The present disclosure relates generally to systems and methods for calibrating mass spectrometers. More particularly, and without limitation, the present disclosure relates to systems and methods for calibrating a mass spectrometer through the use of a calibrant or calibrating chemical.
Mass spectrometers are used for determining the chemical composition of a sample, including the masses and chemical structures of sample molecules. Mass spectrometers are precision instruments and measure the constituent chemicals in a sample by measuring the analog signal from, for example, a detector after ions are sorted according to their mass by, for example, an ion trap analyzer. There is a need to produce a spectrum describing the relationship between the mass/charge of ions and their relative abundance, calculated from signals measured from the mass analyzer such as voltage, time, or current. Also, the mass assignment or calibration may change. These changes may be short term and temporary, for example, by changing the ambient temperature; or they may be long term and/or permanent, for example as the instrument ages. One way mass spectrometers may be tuned and calibrated is by using a calibration algorithm, typically performed at the startup of the mass spectrometer or as needed, which may be as often as several times per day to as infrequent as annual.
Previous systems for calibrating a mass spectrometer typically include using either a sample manually applied to the inlet of the instrument or using a vial of liquid sample that is contained within the instrument and has a volatility sufficiently high to generate a concentration in the headspace sufficient to be measured by the mass spectrometer to perform the calibration. A common calibrant is perfluorotributylamine (PFTBA) but many others exist. When the instrument is being calibrated, a valve may open, allowing gas from the vial to flow into the vacuum chamber of the instrument. However, in the case of a portable mass spectrometer, movement may cause the sample to be agitated and potentially contaminate the system. Additionally, the concentration of sample is dependent upon physical parameters, such as volatility, amount of calibrant remaining, temperature, etc.; therefore, it can be difficult to deliver a consistent amount of calibrant to the mass spectrometer, which not only presents difficulty in calibration but can also contaminate the system. Some particularly sticky liquid samples might even last longer, preventing accurate readings from the mass spectrometer for days or even weeks.
Thus, there exists a need to provide a calibrant container for a portable mass spectrometer that eliminates issues associated with movement and can provide a more consistent, regulated sample to the instrument for calibration.
The present disclosure provides improved systems and methods for calibrating mass spectrometers.
In accordance with some embodiments, improved systems are provided for calibrating mass spectrometers using a calibrant chamber within a housing of the mass spectrometer and a permeation tube enclosed within the calibrant chamber, wherein the tube contains a calibrant chemical that continuously outgasses the calibrant chemical, and wherein the outgassed calibrant chemical may be introduced to the mass spectrometer for analysis.
In accordance with further embodiments, improved methods are provided for calibrating mass spectrometers comprising coupling a calibrant tube to an inlet of a calibrant chamber within a housing of the mass spectrometer, wherein the calibrant tube is made of permeable material and contains a calibrant chemical that continuously outgasses the calibrant chemical, and introducing the outgassed calibrant chemical to the mass spectrometer for analysis.
The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate several embodiments of the present disclosure and together with the description, serve to explain the principles of the disclosed 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.
As described below, systems and methods consistent with the disclosed embodiments relate to calibrating a mass spectrometer by using an internal calibrant device. The internal calibrant device may include one or more liquid calibrants used to calibrate the accuracy of the mass spectrometer. The internal calibrant device may also include one or more calibrant tubes made of a permeable material. The permeable tube may be filled with a liquid calibrant, which may evaporate through the micropores in the permeable material to form a gas in an internal calibrant chamber. In the example embodiments, the internal calibrant device is configured to be attached inside the mass spectrometer, and a user may insert permeation tubes inside the internal calibrant device. Given this configuration, the permeation tubes are designed, in certain embodiments, to be portable, such that a calibrant material within the device may be appropriately contained and protected.
Mass spectrometer systems consistent with this disclosure also allow for various calibration techniques. As also described in greater detail below, techniques for calibrating the mass scale or relative abundance of a mass spectrometer are disclosed.
User interface device 105 may be any type of interface, such as a display device, for viewing and interacting with an output spectrum generated by mass spectrometer 100 and internal calibrant device 200. User interface device 105 may include any type or combination of input/output devices, such as a display monitor, keyboard, touch screen, and/or mouse. Mass spectrometer 100 may also include a database 104 for storing calibration information used in the disclosed embodiments. In one implementation, database 104 may store a library of spectrum data, such as the National Institute of Standards and Technology's (NIST) library spectra for a variety of known calibrant chemicals. As known in the art, NIST provides a mass spectral reference library for many chemicals, which may include calibrants chosen for use in a mass spectrometer. Other reference spectra may also be contemplated.
In reference to
In one embodiment, internal calibrant device 200 may be configured with a filter near outlet 212. For example, calibrant device may include a filter (such as a glass frit or a membrane (e.g., PDMS)) for preventing contaminants, which may have been introduced into calibrant chamber 202 during the replacement of the calibrant tube 204, from being introduced into the analysis chamber.
Calibrant tube 204 may be formed of a permeable material. For example, tube 204 may be formed of Teflon. Other permeable materials may also be contemplated. In this way, a calibrant sample contained within tube 204 may permeate out of tube 204 and into calibrant chamber 202 during a calibration function. In other words, the calibrant sample may allow vapor to permeate through the micropores of tube 204 regardless of the phase of the material in the tube. As described below, when calibrant device 200 is coupled to mass spectrometer 100, device 200 may then be configured to allow the permeated gas to then flow through outlet 212 of calibrant device 200. As also described below, outlet 212 of device 200 may be coupled to an inlet (not shown) of mass spectrometer 100 to allow the permeated calibrant gas to flow towards an analysis chamber of spectrometer 100 as part of a calibration function.
Permeation tube 204 may contain a calibrant chemical for calibrating mass spectrometer 100 of internal calibrant device 200. Permeation tube 204 may be configured to continuously outgas the calibrant chemical at ambient temperature. Therefore, permeation tube 204 does not need to be heated in order to calibrate the mass spectrometer. In other embodiments, as further disclosed herein, permeation tube 204 may be heated to perform further calibration functions, such as calibrating the abundance scale. In one embodiment, permeation tube 204 may be comprised of Teflon, including Teflon rods crimped onto the ends of permeation tube 204. Other materials that allow outgassing at ambient temperatures are contemplated by this disclosure.
In one embodiment, permeation tube 204 may be secured in chamber 202 through the use of spring 210, or similar resilient member. In this way, tube 204 may be easily expelled from chamber 202 when cover 206 is removed. Spring 210 may also function to press tube 204 against cover 206 to help ensure tube 204 is stable or fixedly located in chamber 202.
While permeation tube 204 may provide a known chemical for calibration of mass spectrometer 100 by using a known calibrant chemical stored in tube 204, the concentration of the gas emitting from tube 204 may be unknown and, thus, only allow calibration of the mass scale but not the abundance scale. To address this possibility, other embodiments are disclosed that provide a known gas concentration from tube 204 in order to calibrate the relative abundance scale of mass spectrometer 100.
Moreover, while illustrative embodiments have been described herein, the scope thereof includes any and all embodiments having equivalent elements, modifications, omissions, combinations (e.g., of aspects across various embodiments), adaptations and/or alterations as would be appreciated by those in the art based on the present disclosure. For example, the number and orientation of components shown in the exemplary systems may be modified. Further, with respect to the exemplary methods illustrated in the attached drawings, the order and sequence of steps may be modified, and steps may be added or deleted.
Embodiments of the present disclosure address one or more of the above-identified drawbacks and needs in the art.
The foregoing description has been presented for purposes of illustration. It is not exhaustive and is not limiting to the precise forms or embodiments disclosed. Modifications and adaptations will be apparent to those skilled in the art from consideration of the specification and practice of the disclosed embodiments. For example, the various components of the system of
Programmable instructions, including computer programs, based on the written description and disclosed embodiments are within the skill of an experienced developer. The various programs or program modules described in this disclosure may be created using any of the techniques known to one skilled in the art or may be designed in connection with existing software. For example, program sections or program modules may be designed in or by means of C#, Java, C++, HTML, XML, CSS, JavaScript, or HTML with included Java applets.
The claims are to be interpreted broadly based on the language employed in the claims and not limited to examples described in the present specification, which examples are to be construed as non-exclusive. Further, the steps of the disclosed methods may be modified in any manner, including by reordering steps and/or inserting or deleting steps.
It is intended, therefore, that the specification and examples be considered as exemplary only. Additional embodiments are within the purview of the present disclosure and claims.
Number | Name | Date | Kind |
---|---|---|---|
3948731 | Weaver | Apr 1976 | A |
4260886 | Grilletto et al. | Apr 1981 | A |
4847493 | Sodal et al. | Jul 1989 | A |
5498545 | Vestal | Mar 1996 | A |
5703360 | Fischer et al. | Dec 1997 | A |
RE37485 | Vestal | Dec 2001 | E |
RE39353 | Vestal | Oct 2006 | E |
7320243 | Perkins et al. | Jan 2008 | B2 |
7385190 | Fischer et al. | Jun 2008 | B2 |
7385191 | McMurtry et al. | Jun 2008 | B1 |
7427750 | Grossenbacher et al. | Sep 2008 | B2 |
7576324 | Grossenbacher et al. | Aug 2009 | B2 |
7618576 | Staats | Nov 2009 | B2 |
7679053 | Schneider et al. | Mar 2010 | B2 |
7750292 | Finlay | Jul 2010 | B2 |
7973277 | Rafferty | Jul 2011 | B2 |
8207496 | Makarov et al. | Jun 2012 | B2 |
8299424 | Camilli | Oct 2012 | B2 |
8304718 | Ouyang et al. | Nov 2012 | B2 |
8461517 | Debono et al. | Jun 2013 | B2 |
8975573 | Rafferty et al. | Mar 2015 | B2 |
20040236603 | Heller et al. | Nov 2004 | A1 |
20050211892 | Shimomura | Sep 2005 | A1 |
20070009970 | Heller et al. | Jan 2007 | A1 |
20070295062 | Wang | Dec 2007 | A1 |
20080067348 | Musselman | Mar 2008 | A1 |
20080067358 | Musselman | Mar 2008 | A1 |
20080067359 | Musselman | Mar 2008 | A1 |
20090057550 | Stults et al. | Mar 2009 | A1 |
20110315552 | Stults et al. | Dec 2011 | A1 |
20130043380 | Correale | Feb 2013 | A1 |
Number | Date | Country | |
---|---|---|---|
20150235826 A1 | Aug 2015 | US |
Number | Date | Country | |
---|---|---|---|
Parent | 13794779 | Mar 2013 | US |
Child | 14603017 | US |