The present disclosure relates generally to mass spectrometry and, more particularly, to systems and methods of mass-dependent automatic gain control.
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 detecting the abundance of ions at each m/z. The resulting spectrum can be interpreted to reveal the relative amount of each chemical component in the sample based on the abundance of the mass fragments of these components.
Various mass spectrometers generate ions from the sample utilizing various methods, for example, electrospray ionization, atmospheric pressure chemical ionization, matrix-assisted laser desorption/ionization, and inductively coupled plasmas. In some situations, the ion source that generates the ions is located external to a mass analyzer. The ions are guided from the ion source into a mass analyzer, where the ions are separated based on mass. The ions then arrive at a detector that detects charge and/or current. Information based on the detected charge and/or current is then used to determine the quantity of ions of various masses.
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. 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 in a “cloud” within the central volume of the ion trap. By manipulating the amplitude and/or frequency of the electric fields, ions are selectively scanned out by being 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, and resolution depending on the particular application. For a given instrument, an improvement in one category is usually made at the expense of another. For example, sensitivity can generally be increased by using a slower scan, and in the reverse, a scan can be performed faster at the expense of sensitivity. 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 and collisions between the like-charged ions in the ion cloud increases, resulting in space charge effects. Mass spectrometers achieve resolution by ejecting all ions of the same m/z at close to the exact same moment. However, when space charge effects become significant, ions are ejected from the trap at different times. The result is broadening of spectral peaks and loss of resolution. Also, detectors used in mass spectrometers typically have a limited dynamic range, the difference between the lowest and highest concentration that can be detected. Concentrations lower than the lower bound are undetectable due to, for example, noise; and concentrations above the upper bound may saturate the detector. Additionally, mass analyzers may trap ions preferentially based on their mass, thus for a sample with a range of masses, larger ions may not be trapped as efficiently as lower masses.
There is a need for systems and methods for expanding the range of concentrations detectable by mass spectrometers. The present disclosure is directed to overcoming one or more of the problems set forth above and/or other problems of the prior art.
Embodiments of the present disclosure relate to chemical analysis instruments, such as mass spectrometers, that utilize automatic gain control. Various embodiments of the disclosure may include one or more of the following aspects.
In one aspect, the present disclosure is directed to a mass spectrometer. The mass spectrometer may include a lens configured to receive a supply of ions, and a mass analyzer downstream of the lens. The mass analyzer may include an ion trap and an ion detector. Furthermore, the lens may focus a beam of the ions non-uniformly based on the mass of the ions to compensate for space charge effects reflected in a measurement output of the mass spectrometer.
In another aspect, the present disclosure is directed to a mass analyzing control system for analyzing the mass of a sample. The system may include one or more memories storing instructions. The system may also include one or more processor configured to execute the instructions to perform operations. The processor may obtain a mass spectrum of an ion beam generated from the sample and identify a space charge characteristic based on the mass spectrum. The processor may defocus the lens based on the mass spectrum or detector saturation, wherein defocusing the lens may correspond to preferentially defocusing away lighter ions. The processor may then obtain a mass spectrum of a defocused ion beam generated from the sample.
In yet another aspect, the present disclosure is directed to a method for analyzing the mass fragments of a sample. The method may include focusing an ion beam into a mass analyzer. The method may include obtaining a mass spectrum of the ion beam and identifying a space charge characteristic, or other mass dependent phenomena, based on the mass spectrum. The method may also include defocusing the lens based on the identified space charge characteristic, or other mass dependent phenomena, wherein defocusing the lens corresponds to preferentially defocusing away lighter ions. The method may further include obtaining a mass spectrum of a defocused ion beam generated from the sample.
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:
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.
In various embodiments, ion source 105 may be any apparatus that produces sample ions 107 by ionizing a sample that is introduced into mass spectrometer 100. For example, ion source 105 may include an electron ionization device comprising an electron filament, which is heated to a high enough temperature such that it emits energetic electrons. Ion source 105 may include an electron lens that focuses and accelerates the electrons into the sample, resulting in ionization of the sample and generation of sample ions 107. Alternatively, ion source 105 may be other types of devices that ionize samples by various methods, e.g., chemical ionization or inductively coupled plasma. In various embodiments, ion source 105 may generate ions 107 at a relatively high pressure, such as at around atmospheric pressure. In addition to ions 107, ion source 105 may contain a background gas, such as nitrogen, to which most of the pressure is attributed.
When ions 107 are emitted from ion source 105, ions 107 may begin to disperse unless focused by ion lenses. Ion lenses may be biased at various potentials to activate. The resulting electric field may result in electric forces on ions 107 that accordingly define the path of ions 107. In some embodiments, mass spectrometer 100 may include one or more ion lenses 109 that focus ions 107 into a beam. Mass spectrometer 100 may also include ion lens 110 that controls the degree to which the beam of ions 107 are focused or defocused before entering mass analyzer 115. The direction and acceleration of ions 107 passing through an aperture 113 of ion lens 110 may be controlled based on the voltage applied to ion lens 110. In addition, changing the voltage applied to lens 110 may affect the cross-sectional area of the ion beam. Accordingly, the proportion of ions 107 that pass through lens 110 into mass analyzer 115 may vary based partly on the voltage applied to lens 110. Lens 110 may then act as a voltage-controlled gate for controlling the number of ions 107 that enter the mass analyzer 115.
Mass analyzer 115 may include a first end cap electrode 116, a ring electrode 117, and a second end cap electrode 118. First end cap electrode 116 may have an aperture 119, through which ions 107 are received by mass analyzer 115. By applying voltages to end caps 116 and 118, and a voltage to the ring electrode 117, which may be DC, AC, or combination of AC and DC voltages, an electric field may be generated in mass analyzer 115. By appropriately setting the field strength, shape, and frequency of the field, ions 107 that enter mass analyzer 115 may be trapped as an ion cloud within mass analyzer 115. However, ions 107 are not trapped statically in the ion trap. That is, ions 107 may continue to move within the ion cloud, based on the generated RF fields, electrostatic interactions among ions 107, and collisions with background gas particles.
The strength of the RF field and/or the frequency of the RF field may then be adjusted to selectively scan out ions 107 based on the mass (more specifically, the mass-to-charge ratio) of the ions. Ions 107 may be scanned out through an aperture 121 in second end cap 118, and received by ion detector 128. In some embodiments, a focusing lens 126 may precede ion detector 128. Focusing lens may include an aperture 127 that is covered with a screen or grate that shields mass analyzer 115 from strong electric fields generated by a high voltage on ion detector 128. For example, ion detector 128 may be biased with a voltage on the order of −2,000 V. Ion detector 128 may receive ions 107 and generate a detection signal. The output of ion detector 128 may feed into an ion amplifier 129, which may be positioned in close proximity to ion detector 128. Ion amplifier 129 may serve to buffer the output of the ion detector 128, and allow for transmission to A/D converter 130 via a low-impedance signal line that is less susceptible to electromagnetic interference than the output of ion detector 128. An A/D converter 130 may translate the analog output of the ion amplifier 129 into a digital signal to be read by field-programmable gate array (“FPGA”) 140 and eventually processed into an output spectrum to be read by a user or stored for future use. The output spectrum may depict the number of ions 107 as a function of mass. In some embodiments, the A/D converter 130 and FPGA 140 may be combined into a single complex device such as a digital signal processor (“DSP”), microprocessor, or any combination of analog or digital components known in the art.
In various embodiments, the resolution of the output spectrum may be affected by space charge or other effects that affect the resolution of the mass spectrometer 100. For example, space charge effects are due to numerous like-charged ions 107 being confined to a limited space. In various situations, the electric fields generated within mass analyzer 115 may be working to keep ions 107 close together at the center. But due to the closeness of so many like-charged ions 107, ions 107 may experience counteracting electrostatic repulsive forces. Such space charge effects may introduce irregularities to the motion of ions 107 within the ion cloud and subsequently alter the resulting mass spectrum measured by detector 128. In addition, some effects may preferentially affect ions based upon their mass. For example, collisions with neutral species such as background gasses will affect the trajectory of smaller ions more significantly than larger ions.
Furthermore, the trajectory of the ion will be affected by the electric field created by lens 310 according to the vector force applied to the ion:
{right arrow over (F)}=q{right arrow over (E)}
where F is the vector force applied to the ion, q is the charge on the ion, and E is the vector electric field strength. The change in the trajectory of the ion will be defined by:
{right arrow over (F)}=m{right arrow over (a)}
where F is the vector force from the applied electric field, m is the mass of the ion, and a is the vector acceleration. Since the force applied to the ion is defined only by the electric field strength and the charge, which may be similar for like ions; and the change in trajectory is dependent only upon the mass and applied acceleration, the change in ion trajectory will depend upon the mass of the ion, provided that the ions are travelling at relatively the same velocity. This dependence is shown in
Another way to understand this improvement on space charge effects may be as follows. Lens 310 may preferentially focus and defocus lighter ions 307. A plot of the response of the lens, such as attenuation for a given applied voltage as a function of mass, would have a negative slope. This negative slope is due to the fact that lighter ions are defocused and deflected more than the heavier ions. In addition, a plot of the ion trap with respect to space charge, such as resilience to space charge effects as a function of mass, would have a positive slope. This positive slope is due to, as discussed above, space charge effects affecting lighter mass ions more than heavier mass ions. If these two plots are added, the mass-dependent space charge effects may cancel, to a first order approximation.
In various embodiments, an exemplary method for reducing space charge effects exhibited in a measured spectrum may be as follows. The ion trap may be loaded with ions 307. The resulting spectrum may exhibit space charge effects at the lower end of the mass spectrum. The voltage applied to ion lens 310 may then be adjusted such that the beam of ions 307 is defocused away from aperture 319, preferentially for the lighter ions. Because the lighter ions have been preferentially defocused away, less of the lighter ions may enter the ion trap via aperture 319. As a result, overall space charge effects may be reduced.
In some embodiments, the resulting spectrum after the beam of ions 307 is defocused may show an improvement with respect to space charge effects. However, the proportion of masses trapped in the ion trap and subsequently detected by the detector may be skewed, since lighter ions 307 are preferentially defocused away. A compensation for such spectral skew may be performed by various methods and algorithms after the spectrum has been obtained. For example, a computing processor (not shown) may execute instructions stored in memory for computationally adjusting the measured spectrum. As another example, another run of measurements may be performed, where lighter ions are preferentially focused into the ion trap. The resulting mass spectrum may then be combined with the first mass spectrum to derive a new mass spectrum with spectral skew removed and reduced space charge effects.
In some other embodiments, the beam of ions 307 may be defocused without preference based on mass. For example, ions 307 may be generated and/or manipulated to have uniform momentum. The momentum of each ion 307 is defined by:
{right arrow over (p)}=m{right arrow over (v)}
where p is the vector momentum of the ion, m is the mass of the ion, and v is the vector velocity of the ion. Because ions 307 may have different masses, different ions 307 will travel at different velocities in order for ions 307 to have uniform momentum. Heavier ions may move at a slower velocity while lighter ions may move at a faster velocity. As ions 307 pass through aperture 313 in ion lens 310, the electrostatic force generated by ion lens 310 may focus or defocus ions 307. In some embodiments, as ions 307 travel from ion lens 310 to end cap 316, the lighter ions will be accelerated by ion lens 310 in the y-direction (perpendicular to the axis connecting aperture 313 and aperture 319) more than the heavier ions. As discussed above, in situations where ions 307 have uniform velocity, the larger acceleration causes larger deflection of the lighter ions. However, when ions 307 enter ion lens 310 with uniform momentum, the lighter ions may be traveling at a faster velocity than the heavier ions. Therefore, even if the lighter ions experience greater acceleration in the y-direction, the lighter ions also traverse the distance between ion lens 310 and end cap 316 more quickly. Accordingly, the lighter ions traverse this distance in less time, which results in smaller deflections in the y-direction before the lighter ions arrive at end cap 316. The heavier ions, on the other hand, travel the distance between ion lens 310 and end cap 316 more slowly, allowing for more time during which the heavier ions are deflected in the y-direction. In some embodiments, the fact that lighter ions are accelerated in the y-direction more than the heavier ions, but the heavier ions take longer to arrive at end cap 316 than the lighter ions may result in lighter ions and heavier ions being deflected by relatively the same amount. Therefore, ions 307 of various masses may be focused and defocused by ion lens 310 without preference based on mass.
In embodiments that utilize ions 307 with uniform momentum, ion lens 310 may focus and defocus the beam of ions 307 such that a greater or lesser proportion of ions 307 enter mass analyzer. The group of ions 307 that enter the mass analyzer may maintain the same proportion of the various masses of ions 307 that is originally present in the beam that is focused or defocused by ion lens 310. By reducing the number of ions 307 that are trapped simultaneously in the mass analyzer, space charge effects may be reduced.
It will be apparent to those skilled in the art that various modifications and variations can be made to the disclosed systems and methods. Other embodiments will be apparent to those skilled in the art from consideration of the specification and practice of the disclosed systems and methods. It is intended that the specification and examples be considered as exemplary only, with a true scope being indicated by the following claims and their equivalents.
This application is a non-provisional application claiming priority to U.S. Provisional Patent Application No. 61/799,158, filed Mar. 15, 2013 and titled “Mass Dependent Automatic Gain Control for Mass Spectrometer,” all of which is incorporated herein by reference.
Number | Date | Country | |
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61799158 | Mar 2013 | US |