Patent Publication Number: US-7223965-B2

Title: Method, system, and device for optimizing an FTMS variable

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This application claims priority to, and incorporates by reference herein in its entirety, pending provisional application Ser. No. 60/406,857, filed 29 Aug. 2002. 
    
    
     BACKGROUND 
     U.S. Pat. No. 3,937,955 (Comisarow), titled “Fourier transform ion cyclotron resonance spectroscopy method and apparatus”, allegedly cites that a “gas sample is introduced into an ion cyclotron resonance cell enclosed in a vacuum chamber, and ionized. A magnetic field constrains ions to circular orbits. After an optional delay adequate to allow ion-molecule reactions to occur, a pulsed broad-band oscillating electric field disposed at right angles to the magnetic field is applied to the ions. As the frequency of the applied electric field reaches the resonant frequency of various ions, those ions absorb energy from the field and accelerate on spiral paths to larger radius orbits. The excited motion is sensed and digitized in the time domain. The result of the digitization is Fourier transformed into the frequency domain for analysis. If desired, a sequential series of pulsed broad-band oscillating fields can be applied and the resulting change in motion sensed, digitized and accumulated in a sequential manner prior to Fourier transformation.” See Abstract. 
     U.S. Pat. No. 5,264,697 (Nakagawa), titled “Fourier transform mass spectrometer”, allegedly cites that the “present invention relates to a Fourier transform mass spectrometer suitable for analysis of a particular component of a sample gas made of known components, which is adapted so as to prevent the high-frequency electric field applied to the high vacuum cell from deviating due to a variation in the long cycle of the static magnetic field applied to the high vacuum cell, which is characterized in that the variation in the long cycle of the magnetic field applied is detected as a deviation in the ion cyclotron resonance frequency of the particular component and the high frequency for forming the high-frequency electric field is made variable in accordance with the variation in the ion cyclotron resonance frequency.” See Abstract. 
     U.S. Patent Application No. 20020190205 (Park), titled “Method and apparatus for fourier transform mass spectrometry (FTMS) in a linear multipole ion trap” allegedly cites a “means and method whereby ions from an ion source can be selected and transferred via a multipole analyzer system in such a way that ions are trapped and analyzed by inductive detection. Ions generated at an elevated pressure are transferred by a pump and capillary system into a multipole device. The multipole device is composed of one analyzing section with two trapping sections at both sides. When the proper voltages are applied, the trapping sections trap ions within the analyzing region. The ions are then detected by two sets of detection electrodes.” See Abstract. 
     SUMMARY 
     Certain exemplary embodiments provide a method for automatically optimizing an FTMS. The method can comprise a plurality of potential activities, some of which can be automatically, repeatedly, and/or nestedly performed, and some of which follow. A composite amplitude relating to an FTMS spectral output signal for each of a plurality of FTMS samples can be obtained, each of the samples having an substantially similar number of molecules. The FTMS variable can be changed repeatedly and the composite amplitude re-obtained until a value of an optimization parameter substantially converges, the optimization parameter being a function of the composite amplitude. 
     Certain exemplary embodiments provide a method for performing repeated quantitative analysis using an FTMS. The method can comprise a plurality of potential activities, some of which can be automatically, repeatedly, and/or nestedly performed, and some of which follow. From at least one predetermined sample source, a sample can be obtained and provided to an FTMS. At least one variable for the FTMS can be optimized. A plurality of outputs can be acquired from the FTMS. An identity of at least one predominant ionic component of the sample can be ascertained. A quantity of at least one predominant ionic component can be determined. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       A wide array of potential embodiments can be better understood through the following detailed description and the accompanying drawings in which: 
         FIG. 1  is simplified diagram of an exemplary embodiment of a trapped ion cell; 
         FIG. 2  is a block diagram of an exemplary embodiment of a general FTMS system; 
         FIG. 3  is a block diagram of an exemplary embodiment of an information device; 
         FIG. 4  is a flow chart of an exemplary embodiment of a method for optimizing an FTMS variable; 
         FIG. 5  is a flow chart of an exemplary embodiment of a method for analyzing a sample using an FTMS; 
         FIG. 6  is an exemplary plot of intensity versus time; 
         FIG. 7  is an exemplary plot of intensity versus scan number; 
         FIG. 8  is an exemplary plot of intensity versus mass-to-charge ratio; 
         FIG. 9  is an exemplary plot of intensity versus mass-to-charge ratio; 
         FIG. 10  is an exemplary plot of a fermenter mass correction; and 
         FIG. 11  is an exemplary plot of concentration versus time. 
         FIG. 12  is an exemplary plot of intensity versus concentration; and 
         FIG. 13  is an exemplary plot of intensity versus scan number. 
     
    
    
     DETAILED DESCRIPTION 
     Mass spectrometry, also called mass spectroscopy, is an instrumental approach that allows for the mass measurement of molecules. Nearly every mass spectrometer includes: a vacuum system; a sample introduction device; an ionization source; a mass analyzer; and an ion detector. A mass spectrometer determines the molecular weight of chemical compounds by ionizing, separating, and measuring molecular ions according to their mass-to-charge ratio (m/z) and/or the ions&#39; “molecular mass” (which is sometimes simply referred to Gas an ion&#39;s “mass”). The ions are generated in the ionization source by inducing either the loss or the gain of a charge (e.g. electron ejection, protonation, or deprotonation). Once the ions are formed in the gas phase they can be directed into a mass analyzer, separated according to mass and then detected. The result of ionization, ion separation, and detection is a mass spectrum that can provide molecular weight or even structural information. 
     Mass spectrometers can be useful in a wide range of applications in the analysis of inorganic, organic, and bio-organic chemicals. Among the many examples include dating of geologic samples; sequencing of peptides and proteins; studies of noncovalent complexes and immunological molecules; DNA sequencing; analysis of intact viruses; drug testing and drug discovery; process monitoring in the petroleum, chemical, and pharmaceutical industries; surface analysis; and the structural identification of unknowns. 
     Certain exemplary embodiments comprise a mass spectrometer that can use the Fourier transform ion cyclotron resonance (FTICR) technique (also referred to herein as “Fourier transform mass spectrometry” or “FTMS”) to determine the molecular mass of ions. 
     When a gas phase ion at low pressure is subjected to a uniform static magnetic field, the resulting behavior of the ion can be determined by the magnitude and orientation of the ion velocity with respect to the magnetic field. If the ion is at rest, or if the ion has only a velocity parallel to the applied field, the ion experiences no interaction with the field. 
     If there is a component of the ion velocity that is perpendicular to the applied field, the ion will experience a force that is perpendicular to both the velocity component and the applied field. This force results in a circular ion trajectory that is referred to as ion cyclotron motion. In the absence of any other forces on the ion, the angular frequency of this motion is a simple function of the ion charge, the ion mass, and the magnetic field strength, as shown in the following Equation 1:
 
omega= qB/m  
         where: omega=angular frequency (radians/second)   q=ion charge (coulombs)   B=magnetic field strength (tesla)   m=ion mass (kilograms)       

     An FTMS can exploit the fundamental relationship described in Equation 1 to determine the mass of ions by inducing large amplitude cyclotron motion and then determining the frequency of the motion. 
     The ions to be analyzed can first be introduced to the magnetic field with minimal perpendicular (radial) velocity and dispersion. The cyclotron motion induced by the magnetic field can effect radial confinement of the ions; however, ion movement parallel to the axis of the field is typically constrained by a pair of “trapping” electrodes. These electrodes typically consist of a pair of parallel-plates oriented perpendicular to the magnetic axis and disposed on opposite ends of the axial dimension of initial ion population. These trapping electrodes can be maintained at a potential that is of the same sign as the charge of the ions and of sufficient magnitude to effect axial confinement of the ions between the electrode pair. 
     The trapped ions then can be exposed to an electric field that is perpendicular to the magnetic field and oscillates at the cyclotron frequency of the ions to be analyzed. Such a field is typically created by applying appropriate differential potentials to a second pair of parallel-plate “excite” electrodes oriented parallel to the magnetic axis and disposed on opposing sides of the radial dimension of the initial ion population. 
     If ions of more than one molecular mass are to be analyzed, the frequency of the oscillating field can be swept over an appropriate frequency range, or be comprised of an appropriate mix of individual frequency components. When the frequency of the oscillating field matches the cyclotron frequency for a given ion mass, all of the ions of that mass will experience resonant acceleration by the electric field and the radius of their cyclotron motion will increase. 
     During this resonant acceleration, the initial radial dispersion of the ions is essentially unchanged. The excited ions will tend to remain grouped together on the circumference of the new cyclotron orbit, and to the extent that the dispersion is small relative to the new cyclotron radius, their motion will tend to be mutually in phase or coherent. If the initial ion population consisted of ions of more than one molecular mass, the acceleration process can result in a multiple isomass ion bundles, each orbiting at its respective cyclotron frequency. 
     The acceleration can be continued until the radius of the cyclotron orbit brings the ions near enough to one or more detection electrodes to result in a detectable image charge being induced on the electrodes. Typically these “detect” electrodes will consist of a third pair of parallel-plate electrodes disposed on opposing sides of the radial dimension of the initial ion population and oriented perpendicular to both the excite and trap electrodes. Thus the three pairs of parallel-plate electrodes employed for ion trapping, excitation, and detection can be mutually perpendicular and together can form a closed box-like structure referred to as a trapped ion cell. Other cell designs are possible, including, for example, cylindrical cells. 
       FIG. 1  is simplified diagram of an exemplary embodiment of a trapped ion cell  1000 , comprising excite electrodes  1010 , trap electrodes  1020 , and detect electrodes  1030 . 
     As the coherent cyclotron motion within the cell causes each isomass bundle of ions to alternately approach and recede from a detection electrode  1030 , the image charge on the detection electrode can correspondingly increase and decrease. If the detection electrodes  1030  are made part of an external amplifier circuit (not shown), the alternating image charge will result in a sinusoidal current flow in the external circuit. The amplitude of the current is proportional to the total charge of the orbiting ion bundle and is thus indicative of the number of ions present. This current can be amplified and digitized, and the frequency data can be extracted by means of a time to frequency transform, such as the Fourier transform, which can be provided by computer employing a Fast Fourier transform algorithm or the like. Finally, the resulting frequency spectrum can be converted to a mass spectrum using the relationship in Equation 1. 
     As used herein, the term “ion” means an atom or a group of atoms that has acquired a net electric charge by gaining or losing one or more electrons or gaining or losing one or more protons. An ion can be formed in numerous manners, including by breaking up a molecule of a gas under the action of an electric current, of ultraviolet and certain other rays, and/or of high temperatures. 
     As used herein, the term “species” means the compositional identity of a substance, such as an ion, molecule, or atom. For example, of 1000 molecules in a typical air sample, we might expect the molecular species of about 781 of those molecules to be nitrogen or N2, the molecular species of about 209 of those molecules to be oxygen or O2, and/or the molecular species of about 9 of those molecules to be argon or Ar. 
     As used herein, the term “ionic component” means an ionic species. 
     As used herein, the terms “composite” means a combination of measurements. For example, if a length of one board is 2 feet, and the length of another is 3 feet, then the composite length of the two boards when laid end-to-end is 5 feet, assuming that each board&#39;s length has a weighting factor of 1. A composite need not be a linear combination. 
     As used herein, the term “mass spectrum” means a plot having molecular mass or a function thereof (e.g., mass-to-charge ratio (m/z), ion mass, etc.) as the independent variable. The dependent variable is typically a quantitative measure, such as abundance, relative abundance, intensity, concentration, number of ions, number of molecules, number of atoms, counts/millivolt, counts, etc. For example, in the context of ions, a mass spectrum typically presents mass-to-charge ratio (m/z) as the independent variable, where m is the mass of the ion species and z is the charge of the ion species, and the dependent variable is most commonly an abundance of each molecular ion and/or its fragment ions. 
     As used herein, unless described otherwise, the term “quantity” means any quantitative measure. For example, the quantity of an ion of a particular species can be its abundance, relative abundance, intensity, concentration, and/or count, etc. 
     As used herein, the term “relative abundance”, in the context of ions, means the number of times an ion of a particular m/z ratio is detected. For example, assignment of relative abundance can be obtained by assigning the most abundant ion species a relative abundance of 100%. All other ion species can be shown as a percentage of that most abundant ion species. 
     As used herein, the term “predominant ionic component” means a most abundant ion species of all ionic species under consideration. 
     As used herein, the term “eject” means to make ions of a particular ion species undetectable. For example ejection can occur via physically removing all ions of a currently and apparently predominant ion species from the detection region of the FTMS cell at a rate sufficient to prevent detection. This can be useful so that ions of less abundant species can be more easily detected. 
     A mass spectrum can be used to identify the ion species present in a sample. For example, a mass spectrum might reveal that a sample contains nitrogen, oxygen, carbon dioxide, and argon ions. Moreover, a sufficiently reproducible mass spectrum can be used to quantify the relative numbers of ions of each ion species present in the sample. 
     Knowledge of a sample&#39;s ion species and their quantities can be very useful for sample analysis, process monitoring, and/or process control. Additional applications can include pharmaceutical quality control; precision process monitoring in the flavors and fragrances industry; flavor and smell chemistry; biochemistry; protein, peptide, and DNA analyses; biopolymer sequencing; protein mass fingerprinting; studies of inherited metabolic diseases; viral identification; drug metabolism; analysis of respiratory gases; combinatorial chemistry; environmental studies; water analysis; soil remediation studies; geochemistry; geochronology; fossil studies; petroleum exploration; petrochemical production; atmospheric chemistry; space exploration; the monitoring of public spaces for the introduction of noxious chemical and/or biological agents; explosives and/or contraband detection; and/or forensics, etc. 
       FIG. 2  is a block diagram of an exemplary embodiment of a general implementation of an FTMS system  2000 , which can comprise various subsystems to perform certain methods and/or processes described herein, such as the analytical sequence described above. A trapped ion cell  2100 , such as the trapped ion cell  1000  of  FIG. 1 , can be contained within a vacuum system  2200  comprised of a chamber  2220  which can be evacuated by an appropriate pumping device  2210 . The chamber can be situated within a magnet structure  2300  that can impose a homogeneous static magnetic field over the dimension of the trapped ion cell  2100 . While magnet structure  2300  is shown in  FIG. 2  as a permanent magnet, such as a 1 Tesla SmCO5 utility-free magnet, a superconducting magnet may also be used to provide the magnetic field. 
     Pumping device  2210  can be an ion pump that is an integral part of the vacuum chamber  2220 . Such an ion pump can use the same magnetic field from magnet structure  2300  as is used by the trapped ion cell  2100 , can operate at about 6.5 kV, and/or can automatically provide and/or maintain a vacuum in vacuum chamber  2220  of as low as about 10 −10  Torr. Vacuum chamber  2220  can be automatically maintained at about 60 C and/or can be heated to a user-selectable temperature up to about 220 C. 
     The sample to be analyzed can be admitted to the vacuum chamber  2220  by a gas phase sample introduction system  2400  that can, for example, consist of a gas chromatograph column and/or a leak valve, such as a pulsed mass spectrometer leak valve with controlled energy closure and/or a pulsed sampling valve, etc. If a valve is used, inlet conditions can include a pressure of between about 20 torr and about 30 psia; a user-selectable temperature between about 25 C and about 160 C; filtration down to about 1 micron; and/or a flowrate between about 0.5 ml/min to about 200 ml/min. 
     The sample introduction system  2400  can have the ability to automatically select from among multiple potential sample sources  2410 , and can introduce a sample having a user-adjustable or automatically-adjustable volume of from about a 2 picoliters to about a 200 picoliters. Because the amounts of gas introduced via the valve during the valve pulses can be substantially Gaussian-distributed with a standard deviation of about 10% or less, each sample can have a substantially similar number of molecules. The sampled molecules can be automatically converted to charged ions within the trapped ion cell  2100  by a means for ionizing  2520 , such as a gated electron beam passing through the cell  2100 , a photon source, chemical ionizer, negative ionizer, electron ionization, electrospray ionization (ESI), matrix assisted laser desorption/ionization (MALDI), atmospheric pressure chemical ionization (APCI), fast atom bombardment (FAB), and/or inductively coupled plasma (ICP). Alternatively, the sample molecules can be created external to the vacuum chamber  2220  by any one of many different techniques, including any means for ionizing, and then injected along the magnetic field axis into the chamber  2220  and trapped ion cell  2100 . Prior to injection, ions can encounter an ion guide, such as a quadrupole ion guide and/or an RF quadrupole ion guide. 
     Once inside the ion cell  2100 , the resulting cyclotron motion can be automatically measured for each packet of “exact” mass ions via a time domain measurement. The measured ions can serve as a surrogate for the molecules in the sample. Any of various transforms, such as a Fourier transform, can be automatically applied to convert the measurement data from the time domain to the frequency domain. Because frequency is related to mass by a known non-linear inverse proportional relationship, a very accurate mass value can be automatically determined. 
     Various electronic circuits can be used to automatically monitor, log, and/or control any of the operations or functions of the FTMS system, such as those described above, and can be contained within an electronics package  2600  which can be controlled by, and/or implemented on, an information device  2700 , such as a computer based data system, such as a Windows NT/2000 platform. Information device  2700  also can be employed to automatically perform reduction, manipulation, display, and/or communication of the acquired signal data, such as the various described transforms. Via a network  2800  (e.g., a public, private, circuit-switched, packet-switched, virtual, radio, telephone, cellular, cable, DSL, satellite, microwave, AC power, ethernet, ModBus, OPC, LAN, WAN, Internet, intranet, wireless, Wi-Fi, BlueTooth, Airport, 802.11a, 802.11b, 802.11g, etc., network), one or more remote information devices  2900  can securely monitor, control, and/or communicate with information device  2700  and/or electronics package  2600 . 
     Certain exemplary embodiments of FTMS system  2000  can automatically log data to a database, spreadsheet file, printer, analog output device, etc. Certain exemplary embodiments of FTMS system  2000  can automatically provide an alarm and/or notification if a particular event occurs, such as the detection of a particular ion, a change of a concentration and/or intensity of component above or below a predetermined level, a failed analysis, etc. 
     Certain exemplary embodiments of FTMS system  2000  can interface with a wide variety of inlets, direct insertion probes, membrane introduction mass spectrometry (MIMS) probes, and/or evolved gas analysis (EGA) devices, such as the thermo-gravimetric and/or trap &amp; purge units. 
     Certain exemplary embodiments of FTMS system  2000  can automatically switch from a first sample stream to a second sample stream and introduce a sample from the second sample stream while still analyzing a sample from the first sample stream. Thus, up to about 64 sample streams can be multiplexed and/or controlled. This can potentially substantially improve overall measurement speed, particularly if purging of the first sample stream is a relatively long process. 
     Certain exemplary embodiments of FTMS system  2000  can automatically provide a complete analysis based on an extremely small amount of sample. For example, certain exemplary embodiments of FTMS system  2000  can automatically measure a mass range of from about 2 to about 1000 m/z, including all values therebetween, such as for example about 6.0001, 12.47, 54.94312, 914.356, etc., and including all subranges therebetween, such as for example from about 2 to about 12, from about 6 to about 497, etc. 
     Certain exemplary embodiments of FTMS system  2000  can automatically provide a mass determination to at least 3 significant figures to the right of the decimal point or down to at least about 1/1000 th  of an m/z. 
     Certain exemplary embodiments of FTMS system  2000  can automatically provide a mass measurement resolution of from about 1 to about 20,000, including all values and subranges therebetween, when measured at about 100 m/z to about 120 m/z, including all values and subranges therebetween. 
     Certain exemplary embodiments of FTMS system  2000  can automatically provide a concentration measurement from 100 percent down to about 0.1 to about 1 ppm, including all values therebetween such as about 0.2, 0.51, 0.8, 1, 2.2, 5, 10, 25.6 ppm, etc., including all subranges therebetween, such as from about 1 to about 10 ppm, from about 100 ppm to about 1 percent, from about 1percent to about 100 percent, etc. 
     Certain exemplary embodiments of FTMS system  2000  can automatically provide a mass accuracy from about ±0.0002 m/z to about ±0.001 m/z, including all values and subranges therebetween, when measured at about 28 m/z. 
     Certain exemplary embodiments of FTMS system  2000  can automatically provide a mass repeatability from about 0.001 m/z (about 35 ppm) to about 0.0025 m/z (about 90 ppm), including all values and subranges therebetween, when measured at about 28 m/z. 
     Certain exemplary embodiments of FTMS system  2000  can automatically provide a linearity of from about 1 to about 3 orders of magnitude, including all values and subranges therebetween. 
       FIG. 3  is a block diagram of an exemplary embodiment of an information device  3000 , which can represent any information device  2700 ,  2900  of  FIG. 2 . Information device  3000  can include well-known components such as one or more network interfaces  3100 , one or more processors  3200 , one or more memories  3300  containing instructions  3400 , and/or one or more input/output (I/O) devices  3500 , etc. 
     As used herein, the term “information device” means any device capable of processing information, such as any general purpose and/or special purpose computer, such as a personal computer, workstation, server, minicomputer, mainframe, supercomputer, computer terminal, laptop, wearable computer, and/or Personal Digital Assistant (PDA), mobile terminal, Bluetooth device, communicator, “smart” phone (such as a Handspring Treo-like device), messaging service (e.g., Blackberry) receiver, pager, facsimile, cellular telephone, a traditional telephone, telephonic device, a programmed microprocessor or microcontroller and/or peripheral integrated circuit elements, an ASIC or other integrated circuit, a hardware electronic logic circuit such as a discrete element circuit, and/or a programmable logic device such as a PLD, PLA, FPGA, or PAL, or the like, etc. In general any device on which resides a finite state machine capable of implementing at least a portion of a method, structure, and/or or graphical user interface described herein may be used as an information device. An information device can include well-known components such as one or more network interfaces, one or more processors, one or more memories containing instructions, and/or one or more input/output (I/O) devices, one or more user interfaces, etc. 
     As used herein, the term “network interface” means any device, system, or subsystem capable of coupling an information device to a network. For example, a network interface can be a telephone, cellular phone, cellular modem, telephone data modem, fax modem, wireless transceiver, ethernet card, cable modem, digital subscriber line interface, bridge, hub, router, or other similar device. 
     As used herein, the term “processor” means a device for processing machine-readable instruction. A processor can be a central processing unit, a local processor, a remote processor, parallel processors, and/or distributed processors, etc. The processor can be a general-purpose microprocessor, such the Pentium III series of microprocessors manufactured by the Intel Corporation of Santa Clara, Calif. In another embodiment, the processor can be an Application Specific Integrated Circuit (ASIC) or a Field Programmable Gate Array (FPGA) that has been designed to implement in its hardware and/or firmware at least a part of an embodiment disclosed herein. 
     As used herein, a “memory device” means any hardware element capable of data storage. Memory devices can comprise non-volatile memory, volatile memory, Random Access Memory, RAM, Read Only Memory, ROM, flash memory, magnetic media, a hard disk, a floppy disk, a magnetic tape, an optical media, an optical disk, a compact disk, a CD, a digital versatile disk, a DVD, and/or a raid array, etc. 
     As used herein, the term “firmware” means machine-readable instructions that are stored in a read-only memory (ROM). ROM&#39;s can comprise PROMs and EPROMs. 
     As used herein, the term “I/O device” means any device capable of providing input to, and/or output from, an information device. An I/O device can be any sensory-oriented input and/or output device, such as an audio, visual, tactile (including temperature, pressure, pain, texture, etc.), olfactory, and/or taste-oriented device, including, for example, a monitor, display, keyboard, keypad, touchpad, pointing device, microphone, speaker, video camera, camera, scanner, and/or printer, potentially including a port to which an I/O device can be attached or connected. 
     As used herein, the term “user interface” means any device for rendering information to a user and/or requesting information from the user. A graphical user interface can include one or more elements such as, for example, a window, title bar, panel, sheet, tab, drawer, matrix, table, form, calendar, outline view, frame, dialog box, static text, text box, list, pick list, pop-up list, pull-down list, menu, tool bar, dock, check box, radio button, hyperlink, browser, image, icon, button, control, dial, slider, scroll bar, cursor, status bar, stepper, and/or progress indicator, etc. An audio user interface can include a volume control, pitch control, speed control, voice selector, etc. 
     In certain exemplary embodiments, a user interface of an information device  3000  of FTMS system  2000  (shown in  FIG. 2 ) can provide one or more elements for parameter adjustment, parameter observation, and/or access and/or comparison of mass spectra. In certain exemplary embodiments, a user interface can provide a live operational status window of important analytical and/or operational parameters; simultaneous display of current and/or previous mass spectra, potentially in addition to the original time-domain measurements; side-by-side comparison of two-component trend plots; control of process instrumentation operation on-the-fly; and/or control of multiple FTMS systems. 
       FIG. 4  is a flow chart of an exemplary embodiment  4000  of a method for automatically substantially optimizing one or more FTMS variables, such as for example, ionizing current flux or beam current density which, along with the gas pulse, can determine the number of ions present in the cell of the FTMS); ionizing stage trapping plate voltage; detection stage trapping plate voltage; and/or ion location in the FTMS cell, etc. 
     Prior to optimization, several preliminary activities can occur. For example at activity  4100  of method  4000 , an automated FTMS optimization system can initialize its variables, such as any operational or programming variables. 
     At activity  4200 , the system can request and/or receive user input regarding a sample valve setting (e.g. voltage) that causes a substantially fixed amount (e.g., number of molecules) of gas to be introduced into the FTMS cell, and a chosen starting ionizing current flux. These two parameters—valve voltage and flux—together can determine the initial number of charges formed inside the cell. At activity  4300 , the system can create and load a timed series of operational events (according to an event table or schedule) that include a data acquisition scan. 
     At activity  4400 , the system can perform a sufficient number of data acquisitions to allow the system to stabilize, that is, reach a stable operating state. The acquired data include a current signal having a measured amplitude and time, which can be converted via Fourier transform to a dataset of amplitude and frequency, and which can be additionally converted, typically via applying a linear correction curve, to a dataset of amplitude and a mass function (e.g., molecular mass, mass-to-charge ratio (m/z), etc.). Each ion species present in the sample will generate a characteristic frequency that depends on the molecular mass of the ion species and the magnetic field applied to the cell and an amplitude that depends on the quantity of that particular ion species present in the cell. Thus, when amplitude is plotted versus frequency, multiple amplitude peaks will occur, each representative of a particular ion species. The values of these amplitude peaks, or mass-corrected amplitude peaks, can be mathematically combined, such as via summing, to arrive at a composite amplitude. Note that the composite amplitude can be formed by applying a weighting factor to one or more of the frequency-domain amplitudes or the mass-corrected amplitudes of the constituent ion species. Thus, if a weighting factor of one is applied to the amplitudes of the three most predominant ion species, and a weighting factor of zero is applied to the amplitudes of the remaining ion species, the composite amplitude will represent the summed amplitudes of the three most predominant species. 
     At activity  4500 , the system can select which FTMS variable to substantially optimize, based upon for example, user input, an optimization iteration loop count, and/or a preprogrammed parameter. The system can also select an initial value for the selected FTMS variable. 
     At activity  4600 , the system can acquire FTMS output data, such as the amplitude, time, frequency, and/or a mass function of the output signal, and an optimization parameter, such as a composite amplitude of the output signal, or the variance in that composite amplitude. This data acquisition can repeat for a predetermined (e.g., user-chosen or system-chosen) number of iterations, each acquisition comprising a user specified number of spectra acquisitions, each data acquisition containing both amplitude and frequency or mass data. 
     At activity  4700 , the system can change the value of the FTMS variable. 
     Activities  4600  and  4700  can repeat until, at activity  4800 , the system can determine that the optimization parameter has substantially converged as a result of the most recent change in the value of the FTMS variable, thereby indicating that a substantially optimal value has been found for the FTMS variable. 
     At activity  4900 , results such as the FTMS variable, its values, the optimization parameter, and/or its values, etc., can be output to for example, a file, memory device, I/O device, control system, and/or user interface, etc. The output results can be available for other methods. Then, the system can repeat activities  4500  through  4900  until all FTMS variables have been optimized. 
     Numerous FTMS variables can be optimized. For example, ionizing current flux can be substantially optimized by substantially maximizing the value of the ionizing current flux within the range that changes to the ionizing current flux are substantially linear, that is, by finding a maximum linearly-responsive ionizing current flux. Thus, in effect, the linearly-responsive ionizing current flux is the FTMS variable to be optimized. 
     For example, the composite amplitudes can be compared after doubling the ion current flux and before doubling to determine if the FTMS cell is responding substantially non-linearly, which means the cell has too many ions present, and which can be indicated by a change in total signal current or composite amplitude of a factor of less than about 1.8 to about 1.999, including all values therebetween, such as for example, about 1.832, 1.85, 1.9, 1.977, etc., and all subranges therebetween, such as for example, about 1.88 to about 1.93, etc., or greater than about 2.001 to about 2.2, including all values therebetween, such as for example, about 2.003, 2.05, 2.1, 2.177, etc., and all subranges therebetween, such as for example, about 2.07 to about 2.12, etc. In other words, non-linearity can be indicated when a change in the optimization parameter is less than about 90 percent to about 99.95 or greater than about 100.05 percent to about 110 percent, including all values and subranges therebetween, of a change in the ionization current flux. 
     If too many ions are present in the cell, the system can reduce the ionizing current flux by, for example, a factor of about 20 percent to about 80 percent, including all values therebetween, such as for example, about 0.25, 0.333, 0.4481, 0.5, 0.667, etc., and all subranges therebetween, such as for example, about 0.42 to about 0.60, etc. and then continue the experiment. If not, the system can increase the ionizing current by, for example, a factor of about 1.2 to about 3, including all values therebetween, such as for example, about 1.55, 2, 2.4973, etc., and all subranges therebetween, such as for example, about 1.92 to about 2.1, etc., and then check the linearity again. This pattern can be repeated as necessary until the optimization parameter substantially converges (e.g., reaches a maximum value at which substantial linearity is maintained), thereby indicating that a substantially optimal ionizing current flux value has been found. 
     The system can attempt to optimize the voltage on the trapping plates during the ionizing stage of the experiment. To do this, in certain exemplary embodiments, the system can perform several sub-activities. For example, the system can decrease the voltage from a user-chosen starting value and collect multiple composite amplitudes. Also, the system can compare the optimization parameter, such as the variance, between the composite amplitude associated with the previous voltage value and the composite amplitude associated with the current voltage value. Moreover, the system can decide whether the optimization parameter considered over the number of spectra measured, is diverging or converging (e.g., is increasing or decreasing) and take appropriate action to continue adjusting the voltage until a substantially optimum value for the voltage is found, based on convergence of the optimization parameter (e.g., a minimal variance). 
     The system can apply a similar algorithm to the trapping voltages present during the detection stage of the experiment to substantially converge the optimization parameter (e.g., minimize the totaled average composite spectral amplitude variance) and thereby determine a substantially optimum value for this voltage. 
     The system can substantially optimize the location of the ions relative to the fixed detection plates prior to detection in the cell, by substantially converging the optimization parameter (e.g., substantially maximizing the intensity (composite amplitude) of the total signal current. 
     Note that the substantial optimization of other FTMS variables is possible and contemplated, such as for example, the time delay between sample introduction and detection, the size of gas pulse introduced into the FTMS by the sampling valve, the wait time between individual acquisitions, and/or any function of a measured FTMS variable. Moreover, an optimal sequence to optimizing any chosen group of FTMS variables can be determined and utilized. 
     Moreover, although the optimization parameters described herein have involved either composite amplitude itself or variance in composite amplitude, other statistically-oriented optimization parameters, which can be a function of composite amplitude, are possible and contemplated. For example, at least the following optimization parameters are possible: composite of the average amplitude of the 3 most abundant species, variance of a predominant species amplitude, average composite amplitude, mode of composite amplitude, mode of variance of composite amplitude, variance of maximum composite amplitude, variance of minimum composite amplitude, variance of a time-weighted composite amplitude, second central moment, a bias-corrected variance, covariance, correlation, root mean square, mean deviation, sample variance, variance distribution, standard deviation, standard deviation of maximum composite amplitude, standard deviation of minimum composite amplitude, standard deviation of a time-weighted composite amplitude, and/or spread, etc. 
     Thus, the value of an FTMS variable can be substantially optimized by substantially converging on a convergence target, such as a value and/or range (e.g., substantially converging on a local or absolute minima, maxima, asymptote, and/or inflection point, etc.; etc.) associated with an optimization parameter thereof via repeated changing of the value of the FTMS variable to be optimized. The convergence target can be predetermined or found on-the-fly. 
     For example, optimization can be deemed to occur when, upon changing an FTMS variable, a variance in composite amplitude decreases to within about 2 percent or some other predetermined range. As another example, optimization of an FTMS variable can be deemed to occur when, upon repeatedly changing values of the FTMS variable, the resulting composite amplitude is substantially maximized at a particular, on-the-fly-determined value of the FTMS variable. As yet another example, optimization of an FTMS variable can be deemed to occur when, upon repeatedly changing values of the FTMS variable, an average of the resulting composite amplitudes is substantially minimized. 
       FIG. 5  is a flow chart of an exemplary embodiment  5000  of a method for automatically analyzing a sample using an FTMS. Via method  5000 , an FTMS system can automatically exchange the dynamic range in a quantitative FTMS experiment. That is, the FTMS system can extend the 3 order of magnitude dynamic range of a non-optimized FTMS system to cover a wider range (e.g., from 100% to PPM (6 orders of magnitude)) by dividing up that range into multiple experiments (e.g., 3 experiments) which each cover predetermined orders of magnitude (e.g. 2 orders of magnitude). 
     For example, Experiment 1 can address components (i.e., ion species) that are present from approximately 1% to approximately 100%, Experiment 2 can address components that are present from approximately 100 PPM to approximately 10000 PPM, and Experiment 3 can address components that are present from approximately 1 PPM to approximately 100 PPM. 
     After each experiment is designed and substantially optimized individually (such as via the above-described automated FTMS optimization process of method  4000 ), the results can be transferred to an automated FTMS analysis process of method  5000 , and a combined analysis method can be created. Running method  5000  can produce a complete quantitative analysis over the range the system is capable of analyzing with little or no operator intervention. 
     To implement method  5000 , prior to analysis, several preliminary activities can occur. For example at activity  5100  of method  5000 , an automated FTMS analysis system can initialize its variables, such as any operational or programming variables. At activity  5200 , the system can obtain from the user a number of analysis cycles and number of spectra to collect for each cycle. 
     At activity  5300 , using an automated FTMS optimization process, such as that of method  4000 , the system can substantially optimize any number of FTMS variables, such as the ionizing current flux, set the FTMS variables to their optimal values, and/or determine a corresponding valve voltage and set the valve to that voltage value. 
     At activity  5400 , the system can create and load a list of timed operational events (e.g., at least one event table or schedule) that comprises a data acquisition scan, the list including any appropriate analysis parameters, FTMS variables, factors for determining composite amplitudes, optimization parameters, convergence values and/or ranges, components, calibrations, lock masses, etc. 
     At activity  5500 , the system can acquire data for an experiment by collecting the user-chosen number of spectra, each consisting of the user chosen number of repeated acquisitions, each data acquisition containing time series data convertible to spectral data containing both amplitude and frequency data. 
     At activity  5600 , the system also can process the collected datasets to obtain spectral data; identify qualitative data associated with the predominant ion species (e.g., the identity of the ionic components of the sample, identity of the sample, chemical structure of the sample, etc.); determine quantitative data associated with the predominant ion species (e.g., the fraction, concentration, abundance, relative abundance, and/or relative percentage, etc., of the ion species in the sample, etc.); and/or determine ejection voltages need to eject those predominant ion species. 
     In certain exemplary embodiments of an FTMS system, ejection can occur via exciting these ions sufficiently at their resonant frequency to cause them to spin into and/or beyond the cell&#39;s detection plates, thereby preventing detection. Once a predominant ion species is ejected, it will not be detected. Therefore, the cell can be loaded with substantially more ions, including more of the non-predominant ions, thereby increasing the apparent concentration and the actual detectability of those non-predominant ions. 
     At activity  5700 , the system can output the acquired and processed data, such as to a file, memory device, I/O device, control system, and/or user interface so they can be available for other methods. 
     At activity  5800 , the system can then perform each of the next experiments in turn until all experiments have been completed, by first performing activities  5300  and  5400 , during which the ionizing current flux is set to a next level set point and the valve to a next valve voltage; setting the ejection voltages needed to eject all ion species determined to be predominant in the previous experiment(s); and then performing activities  5500  through  5700 . 
     At activity  5900 , the system can monitor for changes or non-changes in the quantity of the detected ion species by repeating the multiple experiments for a predetermined time, a predetermined number of repetitions, continuously, and/or until a predetermined change and/or quantity is detected. Prior to each repetition, the identity of the predominant ion species and their associated ejection voltages can be cleared so no carryover between repetitions occurs. 
       FIG. 6  is exemplary plot  6000  of intensity versus time. Plot  6000  illustrates actual real time data generated by an exemplary embodiment of an FTMS analysis system based on sampling from a proprietary pilot plant run undergoing development. The system detected four components to the sample, including one unexpected material being created in the pilot plant about which the owner of the pilot plant had no awareness until use of the FTMS analysis system. 
       FIG. 7  is an exemplary plot  7000  of intensity versus scan number. Plot  7000  comprises scan periods  7100  through  7800  that graphically illustrate the actual impacts of the optimization activities of method  4000  on an FTMS sample containing air. Note that the activities of method  4000  are simultaneously completed for each of the plotted components, namely argon, nitrogen, and oxygen. 
     The illustrated scan periods of plot  7000  can correspond to certain embodiments of the optimization activities of method  4000  as shown in Table 1, below: 
     
       
         
           
               
             
               
                 TABLE 1 
               
             
            
               
                   
               
               
                 Correspondence of Plot 7000 to Method 4000 
               
            
           
           
               
               
            
               
                 Scan 
                   
               
               
                 Period 
                 Activity 
               
               
                   
               
               
                 7100 
                 4400 
               
               
                 7200 
                 4700 after initial doubling of the ionization current flux 
               
               
                 7300 
                 4700 after doubling the flux of period 7200 
               
               
                 7400 
                 4700 after doubling the flux of period 7300 
               
               
                 7500 
                 4800 after halving the flux of period 7400 
               
               
                 7600 
                 4500–4800 (for trap voltage during the ionization stage, 
               
               
                   
                 holding the flux of period 7500) 
               
               
                 7700 
                 4500–4800 (for trap voltage during the detection stage) 
               
               
                 7800 
                 4500–4800 (for ion location in the cell) 
               
               
                   
               
            
           
         
       
     
       FIG. 8  is an exemplary plot  8000  of intensity versus mass-to-charge ratio (m/z). The data shown on plot  8000  originated from an FTMS system output that was transformed from the time domain to the frequency domain, and then transformed to the mass domain. The range of masses illustrated is from about 16.99 to about 17.06 m/z. Within the illustrated range are two peaks  8100  and  8200 , with peak  8100  occurring at about 17.0027 m/z, which corresponds to the mass of moisture or an hydroxyl ion (OH), and peak  8200  occurring at about 17.0265 m/z, which corresponds to the mass of an ammonia ion (NH3). 
       FIG. 9  is an exemplary graphical user interface  9000  featuring several plots of intensity versus mass-to-charge ratio (m/z) for an actual sample of fermenter headspace. Plot  9100  shows an initial plot, with N2, CO2, and argon the predominant components. Plot  9200  shows a plot after the dominant components have been substantially ejected. Thus,  FIG. 9  illustrates that by selectively ejecting ions during the ionization phase of the analysis, removing the intense peaks of certain predominant components and enhancing the sensitivity for weaker peaks associated with lower concentration components is possible. 
     An exemplary embodiment of an FTMS system and methods was utilized in an on-site, in-situ demonstration to continuously analyze and monitor off-gas generated by a biotechnology company&#39;s fermenters, which were used to generate (“cook”) certain products. This specific demonstration was performed on a pilot scale fermenter with the size of less than 1000 liter (&lt;250 Gallons). The compact, mobile, high-resolution FT-MS system used was trucked to the pilot facility and the measurement was started without mass calibrating the analyzer. 
     Measuring and monitoring fermentation off-gas was determined to be an effective method to determine the Respiratory Quotient (RQ) or the metabolism of the fermentation broth. Depending on the speed of fermentation and the frequency of the analysis, the demonstration showed that the embodiment could be used to improve process control, improve the process yield, and/or speed up the rate of fermentation by controlling the rate of nutrients, permitting and/or assessing the extent of the reaction, and/or verifying possible presence of undesired compounds. 
     For example, it was learned that although many measurements on fermenters simply look at N2, O2, CO2 and a few other simple gases, a rather wide variety of components actually evolve during fermentation and can be detected in the fermenter&#39;s headspace. It was also learned that individual components can be used as a clue to help establish the optimum operating parameters to get the best yield in any given amount of time. 
     Table 2 presents the detected components in a fermenter headspace, based on analyses performed at a frequency of less than one minute per analysis (1 second per co-added data point). As can be seen in the table, a large number of ion fragments are present in the spectrum ranging between mass numbers from 10 to 60. In that range are 10 doublets and even one triplet with three masses that are almost identical (isobars). 
     
       
         
           
               
             
               
                 TABLE 2 
               
             
            
               
                   
               
               
                 Mass Measurement (m/z) and Corrected Assignment 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Peak # 
                 Observed Mass (m/z) 
                 Fragment 
                 Assignment 
                 Theory 
                 Corrected Mass 
                 Corrected Delta 
               
               
                   
               
               
                  1 
                 12.0029 
                 C 
                 C 
                 12.0000 
                 11.9989 
                 −0.0011 
               
               
                   2 3 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                  NCH2 
                  NCH2 
                  14.003714.0156 
                  14.002314.0180 
                  −0.0014 0.0024 
               
               
                  4 
                 14.7103 
                 noise? 
                 noise 
                   
                 14.7055 
               
               
                  5 
                 15.0281 
                 CH3 
                 acetone/butane/ 
                 15.0234 
                 15.0232 
                 −0.0002 
               
               
                   
                   
                   
                 propane 
               
               
                   6 7 8 910 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                  ONH2CH4OHNH3 
                  H2ONH3CH4 traceH2ONH3 
                  15.994916.018716.031217.002717.0265 
                  15.994816.018716.031017.002917.0267 
                  −0.0001 0.0000−0.0002 0.0002 0.0002 
               
               
                 11 
                 18.0167 
                 H2O 
                 H2O 
                 18.0106 
                 18.0109 
                  0.0003 
               
               
                 12 
                 19.9884 
                 Ar +2   
                 Ar +2   
                 19.9812 
                 19.9820 
                  0.0008 
               
               
                 14 
                 25.0149 
                 C2H 
                 butane/propane 
                 25.0078 
                 25.0070 
                 −0.0008 
               
               
                  15161718 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                  C2H2CNHCNC2H3 
                  butane/propaneHCNHCNbutane 
                  26.015726.003127.010927.0235 
                  26.015326.003927.011027.0228 
                  −0.0004 0.0008 0.0001−0.0007 
               
               
                 19 
                 28.0058 
                 CO 
                 CO 
                 27.9949 
                 27.9970 
                  0.0021 
               
               
                  2021 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                  CHOHN2 
                  acid?HN2 
                  29.002729.0140 
                  29.002629.0133 
                  −0.0001−0.0007 
               
               
                 22 
                 30.0067 
                 NO 
                 NO 
                 29.9980 
                 29.9973 
                 −0.0007 
               
               
                 23 
                 32.0002 
                 O2 
                 O2 
                 31.9898 
                 31.9902 
                  0.0004 
               
               
                 27 
                 39.0352 
                 C3H3 
                 propane 
                 39.0235 
                 39.0231 
                 −0.0004 
               
               
                  2932333435363738 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                  ArC3H5C2H2OC3H6C2H3OC3H7CO2N2O 
                  Arpropaneacetonebutaneacetonebutane &amp;?CO2N2O 
                  39.962441.039142.010642.046943.018443.054843.989844.0010 
                  39.962341.038342.009442.046843.019443.054443.987044.0009 
                  −0.0001−0.0008−0.0012−0.0001 0.0010−0.0004−0.0028−0.0001 
               
               
                 39 
                 45.0117 
                 COOH 
                 acid? 
                 44.9977 
                 44.9978 
                  0.0001 
               
               
                 40 
                 50.0291 
                 C4H2 
                 butane 
                 50.0157 
                 50.0137 
                 −0.0020 
               
               
                  4243 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                  C3H6OC4H10 
                  acetonebutane 
                  58.041958.0782 
                  58.044158.0771 
                   0.0022−0.0011 
               
               
                   
               
            
           
         
       
     
     Note how close many of these doublets and triplets occur. For example, the doublet for the Nitrogen and CH2 components spans a range of less than 0.016 m/z, and the triplet for the O, NH2, and CH4 fragments spans a mass range of less than 0.0363 m/z. Knowing the identity and/or concentration of various fermenter headspace components was useful for improving process control, setting fermentation rates, reducing fermentation duration, and increasing yield. 
     When searching for targeted compounds, such accuracy can help avoid false positives. Such accuracy can avoid the need for gas chromatograph separation. 
     Continuing with Table 2, it is worth noting there is a slight bias between the observed, measured mass and the theoretical mass. However, the bias is mathematically consistent along the mass range. Thus, when plotted, these mass biases fit nicely along a polynomial line, as shown in the exemplary plot  10000  of fermenter mass correction shown in  FIG. 10 . 
     The mass corrections made here were done after the fact. The frequency measurement for 3 or 4 of the known components were used to establish a simple linear fit for the other masses present, thereby allowing correct identification of the components. 
     The need for mass correction could have been circumvented with the use of a lock mass. An FTMS system can comprise the capability of utilizing even multiple lock masses to correct for variables that could affect the accuracy of the measurement. Variation in frequency and temperature are two of the corrections a dual lock mass can resolve. 
     Returning to the concept of resolving ion pairs, Table 3 provides experimental data showing the resolution possible with certain doublets for certain embodiments of an FTMS system. 
     
       
         
           
               
             
               
                 TABLE 3 
               
             
            
               
                   
               
               
                 Resolvable Ion Pairs 
               
            
           
           
               
               
               
               
               
            
               
                   
                 Doublet 
                 Exact Masses 
                 Mass 
                 Resolution 
               
               
                 Compounds 
                 Ions 
                 (m/z) 
                 Difference 
                 (m/Δm) 
               
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 Ethylene 
                 C2H4 
                 28.03129 
                   
                   
               
               
                 Nitrogen 
                 N2 
                 28.00614 
                 0.02515 
                 1113 
               
               
                 Carbon 
                 CO 
                 27.99292 
                 0.01322 
                 2118 
               
               
                 monoxide 
               
               
                 THF 
                 C4H8O 
                 72.05751 
               
               
                 N-pentane 
                 C5H12 
                 72.09389 
                 0.03638 
                 1980 
               
               
                 Benzene 
                 C6H6 
                 78.04694 
               
               
                 Pyridine 
                 C5H4N 
                 78.03437 
                 0.01257 
                 6200 
               
               
                 Water 
                 OH 
                 17.00274 
               
               
                 Ammonia 
                 NH3 
                 17.02655 
                 0.02381 
                 713 
               
               
                   
               
            
           
         
       
     
     Because the identity of each ion species can be firmly and accurately established, amplitudes can be used to accurately establish the relative quantities and/or the actual quantities of ions present for each ion species. For example,  FIG. 11  is an exemplary plot  11000  of concentration versus time. Plot  11000  was derived from actual data sampled by an FTMS system for a reaction that produced phosgene during the conditioning of a catalyst. The FTMS system was also used to monitor reactor shutdown to determine when all of the highly toxic phosgene was removed from the reactor. Note that certain exemplary embodiments of an FTMS system can provide plots of any quantity measure (such as abundance, relative abundance, concentration, relative concentration, percent, relative percent, ppk, ppm, ppb, weight, and/or count, etc.) versus any appropriate independent variable (such as time, molecular mass, m/z ratio, molecular species, ion species, etc.). 
     Certain exemplary experiments demonstrate various quantitative features of certain exemplary embodiments of an FTMS system. For example, certain exemplary embodiments of an FTMS system can generate stable quantitative information, such as from a highly reactive nitrogen trifluoride (“NF3”) gas mixture. Certain exemplary embodiments can generate stable quantitative data for long periods even when using a conventional EI ionization filament. In certain exemplary embodiments, relative changes in concentration of about 5 percent can be easily detected on an instantaneous basis. Certain exemplary embodiments generate quantitative data that is linear in concentration over at least 1 order of magnitude with relative standard deviations (“RSD&#39;s”) of about 1 percent to about 5 percent, including all values and subranges therebetween, for a signal to noise ratio of greater than about 50. Certain exemplary embodiments can be continue to generate stable quantitative data based on a daily calibration using a single known sample. 
     Using an exemplary embodiment, NF3 was analyzed at various concentrations. Via these experiments, certain questions were answered, including:
         A. How stable was the FTMS system when performing the analysis?   B. What was the amount of change that could be detected reproducibly by the FTMS system?   C. How often would the FTMS system require calibration?       

     To perform the experiments, two gas cylinders were used. One contained a known 20% NF3 mixture; the second was pure nitrogen. Two mass flow controllers were utilized. Controller  1  had a full range of 5000 sccm (standard cubic centimeters/minute), and controller  2  had a full range of 100 sccm. Due to the large difference in flow ranges of the two controllers, it was decided to manipulate the NF3 concentration by changing its flow rate rather than adjusting the diluent N2 gas flow rate. Since mass flow controllers are often inaccurate below 2% of their rated capacity, controller  1  was used for N2 at a flow rate of 150 sccm (3% of rated capacity). Controller  2  was used for the NF3 mixture. The flow rate of controller  2  was adjusted between 50 sccm and 3.9 sccm. This corresponds to NF3 concentrations in the sample between 5.0% and 0.5% 
     The two gases were hooked to the flow controllers, controller  1  was at room temperature. Controller  2  was maintained at a temperature of about 75 degrees C. The output of the gas mixing device was attached to an outer bulkhead connection for an FTMS sampling valve. The sample gas passed through the valve and exited via an exit bulkhead connection. The sample then flowed via a ⅛ inch Teflon tube from the exit bulkhead to a working hood, where it was exhausted. 
     An NF3 concentration of 5.0% was maintained for the first 2 hours. After which the NF3 concentration was adjusted to 4.5% for 1 hour, then 4.0% for 1 hour, then 3.0% for 1 hour, then 2.0% for 1 hour, then 1.0% for 1 hour, then 0.5% for 1 hour, then 5.0% for 30 minutes. This data was used to construct a calibration curve. Then a number of random flow rates for NF3 were chosen as given in Table 2. Each of these flow rates was maintained for 10 minutes. This data was used to calculate a measured NF3 concentration that was compared with the predicted NF3 concentration. Lastly the NF3 concentration was reset to 5.0% and data collected for approximately an additional 8 hours. 
     Certain exemplary embodiments of the FTMS system have the ability to generate many different types of data files. In the experiment, five data files were generated automatically. One file was a peak measurement file that recorded raw peak heights for requested quantitation peaks, in this case mass 51.9998 and 70.9982 for NF3. A second file recorded other relevant parameters in a comma delimited text file. These parameters included the sample pressure as measured by the ion pump current reading, the mass position of the 52 and 71 peaks, and the temperature of the valve and the sensor. A third type of file recorded the peak detected mass spectrum for each spectrum processed. The fourth file type archived the state of the instrument status window at the moment the experiment concluded. The last file was an ASCII representation of the last sample introduction peak, which allowed for examination of peak shape and pump response. All of these files were updated every 30 seconds when a new data point was taken. All these files were stored on the workstation in a data sub-directory corresponding to the experimental method used to acquire the data. 
     Based on the experiments, the following Table 4 illustrates the stability of the experimental FTMS system when performing the analysis, thus addressing the first question. 
     
       
         
           
               
               
               
               
               
               
             
               
                 TABLE 4 
               
               
                   
               
               
                 % 
                 Mean 
                 Median 
                 Std. 
                 RSD 
                   
               
               
                 NF3 
                 Intensity 
                 intensity 
                 Dev. 
                 (%) 
                 Signal/Noise 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
               
            
               
                 5 
                 6334 
                 6329 
                 85.2 
                 1.3 
                 159 
               
               
                 4.5 
                 5527 
                 5528 
                 91.1 
                 1.6 
                 138 
               
               
                 4.0 
                 4917 
                 4920 
                 59.8 
                 1.2 
                 123 
               
               
                 3.0 
                 3596 
                 3601 
                 52.9 
                 1.5 
                 90 
               
               
                 2.0 
                 2335 
                 2334 
                 40.0 
                 1.7 
                 58 
               
               
                 1.0 
                 1061 
                 1061 
                 30.5 
                 2.9 
                 27 
               
               
                 0.5 
                 453 
                 452 
                 24.1 
                 5.3 
                 11 
               
               
                   
               
            
           
         
       
     
       FIG. 12  is an exemplary plot  12000  of intensity versus concentration, in this case plotting the data of Table 4 as a calibration curve, in which intensity is dependent upon percent NF3. 
     Some of the early experimental data showed the exemplary FTMS system took about 1 hour to reach stability, after which it maintained that stability for over 10 hours. Also at the end of seven hours the FTMS system sensitivity was within 4% of where it was when the run began. 
     To address the second question, data taken during the experiment show that a 10% relative change was easily detectable between 1% and 5% NF3 absolute concentration. In addition, examination of the very consistent standard deviation and RSD&#39;s obtained showed that at a 99% confidence level a 5% relative concentration change would be detectable. Because certain exemplary embodiments of an FTMS system can work on the basis of the number of molecules introduced, these same detection values can be applied to a 20% concentration target. At that level, the difference between 19% and 20% can be readily detectable. The response of the utilized FTMS system was nearly instantaneous depending only on the flow rate of sample and the analysis rate (2 points per minute here). This is illustrated in  FIG. 13 , which is an exemplary plot  13000  of intensity versus scan number. 
     Running a series of known concentrations over 10 minute intervals performed a quick check on the usefulness of the experimental method. This data appears between scans  900  and  1050  on the plot of  FIG. 13 , and is also summarized in Table 5. 
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 5 
               
               
                   
               
               
                 NF3 flow 
                 Actual 
                 Calc. 
                   
                 99% Confidence 
               
               
                 rate mL/Min 
                 % NF3 
                 % NF3 
                 RSD % 
                 Concentration Intervals 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
               
            
               
                 10 
                 1.25 
                 1.21 
                 3.51 
                 1.28 
                 1.14 
               
               
                 30 
                 3.33 
                 3.18 
                 1.33 
                 3.26 
                 3.11 
               
               
                 22 
                 2.56 
                 2.44 
                 0.91 
                 2.49 
                 2.40 
               
               
                 42 
                 4.38 
                 4.24 
                 1.35 
                 4.35 
                 4.13 
               
               
                 28 
                 3.15 
                 3.02 
                 0.85 
                 3.07 
                 2.97 
               
               
                 8 
                 1.01 
                 0.99 
                 3.76 
                 1.05 
                 0.93 
               
               
                 34 
                 3.70 
                 3.60 
                 1.73 
                 3.73 
                 3.49 
               
               
                 50 
                 5 
                 5.00 
                 1.28 
                 5.13 
                 4.89 
               
               
                   
               
            
           
         
       
     
     In answer to the third question, as shown by the stability of the analysis, RSD&#39;s of about 5% were maintained using daily calibration of a single known sample. Day-to-day sensitivity variations during the approximately 2 weeks the exemplary experimental FTMS system was exposed to the samples varied by no more than 15%. 
     Thus, the data gathered during the NF3 experiments showed that the certain exemplary embodiments of an FTMS system can generate substantially stable quantitative information. 
     In certain exemplary FTMS systems, both qualitation and quantitation can be provided automatically. For example, using a known sample comprising Butane at about 25 ppm in Nitrogen, a base peak at 43.0548 m/z, as well as other fragment peaks can be determined, along with the relative intensities of each peak, thus forming a Butane pattern characterized by a collection of masses and intensities. Similarly, intensity data can be collected for other concentrations of Butane to develop a substantially linear calibration curve. Such a calibration curve can be based upon a fixed known sample temperature, a fixed known differential pressure measured across the sample valve (e.g., the differential between the sample inlet pressure and the ion cell), and operation of the exemplary FTMS system within the linear range of the ionization current flux. 
     This mass and intensity data can be collected and stored in, for example, a database. In certain exemplary FTMS systems, via such a database of mass and intensity data for a wide variety of known samples, unknown samples can be automatically identified (i.e., qualitated) as well as quantitated. For example, if any unknown sample, even a sample containing a large number of species, presents peaks having a substantially identical pattern to that of Butane (including its base and fragment peaks), certain exemplary embodiments can recognize the pattern in the unknown sample as corresponding to Butane, and thereby predict with a high predetermined degree of certainty that Butane is present in the sample. Utilizing the calibration curve developed for Butane from the intensity vs. concentration data, the quantity of Butane present in the unknown sample can be estimated, within a predetermined confidence interval. If the unknown sample is collected at a different temperature or differential pressure than that at which the calibration curve was developed, a new calibration curve can be estimated using the Ideal gas law. 
     In certain exemplary FTMS systems, semi-quantitative measurements can be automatically performed relatively independently of species, and without accessing or needing previously-generated calibration curves or data. For example, as shown in Table 6, for a variety of different light gases, each of which was present in separate samples of Nitrogen at a 25 ppm concentration, an exemplary FTMS system generated similar intensity signals and signal to noise ratios. Thus, unknown samples can be identified and at least semi-quantitiatively determined without utilizing a calibration curve or data. 
     
       
         
           
               
             
               
                 TABLE 6 
               
             
            
               
                   
               
               
                 Compound Independent Semi-Quant 
               
            
           
           
               
               
               
               
               
            
               
                   
                 Signal 
                   
                   
                   
               
               
                   
                 Base Peak 
               
               
                   
                 Mass 
                   
                 Signal 
               
               
                 Species 
                 (m/z) 
                 Noise 
                 Intensity 
                 Signal/Noise 
               
               
                   
               
               
                 Carbon Dioxide 
                 43.9898 
                 12 
                 653 
                 54 
               
               
                 Butane 
                 43.0548 
                 12 
                 611 
                 51 
               
               
                 Acetone 
                 43.0184 
                 12 
                 637 
                 53 
               
               
                 SO2 
                 63.9619 
                 12 
                 610 
                 51 
               
               
                 Ethyl Mercaptan 
                 46.9956 
                 12 
                 603 
                 50 
               
               
                   
               
            
           
         
       
     
     Still other embodiments will become readily apparent to those skilled in this art from reading the above-recited detailed description and drawings of certain exemplary embodiments. It should be understood that numerous variations, modifications, and additional embodiments are possible, and accordingly, all such variations, modifications, and embodiments are to be regarded as being within the spirit and scope of the appended claims. For example, regardless of the content of any portion (e.g., title, field, background, summary, abstract, drawing figure, etc.) of this application, unless clearly specified to the contrary, there is no requirement for the inclusion in any claim of any particular described or illustrated activity or element, any particular sequence of such activities, or any particular interrelationship of such elements. Moreover, any activity can be repeated, any activity can be performed by multiple entities, and/or any element can be duplicated. Further, any activity or element can be excluded, the sequence of activities can vary, and/or the interrelationship of elements can vary. Accordingly, the descriptions and drawings are to be regarded as illustrative in nature, and not as restrictive. Moreover, when any number or numerical range is described herein, unless clearly stated otherwise, that number or range is approximate. When any numerical range is described herein, unless clearly stated otherwise, that range includes all numbers therein and all subranges therein.