Rapid environmental equilibration of detection components in mass spectrometers

Abstract

In one aspect, a method of stabilizing the gain of an ion detector including a microchannel plate (MCP) and a scintillator in communication with the MCP such that electrons generated by the MCP in response to incidence of ions thereon are received by the scintillator to generate photons is disclosed, which includes configuring the MCP for generating a plurality of electrons in response to incidence of ions on the MCP, exposing the MCP to an ion beam so as to generate a plurality of electrons irradiating an input surface of the scintillator and thereby causing degassing of at least a portion of one or more gases adsorbed on the scintillator's input surface, and monitoring a gain of the ion detector during exposure of the MCP to the ion beam over a temporal period until the ion detector exhibits a substantially stable gain profile.

Description

[0001] RAPID ENVIRONMENTAL EQUILIBRATION OF DETECTION COMPONENTS IN MASS SPECTROMETERS

[0002] Technical Field

[0003] The present disclosure relates generally to systems and methods for performing mass spectrometry, and more particularly to workflows for use in mass spectrometry for achieving a stable ion detection signal.

[0004] Background

[0005] The present disclosure provides systems and methods for performing mass spectrometry, and particularly such systems and methods for stabilizing an optical ion detector for acquisition of mass and abundance data.

[0006] Mass spectrometry (MS) is an analytical technique for determining the structure of test chemical substances with both qualitative and quantitative applications. MS can be useful for identifying unknown compounds, determining the composition of atomic elements in a molecule, determining the structure of a compound by observing its fragmentation, and quantifying the amount of a particular chemical compound in a mixed sample. Mass spectrometers detect chemical entities as ions such that a conversion of the analytes to charged ions must occur.

[0007] In mass spectrometry systems, a variety of detectors can be utilized for generating ion detection signals. In particular, the use of optical ion detectors is becoming more prevalent. It is generally desired that such detectors exhibit a substantially stable gain over the time period in which ion detection signals are acquired.

[0008] Summary

[0009] In one aspect, a method of stabilizing the gain of an optical ion detector is disclosed, where the ion detector includes a microchannel plate (MCP) and a scintillator in communication with the MCP such that electrons generated by the MCP in response to incidence of ions thereon are received by the scintillator to generate photons. Typically, and in various embodiments, the optical ion detector includes one or more photomultiplier tubes (PMTs) that can receive the photons generated by the scintillator and generate electrical pulses in response to the detection of the photons. The method includes configuring the MCP for generating a plurality of electrons in response to incidence of ions on the MCP, exposing the MCP to an ion beam so as to generate a plurality of electrons that irradiates an input surface of the scintillator and thereby causing degassing of at least a portion of one or more gases adsorbed on the scintillator’s input surface, and monitoring a gain of the optical ion detector during exposure of the MCP to the ion beam over a temporal period until the ion detector exhibits a substantially stable gain profile.

[0010] The MCP can be configured for the detection of ions via application of a bias voltage thereto. By way of example, the bias voltage applied to the MCP can be in a range of about 600V to about 1200 V.

[0011] In some embodiments, the bias voltage applied to the MCP can be selected such that the plurality of the electrons generated by the MCP provides an electron flux that is non-damaging to the MCP and / or the scintillator. By way of example, in some embodiments, the bias voltage is selected such that the electron flux will not exceed about 3xl08electrons / (second mm2)

[0012] In various embodiments, the optical ion detector is positioned in a low-pressure chamber, e.g., in a chamber that is maintained at a pressure in a range of about IxlO'8Torr to about IxlO'6Torr.

[0013] By way of example, the substantially stable temporal gain profile of the optical ion detector can be characterized by the detector generating a plurality of ion detection pulses having a characteristic pulse height and / or duration, i.e., pulse height and / or duration that remains substantially constant over a target time period, e.g., over a time period corresponding to a typical data acquisition time period. In addition or alternatively, the substantially stable temporal gain profile of the ion detector can be characterized by the detector generating a plurality of ion detection pulses exhibiting a substantially linear relationship between their pulse height and an intensity of an ion beam incident on the ion detector.

[0014] In various embodiments, the bias voltage applied to the MCP and / or the intensity of the ion beam utilized for conditioning the optical ion detector can be selected such that a substantially stable gain of the optical ion detector can be achieved during a temporal period less than about 20 minutes, e.g., in a range of about 1 minute to about 10 minutes, though longer periods may be needed in various embodiments. In various embodiments, the gases that are degassed from the scintillator via impact of the electrons on the scintillator’s input surface can be atmospheric gases, such as any of oxygen (O2), nitrogen (N2), and water vapor (H2O).

[0015] In a related aspect, a method for conditioning an optical ion detector for use in mass spectrometry is disclosed, where the ion detector includes at least one microchannel plate (MCP) for generating electrons in response to ions incident thereon and at least one scintillator for generating photons in response to the electrons being incident on its input surface. The method includes applying a bias voltage to the MCP, and directing an ion beam to the MCP, while the ion detector is exposed to a low-pressure environment, e.g., an ambient pressure in a range of about 1x1 O'8Torr to about 1x1 O'6Torr , to generate a plurality of electrons, where the electrons received by the scintillator via its input surface can cause degassing of at least a portion of one or more gases adsorbed on the input surface of the scintillator. In some embodiments, the ion beam can be directed to the MCP for a predefined temporal period so as to configure the optical ion detector for substantially stable operation. By way of example, and without limitation, the bias voltage applied to the MCP can be in a range of about 900 V to about 1100 V.

[0016] In various embodiments, the temporal period required for conditioning the optical ion detector can be determined based on previous measurements of the variation of the gain of the ion detector in response to incidence of a reference ion beam on the ion detector. For example, such measurements can be utilized to identify the time required for the output of the ion detector, e.g., measured as ion counts per second, to reach a substantially stable condition, e.g., when the temporal variation of the ion detector’s output in response to exposure to the reference ion beam is less than a threshold, e.g., less than about 5%.

[0017] As noted above, various criteria can be employed to assess whether the optical ion detector has achieved a substantially stable operational status. For example, such substantially stable operational status can be based on the ion detector exhibiting a substantially constant gain, e.g., as evidenced by substantially uniform height and / or duration of ion detector’s output pulses in response to the reference ion beam intensity.

[0018] In some embodiments, the stability of the ion detector’s operation can be assessed by varying the intensity of an ion beam incident on the ion detector and determining whether the relationship between the gain provided by the ion detector and the intensity of the incident ion beam is substantially linear.

[0019] Further understanding of various aspects of the present teachings can be obtained by reference to the following detailed description in conjunction with the associated drawings, which are described briefly below.

[0020] Brief Description of the Drawings

[0021] FIG. 1 is a flow chart depicting various steps in a method according to an embodiment for conditioning an optical ion detector employed in a mass spectrometry system,

[0022] FIG. 2A schematically depicts two processes that can be employed for degassing of gases adsorbed on a surface of a scintillator utilized in an optical ion detector employed in a mass spectrometry system,

[0023] FIG. 2B is a schematic view of an optical ion detector that can be conditioned in accordance with various embodiments of the present teachings,

[0024] FIG. 3 schematically depicts a mass spectrometer in which an optical ion detector is incorporated, which can be conditioned in accordance with various embodiments of the present teachings, and

[0025] FIG. 4 shows an example of ion detection data generated by an optical ion detector in response to incidence of an ion beam on the detector.

[0026] Detailed Description

[0027] It will be appreciated that for clarity, the following discussion will explicate various aspects of embodiments of the applicant’s teachings, while omitting certain specific details wherever convenient or appropriate to do so. For example, discussion of like or analogous features in alternative embodiments may be somewhat abbreviated. Well-known ideas or concepts may also for brevity not be discussed in any great detail. The skilled person will recognize that some embodiments of the applicant’s teachings may not require certain of the specifically described details in every implementation, which are set forth herein only to provide a thorough understanding of the embodiments. Similarly, it will be apparent that the described embodiments may be susceptible to alteration or variation according to common general knowledge without departing from the scope of the disclosure. The following detailed description of embodiments is not to be regarded as limiting the scope of the applicant’s teachings in any manner.

[0028] As used herein, the terms “about” and “substantially equal” refer to variations in a numerical quantity that can occur, for example, through measuring or handling procedures in the real world; through inadvertent error in these procedures; through differences in the manufacture, source, or purity of compositions or reagents; and the like. Typically, the terms “about” and “substantially” as used herein means 10% greater or less than the value or range of values stated or the complete condition or state. For instance, a concentration value of about 30% or substantially equal to 30% can mean a concentration between 27% and 33%. The terms also refer to variations that would be recognized by one skilled in the art as being equivalent so long as such variations do not encompass known values practiced by the prior art.

[0029] As used herein the term “and / or” includes any and all combinations of one or more of the associated listed items.

[0030] The term “optical ion detector,” as used herein, refers to a detector for detecting ions via generation of photons in response to incidence of ions on the detector. For example, ions incident on the detector can cause generation of electrons, which in turn are incident on a scintillator to generate photons, which can be detected for example by a photomultiplier tube (PMT), to generate electrical signals.

[0031] The gain of an ion detector refers to a ratio of the output electrical charge to input ion charge, where the gain is typically tuned to be in the range of 1x104to 1x106. This allows the detector to generate a detectable electrical signal that is quantifiable and proportional to the input ion beam flux. In various embodiments, the gain of the ion detector, and its temporal stability, can be assessed using parameters associated with the output signal of the optical ion detector, such as the height and / or the width of the ion detection pulses generated by the ion detector and / or the relationship between the signal intensity, e.g., characterized by the pulse heights, as a function of the intensity of an ion beam incident on the detector. The term “a reference ion beam” as used herein refers to an ion beam having a known and / or uniform intensity, e.g., an intensity that remains substantially constant over a target period, such as a period during which conditioning of the optical ion detector is performed.

[0032] The present disclosure is generally based on an unexpected discovery that an unstable gain exhibited by certain ion detectors that employ scintillators as a component of the ion detection system can be due, at least in part, to the outgassing of atmospheric gases from one or more detection surfaces, e.g., the surface of a scintillator. The gases can be adsorbed on the scintillator’s input surface when the detector is exposed to pressures above that typically found in the low pressure environment of a chamber of the mass spectrometer in which the detector is positioned and operated. Upon exposure to the detector to low pressure environment outgassing of the adsorbed gases can start at a very slow rate, which can in turn adversely affect ion detection signals generated by the detector.

[0033] More specifically and without being bound to any particular theory, when an ion detector is exposed to common atmospheric gases, such as oxygen (O2), nitrogen (N2) and water vapor (H2O), at an atmospheric pressure, the gases can be adsorbed onto metallic surfaces of the ion detector’s components with a significant binding energy. As a result, when the ion detector is exposed to a vacuum environment, e.g., during operation of a mass spectrometer utilizing the ion detector, the adsorbed gases can be released from such surfaces at very slow rates. In optical ion detectors in which light-generating components, such as scintillators, are employed, the release of the adsorbed gases could adversely affect the amount of light that is generated, as well as its temporal properties, which can in turn adversely affect the operation of the ion detector.

[0034] In various embodiments, a workflow for performing mass spectrometry is disclosed, which includes conditioning an ion detector of the mass spectrometer to achieve environmental equilibration of the ion detector before mass spectrometric measurements are initiated. In various embodiments, the present methods of conditioning the ion detector when the ion detector is exposed to a vacuum environment can promote accelerated desorption of adsorbed atmospheric gases such that a new equilibrium distribution of gases on metal surfaces of the ion detector is established. As discussed in more detail below, such conditioning of the ion detector can allow for stable and reproducible performance of the ion detector. In particular, in various embodiments, such conditioning of the ion detector can stabilize the ion detector’s gain and provide linear dynamic range and resolution enhancements.

[0035] As discussed in more detail below, in various embodiments, a workflow for performing mass spectrometry is disclosed that helps rapid removal of adsorbed gases from a scintillator of an optical ion detector, which can in turn allow the scintillator to reach a new equilibrium state suitable for substantially stable operation of the ion detector. More specifically, in some embodiments, such conditioning of the ion detector can be achieved by maximizing the number of electrons that can safely irradiate an input surface of the scintillator. By way of example, in an ion detector that includes a microchannel plate (MCP) for generating electrons in response to incident ions and a scintillator that receives the electrons and generates photons, a DC bias voltage applied to the MCP can be increased as much as safely possible (e.g., by about +100 V relative to a value utilized during normal operation of the ion detector) and the intensity of an ion beam incident on the input surface of MCP can be maximized without damaging the ion detector. In some embodiments, the bias voltage applied to the photomultiplier tubes can be lowered, e.g., to prevent ageing of the photomultiplier tubes that detect the photons generated by the scintillator. While in this state, the ion detection signals can be monitored until a substantially stable operation of the ion detector is achieved, in other embodiments the conditioning of the optical ion detector can be performed for a predetermined temporal period.

[0036] By way of example, FIG. 1 schematically depicts a flow chart providing various steps of a method for conditioning an optical ion detector that is suitable for use in mass spectrometry, where the optical ion detector can include at least one microchannel plate (MCP) for generating electrons in response to ions incident thereon and at least one scintillator for generating photons in response to the incidence of the electrons generated by the MCP on its input surface. In this embodiment, the method includes applying a bias voltage to the MCP (10) and directing an ion beam to the MCP to generate a plurality of electrons (12). By way of example, the bias voltage applied to the MCP can be in a range of about 600V to about 1200V, though other bias voltages can also be employed.

[0037] The incidence of the electrons generated by the MCP on the input surface of the scintillator can cause degassing of at least a portion of gases adsorbed on an input surface of the scintillator (12). Without being limited to any particular theory, the electrons incident on the scintillator can cause degassing of one or more gases adsorbed on the input surface of the scintillator by providing energy to the adsorbed gases so that they can overcome the binding energy associated with their adsorption on the scintillator’s input surface. The exposure of the MCP to the ion beam can be maintained for a temporal period that would lead to a sufficient degassing of the adsorbed gases such that the optical ion detector can be operated in a substantially stable fashion (14). Such a temporal period may be determined dynamically by monitoring the output signal of the ion detector, or alternatively, a predefined temporal period, e.g., based on previously-obtained data, may be employed.

[0038] By way of example, the substantially stable operation of the optical ion detector can be assessed by monitoring the gain exhibited by the ion detector in response to exposure to the ion beam. By way of example, the substantially stable operation of the optical ion detector can be characterized by the ion detector exhibiting a substantially constant gain during a temporal period, e.g., during at least a portion of the period in which the MCP is exposed to the ion beam. Instead of or in addition to the above criteria, the substantially stable operation of the optical ion detector can be characterized by the ion detector generating a plurality of ion detection pulses having a substantially uniform pulse height and / or duration in response to exposure to a reference ion beam.

[0039] Further, instead of or in addition to the above criteria, a substantially stable operation of the optical ion detector can be characterized by the ion detector generating a plurality of ion detection pulses that exhibit a substantially linear relationship between pulse height and an intensity of an ion beam incident on the ion detector. Any other suitable criteria for assessing the stability of the operation of the optical ion detector can also be employed.

[0040] FIG. 2A schematically depicts these two processes for causing the degassing of molecules adsorbed on the input surface of the scintillator. In the process depicted in Panel A, a plurality of electrons emitted by an MCP of the ion detector can impinge on the input surface of the scintillator to impart energy to the adsorbed molecules to cause their degassing, as shown schematically in Panel B. . FIG. 2B schematically depicts a multi-channel optical ion detector 100 according to an embodiment, which includes four ion detection channels (herein referred to as ion channels 1, 2, 3, and 4). The optical ion detector 100 includes a microchannel plate (MCP) 102 that generates electrons 103 in response to incidence of an ion beam 104 on the MCP. More specifically, a DC voltage source 105a operating under control of a controller 107 can apply a bias DC voltage to the MCP 102 to facilitate the generation of electrons in response to the ion beam striking the MCP.

[0041] The optical ion detector further includes a scintillator 106 that receives the electrons generated by the MCP in response to its exposure to the ion beam. While in this embodiment a single scintillator is shared among the four channels of the optical ion detector, in other embodiments, each channel can have its own dedicated scintillator. The scintillator generates photons in response to the incidence of electrons on an input surface 106a thereof. In this embodiment, each of the ion detection channels (1, 2, 3, and 4) includes a photomultiplier tube (PMT), i.e., PMTs 107a, 107b, 107c, 107d, which generates an electronic signal in response to the detection of the photons. The ion detection channels (1, 2, 3, and 4) are optically isolated from one another by a plurality of partitions 109a, 109b, and 109c.

[0042] Generally, during the operation of a mass spectrometer, the optical ion detector is exposed to a vacuum environment, which in absence of conditioning of the optical ion detector, can lead to the release of gases, such as atmospheric gases previously adsorbed onto the input surface of the scintillator, which can in turn cause a degradation of signals generated by the detector.

[0043] For conditioning of the optical ion detector 100 prior to the initiation of mass spectrometric measurements, the controller 107 can cause the DC voltage source 105a to apply a bias voltage to the MCP 102. In various embodiments, the bias voltage can be set to optimize the generation of electrons by the MCP without causing damage to the MCP or the scintillator. By way of example, in various embodiments, the DC bias voltage applied to the MCP can be in a range of about 900 V to about 1100 V. Instead or in addition, in some embodiments, the intensity of the reference ion beam employed for conditioning the optical ion detector can be chosen to maximize the generation of electrons by the MCP, without damaging the MCP or the scintillator. By way of example, and without limitation, the reference ion beam intensity can be in a range of about 1x108cps to about 4x108cps.

[0044] As noted above, in some embodiments, the bias voltage(s) applied to the photomultiplier tubes can be lowered to prevent aging of the photomultiplier tubes by the detector photons generated by the scintillator. By way of example, the controller 107 can control a DC voltage source 105b that applies bias voltage(s) to the PMT’s to set those bias voltages at a desired value.

[0045] The incidence of a higher flux of electrons on the input surface of the scintillator can advantageously reduce the time required for conditioning the ion detector by accelerating the degassing of gases, such as atmospheric gases, adsorbed on the input surface of the scintillator. However, if the electron flux is too high, it may damage the MCP, the scintillator and / or cause ageing of the photomultiplier tubes. Accordingly, in various embodiments, the intensity of the reference ion beam and / or the bias voltage applied to the MCP can be selected to ensure fast conditioning of the optical ion detector, e.g., conditioning of the ion detector within a time period less than about 20 minutes, while ensuring that various components of the ion detector, including the scintillator and the photomultiplier tubes, will not be damaged.

[0046] In some embodiments, the gain of the ion detector is monitored during the conditioning of the detector until a substantially stable gain is achieved. In some embodiments, such monitoring of the ion detector’s gain can be performed automatically, e.g., by monitoring the intensity of a reference mass peak.

[0047] The workflow as discussed herein for conditioning an optical ion detector can be employed in connection with the use of a variety of different mass spectrometric systems for performing a variety of mass spectrometric measurements.

[0048] By way of example, and without limitation, FIG. 3 schematically depicts a mass spectrometric system 400 in which an optical ion detector 420 is incorporated, which can be conditioned in a manner disclosed herein. More specifically, the mass spectrometric system 400 includes an ion source 403 for receiving a sample and ionizing one or more target analytes of interest within the sample. The ion source can include any suitable ion source, including, for example, ion sources that provide ions through electrospray ionization (ESI), matrix-assisted laser desorption ionization (MALDI), ion bombardment, application of electrostatic fields (e.g., field ionization and field desorption), chemical ionization, etc.

[0049] The ions generated by the ion source 403 are received by an ion guide QJet, which includes a set of rods 401 arranged in a quadrupole configuration, two of which 401a / 401b are visible in the figure and employs a combination of gas dynamics and radio frequency fields to cause focusing of the ions. The ions exiting the QJet ion guide are focused by an ion lens IQO into an ion guide Q0, which includes a set of quadrupole rods 404, two of which 404a / 404b are visible in the figure, to which RF voltages can be applied for causing radial confinement of the ions and generate an ion beam that is in turn received by an ion mass filter QI. The ion guides QJet, Q0, and the mass filter QI are disposed in differentially-pumped chambers that are maintained at progressively lower pressures.

[0050] An ion lens IQ1 focuses the ions exiting the Q0 ion guide into the mass filter QI. The mass filter QI includes a stubby lens 406 formed by a set of quadrupole rods (two of which 406a / 406b are visible in the figure) to which RF voltages can be applied to cause focusing of the ions. The mass filter QI further includes a set of quadrupole rods 410, two of which 410a / 410b are visible in the figure, to which a combination of RF and DC voltages can be applied to allow the selection of one or more precursor ions having m / z ratios within a target m / z range for transmission to a downstream ion dissociation device Q2, e.g., a collision cell, in this example via an ion lens IQ2. Although in this embodiment a collision cell is employed as the ion dissociation device, in other embodiments, other types of ion dissociation devices, such as those that employ EAD, e.g., electron capture dissociation, can be used.

[0051] A controller 405 can be employed to configure the mass filter QI to allow, during each measurement cycle, the passage of precursor ions corresponding to a target analyte and its associated internal standard.

[0052] As discussed in more detail below, the mass filter QI can be configured to allow passage of a target analyte ion and an internal standard ion associated with the target analyte.

[0053] More specifically, a DC voltage source 426 and an RF voltage source 428 operating under control of the controller 405 can apply RF and DC voltages to the mass filter QI in a manner known in the art and as informed by the present teachings to configure the bandpass window of the mass filter. By way of example, and without limitation, the RF voltage applied to the rods of the QI mass filter can have a frequency in a range of about 200 kHz to about 12 MHz and a peak-to-peak amplitude (Vpp) in a range of about 100 volts to about 10 kilovolts (kV).

[0054] The ions passing through mass filter QI are received by a collision cell Q2 in which the ions undergo dissociation to generate a plurality of product ions. The product ions are in turn received by a downstream time-of-flight (TOF) mass analyzer 418, which generates ion detection data in response to the detection of the product ions. More specifically, in this embodiment, the TOF mass analyzer 418 includes the optical ion detector 420, which detects ions received by the TOF mass analyzer and generates ion detection data in response to the detection of those ions. The ion detector and other components of the TOF mass analyzer 418 are positioned in a low-pressure chamber, e.g., a chamber maintained at a pressure in a range of about 1x10'8Torr to about 1x1 O'6Torr. As such, the optical ion detector 420 requires conditioning prior to the acquisition of ion detection data. Further, a data processing module 425 receives the ion detection data generated by the optical ion detector and processes the ion detection data to generate a mass spectrum of the detected ions.

[0055] In some embodiments, the conditioning of the ion detector can be achieved by exposing the ion detector to an ion beam of a given ion intensity for a predefined temporal period. For example, the predefined temporal period can be selected based on previously-obtained data regarding the time required for conditioning of the ion detector. Alternatively, the conditioning of the ion detector can be performed dynamically. For example, the dynamic conditioning of the ion detector can involve real-time monitoring of a gain exhibited by the ion detector in response to incidence of an ion beam on the ion detector until the observed gain would exhibit a target temporal stability, e.g., it would remain substantially stable over a time period commensurate with an anticipated data acquisition period.

[0056] By way of example, in some embodiments, the conditioning of the ion detector can be achieved by introducing a reference sample into the ion soure to generate an ion beam. In some such cases, mass filter QI may be employed to select ions having m / z ratios within a particular range for being incident on the ion detector. In some cases, during conditioning of the optical ion detector, the collision cell Q2 may not be employed. The ion detection data generated by the ion detector in response to the incidence of ions on its MCP can then be monitored until a substantially stable operation of the ion detector is achieved. For example, the data processing module can process the ion detection data to generate a mass spectrum of the incident ions. The intensity of one or more mass peaks within the mass spectrum can be monitored as a way of assessing the stability of the operation of the optical ion detector. In some embodiments, the data processing module can be configured to monitor the height of the mass peak(s) and compute the temporal variation of the height. Once the temporal variation exhibited by the height of the mass peak(s) is less than a predefined threshold (e.g., less than about 5%), the data processing module can transmit a signal to the controller indicating that a substantially stable operation of the ion detector has been achieved. In some such cases, the controller can terminate the conditioning process, e.g., via transmission of a control signal to the ion source.

[0057] The following example is provided for further elucidation of various aspects of the present teachings, and is not presented to provide necessarily an optimal way of practicing the present teachings and / or optimal results that may be obtained.

[0058] Example

[0059] FIG. 4 shows the temporal variation of an output signal generated by an optical ion detector utilized in a TOF mass analyzer in response to the incidence of ions on the detector. The detector was a 4-channel optical detector having a configuration similar to that shown in FIG. 2B. The mass spectrometer was qTOF instrument similar to that depicted in FIG. 3. The ions were a set of calibrant ions. The depicted signal is the sum total of all ions in the mass spectrum (TIC). Bias voltage applied to the MCP was approximately 900V.

[0060] The data shows that the ion detection signal, in response to incidence of a constant number of ions on the ion detector, increases exponentially until it reaches a plateau that remains substantially constant. In other words, in this example, the data indicates that in response to conditioning, the ion detector reaches a substantially stable operating state in an exponential fashion.

[0061] In some cases, such data regarding the behavior of the ion detector in response to conditioning, can be utilized to predict the time required for conditioning of a particular ion detector utilized in a particular mass spectrometer. Alternatively, as noted above, in some embodiments, dynamic conditioning of an optical ion detector can be employed, e.g., in a manner discussed above.

[0062] . Although some aspects have been described in the context of an apparatus, it is clear that these aspects also represent a description of the corresponding method, where a block or device corresponds to a method step or a feature of a method step. Analogously, aspects described in the context of a method step also represent description of a corresponding block or item or feature of a corresponding apparatus. Some or all of the method steps may be executed by (or using) a hardware apparatus, like for example, a processor, a microprocessor, a programmable computer or an electronic circuit. In some embodiments, some one or more of the most important method steps may be executed by such an apparatus.

[0063] Depending on certain implementation requirements, embodiments of the invention can be implemented in hardware and / or in software. The implementation can be performed using a non- transitory storage medium such as a digital storage medium, for example a floppy disc, a DVD, a Blu-Ray, a CD, a ROM, a PROM, and EPROM, an EEPROM or a FLASH memory, having electronically readable control signals stored thereon, which cooperate (or are capable of cooperating) with a programmable computer system such that the respective method is performed. Therefore, the digital storage medium may be computer readable.

[0064] While various embodiments have been illustrated and described in detail in the drawings and foregoing description, such illustration and description are to be considered illustrative or exemplary and not restrictive; embodiments of the present disclosure are not limited to the disclosed embodiments. Other variations to the disclosed embodiments can be understood and effected by those skilled in the art in practicing embodiments of the present disclosure, from a study of the drawings, the disclosure, and the appended claims.

[0065] In the claims, the word “comprising” does not exclude other elements or steps, and the indefinite article “a” or “an” does not exclude a plurality. A single processor or other processing unit may fulfill the functions of several items recited in the claims. The mere fact that certain measures are recited in mutually different dependent claims does not indicate that a combination of these measured cannot be used to advantage. Any reference signs in the claims should not be construed as limiting the scope.

Claims

What is claimed is:

1. A method of stabilizing a gain of an ion detector including a microchannel plate (MCP) and a scintillator in communication with the MCP such that electrons generated by the MCP in response to incidence of ions thereon are received by the scintillator to generate photons, the method comprising: configuring the MCP for generating a plurality of electrons in response to incidence of ions on the MCP, exposing the MCP to an ion beam so as to generate a plurality of electrons thereby irradiating an input surface of the scintillator and thereby causing degassing of at least a portion of molecules adsorbed on the scintillator’s input surface, and monitoring a gain of the ion detector during exposure of the MCP to the ion beam over a temporal period until the ion detector exhibits a substantially stable gain profile.

2. The method of Claim 1 , wherein the step of configuring the MCP comprises applying a bias voltage to the MCP.

3. The method of Claim 2, wherein the bias voltage applied to the MCP is in a range between about 600V to about 1200 V.

4. The method of any one of Claims 2 and 3, wherein the bias voltage is selected such that the plurality of the electrons provides an electron flux that is up to or within about 10% of a maximum permissible electron flux for irradiating the scintillator’s input surface.

5. The method of Claim 1, wherein the ion detector is positioned in a low-pressure chamber.

6. The method of Claim 5, wherein the low-pressure chamber is maintained at a pressure in a range of about IxlO'8Torr to about IxlO'6Torr.

7. The method of any one of Claims 1 - 6, wherein said substantially stable gain profile for the ion detector is characterized by the ion detector generating a plurality of ion detection pulses having a substantially uniform pulse duration.

8. The method of any one of Claims 1 - 6, wherein said substantially stable gain profile for the ion detector is characterized by the ion detector generating a plurality of ion detection pulses exhibiting a substantially linear relationship between their pulse height and an intensity of an ion beam incident on the ion detector.

9. The method of Claim 1 , further comprising detecting photons generated by the scintillator by at least one photomultiplier tube (PMT) to generate one or more electrical signals.

10. The method of Claim 1, wherein said molecules adsorbed on the scintillator’s input surface comprise one or more of oxygen (O2), nitrogen (N2), and water vapor (H2O).

11. The method of Claim 2, wherein the bias voltage applied to the MCP is selected such that the substantially stable gain profile of the ion detector is achieved during a time interval of less than about 20 minutes.

12. A method for conditioning an optical ion detector for use in mass spectrometry, wherein the optical ion detector includes at least one microchannel plate (MCP) for generating electrons in response to ions incident thereon and at least one scintillator for generating photons in response to the electrons being incident on an input surface thereof, the method comprising: applying a bias voltage to the MCP, and directing an ion beam to the MCP to generate a plurality of electrons, wherein the electrons are received by the scintillator via an input surface thereof and cause degassing of at least a portion of molecules adsorbed on the input surface of the scintillator,wherein the ion beam is directed to the MCP for a predefined temporal period so as to configure the optical ion detector for substantially stable operation.

13. The method of Claim 12, wherein said predefined temporal period is determined by measuring a variation of a gain of the optical ion detector in response to incidence of a reference ion beam thereon.

14. The method of any one of Claims 12 and 13, wherein the substantially stable operation of the optical ion detector is characterized by the optical ion detector exhibiting a substantially constant gain during a data acquisition period.

15. The method of any one Claims 12 and 13, wherein the substantially stable operation of the optical ion detector is characterized by the optical ion detector generating a plurality of ion detection pulses having a substantially uniform pulse duration.

16. The method of any one Claims 12 and 13, wherein the substantially stable operation of the optical ion detector is characterized by the optical ion detector generating a plurality of ion detection pulses exhibiting a substantially linear relationship between pulse height and intensity of an ion beam incident on the optical ion detector.

17. The method of any one of Claims 12 - 16, wherein the bias voltage applied to the MCP is in a range between about 600V to about 1200V volts.

18. The method of any one of Claims 17, wherein the bias voltage applied to the MCP is in a range between about 900V to about 1100V volts.

19. The method of Claim 12, wherein the optical ion detector is positioned in a low pressure chamber of a mass spectrometer.

20. The method of Claim 19, wherein the low pressure chamber is maintained at a pressure in a range of about IxlO'8Torr to about IxlO'4Torr.Y121. The method of Claim 19, wherein the low pressure chamber is maintained at a pressure in a range of about IxlO'8Torr to about IxlO'6Torr.

22. The method of Claim 12, wherein the bias voltage applied to the MCP is selected such that the substantially stable gain profile of the optical ion detector is achieved during a time interval of less than about 20 minutes.

Images