Abstract:
A method and apparatus for performing mass spectrometry using an electron source, an ion trap, and a voltage-controlled lens located between the electron source and the ion trap. A controller applies a voltage to the lens. Features of the resulting output spectrum can be analyzed to determine whether to adjust the lens voltage.

Description:
RELATED APPLICATION 
     This application claims priority to U.S. Provisional Application 61/851,670, filed Mar. 11, 2013. The content of this application is incorporated herein in its entirety. 
    
    
     FIELD OF THE DISCLOSURE 
     The present invention relates in general to mass spectrometry and, more particularly, to the control of a mass spectrometer apparatus by use of a voltage-controlled lens. 
     BACKGROUND OF THE DISCLOSURE 
     Mass spectrometers are instruments used to analyze the mass and abundance of various chemical components in a sample. Mass spectrometers work by ionizing the molecules of a chemical sample, separating the resulting ions according to their mass-charge ratios (m/z), and then measuring the number of ions at each m/z value. The resulting spectrum reveals the relative amounts of the various chemical components in the sample. 
     Electron ionization (EI) is one common method for generating sample ions. In EI, electrons are produced through a process called thermionic emission. Thermionic emission occurs when the kinetic energy of a charge carrier, in this case electrons, overcomes the work function of the conductor. In the vacuum chamber of the gas analyzer, where there may be virtually no gas to conduct heat away or react with the filament, a current through the filament quickly heats it until it emits electrons. The filament may be set to a voltage potential relative to an electron lens or other conductor, and the resulting electric field accelerates the electron beam towards the sample to be ionized. As the electron beam travels through the gaseous sample, the electrons may interact with and ionize and potentially fragment molecules in the sample. The charged particles can then be transported and analyzed using additional electric fields. EI can be performed either in the mass analyzer itself, or in an adjacent ionization chamber. The advantages of each system will be discussed with reference to the prior art below. 
     One type of mass analyzer used for mass spectrometry is called a quadrupole ion trap. Quadrupole ion traps take several forms, including three-dimensional ion traps, linear ion traps, and cylindrical ion traps. The operation in all cases, however, remains essentially the same. Direct current (DC) and time-varying radio frequency (RF) electric signals are applied to the electrodes to create electric fields within the ion trap. These fields trap ions within the central volume of the ion trap. Then, by manipulating the amplitude and/or frequency of the electric fields, ions are selectively ejected from the ion trap in accordance with their m/z. A detector records the number of ejected ions at each m/z as they arrive. 
     Ion traps are optimized for a combination of speed, sensitivity, resolution, and dynamic range depending on the particular application. For a given instrument, an improvement in one category is usually made at the expense of another. For example, resolution can generally be increased by using a slower scan, and in the reverse a scan can be performed faster at the expense of resolution. Similarly, sensitivity—especially to less abundant components of a sample—can be increased by trapping and scanning a larger total number of ions in a single scan. However, as the quantity of ions in the trap increases, the coulombic forces between the like-charged ions in the trap cause expansion of the ion cloud. When this occurs, ions at different locations within the cloud perceive slightly different electric fields. Mass spectrometers achieve resolution by ejecting all ions of the same m/z at close to the exact same moment, but when different ions of the same m/z perceive different electric fields, they may eject from the trap at different times. The result may cause broadening of spectral peaks referred to as the “space charge” effect. Space charge may also be caused by collisions when ions strike one another, particularly when large ions strike smaller ions. This increases the kinetic energy of some ions, thus ejecting them out of the ion trap before they would otherwise be removed by changes in the ion trap electrode potential. 
     Furthermore, specific components of a mass spectrometer may limit various performance specifications of the instrument. For example, a typical channel electron multiplier (OEM), a common type of ion detector, has a dynamic range of 2-3 orders of magnitude, which sets a ceiling for the overall system dynamic range independently of the performance of the mass analyzer. Thus, the design of other components of the instrument need to take these effects into account. 
     Conventional mass spectrometers have sought to achieve a balance between sensitivity and resolution by optimizing the quantity of ions trapped. For example, mass spectrometers have tried to achieve these benefits by: adjusting the trap loading time, adjusting the ionization time, or adjusting the ionization rate. However, such arrangements still have drawbacks. As a result, there still exists a need for a mass spectrometer that allows for improved control of the rate of ionization, as well as a beneficial balance between sensitivity and resolution, while also minimizing the size of the mass analyzer, the length of mass scans, and the power consumption of the instrument. 
     SUMMARY OF THE DISCLOSURE 
     A mass spectrometer for analyzing sample molecules, consistent with the disclosed embodiments, comprises an electron source, configured to emit electrons; an ion trap for receiving the emitted electrons, such that the received electrons ionize one or more sample molecules in the trap; an ion detector for detecting ions exiting from the ion trap; and a controller. In one embodiment, the controller includes a first voltage-controlled lens located between the electron source and the ion trap, wherein the first lens has an aperture configured to allow the emitted electrons to pass through the first lens and enter the ion trap, and wherein the first lens is configured to adjust a rate by which the electrons enter the ion trap based on a voltage applied to the first lens; and a voltage controller configured to apply a voltage to the first lens. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       The drawings are not necessarily to scale or exhaustive. Instead, emphasis is generally placed upon illustrating the principles of the inventions described herein. The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate several embodiments consistent with the disclosure and together with the description, serve to explain the principles of the disclosure. In the drawings: 
         FIG. 1  is a simplified cross-sectional view of an embodiment of the invention. 
         FIG. 2A  shows example spectra without space charge effects. 
         FIG. 2B  shows example spectra with space charge effects. 
         FIG. 3  shows simulation results of ion abundance versus lens voltage. 
         FIG. 4A  depicts simulated flight paths of electrons emitted from the filament at an exemplary lens voltage. 
         FIG. 4B  depicts simulated flight paths of electrons emitted from the filament at another exemplary lens voltage. 
         FIG. 4C  depicts simulated flight paths of electrons emitted from the filament at yet another exemplary lens voltage. 
         FIG. 5  shows a table of the number of resultant ions in the ion trap for several lens voltages in the simulation depicted in  FIGS. 4A ,  4 B, and  4 C. 
         FIG. 6A  shows a flow chart illustrating steps in a first exemplary method for adjusting the focal length of the lens. 
         FIG. 6B  shows a flow chart illustrating steps in a second exemplary method for adjusting the focal length of the lens. 
         FIG. 6C  shows a flow chart illustrating steps in a third exemplary method for adjusting the focal length of the lens. 
     
    
    
     DETAILED DESCRIPTION OF THE EMBODIMENTS 
     Reference will now be made in detail to the embodiments of the present disclosure described below and illustrated in the accompanying drawings. Wherever possible, the same reference numbers will be used throughout the drawings to refer to same or like parts. 
     Embodiments consistent with the present disclosure relate to a mass spectrometer having a voltage-controlled lens to control the number of electrons allowed into an ion trap of the spectrometer for ionizing the sample molecules. By monitoring a feature of the resulting output spectrum, the lens voltage may be adjusted to efficiently control the number of ions in the trap. For example, for low concentration samples, the number of electrons introduced to the trap may be increased, creating more ions in the trap and improving the detected signal. For higher concentration samples, the number of electrons may be reduced to avoid unwanted interactions in the trap that could reduce performance. Several methods for adjusting the lens voltage are thus disclosed in greater detail below. 
       FIG. 1  is a schematic diagram of a mass spectrometer  100  according to an embodiment of the invention. Mass spectrometer  100  may be used, as known in the art, to analyze a chemical sample. As shown in  FIG. 1 , an example embodiment of spectrometer  100  may include a vacuum chamber  110  that receives a control signal from a voltage controller  120  and that outputs a detection signal to an A/D converter  130 , which is coupled to a field-programmable gate array (“FPGA”)  140 . In some embodiments, FPGA  140  may be a microprocessor, digital signal processor (DSP), or similar element. Turning to vacuum chamber  110  itself, it may further include an electron filament  111  for emitting electrons used to ionize the sample to be analyzed by spectrometer  100 . The emitted electrons may pass through a first lens  112  and into an ion trap  119 , which is shown as formed by a first end cap electrode  113 , a ring electrode  114 , and a second end cap electrode  115 . Chamber  110  may also include a second lens  116 , through which ions leaving the trap may pass before being received by a detector  118 . 
     In one arrangement, electron filament  111  may be formed of an alloy that emits elections when heated with an electrical current. In one embodiment, the first lens  112  may have an aperture  122 , such that lens  112  may be placed between the electron filament  111  and the first end cap electrode  113  of the ion trap  119 . Lens  112  may comprise a single electrode or may comprise multiple electrodes as in an Einzel lens. The voltage controller  120  may then apply a voltage to lens  112  in order to apply an electric field for focusing electrons traveling from filament  111  towards ion trap  119 . As shown in  FIG. 1  and as discussed above, the ion trap  119  generally comprises the ring electrode  114 , the first end cap electrode  113  having an entrance aperture  123 , and the second end cap electrode  115  have an exit aperture. Although not shown in  FIG. 1 , mass spectrometers  100  consistent with embodiments of this disclosure may include a voltage source for applying a DC and RF voltage to the ring electrode  114  in order to create an electric field to trap or “store” molecules in ion trap  119 . 
     As shown in  FIG. 1 , the second lens  116  may have an aperture  126  and be placed between the second end cap electrode  115  and the ion detector  117 . In some embodiments, the second lens  116  shields the trap from the high potential of the detector. In one embodiment, aperture  126  may covered with a screen or grate to allow shielding of the ion trap  119  from the electric field generated by ion detector  117 . For example, ion detector may be configured to have a high negative voltage to attract ions exiting ion trap  119 . In one implementation, the ion detector  117  may be biased with a voltage on the order of −2,000 V. The output of ion detector  117  may be supplied to an ion amplifier  118 . In an example embodiment, the ion amplifier  118  is in close proximity to the ion detector  117 . In some embodiments, the ion amplifier  118  is a transimpedance amplifier that converts the low-level current output into a voltage. The ion amplifier  118  may thus serve to buffer the output of the ion detector  117 , and allow for transmission of the detector&#39;s output signal to the A/D converter  130  via a low-impedance signal line that is less susceptible to electromagnetic interference than the output of the ion detector  117 . The A/D converter  130  may thus translate the analog output of the ion amplifier  118  into a digital signal that may be read by the FPGA  140 . As known in the art, the digital signal stored by FPGA  140  may be subsequently processed into an output spectrum to be read by the user or stored for future use. In other embodiments, the A/D converter  130  and FPGA  140  can be combined into a single complex device such as a DSP, microprocessor, or any combination of analog or digital components known in the art. 
     In the preferred embodiment, a current is run through electron filament  111  sufficient to heat it to a temperature high enough to cause it to emit electrons. When the voltage controller  120  applies a voltage to the lens  112 , the resulting electric field focuses the emitted electrons into an electron beam, which may travel through the aperture  122  of lens  112 . A portion of the electron beam may then enter the ion trap  119  through the aperture  123  in the first end cap electrode  113 . The electrons in the beam will normally accelerate in accordance with the surrounding electric field. Accordingly, mass spectrometers  100  consistent with the example embodiments allow changing the relative voltages applied to the electron filament  111  and the lens  112  in order to influence the flight path of the electrons and the cross-sectional area of the electron beam, and thereby influence the proportion of electrons that pass through lens  112  and enter the ion trap  119 . The lens  112  may thus function, in one example embodiment, as a voltage-controlled gate for controlling the number of electrons that enter the ion trap  119 , and, in turn, the number of sample molecules ionized in the trap. 
     During the ionization period (the period during which sample molecules are ionized in the trap by the emitted electron beam), the DC and RF fields are applied to the ring electrode  114  in order to trap or “store” molecules of all m/z values within the range set for that scan. In some embodiments, a DC and RF voltage may also be applied to the first end cap electrode  113  and to the second end cap electrode  115 . When the ionized sample molecules in the trap  119  are ready to be analyzed, the DC and RF electric signals are altered to eject ions progressively from ion trap  119  according to their m/z. 
       FIG. 2A  shows example spectra without space charge effects, and  FIG. 2B  shows example spectra with space charge effects. As described above, “space charge effects” generally refers to the effect caused by other charged molecules in the trap in addition to that caused by the external electrical field. In  FIG. 2A , peaks  211  and  212  indicate the presence of two isotopes of the same ion. In the absence of space charge effects, the peaks are easily discernible. As the number of electron-molecule strikes increases, and thus the ion quantity inside the trap  119  increases, mass charge effects begin to manifest such that the spectral peaks widen and isotopes blur together. For instance, in  FIG. 2B , the midpoint between peaks  221  and  222 , which represent the same isotopes as peaks  211  and  212  in  FIG. 2A , no longer drops back to baseline. 
       FIG. 2B  also illustrates how space charge effects can be more pronounced at lower masses. The loss in resolution from peak  212  to  222  is not as severe as the loss of resolution from  213  to  223 , where identification of isotopes, and in fact the identity of the main peak, has become impossible. Space charge effects manifest more at lower masses because ions are ejected in order from low mass to high mass. Low mass ions are ejected while the trap is still full, and are thus ejected when space charge effects are at their worst. By the time higher mass ions are ejected later in the scan, the quantity of ions in the trap has been reduced and the space charge effects have subsided. The spectra of  FIGS. 2A and 2B  thus illustrate the importance of controlling the quantity of ions analyzed in a single scan to properly balance sensitivity and resolution. If not enough ions introduced into the trap for analysis, then a peak, such as peak  213 , may not be visible above the noise floor even though the taller peaks remain visible and identifiable. At the other end of the scale, when too many ions are introduced into the trap, then the ability to identify a peak precisely may be lost, even though the peak itself can be generally detected. In additional to the degradation in resolution, space charge also manifests itself as an unwanted shift in the m/z values of the spectral peaks. 
       FIG. 3  shows data correlating ion abundance versus lens voltage. In other words,  FIG. 3  illustrates how changes in the voltage applied to lens  112  by voltage source  120  may influence the amount of electrons emitted into ion trap  119  and thus, in turn, influence the amount of ions in trap  119 . In the preferred embodiment, the lens  112  is operated on the left side of the operating curve, or at voltages between approximately −75 V and −70 V. On this side of the curve, the electron flux into the trap  119  is most sensitive to changes in the voltage applied to lens  112  by the voltage source  120 . Specifically, on this side of the curve, the ion trap  119  may go from nearly pinched off (minimal emitted electrons) at operating point  330  to full electron flux at point  310  over a narrow voltage range. 
       FIGS. 4A ,  4 B, and  4 C depict simulated flight paths of electrons emitted from the filament  111  for various lens voltages. These simulations, for purposes of illustration only, were produced with SIMION, an ion optics simulation software program. At the highest negative potential, as shown in  FIG. 4A , most of the electrons are ejected to the left  414  away from the lens  112 , and only a relatively small portion of the electrons  415  pass through the lens  112 . As the voltage is increased, as shown in  FIG. 4B , fewer electrons  424  are directed away from lens  112 , and a greater proportion of electrons  425  pass through the lens  112 , resulting in more electrons  426  entering the ion trap. Finally, when the voltage is increased to that as shown in  FIG. 4C , the maximum proportion of electrons  435  pass through the lens  112 , which results in the maximum number of electrons  436  entering the ion trap  119 . The number of ions resulting from the electrons that enter the ion trap for several lens voltages between −81 V and −70 V are displayed in a table in  FIG. 5 . The data of  FIG. 5  is intended to be exemplary and for illustrative purposes, as the actual number of electrons entering the trap at various voltages may depend on a variety of factors, such as the structure and geometry of the lens  112  and of ion trap  119 . As shown in the data of  FIG. 5 , however, increasing the voltage of lens  112  from −81 V to −72 V, causes an increase in the amount of ions in the ion trap. Increasing the voltage beyond −72 V in this example, however, causes the number of ions to decrease. 
     In embodiments consistent with this disclosure, lens  112  can also be used to prevent positive ions caused by contamination of the filament  111  or ions generated by thermal ionization due to neutrals getting close to the filament  111  from corrupting the output spectrum of mass spectrometer  100 . In one preferred embodiment, the electron filament  111  is an yttria-coated iridium disc. If such a filament becomes contaminated, it can emit positive ions. This can occur even when the filament current is well below the specified value for electron production. When the filament emits positive contaminant ions during the ejection phase of a scan, those ions can find their way into the ion trap  119  and cause noise or spurious peaks in the mass spectrum. 
     In one embodiment, lens  112  may be set to approximately −70 V during the ionization period of the scan, during which the electron beam enters the trap and ionizes the sample molecules. During the ejection period of the scan, lens  112  may be set to +70 V to attract all of the electrons away from end cap entrance aperture  123 . A possible problem with this method is that the +70 V applied to the lens during the ejection period of the scan can cause focusing of the positive contaminant ions in the same manner that the −70 V on the lens during the ionization period focuses electrons. Focusing of the positive ions can increase the amount of noise or spurious peaks due to the positive contaminant ions. 
     In one preferred embodiment, electron filament  111  may be switched to a moderate negative voltage, such as −15 V, during the ejection period of the scan. With lens  112  set to −70 V and the filament  111  set to −15 V, electrons are confined to the ionizer surface preventing electron ionization. At the same time, any ions generated at or near the filament due to contaminants on the filament or thermal ionization of nearby neutrals will be attracted to the more negative voltage of the lens disk, preventing them from reaching the detector. Alternately, during the ejection period, the filament  111  may be biased to a fraction of the lens  112  voltage, such as 50%, and the first end cap  113  set to at or near ground, the electric field will still repel electrons away from the trap to prevent unwanted ionization during the scan. The negative voltage applied to lens  112  is still high enough, however, to attract any positive contaminant ions that may form in ion trap  119 , and prevent them from entering the trap. 
       FIGS. 6A ,  6 B, and  6 C show several flow charts illustrating steps in exemplary methods for adjusting the focal length of the lens.  FIG. 6A  illustrates a process  600 , that begins at step  601 , for adjusting the lens voltage for purposes of optimizing the resolution or sensitivity of the mass spectrometer  100 . In the embodiment shown in  FIG. 6A , an initial voltage is set and applied to the lens in step  602 . This voltage may be adjusted to set the focal length of the lens, e.g., lens  112 . In one implementation, the initial voltage is a predetermined value set to a low end of the relevant operating range. Next, the mass spectrometer  100  operates, in step  603 , to performs a mass spectrum scan of a sample introduced into trap  119 . 
     When the spectrometer  100  performs the scan of the sample during step  603 , the spectrometer  100  will operate during its ionization period based on the voltage value set in step  602 . The mass spectrometer  100  may then monitor the spectrum resolution and/or total ion current in step  604 . In some embodiments, the spectrum resolution may be in terms of the full width at half maximum (FWHM) of a peak in the spectrum. If the resolution and sensitivity of the resulting spectrum are optimal or meet predetermined criteria, as decided in step  605 , then that lens voltage may be used for subsequent scans in steps  607  to  608 . Otherwise, the lens voltage is adjusted in step  606  and repeats the mass spectrum scan of step  603 . In example embodiments, the voltage source  120  may incrementally adjust the lens voltage according to preset amounts. For example, in one embodiment, the lens voltage is adjusted in 10% increments of an identified operating range. If, for instance, the operating range is identified to be −75 to −70 volts, as described above with respect to  FIG. 3 , then the lens voltage may be adjusted in 0.5 V increments, beginning at −75 V. 
     The iterative process of steps  603  to  606  may continue until the resolution and sensitivity of the spectrum are considered to be optimal or meet the predetermined criteria. By setting the predetermined parameters to be evaluated in step  605 , a user can decide based on the application whether to sacrifice spectral resolution at the cost of improving sensitivity, or whether to increase sensitivity at the expense of resolution in the low end of the mass range. This is not always a trade-off; resolution may be maintained over the dynamic range of the instrument until the onset of space charge, so long as the instrument is operating below the maximum resolution. In other embodiments, the optimal point is preprogrammed and unchangeable, which may be beneficial in applications where simplicity of use is valued over flexibility. 
       FIG. 6B  illustrates a process  610 , that begins at step  611 , for adjusting the lens voltage for purposes of controlling space charge effects of the mass spectrometer  100 . In the embodiment shown in  FIG. 6B , the method begins by setting the voltage applied by voltage source  120  to the lens  112  in step  612 . This voltage sets the focal length of the lens. Next, the instrument performs a mass spectrum scan in step  613 , and monitors the spectrum resolution and/or total ion current in step  614 . If there are no space charge effects, as decided in step  615 , the previous voltage is accepted and used for subsequent scans. For extremely low concentrations, the user may monitor the signal-to-noise ratio and increase accordingly the number of ions created in a reverse of this process. Otherwise, the lens voltage is increased in step  616  and another mass spectrum scan is performed in step  613 . This iterative process continues until space charge effects are no longer observed. In this manner, the voltage on lens  112  is increased step by step to allow more electrons into the trap and generate more ions. At each step, a mass spectrum is taken and observed for signs of space charge effects. When a space charge effect is detected, the instrument reverts to the previous lens voltage that didn&#39;t result in space charge effects. 
     In yet another embodiment, as shown in  FIG. 6C , the instrument steps through a finite list of possible voltage settings. The method begins by setting the voltage of voltage source  120  to be applied to the lens  112  to one of the voltages in the list in step  622 . Next, the mass spectrometer  100  performs a mass spectrum scan in step  623 , and monitors the spectrum resolution and/or total ion current in step  624 . If there are more possible voltages in the list to test (step  625 ; yes), then the lens voltage is adjusted to the next lens voltage on the list in step  626  and repeats the mass spectrum scan of step  623 . The iterative process continues until all lens voltages have been tested. In step  627 , the optimal lens voltage, as determined by the monitored spectrum resolution and/or total ion current in step  624  for each voltage, is used for subsequent scans. 
     The foregoing description, along with its associated embodiments, has been presented for purposes of illustration only. It is not exhaustive and does not limit the invention to the precise form disclosed. Those skilled in the art will appreciate from the foregoing description that modifications and variations are possible in light of the above teachings or may be acquired from practicing the invention. The steps described need not be performed in the same sequence discussed or with the same degree of separation. Likewise various steps may be omitted, repeated, or combined, as necessary, to achieve the same or similar objectives. Accordingly, the invention is not limited to the above-described embodiments, but instead is defined by the appended claims in light of their full scope of equivalents.