Patent Publication Number: US-2003224529-A1

Title: Dual ion source assembly

Description:
TECHNICAL FIELD  
       [0001] The present invention relates to multiple ion source assemblies. More specifically, the present invention is directed to multiple ion source assemblies in which at least two different ion sources operate simultaneously.  
       BACKGROUND  
       [0002] High throughput purification systems often use mass analyzers to determine if a target compound is within a selected sample portion. One such system is disclosed in U.S. Pat. No. 6,309,541 to Maiefski et al., which is hereby incorporated by reference. Mass analyzers, such as mass spectrometers, work by using magnetic and/or electrical fields to exert forces on charged particles (ions). Accordingly, a compound must be charged or ionized in order to be examined by a mass analyzer. Moreover, in many applications, ions must be in a gaseous phase before they can be introduced into the mass analyzer. Atmospheric pressure ionization sources, including electrospray ionization (ESI) and atmospheric pressure chemical ionization (“APCI”) sources, can be interfaced with mass analyzers to examine samples. In atmospheric pressure ionization methods, a combination of thermal and pneumatic means is used to desolvate the ions in the ionization source. For example, ESI includes spraying a sample solution across a high potential difference (a few kilovolts) from a needle into an orifice. Heat and gas flows are used desolvate the ions existing in the sample solution. APCI is similar to ESI; however, it utilizes a corona discharge needle to ionize the sample in the atmospheric pressure region.  
       [0003] Each of the APCI and ESI sources are typically optimized for certain selected chemical classes or functionalities. APCI sources are typically known to work better than ESI sources for ionizing non-polar compounds, and ESI sources are typically known to work better than APCI sources for ionizing polar compounds. Often times a sample flow may contain mulitple chemical species including both polar and non-polar compounds. Accordingly, it is advantageous to have multiple ionizing sources to maximize the number of chemical species that will be ionized for analysis. U.S. Pat. No. 6,207,954 to Andrien, Jr., et al. (“&#39;954 patent”), which is hereby incorporated by reference, discloses ESI and APCI sources with multiple sample introduction means interfaced with mass analyzers. The &#39;954 patent further discloses a configuration with ESI and APCI sources in a single atmospheric pressure ionization assembly. Such a configuration, however, can experience significant difficulties if both ion sources operate simultaneously because interference between the two sources can hamper proper operation of the system. For example, the voltage applied to the ESI probe tip can interfere with the electrical field in the corona discharge region, and similarly, the voltage applied to the corona discharge needle can interfere with the ESI process.  
       SUMMARY  
       [0004] The present invention is directed to apparatuses for producing ions from chemical species, apparatuses for analyzing chemical species, and methods for analyzing chemical species. In one embodiment, an apparatus for producing ions from chemical species includes a first ion source assembly that produces a first sample flow, and a second ion source assembly that produces a second sample flow. The first and second ion source assemblies operate substantially at atmospheric pressure, and the second ion source assembly is different from the first ion source. The apparatus also includes a separation member that reduces interference between the first sample flow and the second ion source assembly and between the second sample flow and the first ion source assembly. In one embodiment, the first ion source assembly can include an electrospray ion source, and the second ion source assembly can include an atmospheric pressure chemical ionization source.  
       [0005] An embodiment for analyzing chemical species includes a first ion source assembly that produces a first sample flow and a second ion source assembly that produces a second sample flow. The first and second ion source assemblies operate substantially at atmospheric pressure, and the second ion source assembly is different from the first ion source assembly. The apparatus also includes a separation member that temporarily separates the first sample flow from the second sample flow and reduces interference between the first ion source assembly and the second sample flow and between the second ion source assembly and the first sample flow. The apparatus can also include a mass analyzer configured to receive the first sample flow and the second sample flow.  
       [0006] In another embodiment, an apparatus for analyzing chemical species includes providing a first ion source assembly, a second ion source assembly different from the first ion source, a separation member, and a mass analyzer. Simultaneously producing a first plurality of ions in a first sample flow from the first ion source assembly and a second plurality of ions in a second sample flow from the second ion source assembly. The method further includes reducing interference between the first ion source assembly and the second sample flow and between the second ion source assembly and the first sample flow with the separation member.  
       [0007] Another embodiment for analyzing chemical species includes providing a first ion source assembly, a second ion source assembly different from the first ion source assembly, a separation member, and a mass analyzer. Simultaneously producing a first plurality of ions in a first sample flow from the first ion source assembly and a second plurality of ions in a second sample flow from the second ion source assembly. The method further includes temporarily separating the first sample flow and the second sample flow with the separation member.  
       [0008] An embodiment for manufacturing an apparatus for analyzing chemical species includes positioning an electrospray ion source and an atmospheric pressure chemical ionization source proximate to a mass analyzer. The method further includes placing a separation member that extends at least partially between the electrospray ion source assembly and the atmospheric pressure chemical ionization source assembly. The separation member is configured to temporarily separate a first flow from the electrospray ion source assembly and a second flow from the atmospheric pressure chemical ionization source assembly before the first and second flows enter the mass analyzer. 
     
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
     [0009]FIG. 1 is a front isometric view of a dual ion source assembly having first and second ion sources coupled to a mass analyzer.  
     [0010]FIG. 2 is an enlarged isometric view of the dual ion source assembly of FIG. 1.  
     [0011]FIG. 3 is an enlarged isometric view of an ESI source assembly of FIG. 2 shown removed from the mounting plate.  
     [0012]FIG. 4 is an enlarged isometric view of an APCI source assembly of FIG. 2 shown removed from the mounting plate.  
     [0013]FIG. 5 is an isometric view of a dual ion source assembly in accordance with an alternate embodiment having a multi-component separator assembly. 
    
    
     DETAILED DESCRIPTION  
     [0014] In the following description, certain specific details are set forth in order to provide a thorough understanding of embodiments of the invention. The present disclosure describes dual ion source assemblies couplable to mass analyzers in accordance with embodiments of the present invention. Many specific details of certain embodiments are set forth in the following description and in FIGS.  1 - 4  to provide a thorough understanding of these embodiments. One skilled in the relevant art will understand, however, that the present invention may have additional embodiments, and that the invention may be practiced without several of the details described below. For example, even though the embodiments of the dual ion source assemblies are described with reference to electrospray and atmospheric pressure chemical ionization sources, other ionization methods may be used. Moreover, well known devices associated with ion source assemblies, such as mass spectrometers, have not been shown or described in detail to avoid unnecessarily obscuring the description of the embodiments of the invention.  
     [0015]FIG. 1 is a front isometric view of a dual ion source assembly  10  having a first ion source assembly and a second ion source assembly coupled to a mass spectrometer  20 , or other mass analyzer. Samples to be analyzed are passed as a solution through the dual ion source assembly  10  in which the solution vaporizes and emerges as a spray or mist of droplets. As the droplets evaporate, residual sample ions are swept into a mass analyzer for analysis. In the illustrated embodiment, the first ion source assembly is an APCI source assembly  30 , and the second ion source assembly is an ESI source assembly  40 . The APCI source assembly  30  and the ESI source assembly  40  are connected to a fluid system, such as a sample purification system that receives selected samples from at least one sample source  50 . In the illustrated embodiment, the APCI source assembly  30  and the ESI source assembly  40  are both coupled to a sample flow line  52  that receives a selected flow of fluid carrying samples from the sample source  50 . In other embodiments, the APCI and ESI source assemblies  30  and  40  can be coupled to multiple sample sources and/or separate sample sources.  
     [0016] In the illustrated embodiment, the sample flow line  52  is connected to a splitter  54  that divides the flow of samples into two separate flows. These two separate flows are delivered by sample delivery lines  56  to the APCI and ESI source assemblies  30  and  40  for ionization. The APCI and ESI source assemblies  30  and  40  deliver the ionized sample flows substantially simultaneously to an inlet  58  of the mass spectrometer  20 , for analysis. A separation member  60  is positioned adjacent to the mass spectrometer&#39;s inlet  58  and at least partially between the APCI and ESI source assemblies  30  and  40 . The separation member  60 , as discussed in greater detail below, helps separate and isolate the two flows of ions from each other before they enter the mass spectrometer  20 . The separation member  60  also minimizes any cross interference that the APCI or ESI source assembly  30  or  40  may have on the flow of ions from the other source assembly, thereby maximizing the amount of the ionized sample entering the mass spectrometer  20  for analysis.  
     [0017]FIG. 2 is an enlarged isometric view of the dual ion source assembly  10  coupled to the mass spectrometer  20 . The APCI and ESI source assemblies  30  and  40  are shown mounted on the mass spectrometer  20  in a generally side-by-side arrangement, but on opposite sides of the separation member  60 . The APCI and ESI source assemblies  30  and  40  can be positioned to optimize the production of ions proximate to the inlet  58  leading into the mass spectrometer  20 . In the illustrated embodiment, the APCI and ESI source assemblies  30  and  40  are moveably connected to a mounting plate  62 , which is releasably mounted to the front of the mass spectrometer  20 .  
     [0018] An adjustable mount  64  connects the APCI source assembly  30  to the mounting plate  62 . The mount  64  includes an adjustment member  66  that enables the user to selectively aim the APCI source assembly  30  toward the inlet  58  of the mass spectrometer exposed on one side of the separation member  60 . Similarly, an adjustable mount  68  connects the ESI source assembly  40  to the mounting plate  62 . The mount  68  also includes an adjustment member  70  that enables a user to aim the ESI source assembly  40  toward the inlet  58  of the mass spectrometer exposed on the other side of the separation member  60 . Once the APCI source assembly  30  or the ESI source assembly  40  has been properly aimed, the respective adjustment member  66  or  70  can be tightened to securely hold the APCI or ESI source assembly  30  or  40  in place. In one embodiment, locking mechanisms can be used to prevent inadvertent movement of the APCI or ESI source assembly  30  or  40  after it has been aimed at the mass spectrometer&#39;s inlet  58 . The ability to position the APCI and ESI source assemblies  30  and  40  allows for optimization of the simultaneous delivery of the ionized sample flows to the mass spectrometer  20  over a wide range of liquid flow rates, solutions, and sample chemistries.  
     [0019]FIG. 3 is an enlarged isometric view of  30 the ESI source assembly  40  shown removed from the mounting plate  62  and aimed toward locations on opposite sides of the separation member  60 . Referring to FIGS. 2 and 3, the ESI source assembly  40  uses an electric field to produce a fine spray of sample flow, including charged droplets that may be passed to the mass spectrometer  20  (FIG. 2). The ESI source assembly  40  includes a regulator assembly  72  attached to a nebulizer assembly  74 . The regulator assembly  72  regulates the sample flow rate and pressure after the sample solution is received from the sample delivery line  56 . The nebulizer assembly  74  includes an elongated tube  76  with a distal tip  78  aimed toward the inlet  58  of the mass spectrometer  20 . The nebulizer assembly  74  may also include a pneumatic nebulization assist. A gas line may be coupled to an inlet port  80  to supply the gas used in the pneumatic nebulization assist.  
     [0020] The ESI source assembly  40  of the illustrated embodiment also includes a heater assembly  82  that generates a flow of heated gas, such as nitrogen, to facilitate evaporation of the nebulized sample flow. The heater assembly  82  can include a heating element disposed within a gas tube  84  and removably connect to a power source via an integral connector  86  . In one embodiment, the heating element can include a coil that heats the gas as it passes through the gas tube  84 . A nozzle  88  can be attached to the distal end of the gas tube  84  to direct the flow of the heated gas toward the flow of ions as they approach the mass spectrometer&#39;s inlet  58 . The flow of heated gas helps direct the ions into the mass spectrometer&#39;s inlet  58 . The gas can be supplied through a gas line  90  coupled to an inlet  92  in the heater assembly  82 . In additional embodiments, the ESI source assembly  40  can use other techniques, as needed, to assist in providing the flow of ions into the mass analyzer.  
     [0021] In one embodiment, mass spectrometer  20  (FIG. 2) has a metal or other electrically conductive material that forms an end plate  94  that includes the inlet  58 . The end plate  94  has a voltage potential of approximately 0-200 Volts. The tube  76  of the ESI source assembly  40  is charged at approximately 700 Volts. To produce positive ions, a negative potential is applied to the tube  76 . To produce negative ions, the polarity of the potential applied to the tube  76  is reversed. The separation member  60  is maintained at ground potential and is not in direct engagement with the end plate  94 .  
     [0022] In operation, the sample solution flows from the sample source  50  (FIG. 1) along the sample flow line  52  to the splitter  54 , wherein a portion of the sample flow is directed to the ESI source assembly  40  and the other portion is directed to the APCI source assembly  30 . The splitter  54  can selectively control how the flow is divided between the APCI and ESI source assemblies  30  and  40 . The flow of sample solution enters the ESI source assembly  40  through a sample inlet port  96  (FIG. 2) and the pressure and sample flow rate are regulated by the regulator assembly  72 . The sample solution then flows through the nebulizer assembly  74  and out of the tube&#39;s tip  78  as a fine spray. The sample can be sprayed from the tip  78  at flow rates ranging from below 2 ml/min to above 0.01 ml/min. When the appropriate potentials are applied to the tube  76  and the tip  78 , charged liquid droplets are produced from the ESI source assembly  40 . The charged droplets exit the tip  78  and are driven by the electric field through the heated gas flow. As the droplets pass through the heated gas flow, they evaporate and rapidly become much smaller through vaporization of solvent that makes up portions of the droplets. At the same time, because the surface area of the droplets gets smaller and smaller, the density of electrical charge on the surface increases until a point of instability is reached. Eventually, not only solvent molecules but also ions start to desorb from the surface of each droplet, thereby providing the flow of charged ions. The flow of ions is swept into the inlet  58  and directed into the mass spectrometer for analysis.  
     [0023] While the ESI source assembly  40  is generating the flow of ions, the APCI source assembly  30  is simultaneously generating its flow of ions on the opposite side of the separation member  60 . FIG. 4 is an enlarged isometric view of an APCI source assembly of FIG. 2 shown removed from the mounting plate. Referring to FIGS. 2 and 4, the APCI source assembly  30  can include a regulator assembly  100 , a corona needle  102  (FIG. 2), an injector assembly  104 , and a heater assembly  106 . In the illustrated embodiment, the regulator assembly  100  is similar to the regulator assembly  72  discussed above. The regulator assembly  100  receives the flow of sample solution through a sample inlet port  108  (FIG. 2) and regulates the flow rate and pressure of the solution. In an alternate embodiment, the flow rates and pressure of the solution is sufficiently stable, so that the regulator assembly  100  is not needed. In the illustrated embodiment, the injector assembly  104 , including a housing  110  and a nebulizer tube  112 , is attached to the regulator assembly  100 . The injector assembly  104  can also include a pneumatic nebulization assist, wherein a selected gas is supplied through gas lines (not shown) coupled to inlet ports  114 .  
     [0024] The nebulizer tube  112  produces sprayed liquid droplets that flow into the heater assembly  106 . In one embodiment, the heater assembly  106  includes a chamber surrounded by a heating element  116 , such as a coil. Within the heater assembly  106 , the nebulized liquid droplets evaporate, forming a vapor prior to exiting from a heat shield  118 . The flow of vapor containing the ions is directed toward the inlet  58  in the mass spectrometer  20 , such that the flow of vapor enters a region B surrounding the corona needle  102  (FIG. 2) and adjacent to the separation member  60 .  
     [0025] In operation, the corona needle  102  is connected to a high voltage source so as to generate an electrical field proximate to the APCI source assembly  30 . In one embodiment, the corona needle  102  (FIG. 2) can be maintained with an electrical potential of approximately 2600-3200 Volts. The resulting electrical field acts on the gas flow through the heater assembly  106  to establish a stable corona discharge in region B around the corona needle  102  to produce the flow of charged ions. The ions produced in region B by the atmospheric pressure chemical ionization are driven by the electric field toward the inlet  58 , such that the ions are swept into the mass spectrometer  20  through the inlet to be analyzed. The separation member  60  separates the flow of vapor and resulting ions from the APCI source assembly  30  from the flow of vapor and ions produced by the ESI source assembly  40 . The separation member  60  also minimizes the effect that the APCI and the ESI source assemblies  30  and  40  have on each other&#39;s flow of ions toward the inlet  58 . In the illustrated embodiment, the corona needle  102  is physically secured and electrically connected to an electrical connector  120 . One end  122  of the corona needle  102  is threaded through an aperture in a first end  124  of the electrical connector  120 . The electrical connector  120  includes a second end  126  configured to be connected to an external voltage source. The electrical connector  120  is electrically connected to the corona needle  102  to provide the corona needle  102  with the necessary voltage. An insulator  128 , such as a banana jack, surrounds a portion of the electrical connector  120  between the first and second ends  124  and  126 . The insulator  128  is attached to the mounting plate  62  by a mounting bracket  130 . In the illustrated embodiment, the corona needle  102  is moveable so that it may be properly oriented to create the electric field. For example, the corona needle  102  can be rotated in a direction R by pivoting the insulator  128 , and the corona needle  102  can be moved axially D by sliding the corona needle  102  through the aperture in the electrical connector  120 . Accordingly, the electrical field can be precisely positioned and the flow of vapor from the nebulizer tube  112  can be precisely aimed so as to maximize the number of ions swept into the mass spectrometer  20 .  
     [0026] As best seen in FIGS. 1 and 2, the separation member  60  is a generally flat plate that extends across an aperture  140  in the mounting plate  62  and is attached to the mounting plate  62  by fasteners  142 . The aperture  140  is concentrically arranged around the mass spectrometer&#39;s inlet  58 , so that the separation member  60  extends directly in front of the inlet  58  so as to separate region B (FIG. 3) from region C (FIG. 3) when the two different ion source assemblies are used simultaneously. The separation member  60  of the illustrated embodiment forms a plane generally transverse to the mounting plate  62  and is positioned such that a center axis A extending from the inlet  58  passes through and approximately bisects the separation member  60 . In other embodiments, the separation member can have a different shape, size, orientation, or electrical potential.  
     [0027] In the illustrated embodiment, the separation member  60  includes a cutout section  144  proximate to the inlet  58 . The cutout section  144  is shaped and sized to provide the flows of ions sufficient access into the mass spectrometer  20  through the inlet  58 , while still allowing the separation member  60  to separate and isolate regions B and C from each other to minimize interference therebetween. In one embodiment, the cutout section  144  is a semicircular void in the separation member  60  positioned proximate to the inlet  58 . In other embodiments, other cutout shapes and sizes can be used. In additional embodiments, the separation member  60  may not have a cutout section while being able to isolate regions B and C and also maximizing the results from the simultaneous operation of the APCI source assembly  30  and the ESI source assembly  40  for delivery of ions to the mass spectrometer  20  for analysis.  
     [0028]FIG. 5 is an isometric view of a dual ion source assembly  10  in accordance with an alternate embodiment. The APCI source assembly  30  and the ESI source assembly  40  are mounted to the mounting plate  62  adjacent to the mass spectrometer  20  with the separator member  60  between at least portions of the assemblies, as discussed above. In the illustrated embodiment, the separation member  60  is a multi-component assembly with an APCI shield  150  and a separate ESI shield  152 . The APCI shield  150  is mounted to the mounting plate  62  out of engagement with the mass spectrometer&#39;s end plate  94  and positioned to generally face a portion of the APCI source assembly  30 . The APCI shield  150  extends generally adjacent to the inlet  58  of the mass spectrometer  20  while allowing the flow of ions from the APCI source assembly  30  to enter the inlet. The APCI shield  150  can be constructed of an electrically conductive material and maintained at a selected electrical potential to facilitate the flow of ions from the APCI source assembly  30  into the mass spectrometer&#39;s inlet  58 .  
     [0029] The ESI shield  152  is also mounted to the mounting plate  62  and positioned to face at least a portion of the ESI source assembly  40 . The ESI shield  152  is adjacent to the APCI shield  150  but is not in direct contact with the APCI shield. The ESI shield  152  can also be constructed of an electrically conductive material and maintained at a selected electrical potential to facilitate the flow of ions from the ESI source assembly  40  into the inlet  58 . The electrical potential of the ESI shield  152  can be the same or different than the electrical potential of the APCI shield  150 . In one embodiment, the ESI shield  152  and the APCI shield  150  are spaced apart and electrically isolated from each other. A layer of electrically insulative material  154  can be sandwiched between the ESI shield  152  and the APCI shield  150 . In another embodiment, the ESI shield  152  and the APCI shield  150  can be spaced apart from each other by a small air gap.  
     [0030] In the illustrated embodiment, the APCI shield  150  and the ESI shield  152  each have a cutout section  156  proximate to the mass spectrometer&#39;s inlet  58 . The cutout sections  156  can be the same size or can be different sizes as is suitable for the flow of ions from the respective APCI and ESI source assemblies  30  and  40 . The layer of electrically insulative material  154  can also have the same size cutout section  156  or a different size cutout section than is provided in the APCI or ESI shields  150  or  152 . Accordingly, the separation member  60  can configured for the selected ion source assemblies mounted on the mass spectrometer to facilitate the efficient simultaneous delivery of two flows of ions to the mass spectrometer for analysis.  
     [0031] From the foregoing, it will be appreciated that specific embodiments of the invention have been described herein for purposes of illustration, but that various modifications may be made without deviating from the spirit and scope of the invention. Accordingly, the invention is not limited except as by the appended claims.