Abstract:
An apparatus for ionizing analyte molecules comprised in a flow of a first gas. The apparatus includes an inlet tube through which the first gas may be discharged into an ionization region. The apparatus also includes a nozzle electrode disposed around the inlet tube to define a substantially annular space between the exterior of the inlet tube and the interior of the nozzle electrode. The sheath tube includes an inlet for introducing a fluid into the substantially annular space and an outlet through which the fluid may be discharged into the ionization region. The apparatus is configured to ionize the analyte molecules optionally via electrospray or chemical ionization.

Description:
RELATED APPLICATIONS 
       [0001]    This application claims priority to and benefit of U.S. Provisional Patent Application No. 61/597,975 entitled “Ionization of Analyte Molecules Comprised In A Flow of Gas,” filed Feb. 13, 2012, which is incorporated by reference herein in its entirety. 
     
    
     TECHNICAL FIELD 
       [0002]    This disclosure relates to ionization of analyte molecules comprised in a flow of gas. 
       BACKGROUND 
       [0003]    In gas chromatography, a flow of a mobile phase gas (or “carrier gas”), typically an inert gas, sweeps a sample through a gas chromatography (GC) column. Generally, the GC column includes a layer of polymer or liquid that acts as a stationary phase. The sample is separated into its constituent parts (i.e., separate compounds) as it passes through the column and interacts with the stationary phase material. As a result, the various compounds that make up the sample elute from the column at different times. Often, the effluent from the column is exposed to an ionization source to ionize analyte molecules in the effluent so that ionized analyte molecules can then be detected. 
       SUMMARY 
       [0004]    This disclosure is based, in part, on the realization that a nozzle electrode can be arranged near the outlet of chromatography column and configured such that analyte molecules in a flow of gas, such as the effluent from a gas chromatography column, can be ionized by electrospray or chemical ionization techniques. 
         [0005]    One aspect provides an apparatus for ionizing analyte molecules comprised in a flow of a first gas. The apparatus includes an inlet tube through which the first gas may be discharged into an ionization region. The apparatus also includes a nozzle electrode disposed around the inlet tube to define a substantially annular space between the exterior of the inlet tube and the interior of the nozzle electrode. The sheath tube includes an inlet for introducing a fluid into the substantially annular space and an outlet through which the fluid may be discharged into the ionization region. The apparatus is configured to ionize the analyte molecules optionally via electrospray or chemical ionization. 
         [0006]    Another aspect features a method of ionizing analyte molecules comprised in a flow of a first gas. The method includes passing the first gas through an inlet tube into an ionization region; passing a fluid (a second gas or a liquid) through a substantially annular space between the exterior of the inlet tube and the interior of a nozzle electrode such that the fluid is discharged toward the ionization region; and ionizing at least some of the analyte molecules in the ionization region via electrospray or chemical ionization. 
         [0007]    Implementations may include one or more of the following features. 
         [0008]    In some implementations, the inlet tube and the nozzle electrode are concentrically disposed about an axis such that a flow of the first gas and a flow of the fluid are coaxial. 
         [0009]    In certain implementations, the first gas is discharged into the ionization region at approximately atmospheric pressure. 
         [0010]    In some implementations, the nozzle electrode is configured to provide a corona discharge so that the analyte molecules may be ionized by chemical ionization. 
         [0011]    In certain cases, the apparatus also includes a gas chromatography column, and the flow of the first gas includes effluent from the chromatography column. 
         [0012]    In some implementations, the apparatus includes a heated transfer line for heating the flow of the first gas within the inlet tube. 
         [0013]    In certain implementations, the apparatus includes a mass spectrometer having an entrance orifice disposed to receive ions formed in the ionization region. 
         [0014]    In some examples, the entrance orifice is arranged to be coaxial with the flow of the first gas exiting the inlet tube. 
         [0015]    In certain examples, the apparatus includes a reaction chamber disposed between the nozzle electrode and the mass spectrometer for enclosing the ionization region. 
         [0016]    In some implementations, the fluid comprises a second gas (e.g., nitrogen), and the analyte molecules are ionized by chemical ionization using a corona discharge provided via the nozzle electrode. 
         [0017]    In certain implementations, the fluid is a liquid that is vaporized as it is passed through the nozzle electrode, and the analyte molecules are ionized by chemical ionization using a corona discharge provided via the nozzle electrode. 
         [0018]    In some cases, the analyte molecules are ionized by electrospray ionization via the nozzle electrode. 
         [0019]    In some implementations, the first gas is passed through a chromatography column, and passing the first gas through the inlet tube includes passing the effluent from the chromatography column through the inlet tube. 
         [0020]    In certain implementations, ions generated in the ionization region are passed into a mass spectrometer for mass analysis. 
         [0021]    In some examples, the ions generates in the ionization region are passed towards a collector electrode to perform non-mass spectrometric detection of the generated ions. 
         [0022]    In certain examples, flows of the first gas and the fluid are discharged into the ionization region coaxially. 
         [0023]    Implementations can provide one or more of the following advantages. 
         [0024]    Some implementations allow electrospray ionization to be used for ionizing analyte molecules in a flow of gas. 
         [0025]    Implementations can provide the flexibility of applying either electrospray or chemical ionization techniques for ionizing analyte molecules comprised in a flow of gas. 
         [0026]    Certain implementations provide sensitivity and selectivity differences as compared to known atmospheric pressure chemical ionization (APCI) techniques. 
         [0027]    The introduction of liquid for electrospray ionization can be decoupled from chromatography. Consequently, the polarity, pH, and salt content of a liquid used for electrospray ionization may be varied to adjust selectivity and sensitivity of the ionization. 
         [0028]    Other aspects, features, and advantages are in the description, drawings, and claims. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0029]      FIG. 1  is a schematic view of a gas chromatography/mass spectrometry (GC/MS) instrument. 
           [0030]      FIG. 2  is a detailed view of one arrangement of part of the instrument shown in  FIG. 1 . 
           [0031]      FIG. 3  is a schematic view of a gas chromatography instrument including a collector electrode arrangement for detecting analyte ions. 
       
    
    
       [0032]    Like reference numbers indicate like elements. 
       DETAILED DESCRIPTION 
       [0033]    Referring to  FIG. 1 , a gas chromatograph  10  includes a gas chromatography (GC) column  12  inside a temperature controlled oven  14 . A sample is introduced on to the GC column  12  through a sample injector  16  into a flow of a first fluid (carrier gas) from a first reservoir  18 . A first flow controller  19  is provided to maintain a constant flow of the carrier gas (mobile phase), which may be nitrogen (N 2 ) or helium (He) gas. A flow of about 0.5 ml/minute to about 10 ml/minute (e.g., about 1 ml/minute) would be suitable for many capillary GC columns. The GC column  12  is a coil of metal, glass, or fused silica capillary tubing, typically 0.53 mm or smaller internal diameter and 0.8 mm or smaller outside diameter, internally coated with a stationary phase suitable for effecting separation of different chemical components of the sample. The effluent from the GC column  12 , including analyte molecules in a flow of the carrier gas at a pressure approximately equal to atmospheric pressure (e.g., about 980 millibars (mb) to about 1050 mb), passes into an interface device generally indicated at  20 . Ionized analyte molecules emerge from the interface device  20  and are sampled through a small orifice  22  in a sampling cone  24  of a mass spectrometer generally indicated by  26 . 
         [0034]    An implementation of the interface device  20  is shown in  FIG. 2 . An inlet tube  28  is either integral with, or is connected to, the outlet of the GC column  12 . For example, the inlet tube  28  may be a distal end portion of the GC column  12 . Alternatively, the inlet tube  28  may be a fused silica tube connected to the distal (outlet) end of the GC column  12 . The inlet tube  28  extends through a wall of the oven  14  towards the sampling cone  24  of the mass spectrometer  26 . The inlet tube  28  passes through a heated transfer line  30 , which circumferentially surrounds a portion of the inlet tube  28 . The transfer line  30  can include a tube of thermally conductive material, such as a metal or metal alloy, e.g., stainless steel, surrounded by a heater, such as a coiled resistance wire or tape heater. The transfer line  30  is capable of maintaining the temperature of the inlet tube  28  sufficiently high to prevent loss of analyte molecules as they travel through the inlet tube  28 . The necessary temperature is dependent on the nature of the analyte molecules, but may typically be in the range 100° C.-300° C. 
         [0035]    A distal end portion  32  of the inlet tube  28  extends beyond the distal end  34  of the transfer line  30  and into a nozzle electrode  36 . The nozzle electrode  36  has a generally cylindrical shape and is formed of an electrically conductive material such as a metal or metal alloy, e.g., stainless steel. The nozzle electrode  36  circumferentially surrounds the inlet tube  28  with the distal (outlet) end  38  of the inlet tube  28  extending outwardly from an outlet  40  of the nozzle electrode  36 . The nozzle electrode  36  can be electrically isolated from the transfer line  30 . For example, in some cases a threaded ceramic insulator which screws into the distal end  34  of the transfer line  30  and into which the nozzle electrode  36  screws can provide for electrical isolation. Both the inlet tube  28  and the nozzle electrode  36  can have circular cross sections and are concentrically disposed. However, any cross-sectional shapes can be used. 
         [0036]    The nozzle electrode  36  includes a fluid inlet  42 . A supply of a second fluid (e.g., a liquid, such as methanol, or a gas, such as nitrogen) from a second reservoir  44  ( FIG. 1 ) is connected to the fluid inlet  42  via a second flow controller  46  ( FIG. 1 ). The second fluid flows, coaxially to the flow of the GC column effluent, in the annular space  48  between the inside of the nozzle electrode  36  and the exterior of the inlet tube  28 . The second fluid exits through the outlet  40  of the nozzle electrode  36  and merges with the effluent exiting the inlet tube  28  in an ionization region  50  where the analyte molecules are ionized. 
         [0037]    A reaction chamber  52  including a housing  54  and a vent  56  surrounds the ionization region  50 . The vent  56  discharges to atmospheric pressure so that the pressure in the inner volume  58  of the housing  54  is substantially equal to atmospheric pressure. Some implementations may include a variable flow restrictor or a pump connected to the vent  56  for controlling pressure and/or gas concentration in the reaction chamber  52 . The distal end  34  of the transfer line  30  is mounted through a wall of the housing  54  such that the nozzle electrode  36  is enclosed within the inner volume  58 . The housing  54  can be formed of a metal or metal alloy. Fluidic connection between the nozzle electrode  36  and the second reservoir  44  ( FIG. 1 ) can be established via a feedthrough  60  in the housing  54 . 
         [0038]    Ionization may be effected through electrospray or a corona discharge established by application of a suitable electrical potential difference between the nozzle electrode  36  and at least the sampling cone  24  of the mass spectrometer  26 . In this regard, a power supply  64  connected to the nozzle electrode  36  via a current limiting resistor  66  may be employed to provide this potential difference. The power supply  64  can apply a high voltage of about 2000 Volts to about 5000 Volts to the nozzle electrode  36  to promote ionization. 
         [0039]    Analyte molecules present in the ionization region  50  are ionized through electrospray ionization or chemical ionization techniques (e.g., charge exchange, protonation, and deprotonation). The ionization technique can be controlled, at least in part, based on the type of fluid that is introduced in the nozzle electrode  36  through the fluid inlet  42 . And, since the second fluid is effectively decoupled from the chromatography, either a gas or a liquid can be used. For example, ionization via a chemical ionization technique can be achieved by introducing a gas, such as N 2 , into the fluid inlet  42  of the nozzle electrode  36 . In this case, the applied voltage allows the nozzle electrode  36  to take the place of a corona pin as a discharge electrode providing a corona discharge in the ionization region  50  to promote ionization by charge exchange. Charge exchange chemical ionization can be beneficial for analyzing less polar analytes. 
         [0040]    Alternatively, a liquid, such as methanol, could support protonation or electrospray ionization depending on how much of the liquid is introduced. For example, if only a trickle of methanol is provided it may vaporize before exiting the nozzle electrode  36  and proton transfer may be initiated by a corona discharge provided by the nozzle electrode  36  acting as a corona pin. On the other hand, a sustained electrospray may be supported if a relatively large amount of liquid methanol is introduced into the nozzle electrode  36  such that the liquid, upon reaching the outlet  40  of the nozzle electrode  36 , forms a Taylor cone. Electrospray ionization can be beneficial when analyzing high polar analytes by providing a selectively higher response. Since the second fluid is effectively decoupled from the chromatography, the polarity of the liquid, pH, and salt content can be varied to alter the selectivity and sensitivity of the ionization. 
         [0041]    Ions generated in the ionization region  50  by electrospray or chemical ionization flow into the mass spectrometer  26  induced by the combined effects of electrostatic attraction and vacuum. The ions pass through the orifice  22  in the sampling cone  24  and are subsequently analyzed by the mass spectrometer  26 . 
       Other Implementations 
       [0042]    Although a few implementations have been described in detail above, other modifications are possible. For example, while an implementation has been described in which the distal end of the inlet tube extends beyond the outlet of the nozzle electrode, in some implementations, the distal end of the inlet tube may instead be substantially aligned with the outlet of the nozzle electrode or refracted within the nozzle electrode. 
         [0043]    Although implementations have been described in which analyte ions are detected using a mass spectrometer, in some implementations, a non-mass spectrometric detector may be used for detecting the analyte ions.  FIG. 3  illustrates an implementation that utilizes a collector electrode  100  for detecting a total current of ions formed, rather than individual ion intensities as in mass spectrometry. As shown in  FIG. 3 , a reaction chamber  102  is provided to contain the ionization region  50 . The reaction chamber  102  includes a housing  104  that defines an inlet  106  and an outlet  108  and can be formed of a metal or metal alloy. The distal end  34  of the transfer line  30  is mounted through the inlet  106  of the housing  104  such that the nozzle electrode  36  is substantially enclosed within the housing  104 . Again, fluidic connection between the nozzle electrode  36  and the second reservoir  44  can be established via a feedthrough  60  in the housing  54 . 
         [0044]    The collector electrode  100  is a cylindrical electrode formed of an electrically conductive material such as a metal or metal alloy, e.g., stainless steel. The collector electrode  100  is mounted adjacent the outlet  108  of the reaction chamber  102 . An insulator  112  can be positioned between the collector electrode  100  and the reaction chamber  102  to electrically isolate the collector electrode  100 . The collector electrode  100  is configured to attract ions from the reaction chamber  102  for detection. The collector electrode  100  also includes an exhaust  114  for venting remaining gases, including neutral species and ions having polarity that is the same as that of the collector electrode  100 . Some implementations may include a variable flow restrictor or a pump disposed at the exhaust  114  of the collector electrode  100  for controlling pressure and/or gas concentration in the reaction chamber  102 . 
         [0045]    A power supply  116  is connected to the nozzle electrode  36  for providing a high voltage (e.g., about 5 kV) and an applied current of about 0.5 μA to about 50 μA (e.g., about 2 μA to about 5 μA) thereto. The power supply  116  can be a high voltage power supply (e.g., 6 kV, 50 μA) capable of reversing the output polarity (e.g., within milliseconds). 
         [0046]    In some cases, the collector electrode  100  can be electrically connected to the inverting input of a virtual ground  118 . The virtual ground  118  can be provided by a current amplifier, such as the Model  428  current amplifier available from Keithley Instruments, Inc., Cleveland, Ohio. The output of the virtual ground can be connected to a voltage monitoring instrument (e.g., an A/D converter), which, in turn, can provide a corresponding signal to a computing system for analysis and display. 
         [0047]    While an implementation has been described in which an ionization region is enclosed within a reaction chamber, in some implementation, the nozzle electrode output may merely be positioned to provide an ionization region adjacent to an inlet of a mass spectrometer in the absence of a reaction chamber. 
         [0048]    In some implementations, the respective polarities of the nozzle electrode and the cone are switched rapidly (e.g., every 20 milliseconds or a 50 Hz switching frequency), which can allow for the detection of a wider range of analytes. 
         [0049]    Although implementations have been described in which an interface device is employed for ionizing effluent from a gas chromatography column. The interface devices described herein may similarly be employed for ionizing effluent from a super critical fluid chromatography (SFC) source. In such cases, the inlet tube can be connected to, or may be an integral part of, an SFC source such that analyte molecules in effluent from the SFC source are ionized by electrospray or chemical ionization before they are introduced into a mass spectrometer or collector electrode for detection. 
         [0050]    Accordingly, other implementations are within the scope of the following claims.