's method includes the steps of (a) generating a discrete particle; (b) levitating the discrete particle; and (c) delivering the discrete particle to the target. As indicated above, the discrete particle may be levitated electrodynamically.
A method of mass spectrometry is also disclosed comprising:
(a) generating a discrete particle; (b) ionizing the discrete particle; (c) electrodynamically levitating the ionized discrete particle; (d) delivering the ionized discrete particle to a vacuum chamber of an atmospheric pressure gas sampling mass spectrometer; and (e) detecting the passage of the ionized discrete particle through the vacuum chamber.
Brief Description of Drawings FIGURE 1 is a schematic drawing of a prior art electrospray ionization arrangement;
FIGURE 2 is a schematic drawing of an exemplary apparatus of the invention;
FIGURE 3 is a schematic drawing of an alternative embodi-ment of the apparatus in Figure 2;
FIGURE 4 is a schematic drawing of a further alternative embodiment of the apparatus in Figure 2;
FIGURE 5 is a schematic drawing of a further alternative embodiment of the apparatus in Figure 2;
FIGURE 6 is a schematic drawing of a further alternative embodiment of the apparatus in Figure 2;
FIGURE 7 is a cross sectional view taken along line 7-7 of Figure 6;
FIGURE 8 is an illustration of the levitation device of the apparatuses illustrated in Figures 2-6;
FIGURE 9 is an illustration of the levitation ring electrodes and above-positioned guide ring electrodes of the apparatus in Figure 5;
FIGURE 10 is a perspective view of an exemplary apparatus of the invention with a MALDI plate positioned above the levitation device;
FIGURE 11 is a graph plotting the ion counts over 10 s time integrals of the apparatuses tested in Example 1; and FIGURE 12 is a cross-sectional view of the nozzle of the droplet generator of the apparatuses in Figures 3-6.
Description Throughout the following description specific details are set forth in order to provide a more thorough understanding of the invention.
However, the invention may be practiced without these particulars. In other instances, well known elemeiits have not been shown or described in detail to avoid unnecessarily obscuring the present invention. Accord-ingly, the specification and drawings are to be regarded in an illustrative, rather than a restrictive, sense.
Figure 1 is a schematic drawing depicting a prior art ESI
arrangement. In ESI arrangement 10, a metallic capillary 12 having an applied DC voltage is separated from a counter electrode 14 held at a lower DC potential. A plate 16 is positioned behind the counter electrode 14 and has an orifice 18 therein to allow the passage of ionized analyte molecules. To the right of sampling orifice 18 are the first and second stages of a differential vacuunl. The region between plate 16 and a skimmer 19 is held at a first pressure and the pressure in the main vacuum chamber to the right of skimmer 19 is held at a lower pressure. The ionized molecules pass through a niass-to-charge analyzer 20 and are detected by a detector 22. In ESI arrangement 10, the liquid emerging f'rom capillary 12 is dispersed into a fine spray 24 of droplets 26. The cyclical process of Coloumb fission and solvent evaporation ultimately leads to the deposition of a net charge onto the analyte molecules in the dl-oplets. Unfortunately, much of the saniple is wasted with ESI arrange-ment 10 because the droplets 26, all having net charge of the same polarity, repel, resulting in the spray 24 spreading out over an area that is many times greater thari the aperture 28 in the counter electrode 14 and the orifice 18 leading into the vacuuni. Thus, the overall sample utilization efficiency is low in conventional ESI arrangement 10.
Rather than producing millions of droplets per second that are susceptible to space charge effects as with ESI, this invention is based on the generation of a discrete particle. 'The "particle" discussed herein is a single isolated droplet comprising an analyte (e.g. bio-molecule) and solvent. A net charge is placed onto the particle as it is generated. As used herein the term "ion" means a particle having a net charge.
The discrete particle is delivered to a levitation device.
Delivery of the discrete particle could be accomplished, for exaniple, by the particle generator used to generate the discrete particle. For example, where the particle generator is a droplet generator, the application of an electric pulse to a piezoelectric crystal in the droplet generator (with suitable backing pressure) will eject an isolated droplet with sufficient velocity to travel to the levitation device.
The discrete particle is electrodynamically levitated by a levitation device. As used herein, the term "levitated" means that the particle is suspended or "stored" within the levitation device. The period of time a particle is levitated may be varied depending upon the particular circumstances. The particle is then delivered from the levitation device to a remote target. As used herein the target is "remote" from the levitation device in the sense that it is spacially separated from the center or null position of the levitation device to some degree, although the quantum of separation may be small. In one aspect of the invention, the target is an orifice leading into (or otherwise in communication with) the vacuum of an atmospheric gas (and ion) sampling mass spectronleter. In another aspect of the invention, the target is a plate to be subjected to MALDI
mass spectrometry following deposition of the particle on the plate. The discrete particle may be delivered to the target by an electrode assembly.
Where the discrete particle is a droplet, the net charge lost from the droplet (referred to as a"parent" droplet) by Coloumb fission is delivered to the orifice of the mass spectronleter by manipulating the smaller droplets (referred to as "progeny" droplets). It is possible to levitate one or more particles in the levitation device simultaneously.
Figure 2 is a schematic illustration of an apparatus 29 of the invention. Apparatus 29 comprises a particle generator 32 and a levitation device 30. Particle generator 32 can be a droplet generator. Levitation device 30 can be any nleans to levitate a discrete particle. For illustration purposes, levitation device 30 has been described herein as comprising an electrodynamic balance comprised of two ring electrodes 48, 50. Those skilled in the art will appreciate that there are many configurations of electrodynamic balances and the like that fall within the scope of this invention. For exaniple, ring electrodes 48, 50 may have different geometric configurations (e.g. annular and non-annular) without departing from the invention.
In operation, a discrete particle (not shown) is generated by particle generator 32, delivered to levitation device 30 and then levitated by levitation device 30 between ring electrodes 48, 50. Positioned between droplet generator 32 and levitation device 30 is an induction electrode 52.
An electric potential is applied to induction electrode so as to induce a net charge of a desired polarity onto the discrete particle generated by particle generator 32.
FIGURE 2 is a schematic drawing of an exemplary apparatus of the invention;
FIGURE 3 is a schematic drawing of an alternative embodi-ment of the apparatus in Figure 2;
FIGURE 4 is a schematic drawing of a further alternative embodiment of the apparatus in Figure 2;
FIGURE 5 is a schematic drawing of a further alternative embodiment of the apparatus in Figure 2;
FIGURE 6 is a schematic drawing of a further alternative embodiment of the apparatus in Figure 2;
FIGURE 7 is a cross sectional view taken along line 7-7 of Figure 6;
FIGURE 8 is an illustration of the levitation device of the apparatuses illustrated in Figures 2-6;
FIGURE 9 is an illustration of the levitation ring electrodes and above-positioned guide ring electrodes of the apparatus in Figure 5;
FIGURE 10 is a perspective view of an exemplary apparatus of the invention with a MALDI plate positioned above the levitation device;
FIGURE 11 is a graph plotting the ion counts over 10 s time integrals of the apparatuses tested in Example 1; and FIGURE 12 is a cross-sectional view of the nozzle of the droplet generator of the apparatuses in Figures 3-6.
Description Throughout the following description specific details are set forth in order to provide a more thorough understanding of the invention.
However, the invention may be practiced without these particulars. In other instances, well known elemeiits have not been shown or described in detail to avoid unnecessarily obscuring the present invention. Accord-ingly, the specification and drawings are to be regarded in an illustrative, rather than a restrictive, sense.
Figure 1 is a schematic drawing depicting a prior art ESI
arrangement. In ESI arrangement 10, a metallic capillary 12 having an applied DC voltage is separated from a counter electrode 14 held at a lower DC potential. A plate 16 is positioned behind the counter electrode 14 and has an orifice 18 therein to allow the passage of ionized analyte molecules. To the right of sampling orifice 18 are the first and second stages of a differential vacuunl. The region between plate 16 and a skimmer 19 is held at a first pressure and the pressure in the main vacuum chamber to the right of skimmer 19 is held at a lower pressure. The ionized molecules pass through a niass-to-charge analyzer 20 and are detected by a detector 22. In ESI arrangement 10, the liquid emerging f'rom capillary 12 is dispersed into a fine spray 24 of droplets 26. The cyclical process of Coloumb fission and solvent evaporation ultimately leads to the deposition of a net charge onto the analyte molecules in the dl-oplets. Unfortunately, much of the saniple is wasted with ESI arrange-ment 10 because the droplets 26, all having net charge of the same polarity, repel, resulting in the spray 24 spreading out over an area that is many times greater thari the aperture 28 in the counter electrode 14 and the orifice 18 leading into the vacuuni. Thus, the overall sample utilization efficiency is low in conventional ESI arrangement 10.
Rather than producing millions of droplets per second that are susceptible to space charge effects as with ESI, this invention is based on the generation of a discrete particle. 'The "particle" discussed herein is a single isolated droplet comprising an analyte (e.g. bio-molecule) and solvent. A net charge is placed onto the particle as it is generated. As used herein the term "ion" means a particle having a net charge.
The discrete particle is delivered to a levitation device.
Delivery of the discrete particle could be accomplished, for exaniple, by the particle generator used to generate the discrete particle. For example, where the particle generator is a droplet generator, the application of an electric pulse to a piezoelectric crystal in the droplet generator (with suitable backing pressure) will eject an isolated droplet with sufficient velocity to travel to the levitation device.
The discrete particle is electrodynamically levitated by a levitation device. As used herein, the term "levitated" means that the particle is suspended or "stored" within the levitation device. The period of time a particle is levitated may be varied depending upon the particular circumstances. The particle is then delivered from the levitation device to a remote target. As used herein the target is "remote" from the levitation device in the sense that it is spacially separated from the center or null position of the levitation device to some degree, although the quantum of separation may be small. In one aspect of the invention, the target is an orifice leading into (or otherwise in communication with) the vacuum of an atmospheric gas (and ion) sampling mass spectronleter. In another aspect of the invention, the target is a plate to be subjected to MALDI
mass spectrometry following deposition of the particle on the plate. The discrete particle may be delivered to the target by an electrode assembly.
Where the discrete particle is a droplet, the net charge lost from the droplet (referred to as a"parent" droplet) by Coloumb fission is delivered to the orifice of the mass spectronleter by manipulating the smaller droplets (referred to as "progeny" droplets). It is possible to levitate one or more particles in the levitation device simultaneously.
Figure 2 is a schematic illustration of an apparatus 29 of the invention. Apparatus 29 comprises a particle generator 32 and a levitation device 30. Particle generator 32 can be a droplet generator. Levitation device 30 can be any nleans to levitate a discrete particle. For illustration purposes, levitation device 30 has been described herein as comprising an electrodynamic balance comprised of two ring electrodes 48, 50. Those skilled in the art will appreciate that there are many configurations of electrodynamic balances and the like that fall within the scope of this invention. For exaniple, ring electrodes 48, 50 may have different geometric configurations (e.g. annular and non-annular) without departing from the invention.
In operation, a discrete particle (not shown) is generated by particle generator 32, delivered to levitation device 30 and then levitated by levitation device 30 between ring electrodes 48, 50. Positioned between droplet generator 32 and levitation device 30 is an induction electrode 52.
An electric potential is applied to induction electrode so as to induce a net charge of a desired polarity onto the discrete particle generated by particle generator 32.
Figure 2 also illustrates an atmospheric gas (and ion) sampling mass spectrometer 31 having an orifice 33, a mass filter 35 in a vacuum chamber 37 and a detector 39. Following levitation of the particle in electrodynamic balance 30, it is delivered to the orifice :33 for analysis by mass spectrometer 31. As will be explained further, in another aspect of the invention, the discrete particle may be delivered from the electrody-namic balance 30 and deposited onto a plate that is to be subjected to MALDI mass spectrometry analysis.
Figures 3-6 and 10 are schematic drawings of further exemplary apparatuses 68, 76, 78, 81, 88 of the invention in which the particle generator 32 is a droplet generator and the levitation device 30 is an electrodynamic balance comprised of ring electrodes 48, 50.
The apparatuses 68, 76, 78, 81, 88 each comprise a levitation device 30 and a droplet generator 32. Droplet generator 32 is operatively connected to a liquid sample containing the analyte in solution. As illustrated in Figures 3-6 and 10, the droplet generator 32 may be connected at a bottom portion 32b to a syringe 34 by tubing 36.
A nozzle 38 is fitted to an upper portion 32a of the droplet generator 32 in the embodiments illustrated in Figures 3-6. Nozzle 38 assists in maintaining stable droplet generation. Nozzle 38 is illustrated in more detail in Figure 12. Nozzle 38 has a flat tip 40 surrounding an aperture 42. Aperture 42 is vertically coaxial with the center of the levitation device 30 and the orifice 44 leading to the vacuum chamber 46.
Levitation device 30 is positioned above droplet generator 32.
In the illustrated embodiments of the invention, levitation device 30 is an electrodynamic balance comprised of two parallel vertically spaced-apart ring electrodes 48, 50. Ring electrodes 48, 50 may be constructed of c.opper wire. Ring electrodes 48, 50 are also depicted in Figure 8.
Positioned between droplet generator 32 and electrodynamic balance 30 is an induction electrode 52. A potential is applied to induction electrode 52 so that a net charge is induced onto each droplet generated from droplet generator 32 before it is delivered to the electrodynamic balance 30.
The apparatuses 68, 76, 78, 81 are illustrated in positions below an atmospheric gas (and ion) sampling mass spectrometer 65. In the Figures 3-6, mass spectrometer 65 comprises a vacuum chamber 46, a skimmer 58 having an. orifice 57 in alignment with droplet generator 52, and a delrin spacer 62 electrically isolating the skimmer 58 from the vacuum chamber 46. The vacuum chamber 46 houses a channel electron multiplier 64, which passes the CEM ion current 'to an appropriate counting unit (not shown). The vacuum chamber 46 may be differentially pumped.
The apparatuses 68, 76, 78, 81 of Figures 3-6 also comprise a plexiglass chamber 66 enclosing the electrodynanlic balance 30 in order to minimize convection currents that might otherwise preclude levitation of the droplet(s). An orifice 44 in a top plate 67 leads into the vacuum chamber 46 of mass spectrometer 65.
The apparatuses 68, 76, 78, 81 illustrated in Figures 3-6 are identical with respect to: (a) the structure of electrodynamic balance 30 and droplet generator 32; and (b) the separation between nozzle 38 of droplet generator 32 and electrodynamic balance 30. The structural differences between the apparatuses 68, 76, 78, 81 relate to the arrangement of various electrode assemblies for the manipulation and direction of progeny droplets and ions from the electrodynamic balance 30 toward the orifice 44 leading into vacuum chamber 46 of a mass spectrometer 65.
Referring to Figure 3, apparatus 68 comprises a two electrode assembly to guide progeny droplets and the ions desorbed from such droplets toward the sanlpling orifice 44. The two electrode assembly comprises a bottom electrode and a top electrode. Bottom electrode comprises a bottom plate electrode 70 that is positioned above droplet generator 32 and below electrodynamic balance 30, while top electrode comprises a top plate electrode 72 positioned above electrodynamic balance 30. Top plate electrode 72 could be a conventional counter electrode, such as that used in ESI arrangement 10. Bottom plate electrode 70 defines an aperture 74 therein to allow droplets generated from droplet generator 32 to be delivered to electrodynamic balance 30. Top plate electrode 72 defines an aperture 73 therein to allow passage of droplets to be delivered from electrodynamic balance 30 to orifice 44.
Referring to Figure 4, the only electrodes in apparatus 76 are ring electrodes 48, 50. That is, relative to apparatus 68 of Figure 3, bottom plate electrode 70 and top plate electrode 72 are omitted.
Levitation ring electrodes 48, 50 are positioned proximal to sampling orifice 44 in apparatus 76.
Referring to Figure 5, apparatus 78 includes four guide ring electrodes 80, 82, 84, 86 positioned above levitation ring electrodes 48, 50. Each higher positioned guide electrode has a smaller diameter than the immediately lower guide electrode. That is, the diameter of electrode 80 > the diameter of electrode 82 > the diameter of electrode 84 > the diameter of electrode 86. The spacing between guide electrodes 80, 82, 84, 86 may be fixed such that the spacing between guide electrodes 80 and 82 is the same as, for example, that between electrodes 84 and 86. The guide ring electrodes 80, 82, 84, 86 are also illustrated in Figure 9. It will be appreciated that any number of guide electrodes (within design constraints) could be utilized instead of the four that are illustrated in the embodiment of the apparatus 78 in Figure 5.
Referring to Figure 6, apparatus 81 is similar to apparatus 78 (Figure 5) with the exception that a quadrupole of four cylindrical electrodes 83 is positioned where the stack of guide ring electrodes 80, 82, 84, 86 was positioned in apparatus 78. Figure 7 is a cross-sectioiial view showing the quadrupole electrode arrangement of apparatus 81.
In operation, droplets (not shown) are generated by and ejected upwardly one at a time from droplet generator 32 at an initial velocity sufficient to rise to the center of the electrodynamic balance 30 (i.e. mid-point between rings 48, 50 and vertically coaxial with sampling orifice 44) without the assistance of an electric field. A net charge is induced onto droplet at the time it is generated by passing through an aperture 53 of induction electrode 52.
It is possible to levitate a charged droplet between levitation ring electrodes 48, 50 without the application of DC potential to the levitation ring electrodes 48, 50 to offset gravity, though as explained later, DC voltages are applied to manipulate and guide progeny droplets and particles out of electrodynamic balance 30. In one embodiment, charged droplets may be levitated between levitation ring electrodes 48, 50 through the application, to both ring electrodes 48, 50, of an AC potential (60 Hz) of 1300 V with 0 phase difference. Differing waveforms (e.g.
AC, DC or AC and DC) could be applied to electrodynamic balance 30 to levitate the particle.
Droplets levitated in the levitation device 30 (i.e. between levitation ring electrodes 48, 50) will shrink, via evaporation of solvent, to the Coulomb limit. At the Coulomb limit, the droplet will fragment or "explode" releasing ions and progeny droplets.
The ions and the progeny droplets may be guided to the sampling orifice 44 (and into vacuum chanlber 46) for mass spectrometry.
This could be accomplished, for example, using the electrode assemblies of apparatuses 68, 76, 78, 81 illustrated, respectively, iri Figures 3-6. As compared to prior art ESI, this approach significantly reduces space charge repulsion, enabling higher transmission efficiency of net charge in the parent droplet inside the electrodynamic balance 30 to the mass spectrome-ter 65. Previously, there have been no attempts to collect the current ejected from a single droplet for study by a mass spectrometer. This invention thus allows the collection, with a mass spectrometer, of a higher fraction of current originating from a single parent droplet with net charge.
This creates an ion source that permits very high sensitivity (low concen-tration detection limits) coupled with the high chemical specificity of a mass spectrometer.
As noted above, the electrode assemblies described above for the apparatuses 68, 76, 78 of Figures 3-6 may allow the control of the delivery of the progeny droplets and ions from the electrodynamic balance towards the orifice 44 into the vacuum chamber 46.
Referring to the apparatus 68 of Figure 3, the vertical position 25 of the progeny droplets and ions desorbed therefrorn can be manipulated by, for example, varying the DC potentials across bottom plate electrode 70 and top plate electrode 72. Droplets and ions are directed upwardly to orifice 44 through aperture 73 in top plate electrode 72.
30 Referring to the apparatus 76 of Figure 4, a constant voltage difference applied across the two levitation ring electrodes 48, 50 causes progeny droplets and ions to be directed upwardly from the electrodynamic balance 30. In one enibodiment of the apparatus, a constant DC voltage across the ring electrodes 48, 50 is defined as (V,,,op -Vr,,,o om) _-20 V, where Vr, top is the DC voltage applied to the top ring electrode 48 and Vr, bottom is the DC voltage of the bottom ring electrode 50, and where Vr, top was varied between 30 and 280 V.
Referring to the apparatus 78 of Figure 5, the manipulation of the progeny droplets and ions is effected by guide ring electrodes 80, 82, 84, 86 positioned above electrodynamic balance 30. It has been found that the same DC and AC potentials applied to the top ring electrode 48 can be applied to guide ring electrodes 80, 82, 84, 86. Droplets and ions are directed upwardly to orifice 44 through guide ring electrodes 80, 82, 84, 86.
Referring to apparatus 81 of Figure 6, the manipulation of the progeny droplets and ions is effected by the vertically-oriented quadrupole electrode assembly of cylindrical electrodes 83 that is positioned above electrodynamic balance 30. Figure 6 shows only two cylindrical electrodes 83, though the cross sectional view of Figure 7 shows all four cylindrical electrodes 83.
In an another aspect of the invention, droplets and particles may be ejected from the electrodynamic balance 30 for deposition onto a plate for mass spectrometric analysis by MALDI, rather than being ejected for direct mass spectrometry as described above. The analyte-containing droplet may be deposited onto a MALDI plate which has been pre-coated with a matrix.
An apparatus 88 for depositing droplets onto a MALDI plate 90 is illustrated in Figure 10. The apparatus 88 is similar in structure to apparatus 76 of Figure 4 in that droplet generator 32, tube 36, syringe 34, induction electrode 52, an electrodynanlic balance 30 comprising two levitation ring electrodes 48, 50 and plexiglass chamber 66 are all present as with apparatus 76 of Figure 5. Apparatus 88, however, has a MALDI
plate 90 positioned above levitation r=ing electrodes 48, 50 in place for deposition of droplets ejected from the electrodynamic balance 30.
The operation of apparatus 88 is similar to that described above in that droplets are generated by droplet generator 32, have a net charge placed thereon by induction electrode 52 and are levitated in levitation device 30 (i.e. between levitation ring electrodes 48, 50) for Coloumb fission. In order to eject the droplets from the ring electrodes 48, 50, an increasing potential can be applied to the MALDI plate 90. The droplets, due to their net charge, are increasingly attracted towards the MALDI plate 90 and, eventually, are deposited thereon. The MALDI
plate 90 can be pre-coated with a. matrix 100.
The plate 90 onto which the droplets have been deposited is then inserted into a mass spectrometer for analysis using MALDI in a conventional manner.
The following example will further illustrate the invention in greater detail although it will be appreciated that the invention is not limited to the specific example.
The current utilizatiori rates of several embodiments of the apparatus of this invention were tested and compared with that obtained from a prior art ESI arrangement. The apparatuses tested were substan-tially similar to the embodiments of the apparatuses 68, 76, 78 illustrated in Figures 3-5, with the following parameters. For ease of reference, the tested apparatuses will be referred to as tested apparatuses 68, 76 or 78, as the case may be. For comparison purposes, an ESI arrangement having the following parameters was also tested ACS grade sodium chloride and tetrabutylammonium chloride salts were used to prepare 10 mM stock solutions using distilled deionized water. These two stock solutions were then diluted to 5 M using ACS
grade methanol prior to use in either the ESI apparatus or the tested apparatuses 68, 76, '78.
The ESI apparatus consisted of a stainless steel capillary (0.1 rnm inner diameter x 0.2 nlm outer diameter) that was biased to 3 kV .
Sample solutions were pumped into this capillary at a rate of 5,uL miri 1 with a syringe pump (Cole-Parmer, model 74900). A nitrogen curtain gas flow rate of 1 L min -' was delivered to the region between the sampling orifice and the counter electrode (held at 300V). The ES capillary was positioned 2-3 mm off the ion axis of the vacuum chamber and the capillary tip to counter electrode separation was 10 mm.
For tested apparatuses 68, 76, 78, a droplet generator (obtained from Uni-photon Systems, model 201, Brooklyn, New York, U.S.A.) was employed and set to generate droplets at 1 Hz. The droplet generator was housed in an 8-cm-long x 1-cm-diameter stainless steel tube. Another stainless steel tube, terminated at both ends with standard plumbing fittings, ran through this housing. A piezoelectic crystal surrounded the inner tube inside the housing.
A nozzle (similar to nozzle 38 of Figure 12) for the droplet generator was constructed by sealing a short piece of uncoated fused silica (35 m i.d. x 150 nl o.d.) into a borosilicate glass tube (1.6 mm i.d. x 3.2 mm o.d.) using a laboratory flame. This newly formed fire-polished tip was rounded, and this was polished flat on optical lapping paper using a high speed drill to form the nozzle.
The end of the droplet generator housing opposite the nozzle was connected by a short length of tubing to a syringe. With the applica-tion of a high voltage pulse to the piezoelectric crystal, the stainless steel sample tube inside the droplet generator assembly constricted. With a suitable backing pressure froni a syringe pump, a droplet was squeezed out of the nozzle and delivered to electrodynamic balance 30.
Droplets were caused to have a net positive charge through the use of an induction electrode, set at -125 V DC, that imparted a charge onto each droplet as it was formed. The induction electrode was posi-tioned proximal to the nozzle of droplet generator.
The nozzle of the droplet generator was positioned 20 mm below the bottom ring of the electrodynamic balance, and on-axis with respect to both the center of the electrodynamic balance and the orifice leading to the vacuum chamber. The electrodynarnic balance was constructed of two levitation ring electrodes (6.5 mm radius), made with 1.7-mm-diameter copper wire and aligned parallel at a separation distance of 4.6 mm. Charged particles were stored in the center of the electrody-namic balance, by applying a 60 Hz line signal, amplified to 1300 V oP, with 0 phase difference to both levitation ring electrodes. The droplets could be levitated with no DC voltages applied to the levitation ring electrodes. DC voltages applied were solely for the purpose of manipulat-ing the progeny droplets.
Droplets ejected from the nozzle of the droplet generator were measured to have initial velocities of approximately 0.8 ms-I and were able to rise the distance (approximately 22 mm) to the center of the electrody-namic balance without the assistance of an electric field. A plexiglass chamber was used to minimize convection current:s that may have otherwise precluded levitation of the primary droplet.
The magnitude of the DC voltage on the top levitation ring electrode was varied between 30 and 280 V, and the DC voltage applied to the bottom levitation ring electrode tracked that of the top electrode with a fixed offset of (V'r,toP-Vr,bo om =) - 20 V. The magnitude of the DC
potential of the top ring electrode affected the velocity of the progeny droplets expelled by coulomb fission after they left the levitation device toward the sampling orifice. The constant DC voltage difference between the two levitation ring electrodes (Vr, ,p - V~,,o om) of -20 V was sufficient to cause all progeny droplets to be ejected from the fissioning parent droplet in the upward direction only. From initiation of the first coulomb fission event, the droplet was observed to eject progeny droplets for less than 100 ms, with brief discontinuities, until the remnant of the primary droplet itself was ejected upwards, out of the electrodynamic balance.
Laser light scatter from the progeny droplets allowed this behaviour to be observed with the naked eye. The DC offset potential applied between the two levitation ring electrodes did iiot noticeably affect the vertical position of the evaporating primary droplet within the electrodynamic balance. In contrast, during the time period following the initiation of the first Coulomb fission event (< 100 ms), the primary droplet could be seen oscillating in the vertical direction with an amplitude less than 1 mm, presumably due to electrostatic recoil from the ejected progeny droplets.
A vacuum chamber was fitted to the tested apparatuses 68, 76, 78, as illustrated in Figures 3-5, and to the tested ESI arrangement. Two stages of differential pumping were used. A 50- m-thick stainless steel foil with a 100- m-diameter orifice (Harvard Apparatus, Canada, St.
Laurent, Quebec, Canada) was used to sample the gas at atmospheric pressure into the first. stage of pressure reduction (1 Torr). This foil was biased to 70 V DC. The differentially pumped chamber was evacuated by a 5.5 L/s rotary pump (Leybold, model D16A, Mississauga, Ontario, Canada). The orifice of the skimmer was 0.50 mm dimeter and the separation distance between the orifice and skimmer tip was 3.2 mm. The skimmer was biased to 5 V. A delrin spacer electrically isolated the skimmer from the grounded vacuum chamber. A 50 L/s turbomolecular pump (Leybold, model TMP050) was used to evacuate the chamber that housed the channel electron multiplier (CEM) (Detect, model 310G, Palmer, MA). The bias potential for the CEM was -2400 V. The CEM
ion current was passed through a photon counting unit (Hamamatsu, model 3866) and the resulting TTL signal counted. The separation distance between the skimmer tip and the CEM was 82 mm, and there were no electrode guides used in this region.
In the tested apparatus 68, a two plate electrode assembly, with one plate electrode above and one below the electrodynamic balance, was used to guide the progeny droplets. The bottom plate had a 5-mm-diameter aperture to allow droplets ejected from the droplet generator nozzle to pass directly up into the electi-odynamic balance. Though Figure 3 illustrates apparatus 68 with the bottom plate electrode 70, tests were also conducted with this bottom plate electrode 70 removed. A flow of nitrogen gas was delivered to the region between the sampling orifice plate and the counter electrode in the range of 0 to 0.5 L miri `.
In the tested apparatus 76, the only electrodes at atmospheric pressure were the two levitation ring electrodes of electrodynamic balance 30. The DC potential. applied to the top levitation ring electrode was varied from 150 to 280 V, with the DC voltage difference between the top and bottom levitation ring maintained at -20 V.
The tested apparatus 78 employs a series of four guide ring electrodes, positioned above the electrodynamic balance, to guide progency droplets. Each higher positioned guide ring electrode has a smaller radius than the immediately lower one. The guide ring electrodes were fabricated by making a ring frorn a short strand of 0.8-mm diameter copper wire.
The guide ring electrodes were positioned above the levitation ring electrodes of electrodynamic balance in equal separation gaps of 3 mm.
The same DC and AC electrode biasing applied to the top levitation ring electrode was applied to each of the guide ring electrodes. The top and bottom levitation ring electrodes of electrodynamic balance were DC
biased to 280 and 300 V, respectively.
In the tested apparatuses 68 (both with and without bottom plate electrode 70), 76 and 78, a droplet generated by the droplet generator flew to the center of the electrodynamic balance (approximately 22 mm) in about 75 ms and was then levitated there while it desolvated. The droplet desolvated to the first coulomb limit 550 75 ms after the droplet was formed. The droplet fissioned, discontinuously, for less than 100 ms, after which the remnant of the original droplet was itself ejected from the electrodynamic balance. These observations were made by viewing the droplet, unaided by lenses, inside the electrodynamic balance by illuminat-ing the droplet with a diode laser and manually measuring with a stopwatch the time from droplet generation to the initiation of the first coulomb fission event. The value of 550 ms is the average of 103 such nieasure-ments.
The levitation of the particles in electrodynamic balance 30 was carried out in tested apparatuses 68, 76 and 78 at atmospheric pressure.
The posii:ive ion current from the CEM in the vacuum chamber with the tested ESI arrangement was s3 x 103counts/s. The ion current was not dependent on the nature of the cation in solution, as both test solutions yielded the same ion count rate. In a separate experiment, the current arriving at a solid counter electrode plate was measured to be 500nA, for both sample solutions. This corresponds to a current utilization efficiency of __ I x 10-`'.
As with the ESI arrangement 10, the ion currents measured from single droplets with a net chai=ge were not dependent on the nature of the cation in solution as both test solutions yielded the same ion count rates.
With the bottom plate electrode 70 of the tested apparatus 68 (of Figure 3) in position, or removed, the mean ion count per droplet ranged from 0. 3 to 1. 8 counts, respectively. The tested apparatus 68 (with or without bottom plate electrode 70) thus yielded ion utilization efficiency per 10 s integral of approximately 1 x 10-7 , an improvement by two orders of magnitude in ion utilization over that measured for the ESI arrangement, which was measured to be <_ 1 x 10 y.
For tested apparatus 76, levitation ring electrode 48 was positioned 2 mm frorn the sampling orifice (the separation between the levitation ring electrodes remained constant). Tested apparatus 76 yielded improved ion currents ranging between 2.5 to 5 counts per droplet, depending on the magnitude of the DC voltage bias applied to the levitation ring electrodes. It is surmised that the reason for the increase in counts is likely that with larger DC bias potentials applied to the levitation ring electrodes the progeny droplets, and ions, were caused to drift toward the sampling orifice at higher velocities, reducing the extent of off-axis diffusion of the progeny droplets and ions.
The highest ions currents measured from isolated droplets were recorded with tested apparatus 78. The top guide ring electrode 86 was positioned 2 mm fi-om the sampling orifice, and the bottom guide ring electrode 80 was 3 mm above the top levitation ring electrode 48. Ion count rates of approximately 40 per droplet were measured with tested apparatus 78, and the ion utilization efficiency demonstrated with this data set was approximately 4 x 10-6, a marked increase over the tested ESI
arrangement.
Figure 1.1 is a graph plotting the ion counts over 10 s time integrals of the tested apparatuses 68 (with and without bottom plate electrode 70), 76 and 78. The symbols in Figure 11 represent the results obtained from the following apparatuses:
(a) open dianlond - tested apparatus 68 with the top (counter electrode) and bottom plate electrode biased to 30 and 500 V
DC, respectively and the top and bottom electrodynamic balance electrode rings at 50 and 70 V DC, respectively;
(b) filled diamond - tested apparatus 68 with the top (counter electrode) and bottom plate electrode biased to 150 V and 500 V DC, respectively and the top and bottom electrodynamic balance electrode rings at 180 and 200 V I)C, respectively;
(c) filled triangles - tested apparatus 68 with the bottom plate electrode 70 reinoved and the top (counter electrode) elec-trode biased to 150 V DC and the top and bottom electrody-naniic balance electrode rings at 180 and 200 V DC, respec-tively;
(d) open squares - tested apparatus 76 with the electrodynamic balance rings at 180 and 200 V DC, respectively;
(e) filled squares - tested apparatus 76 with the electrodynamic balance rings at 280 and 300 V DC, respectively; and (f) filled circles - tested apparatus 78 with the electrodynamic balance rings at 280 and 300 V DC, respectively and the circular electrodes biased to 280 V DC.
As will be apparent to those skilled in the art in the liglit of the foregoing disclosure, many alterations and modifications are possible in the practice of this invention without departing from the scope thereof.
.,.-3inWaA}c,, j.t is within the scope of this invention to utilize electrode assemblies other than those specifically illustrated in Figures 3-7 to deliver the progeny droplets/ioiis to the target.
It may be advantageous to subject a levitated droplet to a flow of gas to control (e.g. promote or retard) the evapoi-ation rate of the solvent in the droplet.
Another possible application of this invention is as a "wall-less" chemical reaction vessel. The advantage to this technique is that the surface-to-volume ratio is enhanced (relative to performing the same raction in a traditional reaction vessel). This adaptiori of the invention could have many application, such as medical diagnostic purposes.
Further still, the invention could have application for polymerizing progeny droplets, which at the moment of their formation, are approximately 100-1000 nm in diameter. With care, it would be possible to allow these progeny droplets to desolvate to smaller diameters before polymerizing their surface to encapsulate the contents of these droplets. This procedure could be used to prepare round nanometer sized niaterials that could be designed to be either hollow or solid.
Accordingly, the scope of the invention is to be construed in accordance with the substance defined by the following claims.
Figures 3-6 and 10 are schematic drawings of further exemplary apparatuses 68, 76, 78, 81, 88 of the invention in which the particle generator 32 is a droplet generator and the levitation device 30 is an electrodynamic balance comprised of ring electrodes 48, 50.
The apparatuses 68, 76, 78, 81, 88 each comprise a levitation device 30 and a droplet generator 32. Droplet generator 32 is operatively connected to a liquid sample containing the analyte in solution. As illustrated in Figures 3-6 and 10, the droplet generator 32 may be connected at a bottom portion 32b to a syringe 34 by tubing 36.
A nozzle 38 is fitted to an upper portion 32a of the droplet generator 32 in the embodiments illustrated in Figures 3-6. Nozzle 38 assists in maintaining stable droplet generation. Nozzle 38 is illustrated in more detail in Figure 12. Nozzle 38 has a flat tip 40 surrounding an aperture 42. Aperture 42 is vertically coaxial with the center of the levitation device 30 and the orifice 44 leading to the vacuum chamber 46.
Levitation device 30 is positioned above droplet generator 32.
In the illustrated embodiments of the invention, levitation device 30 is an electrodynamic balance comprised of two parallel vertically spaced-apart ring electrodes 48, 50. Ring electrodes 48, 50 may be constructed of c.opper wire. Ring electrodes 48, 50 are also depicted in Figure 8.
Positioned between droplet generator 32 and electrodynamic balance 30 is an induction electrode 52. A potential is applied to induction electrode 52 so that a net charge is induced onto each droplet generated from droplet generator 32 before it is delivered to the electrodynamic balance 30.
The apparatuses 68, 76, 78, 81 are illustrated in positions below an atmospheric gas (and ion) sampling mass spectrometer 65. In the Figures 3-6, mass spectrometer 65 comprises a vacuum chamber 46, a skimmer 58 having an. orifice 57 in alignment with droplet generator 52, and a delrin spacer 62 electrically isolating the skimmer 58 from the vacuum chamber 46. The vacuum chamber 46 houses a channel electron multiplier 64, which passes the CEM ion current 'to an appropriate counting unit (not shown). The vacuum chamber 46 may be differentially pumped.
The apparatuses 68, 76, 78, 81 of Figures 3-6 also comprise a plexiglass chamber 66 enclosing the electrodynanlic balance 30 in order to minimize convection currents that might otherwise preclude levitation of the droplet(s). An orifice 44 in a top plate 67 leads into the vacuum chamber 46 of mass spectrometer 65.
The apparatuses 68, 76, 78, 81 illustrated in Figures 3-6 are identical with respect to: (a) the structure of electrodynamic balance 30 and droplet generator 32; and (b) the separation between nozzle 38 of droplet generator 32 and electrodynamic balance 30. The structural differences between the apparatuses 68, 76, 78, 81 relate to the arrangement of various electrode assemblies for the manipulation and direction of progeny droplets and ions from the electrodynamic balance 30 toward the orifice 44 leading into vacuum chamber 46 of a mass spectrometer 65.
Referring to Figure 3, apparatus 68 comprises a two electrode assembly to guide progeny droplets and the ions desorbed from such droplets toward the sanlpling orifice 44. The two electrode assembly comprises a bottom electrode and a top electrode. Bottom electrode comprises a bottom plate electrode 70 that is positioned above droplet generator 32 and below electrodynamic balance 30, while top electrode comprises a top plate electrode 72 positioned above electrodynamic balance 30. Top plate electrode 72 could be a conventional counter electrode, such as that used in ESI arrangement 10. Bottom plate electrode 70 defines an aperture 74 therein to allow droplets generated from droplet generator 32 to be delivered to electrodynamic balance 30. Top plate electrode 72 defines an aperture 73 therein to allow passage of droplets to be delivered from electrodynamic balance 30 to orifice 44.
Referring to Figure 4, the only electrodes in apparatus 76 are ring electrodes 48, 50. That is, relative to apparatus 68 of Figure 3, bottom plate electrode 70 and top plate electrode 72 are omitted.
Levitation ring electrodes 48, 50 are positioned proximal to sampling orifice 44 in apparatus 76.
Referring to Figure 5, apparatus 78 includes four guide ring electrodes 80, 82, 84, 86 positioned above levitation ring electrodes 48, 50. Each higher positioned guide electrode has a smaller diameter than the immediately lower guide electrode. That is, the diameter of electrode 80 > the diameter of electrode 82 > the diameter of electrode 84 > the diameter of electrode 86. The spacing between guide electrodes 80, 82, 84, 86 may be fixed such that the spacing between guide electrodes 80 and 82 is the same as, for example, that between electrodes 84 and 86. The guide ring electrodes 80, 82, 84, 86 are also illustrated in Figure 9. It will be appreciated that any number of guide electrodes (within design constraints) could be utilized instead of the four that are illustrated in the embodiment of the apparatus 78 in Figure 5.
Referring to Figure 6, apparatus 81 is similar to apparatus 78 (Figure 5) with the exception that a quadrupole of four cylindrical electrodes 83 is positioned where the stack of guide ring electrodes 80, 82, 84, 86 was positioned in apparatus 78. Figure 7 is a cross-sectioiial view showing the quadrupole electrode arrangement of apparatus 81.
In operation, droplets (not shown) are generated by and ejected upwardly one at a time from droplet generator 32 at an initial velocity sufficient to rise to the center of the electrodynamic balance 30 (i.e. mid-point between rings 48, 50 and vertically coaxial with sampling orifice 44) without the assistance of an electric field. A net charge is induced onto droplet at the time it is generated by passing through an aperture 53 of induction electrode 52.
It is possible to levitate a charged droplet between levitation ring electrodes 48, 50 without the application of DC potential to the levitation ring electrodes 48, 50 to offset gravity, though as explained later, DC voltages are applied to manipulate and guide progeny droplets and particles out of electrodynamic balance 30. In one embodiment, charged droplets may be levitated between levitation ring electrodes 48, 50 through the application, to both ring electrodes 48, 50, of an AC potential (60 Hz) of 1300 V with 0 phase difference. Differing waveforms (e.g.
AC, DC or AC and DC) could be applied to electrodynamic balance 30 to levitate the particle.
Droplets levitated in the levitation device 30 (i.e. between levitation ring electrodes 48, 50) will shrink, via evaporation of solvent, to the Coulomb limit. At the Coulomb limit, the droplet will fragment or "explode" releasing ions and progeny droplets.
The ions and the progeny droplets may be guided to the sampling orifice 44 (and into vacuum chanlber 46) for mass spectrometry.
This could be accomplished, for example, using the electrode assemblies of apparatuses 68, 76, 78, 81 illustrated, respectively, iri Figures 3-6. As compared to prior art ESI, this approach significantly reduces space charge repulsion, enabling higher transmission efficiency of net charge in the parent droplet inside the electrodynamic balance 30 to the mass spectrome-ter 65. Previously, there have been no attempts to collect the current ejected from a single droplet for study by a mass spectrometer. This invention thus allows the collection, with a mass spectrometer, of a higher fraction of current originating from a single parent droplet with net charge.
This creates an ion source that permits very high sensitivity (low concen-tration detection limits) coupled with the high chemical specificity of a mass spectrometer.
As noted above, the electrode assemblies described above for the apparatuses 68, 76, 78 of Figures 3-6 may allow the control of the delivery of the progeny droplets and ions from the electrodynamic balance towards the orifice 44 into the vacuum chamber 46.
Referring to the apparatus 68 of Figure 3, the vertical position 25 of the progeny droplets and ions desorbed therefrorn can be manipulated by, for example, varying the DC potentials across bottom plate electrode 70 and top plate electrode 72. Droplets and ions are directed upwardly to orifice 44 through aperture 73 in top plate electrode 72.
30 Referring to the apparatus 76 of Figure 4, a constant voltage difference applied across the two levitation ring electrodes 48, 50 causes progeny droplets and ions to be directed upwardly from the electrodynamic balance 30. In one enibodiment of the apparatus, a constant DC voltage across the ring electrodes 48, 50 is defined as (V,,,op -Vr,,,o om) _-20 V, where Vr, top is the DC voltage applied to the top ring electrode 48 and Vr, bottom is the DC voltage of the bottom ring electrode 50, and where Vr, top was varied between 30 and 280 V.
Referring to the apparatus 78 of Figure 5, the manipulation of the progeny droplets and ions is effected by guide ring electrodes 80, 82, 84, 86 positioned above electrodynamic balance 30. It has been found that the same DC and AC potentials applied to the top ring electrode 48 can be applied to guide ring electrodes 80, 82, 84, 86. Droplets and ions are directed upwardly to orifice 44 through guide ring electrodes 80, 82, 84, 86.
Referring to apparatus 81 of Figure 6, the manipulation of the progeny droplets and ions is effected by the vertically-oriented quadrupole electrode assembly of cylindrical electrodes 83 that is positioned above electrodynamic balance 30. Figure 6 shows only two cylindrical electrodes 83, though the cross sectional view of Figure 7 shows all four cylindrical electrodes 83.
In an another aspect of the invention, droplets and particles may be ejected from the electrodynamic balance 30 for deposition onto a plate for mass spectrometric analysis by MALDI, rather than being ejected for direct mass spectrometry as described above. The analyte-containing droplet may be deposited onto a MALDI plate which has been pre-coated with a matrix.
An apparatus 88 for depositing droplets onto a MALDI plate 90 is illustrated in Figure 10. The apparatus 88 is similar in structure to apparatus 76 of Figure 4 in that droplet generator 32, tube 36, syringe 34, induction electrode 52, an electrodynanlic balance 30 comprising two levitation ring electrodes 48, 50 and plexiglass chamber 66 are all present as with apparatus 76 of Figure 5. Apparatus 88, however, has a MALDI
plate 90 positioned above levitation r=ing electrodes 48, 50 in place for deposition of droplets ejected from the electrodynamic balance 30.
The operation of apparatus 88 is similar to that described above in that droplets are generated by droplet generator 32, have a net charge placed thereon by induction electrode 52 and are levitated in levitation device 30 (i.e. between levitation ring electrodes 48, 50) for Coloumb fission. In order to eject the droplets from the ring electrodes 48, 50, an increasing potential can be applied to the MALDI plate 90. The droplets, due to their net charge, are increasingly attracted towards the MALDI plate 90 and, eventually, are deposited thereon. The MALDI
plate 90 can be pre-coated with a. matrix 100.
The plate 90 onto which the droplets have been deposited is then inserted into a mass spectrometer for analysis using MALDI in a conventional manner.
The following example will further illustrate the invention in greater detail although it will be appreciated that the invention is not limited to the specific example.
The current utilizatiori rates of several embodiments of the apparatus of this invention were tested and compared with that obtained from a prior art ESI arrangement. The apparatuses tested were substan-tially similar to the embodiments of the apparatuses 68, 76, 78 illustrated in Figures 3-5, with the following parameters. For ease of reference, the tested apparatuses will be referred to as tested apparatuses 68, 76 or 78, as the case may be. For comparison purposes, an ESI arrangement having the following parameters was also tested ACS grade sodium chloride and tetrabutylammonium chloride salts were used to prepare 10 mM stock solutions using distilled deionized water. These two stock solutions were then diluted to 5 M using ACS
grade methanol prior to use in either the ESI apparatus or the tested apparatuses 68, 76, '78.
The ESI apparatus consisted of a stainless steel capillary (0.1 rnm inner diameter x 0.2 nlm outer diameter) that was biased to 3 kV .
Sample solutions were pumped into this capillary at a rate of 5,uL miri 1 with a syringe pump (Cole-Parmer, model 74900). A nitrogen curtain gas flow rate of 1 L min -' was delivered to the region between the sampling orifice and the counter electrode (held at 300V). The ES capillary was positioned 2-3 mm off the ion axis of the vacuum chamber and the capillary tip to counter electrode separation was 10 mm.
For tested apparatuses 68, 76, 78, a droplet generator (obtained from Uni-photon Systems, model 201, Brooklyn, New York, U.S.A.) was employed and set to generate droplets at 1 Hz. The droplet generator was housed in an 8-cm-long x 1-cm-diameter stainless steel tube. Another stainless steel tube, terminated at both ends with standard plumbing fittings, ran through this housing. A piezoelectic crystal surrounded the inner tube inside the housing.
A nozzle (similar to nozzle 38 of Figure 12) for the droplet generator was constructed by sealing a short piece of uncoated fused silica (35 m i.d. x 150 nl o.d.) into a borosilicate glass tube (1.6 mm i.d. x 3.2 mm o.d.) using a laboratory flame. This newly formed fire-polished tip was rounded, and this was polished flat on optical lapping paper using a high speed drill to form the nozzle.
The end of the droplet generator housing opposite the nozzle was connected by a short length of tubing to a syringe. With the applica-tion of a high voltage pulse to the piezoelectric crystal, the stainless steel sample tube inside the droplet generator assembly constricted. With a suitable backing pressure froni a syringe pump, a droplet was squeezed out of the nozzle and delivered to electrodynamic balance 30.
Droplets were caused to have a net positive charge through the use of an induction electrode, set at -125 V DC, that imparted a charge onto each droplet as it was formed. The induction electrode was posi-tioned proximal to the nozzle of droplet generator.
The nozzle of the droplet generator was positioned 20 mm below the bottom ring of the electrodynamic balance, and on-axis with respect to both the center of the electrodynamic balance and the orifice leading to the vacuum chamber. The electrodynarnic balance was constructed of two levitation ring electrodes (6.5 mm radius), made with 1.7-mm-diameter copper wire and aligned parallel at a separation distance of 4.6 mm. Charged particles were stored in the center of the electrody-namic balance, by applying a 60 Hz line signal, amplified to 1300 V oP, with 0 phase difference to both levitation ring electrodes. The droplets could be levitated with no DC voltages applied to the levitation ring electrodes. DC voltages applied were solely for the purpose of manipulat-ing the progeny droplets.
Droplets ejected from the nozzle of the droplet generator were measured to have initial velocities of approximately 0.8 ms-I and were able to rise the distance (approximately 22 mm) to the center of the electrody-namic balance without the assistance of an electric field. A plexiglass chamber was used to minimize convection current:s that may have otherwise precluded levitation of the primary droplet.
The magnitude of the DC voltage on the top levitation ring electrode was varied between 30 and 280 V, and the DC voltage applied to the bottom levitation ring electrode tracked that of the top electrode with a fixed offset of (V'r,toP-Vr,bo om =) - 20 V. The magnitude of the DC
potential of the top ring electrode affected the velocity of the progeny droplets expelled by coulomb fission after they left the levitation device toward the sampling orifice. The constant DC voltage difference between the two levitation ring electrodes (Vr, ,p - V~,,o om) of -20 V was sufficient to cause all progeny droplets to be ejected from the fissioning parent droplet in the upward direction only. From initiation of the first coulomb fission event, the droplet was observed to eject progeny droplets for less than 100 ms, with brief discontinuities, until the remnant of the primary droplet itself was ejected upwards, out of the electrodynamic balance.
Laser light scatter from the progeny droplets allowed this behaviour to be observed with the naked eye. The DC offset potential applied between the two levitation ring electrodes did iiot noticeably affect the vertical position of the evaporating primary droplet within the electrodynamic balance. In contrast, during the time period following the initiation of the first Coulomb fission event (< 100 ms), the primary droplet could be seen oscillating in the vertical direction with an amplitude less than 1 mm, presumably due to electrostatic recoil from the ejected progeny droplets.
A vacuum chamber was fitted to the tested apparatuses 68, 76, 78, as illustrated in Figures 3-5, and to the tested ESI arrangement. Two stages of differential pumping were used. A 50- m-thick stainless steel foil with a 100- m-diameter orifice (Harvard Apparatus, Canada, St.
Laurent, Quebec, Canada) was used to sample the gas at atmospheric pressure into the first. stage of pressure reduction (1 Torr). This foil was biased to 70 V DC. The differentially pumped chamber was evacuated by a 5.5 L/s rotary pump (Leybold, model D16A, Mississauga, Ontario, Canada). The orifice of the skimmer was 0.50 mm dimeter and the separation distance between the orifice and skimmer tip was 3.2 mm. The skimmer was biased to 5 V. A delrin spacer electrically isolated the skimmer from the grounded vacuum chamber. A 50 L/s turbomolecular pump (Leybold, model TMP050) was used to evacuate the chamber that housed the channel electron multiplier (CEM) (Detect, model 310G, Palmer, MA). The bias potential for the CEM was -2400 V. The CEM
ion current was passed through a photon counting unit (Hamamatsu, model 3866) and the resulting TTL signal counted. The separation distance between the skimmer tip and the CEM was 82 mm, and there were no electrode guides used in this region.
In the tested apparatus 68, a two plate electrode assembly, with one plate electrode above and one below the electrodynamic balance, was used to guide the progeny droplets. The bottom plate had a 5-mm-diameter aperture to allow droplets ejected from the droplet generator nozzle to pass directly up into the electi-odynamic balance. Though Figure 3 illustrates apparatus 68 with the bottom plate electrode 70, tests were also conducted with this bottom plate electrode 70 removed. A flow of nitrogen gas was delivered to the region between the sampling orifice plate and the counter electrode in the range of 0 to 0.5 L miri `.
In the tested apparatus 76, the only electrodes at atmospheric pressure were the two levitation ring electrodes of electrodynamic balance 30. The DC potential. applied to the top levitation ring electrode was varied from 150 to 280 V, with the DC voltage difference between the top and bottom levitation ring maintained at -20 V.
The tested apparatus 78 employs a series of four guide ring electrodes, positioned above the electrodynamic balance, to guide progency droplets. Each higher positioned guide ring electrode has a smaller radius than the immediately lower one. The guide ring electrodes were fabricated by making a ring frorn a short strand of 0.8-mm diameter copper wire.
The guide ring electrodes were positioned above the levitation ring electrodes of electrodynamic balance in equal separation gaps of 3 mm.
The same DC and AC electrode biasing applied to the top levitation ring electrode was applied to each of the guide ring electrodes. The top and bottom levitation ring electrodes of electrodynamic balance were DC
biased to 280 and 300 V, respectively.
In the tested apparatuses 68 (both with and without bottom plate electrode 70), 76 and 78, a droplet generated by the droplet generator flew to the center of the electrodynamic balance (approximately 22 mm) in about 75 ms and was then levitated there while it desolvated. The droplet desolvated to the first coulomb limit 550 75 ms after the droplet was formed. The droplet fissioned, discontinuously, for less than 100 ms, after which the remnant of the original droplet was itself ejected from the electrodynamic balance. These observations were made by viewing the droplet, unaided by lenses, inside the electrodynamic balance by illuminat-ing the droplet with a diode laser and manually measuring with a stopwatch the time from droplet generation to the initiation of the first coulomb fission event. The value of 550 ms is the average of 103 such nieasure-ments.
The levitation of the particles in electrodynamic balance 30 was carried out in tested apparatuses 68, 76 and 78 at atmospheric pressure.
The posii:ive ion current from the CEM in the vacuum chamber with the tested ESI arrangement was s3 x 103counts/s. The ion current was not dependent on the nature of the cation in solution, as both test solutions yielded the same ion count rate. In a separate experiment, the current arriving at a solid counter electrode plate was measured to be 500nA, for both sample solutions. This corresponds to a current utilization efficiency of __ I x 10-`'.
As with the ESI arrangement 10, the ion currents measured from single droplets with a net chai=ge were not dependent on the nature of the cation in solution as both test solutions yielded the same ion count rates.
With the bottom plate electrode 70 of the tested apparatus 68 (of Figure 3) in position, or removed, the mean ion count per droplet ranged from 0. 3 to 1. 8 counts, respectively. The tested apparatus 68 (with or without bottom plate electrode 70) thus yielded ion utilization efficiency per 10 s integral of approximately 1 x 10-7 , an improvement by two orders of magnitude in ion utilization over that measured for the ESI arrangement, which was measured to be <_ 1 x 10 y.
For tested apparatus 76, levitation ring electrode 48 was positioned 2 mm frorn the sampling orifice (the separation between the levitation ring electrodes remained constant). Tested apparatus 76 yielded improved ion currents ranging between 2.5 to 5 counts per droplet, depending on the magnitude of the DC voltage bias applied to the levitation ring electrodes. It is surmised that the reason for the increase in counts is likely that with larger DC bias potentials applied to the levitation ring electrodes the progeny droplets, and ions, were caused to drift toward the sampling orifice at higher velocities, reducing the extent of off-axis diffusion of the progeny droplets and ions.
The highest ions currents measured from isolated droplets were recorded with tested apparatus 78. The top guide ring electrode 86 was positioned 2 mm fi-om the sampling orifice, and the bottom guide ring electrode 80 was 3 mm above the top levitation ring electrode 48. Ion count rates of approximately 40 per droplet were measured with tested apparatus 78, and the ion utilization efficiency demonstrated with this data set was approximately 4 x 10-6, a marked increase over the tested ESI
arrangement.
Figure 1.1 is a graph plotting the ion counts over 10 s time integrals of the tested apparatuses 68 (with and without bottom plate electrode 70), 76 and 78. The symbols in Figure 11 represent the results obtained from the following apparatuses:
(a) open dianlond - tested apparatus 68 with the top (counter electrode) and bottom plate electrode biased to 30 and 500 V
DC, respectively and the top and bottom electrodynamic balance electrode rings at 50 and 70 V DC, respectively;
(b) filled diamond - tested apparatus 68 with the top (counter electrode) and bottom plate electrode biased to 150 V and 500 V DC, respectively and the top and bottom electrodynamic balance electrode rings at 180 and 200 V I)C, respectively;
(c) filled triangles - tested apparatus 68 with the bottom plate electrode 70 reinoved and the top (counter electrode) elec-trode biased to 150 V DC and the top and bottom electrody-naniic balance electrode rings at 180 and 200 V DC, respec-tively;
(d) open squares - tested apparatus 76 with the electrodynamic balance rings at 180 and 200 V DC, respectively;
(e) filled squares - tested apparatus 76 with the electrodynamic balance rings at 280 and 300 V DC, respectively; and (f) filled circles - tested apparatus 78 with the electrodynamic balance rings at 280 and 300 V DC, respectively and the circular electrodes biased to 280 V DC.
As will be apparent to those skilled in the art in the liglit of the foregoing disclosure, many alterations and modifications are possible in the practice of this invention without departing from the scope thereof.
.,.-3inWaA}c,, j.t is within the scope of this invention to utilize electrode assemblies other than those specifically illustrated in Figures 3-7 to deliver the progeny droplets/ioiis to the target.
It may be advantageous to subject a levitated droplet to a flow of gas to control (e.g. promote or retard) the evapoi-ation rate of the solvent in the droplet.
Another possible application of this invention is as a "wall-less" chemical reaction vessel. The advantage to this technique is that the surface-to-volume ratio is enhanced (relative to performing the same raction in a traditional reaction vessel). This adaptiori of the invention could have many application, such as medical diagnostic purposes.
Further still, the invention could have application for polymerizing progeny droplets, which at the moment of their formation, are approximately 100-1000 nm in diameter. With care, it would be possible to allow these progeny droplets to desolvate to smaller diameters before polymerizing their surface to encapsulate the contents of these droplets. This procedure could be used to prepare round nanometer sized niaterials that could be designed to be either hollow or solid.
Accordingly, the scope of the invention is to be construed in accordance with the substance defined by the following claims.
Claims (72)
1. An apparatus for producing a discrete particle for subsequent analysis or manipulation, said apparatus comprising:
(a) a particle generator for generating a discrete particle;
(b) an induction electrode for inducing a net charge onto said discrete particle;
(c) a levitation device for electrodynamically levitating said discrete particle following the induction of said net charge; and (d) an electrode assembly for delivering said discrete particle from said levitation device to a target remote from said levitation device.
(a) a particle generator for generating a discrete particle;
(b) an induction electrode for inducing a net charge onto said discrete particle;
(c) a levitation device for electrodynamically levitating said discrete particle following the induction of said net charge; and (d) an electrode assembly for delivering said discrete particle from said levitation device to a target remote from said levitation device.
2. The apparatus of claim 1, wherein said electrode assembly is adapted for controllably delivering said discrete particle to said target for said subsequent analysis or manipulation.
3. The apparatus of claim 2, comprising an atmospheric gas sampling mass spectrometer and wherein said target is an orifice in communication with a vacuum chamber of said mass spectrometer.
4. The apparatus of claim 2, comprising a substrate and wherein said target is said substrate.
5. The apparatus of claim 4, wherein said substrate is a plate suitable for matrix assisted laser desorption and ionization mass spectrometric analysis.
6. The apparatus of claim 5, wherein said plate comprises a material for receiving said particle.
7. The apparatus of claim 6, wherein said material is a matrix.
8. The apparatus of claim 2, wherein said levitation device comprises said electrode assembly.
9. The apparatus of claim 1, wherein said particle generator is a droplet generator for generating a discrete droplet comprising an analyte and solvent.
10. The apparatus of claim 1, wherein said levitation device is an electrodynamic balance.
11. The apparatus of claim 10, wherein said electrodynamic balance is a pair of separated levitation electrodes.
12. The apparatus of claim 11, wherein said pair of levitation electrodes are a pair of first ring electrodes extending in parallel planes.
13. The apparatus of claim 12, wherein a voltage difference is main-tained across said first ring electrodes.
14. The apparatus of claim 1, wherein said induction electrode is located proximal to said particle generator.
15. The apparatus of claim 1, wherein said apparatus comprises a chamber substantially enclosing said levitation device.
16. The apparatus of claim 3, wherein said electrode assembly comprises a first plate electrode positioned between said particle generator and said levitation device and a second plate electrode positioned between said levitation device and said orifice.
17. The apparatus of claim 16, wherein said first plate electrode and said second plate electrode each have apertures formed therein to permit the passage of said discrete particle therethrough.
18. The apparatus of claim 3, wherein said electrode assembly is opera-ble at atmospheric pressure.
19. The apparatus of claim 3, wherein said levitation device comprises said electrode assembly.
20. The apparatus of claim 19, wherein said levitation device is located proximal to said orifice.
21. The apparatus of claim 3, wherein said electrode assembly comprises a stack of separated second ring electrodes disposed in parallel planes between said levitation device and said orifice.
22. The apparatus of claim 21, wherein said second ring electrodes are progressively smaller in diameter in the direction from the levitation device toward the said orifice.
23. The apparatus of claim 22, comprising four separate second ring electrodes, each spaced approximately 3 mm apart from one another.
24. The apparatus of claim 13, wherein the voltage difference across said first ring electrodes is approximately 20 V.
25. The apparatus of claim 3, wherein said electrode assembly comprises a quadrupole electrode assembly between said levitation device and said orifice.
26. The apparatus of claim 4, wherein said electrode assembly comprises a first plate electrode positioned between said particle generator and said levitation device and a second plate electrode positioned between said levitation device and said substrate.
27. The apparatus of claim 26, wherein said first plate electrode and said second plate electrode each have apertures formed therein to permit the passage of said discrete particle therethrough.
28. The apparatus of claim 4, wherein said levitation device comprises said electrode assembly.
29. The apparatus of claim 28, wherein said levitation device is located proximal to said substrate.
30. The apparatus of claim 4, wherein said electrode assembly comprises a stack of separated second ring electrodes disposed in parallel planes between said levitation device and said substrate.
31. The apparatus of claim 30, wherein said second ring electrodes are progressively smaller in diameter in the direction from the levitation device toward the said substrate.
32. The apparatus of claim 31, comprising four separate second ring electrodes, each spaced approximately 3 mm apart from one another.
33. The apparatus of claim 4, wherein said electrode assembly comprises a quadrupole electrode assembly between said levitation device and said sub-strate.
34. The apparatus of claim 1, wherein said induction electrode has an aperture formed therein for passage therethrough of said discrete particle.
35. The apparatus of claim 9, wherein said droplet generator comprises a hollow, flat-tipped nozzle through which said discrete droplet is dispensed.
36. An apparatus for preparing and delivering a discrete particle to a target for subsequent analysis, said apparatus comprising:
(a) a particle generator for generating a discrete particle;
(b) a levitation device for levitating said discrete particle; and (c) an electrode assembly for delivering said discrete particle from said levitation device to a target remote from said levitation device.
(a) a particle generator for generating a discrete particle;
(b) a levitation device for levitating said discrete particle; and (c) an electrode assembly for delivering said discrete particle from said levitation device to a target remote from said levitation device.
37. The apparatus of claim 36, comprising an induction electrode for inducing a net charge onto said discrete particle.
38. The apparatus of claim 37, wherein said levitation device is an electrodynamic balance.
39. The apparatus of claim 37, wherein said electrode assembly is adapted for controllably delivering said particle to said target for said subsequent analysis.
40. The apparatus of claim 39, comprising an atmospheric gas sampling mass spectrometer and wherein said target is an orifice in communication with a vacuum chamber of said mass spectrometer.
41. The apparatus of claim 39, comprising a substrate and wherein said target is said substrate.
42. The apparatus of claim 39, wherein said substrate is a plate suitable for matrix assisted laser desorption and ionization mass spectrometric analysis.
43. An apparatus for delivering a source of ions to a vacuum chamber of a mass spectrometer comprising:
(a) a droplet generator for generating a single isolated droplet, said droplet comprising solvent;
(b) an induction electrode for applying a net charge onto said droplet;
(c) a levitation device for levitating said droplet for a period of time sufficient to permit desolvation of said droplet to cause said droplet to become unstable, thereby releasing ions by droplet Coulomb fission;
(d) an orifice in communication with said vacuum chamber; and (e) an electrode assembly for delivering said ions from said levitation device to said orifice.
(a) a droplet generator for generating a single isolated droplet, said droplet comprising solvent;
(b) an induction electrode for applying a net charge onto said droplet;
(c) a levitation device for levitating said droplet for a period of time sufficient to permit desolvation of said droplet to cause said droplet to become unstable, thereby releasing ions by droplet Coulomb fission;
(d) an orifice in communication with said vacuum chamber; and (e) an electrode assembly for delivering said ions from said levitation device to said orifice.
44. A mass spectrometer comprising:
(a) a vacuum chamber;
(b) a detector for detecting the passage of ions through said vacuum chamber;
(c) a particle generator for generating a discrete particle;
(d) an induction electrode for ionizing said particle;
(e) a levitation device for electrodynamically levitating said discrete particle following said ionization;
(f) an orifice in communication with said vacuum chamber; and (g) means to deliver said ionized particle from said levitation device to said orifice.
(a) a vacuum chamber;
(b) a detector for detecting the passage of ions through said vacuum chamber;
(c) a particle generator for generating a discrete particle;
(d) an induction electrode for ionizing said particle;
(e) a levitation device for electrodynamically levitating said discrete particle following said ionization;
(f) an orifice in communication with said vacuum chamber; and (g) means to deliver said ionized particle from said levitation device to said orifice.
45. The mass spectrometer of claim 44, wherein said means to deliver said ionized particle from said levitation device to said orifice is an electrode assembly.
46. A method for producing a discrete particle for subsequent analysis or manipulation, said method comprising:
(a) generating a discrete particle;
(b) inducing a net charge onto said discrete particle;
(c) electrodynamically levitating said discrete particle in a levitation device following the induction of said net charge; and (d) delivering said discrete particle to a target remote from said levitation device for said subsequent analysis or manipulation.
(a) generating a discrete particle;
(b) inducing a net charge onto said discrete particle;
(c) electrodynamically levitating said discrete particle in a levitation device following the induction of said net charge; and (d) delivering said discrete particle to a target remote from said levitation device for said subsequent analysis or manipulation.
47. The method of claim 46, wherein said delivering comprises controllably moving said discrete particle to an atmospheric gas sampling mass spectrometer.
48. The method of claim 46, wherein said delivering comprises controllably moving said discrete particle to a substrate.
49. The method of claim 48, wherein said substrate is a plate, said method comprising the step of subjecting said plate to matrix assisted laser desorption and ionization mass spectrometric analysis.
50. The method of claim 49, comprising the step of applying a material to said plate for receiving said particle.
51. The method of claim 50, wherein said material is a matrix.
52. The method of claim 46, wherein said discrete particle is a discrete droplet comprising an analyte and solvent, wherein said discrete droplet is electrodynamically levitated for a period of time sufficient to permit at least partial desolvation of said discrete droplet.
53. The method of claim 46, wherein step (c) is carried out at atmospheric pressure.
54. The method of claim 46, wherein said discrete particle is levitated by applying a constant voltage difference across an electrodynamic balance.
55. The method of claim 46, wherein said net charge is induced when said particle is generated.
56. The method of claim 52, comprising the step of subjecting said discrete particle to a gas while said discrete particle is levitated to control the evaporation rate of said solvent.
57. A method for preparing and delivering a discrete particle to a target for subsequent analysis, said method comprising:
(a) generating a discrete particle;
(b) levitating said discrete particle in a levitation device; and (c) delivering said discrete particle to said target remote from said levitation device.
(a) generating a discrete particle;
(b) levitating said discrete particle in a levitation device; and (c) delivering said discrete particle to said target remote from said levitation device.
58. The method of claim 57, wherein said discrete particle is levitated electrodynamically.
59. The method of claim 57, wherein said target is an orifice in communication with an atmospheric gas sampling mass spectrometer.
60. The method of claim 57, wherein said target is a substrate.
61. The method of claim 60, wherein said substrate is a plate, said method comprising the step of subjecting said plate to matrix assisted laser desorption and ionization mass spectrometric analysis.
62. A method of mass spectrometry:
(a) generating a discrete particle;
(b) ionizing said discrete particle;
(c) electrodynamically levitating said ionized discrete particle;
(d) delivering said ionized discrete particle to a vacuum chamber of an atmospheric pressure gas sampling mass spectrometer; and (e) detecting the passage of said ionized discrete particle through said vacuum chamber.
(a) generating a discrete particle;
(b) ionizing said discrete particle;
(c) electrodynamically levitating said ionized discrete particle;
(d) delivering said ionized discrete particle to a vacuum chamber of an atmospheric pressure gas sampling mass spectrometer; and (e) detecting the passage of said ionized discrete particle through said vacuum chamber.
63. A method for preparing an ion source suitable for mass spectromet-ric analysis comprising:
(a) generating a single isolated droplet comprising an analyte and a solvent;
(b) applying a net charge to said droplet; and (c) levitating said droplet for a period of time sufficient to allow desolvation of said droplet so that said analyte becomes charged, thereby yielding said source of ions.
(a) generating a single isolated droplet comprising an analyte and a solvent;
(b) applying a net charge to said droplet; and (c) levitating said droplet for a period of time sufficient to allow desolvation of said droplet so that said analyte becomes charged, thereby yielding said source of ions.
64. The method of claim 63, wherein said desolvation causes coulomb fissioning of said droplet into a plurality of progeny droplets.
65. The method of claim 63 wherein each of said progeny droplets is levitated for a period of time sufficient to allow desolvation of that progeny droplet so that any analyte in that progeny droplet becomes charged, thereby contributing to said source of ions.
66. The method of claim 63, comprising the step of subjecting said ions to mass spectrometric analysis.
67. The method of claim 65, comprising the step of subjecting said ions to mass spectrometric analysis.
68. A method of mass spectrometry comprising:
(a) generating a single isolated droplet comprising an analyte and a solvent;
(b) applying a net charge to said droplet;
(c) levitating said droplet in a levitation device for a period of time sufficient to allow desolvation of said droplet so that said analyte becomes charged, thereby yielding ions; and (d) controllably delivering said ions to a location remote from said levitation device for mass spectrometric analysis.
(a) generating a single isolated droplet comprising an analyte and a solvent;
(b) applying a net charge to said droplet;
(c) levitating said droplet in a levitation device for a period of time sufficient to allow desolvation of said droplet so that said analyte becomes charged, thereby yielding ions; and (d) controllably delivering said ions to a location remote from said levitation device for mass spectrometric analysis.
69. The method of claim 68, wherein the ions are deposited onto a plate after step (c) and wherein step (d) comprises matrix-assisted laser desorption and ionization mass spectrometry.
70. The method of claim 69, wherein matrix is applied to the plate before the ions are deposited.
71. An apparatus for producing a discrete particle and delivering the particle to a target for subsequent analysis or manipulation, said apparatus comprising:
(a) a particle generator for generating a discrete particle, wherein said particle generator is a droplet generator for generating a discrete droplet comprising an analyte and solvent;
(b) a levitation device for electrodynamically levitating said discrete particle; and (d) delivery means for delivering said discrete particle to said target, characterized in that said target is located at a position remote from said levitation device and wherein said delivery means controllably delivers said discrete particle to said target for subsequent analysis or manipulation.
(a) a particle generator for generating a discrete particle, wherein said particle generator is a droplet generator for generating a discrete droplet comprising an analyte and solvent;
(b) a levitation device for electrodynamically levitating said discrete particle; and (d) delivery means for delivering said discrete particle to said target, characterized in that said target is located at a position remote from said levitation device and wherein said delivery means controllably delivers said discrete particle to said target for subsequent analysis or manipulation.
72. A method for producing a discrete particle and delivering the particle to a target for subsequent analysis or manipulation, said method com-prising:
(a) generating a discrete particle, wherein said particle is a droplet comprising an analyte and a solvent;
(b) levitating said discrete particle using a levitation device; and (c) moving said discrete particle away from said levitation device, characterized in that said discrete particle is controllably delivered to a remote target for subsequent analysis or manipulation.
(a) generating a discrete particle, wherein said particle is a droplet comprising an analyte and a solvent;
(b) levitating said discrete particle using a levitation device; and (c) moving said discrete particle away from said levitation device, characterized in that said discrete particle is controllably delivered to a remote target for subsequent analysis or manipulation.
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