Patent Application
20180374693
This disclosure relates to analytical machinery and the identification and separation of molecules.
Differential mobility spectrometers (hereinafter, “DMS”), also called field asymmetric ion mobility spectrometers (FAIMS) operate by applying an asymmetric transverse alternating current field to a stream of ions moving in a carrier gas, for example, air. The asymmetric field has a high field portion which is on for a short duration, and a low field portion of opposite polarity which is on for a longer duration. Unlike vacuum ion sorting methods which operate in the ballistic flow regime (no atom collisions), for example, mass spectrometers, ion mobility spectrometers operate in the viscous flow regime (e.g. atmospheric pressure). This means that molecules are rapidly colliding and ions in an electric field (E) experience a terminal velocity (v) that depends on their collision cross section, which is related to their mobility (K) in the following way: v=K*E.
Mobility may be a function of electric field K(E)=K0*(1+αE). Under high field conditions, molecules experience high energy collisions, collisional orienting, and lose adducted molecules such as water, which tends to increase their mobility. Therefore, molecules with larger a (ion mobility function) tend to travel further in the high field portion of the cycle than the low field portion of the cycle and tend to drift toward one of the electrodes. A counter voltage (hereinafter, “CV”) applies a direct current field component to re-center an analyte with a particular differential mobility. By sweeping CV, a differential mobility spectrum may be obtained by an ion detector downstream of the DMS. Notably, ions of opposite polarity can be measured independently. By selecting a particular CV, a DMS can function as an ion differential mobility filter for downstream analyzers, including mass spectrometers.
However, larger molecules have small differential ion-mobility function (hereinafter, “α”), and can experience drag, so large molecules are not well sorted or differentiated by a DMS. This limits the practical use of the DMS technique to small molecules. Traditional ion mobility spectrometer (IMS) systems, including a drift tube IMS, do not have this limitation because they measure mobility directly, not differential mobility. However, a DMS is a very small and simple instrument compared to a traditional drift tube IMS. A solution is needed for extending the useful range of DMS spectrometry to larger molecules.
We disclose an ion modulating differential mobility spectrometer which may include a channel through which ions in a carrier gas may pass along an axis of gas propagation. The ion modulating differential mobility spectrometer may include a differential mobility selector region located within the channel which may include an opposed pair of electrodes creates an asymmetric alternative current voltage and a variable direct current component transverse to the axis of gas propagation. The ion modulating differential mobility spectrometer may include an ion modulator region within the channel. The ion modulator region may include a longitudinal alternating current electric field along the axis of gas propagation and the longitudinal alternating current electric field may include a modulation period. The modulation period may be equal to a transit time of the carrier gas through the ion modulator region. Alternatively, the modulation period may be inversely proportional to a transit time of the carrier gas through the ion modulator region. The ion modulating differential mobility spectrometer may include an ion detector disposed in the channel.
The longitudinal alternating current field may cause ions to bunch by alternately pushing and pulling ions as they pass through the modulator. High mobility ions bunch more readily and produce a larger alternating current ion current modulation. Low mobility ions are more difficult to bunch and thus produce a smaller alternating current ion current modulation relative to the direct current which is the ion concentration. Thus, the mobility (or average mobility) of the differential mobility spectrometer output may be measured by comparing the ratio of the alternating current to the direct current.
While this invention is susceptible of embodiment in many different forms, there are shown in the drawings, which will herein be described in detail, several specific embodiments with the understanding that the present disclosure is to be considered as an exemplification of the principals of the invention and is not intended to limit the invention to the illustrated embodiments.
We disclose an ion modulating differential mobility spectrometer for measuring the linear mobility of a selected differential mobility. For instance, ions first pass through a differential mobility spectrometer (hereinafter, “DMS”) which selects ions with low or zero differential mobility. Significantly, this step may remove reactant ions, for example, charged water complexes, leaving only large ions and their adducted molecules. Ions may pass from the DMS through an ion modulator which applies a longitudinal alternating current (hereinafter, “AC”) field. The longitudinal AC field may cause ions to bunch by alternately pushing and pulling ions as they pass through the modulator. High mobility ions bunch more readily and produce a larger AC ion current modulation. Low mobility ions are more difficult to bunch and thus produce a smaller AC ion current modulation relative to the direct current (hereinafter, “DC”) which is the ion concentration. Thus, the mobility (or average mobility) of the DMS output may be measured by comparing the AC/DC ratio.
Others have used DMS and ion modulators to prepare ion pulses for time of flight spectrometers (US20160071714 A1). However, such devices operate in a field regime where ion flow is dominated by the applied field and ions are bunched regardless of their mobility. Nothing is disclosed about timing the AC field of an electrode region to be synchronous with the transit time of ions moving in a stream of air or carrier gas. Rather, the disclosed ion modulating differential mobility spectrometer relies on an asymmetric field to drive ions forward.
The disclosed ion modulating differential mobility spectrometer requires no asymmetric field. A pure sinusoid waveform or other AC waveform is suitable. The more ground and AC electrode pairs are used in sequence, the lower the necessary voltage. Therefore, repeated ion bunching produces results which are equivalent to using a higher voltage. The ion modulator region may be divided into two sub-regions with opposed longitudinal electric fields which alternately point toward a center electrode and away from the center electrode when the central point is driven by an AC field. The ion modulating region may include additional repetitions of the opposed regions along the channel.
The operation is linear, and limited by diffusion and space charge effects. The time resolution with which the modulation may be detected is limited by the size of the detector electrodes and thickness of the stream of ions (i.e. the maximum ion transverse diffusion distance to electrode). Larger electrodes and channels will result in less time resolution. Detector electrodes operating at higher voltages may obtain higher resolution at the cost of higher background current and 1/f noise.
There are two regimes of operation: linear regime and nonlinear regime. In the low field linear regime, a sinusoidal field generates a sinusoidal modulation of the ion current. In the nonlinear regime ions are pressed into dense spikes. Either the linear field region or nonlinear field region may be used, or used alternately. Because this technique in the linear range measures the average mobility, if there is more than one analyte present, it is not distinguished. However, in the nonlinear regime, the waveforms from ions of differing mobility have some functional orthogonality and the presence of multiple species can be observed. Namely, where one ion is bunched tightly in a spike there may be few ions between the spikes. But where a low mobility ion is present, there is a higher-than-expected ion concentration in the rarefaction between spikes.
Multivariate analysis may be used to estimate the several values of mobility present. Note that without the pre-filtering of the DMS, the resulting waveform could be dominated by the reactant ion peak and the modulation of bulkier ion complexes would be less observable.
Another application of the disclosed ion modulator is to change the ion concentration. It is well known that the ion mobility spectrum is affected by the concentration of the ion and the concentration of the reactant ion (e.g. water). At low concentrations of analyte, monomers are principally observed. At high concentrations, increasing amounts of dimer are observed. This changing spectrum as a function of intensity may complicate analysis and quantitation. By placing an ion modulator (ion buncher) in front of a DMS, regions of high and low ion concentration may be generated. By time resolving the CV scan from the high regions and low regions and/or intermediate regions, many scans of varied concentration may be obtained simultaneously without changing the concentration of ion input to the system. Therefore, the evolution of the monomer/dimer ratios vs. concentrations may be observed and used as a method of identification, or to optimized operation conditions.
In another example, an ion may saturate a detector. The disclosed modulation scheme may provide a means to measure the ion concentration in time over a wider dynamic range without altering the system operating parameters.
Each of these applications are of potential benefit for material identification and on-line monitoring applications.
In general, an ion modulator may be used before or after a DMS or between tandem DMS sections. In an example, the ion modulator may be used before a DMS. The reactant ion may have a high mobility and peak at the center of the bunch, creating regions of high and low reactant ion concentration. If negative and positive reactant ions are present, which is usually the case for water, the negative reactant ion and positive reactant ion clusters bunch out of phase. The negative reactant ion bunching peak may occur at the rarefaction of the positive reactant ion bunching peak and vice versa. The probability of neutralization of ions by collisions of positive and negative ion clusters may also be reduced by spatial separation of ion types.
Traditional ion modulators operate with asymmetric AC fields and use the electric field to move ions. Therefore, they can only be used with one polarity of ion. The other polarity is moved in the opposite (i.e. not intended) direction. Conversely, in the disclosed ion modulating differential mobility spectrometer, ion motion may be controlled by the flow rate of a carrier gas so both polarities of ions may be both bunched and transported.
Some embodiments, the distance between the ground and signal electrodes in the ion modulator may be larger than the thickness of the dielectric spacer. In an example, the spacer is between approximately 0.25 mm to approximately 1 mm thick and the longitudinal distance from the ground to the AC electrode is between approximately 2.5 to approximately 10 mm. In another example, the channel depth is between approximately 0.25 mm to approximately 1 mm. In another example, the channel width is between approximately 2 mm to approximately 8 mm. In another example, the spacer is approximately 0.5 mm, the channel width is approximately 4 mm, the AC to ground electrode distance is approximately 0.5 mm, and the air flow velocity is approximately 300 cm/s. The transit distance from ground through the AC field region to ground is 1 cm, so the transit time is 1/300 s. The AC frequency may therefore be approximately 300 Hz.
An advantage of modulating the ion current is improved detection. Noise at low frequencies tends to be larger, so-called 1/f noise. By modulating the ions, the signal may be moved to a higher (e.g hundreds of hertz) frequency. Demodulation may be accomplished by modulating the detector voltage, or by holding the detector voltage constant and demodulating detected current with a mixer and low pass filter. DC changes in background current, which is a source of drift, is eliminated while the noise bandwidth may be arbitrarily narrowed by the selection of the band pass filter. Because the bunching phase is known and/or can be controlled, a quadrature mixer is not needed. Alternatively, a phase moduation on the mixer may be used to close loop control the modulator frequency or gas flow speed to keep modulation period and modulator transit time in-phase. Alternatively, the modulation period may be inversely proportional to a transit time of the carrier gas through the ion modulator region.
In some embodiments, the ion modulating differential mobility spectrometer may include a channel through which ions in a carrier gas may be passed along an axis of gas propagation. The ion modulating differential mobility spectrometer may further include a differential mobility selector region within the channel which may include multiple pairs of electrodes. These pairs of electrodes may provide an asymmetric AC voltage and a variable DC component which may be transverse to the axis of gas propagation. The ion modulating differential mobility spectrometer may include an ion modulator region disposed within the channel. The ion modulator region may include a longitudinal AC electric field along the axis of gas propagation. In some embodiments, the ion modulator region comprises a length of between approximately 5 mm to approximately 25 mm. The longitudinal AC electric field may include a modulation period which may be equal to a transit time of the carrier gas through the ion modulator region. An ion detector may also be disposed within the channel.
The ion modulator region may include multiple pairs of ground electrodes which may define a gap or slot along the axis of gas propagation. The gap or slot may define the ion modulator region. The ion modulator region may further include a drive electrode, which may be positioned within the gap or slot. AC voltage may be applied to generate the longitudinal AC electric field. Other embodiments may include multiple drive electrodes, each separated by a counting number of transit times.
In some embodiments, the ion modulator region may be positioned further along the axis of gas propagation than the differential mobility selector region. Furthermore, the ion detector may be positioned further along the axis of gas propagation than the ion modulator region.
In some embodiments, the differential mobility sector region and ion modulator region may include planar electrodes adhered to a pair of dielectric substrates. The dielectric substrates may be separated by a dielectric space with a gap or slot running through the dielectric spacer. The gap or slot may define the channel through which gas and ions travel. In some embodiments, the ion detector may include a planar electrode.
In some embodiments, the differential mobility sector region, the ion modulator region, and the ion detector may be fabricated on a single dielectric substrate. Alternatively, the differential mobility sector region, the ion modulator region, and the ion detector may be fabricated on different dielectric substrates.
In some embodiments, the channel may include an ion interaction region between the ion modulator region and the ion detector. The ion detector may include a demodulator which may demodulate ion current at the modulation period.
The ion modulating differential mobility spectrometer may include a controller. The controller may adjust the transit time or the modulation period based on a detected modulation current magnitude. The controller may adjust the longitudinal AC electric field based on a detected modulation current magnitude. Furthermore, the controller may scan the variable DC component of the differential mobility selector through a series of direct current levels. Alternatively, the modulation period may be inversely proportional to a transit time of the carrier gas through the ion modulator region.
The ion modulating differential mobility spectrometer may include a recorder, which may record a time-resolved measurement of the detected modulation current magnitude.
Some embodiments may include a boxcar averager which may obtain an average of a time-resolved measurement of the detected modulation current magnitude. Some embodiments may include a controller, a recorder, and a boxcar averager.
Some embodiments may include an analyzer which may estimate one of more ion mobilities from the time-resolved of the detected modulation current magnitude.
Referring now to the drawings,
The top left of
As a practical consideration, the operation of ion modulators is approximately linear, so tandem bunchers allow a smaller voltage to be used to achieve a similar level of ion bunching, limited by diffusion effects and field irregularities.
Uniform axial fields are desirable for bunching ions distributed through the entire sample cross sectional area. In a planar design, two plates with metal traces for forming the electrodes are spaced by a dielectric. The dielectric tends to attract electric field. To compensate the ground and signal electrode shapes can be altered to focus the fields to achieve a better longitudinal field.
While specific embodiments have been described above, it is to be understood that the disclosure provided is not limited to the precise configuration, steps, and components disclosed. Various modifications, changes, and variations apparent to those of skill in the art may be made in the arrangement, operation, and details of the methods and systems disclosed, with the aid of the present disclosure.
Without further elaboration, it is believed that one skilled in the art can use the preceding description to utilize the present disclosure to its fullest extent. The examples and embodiments disclosed herein are to be construed as merely illustrative and exemplary and not a limitation of the scope of the present disclosure in any way. It will be apparent to those having skill in the art that changes may be made to the details of the above-described embodiments without departing from the underlying principles of the disclosure herein.
