![U](https://upload.wikimedia.org/wikipedia/commons/a/a2/U.S._Department_of_Energy_-_Science_-_395_010_003_%289474983458%29.jpg)
Ion mobility spectrometry (IMS) is an analytical technique used to separate and identify ionized molecules in the gas phase based on their mobility in a carrier buffer gas. Though heavily employed for military or security purposes, such as detecting drugs and explosives, the technique also has many laboratory analytical applications, including the analysis of both small and large biomolecules. IMS instruments are extremely sensitive stand-alone devices, but are often coupled with
mass spectrometry,
gas chromatography or
high-performance liquid chromatography
High-performance liquid chromatography (HPLC), formerly referred to as high-pressure liquid chromatography, is a technique in analytical chemistry used to separate, identify, and quantify each component in a mixture. It relies on pumps to pa ...
in order to achieve a multi-dimensional separation. They come in various sizes, ranging from a few millimeters to several meters depending on the specific application, and are capable of operating under a broad range of conditions. IMS instruments such as microscale
high-field asymmetric-waveform ion mobility spectrometry can be palm-portable for use in a range of applications including
volatile organic compound
Volatile organic compounds (VOCs) are organic compounds that have a high vapour pressure at room temperature. High vapor pressure correlates with a low boiling point, which relates to the number of the sample's molecules in the surrounding air, a ...
(VOC) monitoring, biological sample analysis, medical diagnosis and food quality monitoring. Systems operated at higher pressure (i.e. atmospheric conditions, 1 atm or 1013 hPa) are often accompanied by elevated temperature (above 100 °C), while lower pressure systems (1-20 hPa) do not require heating.
History
IMS was first developed primarily by
Earl W. McDaniel of
Georgia Institute of Technology in the 1950s and 1960s when he used drift cells with low applied electric fields to study gas phase ion mobilities and reactions.
In the following decades, he coupled his new technique with a magnetic-sector mass spectrometer, with others also utilizing his techniques in new ways. IMS cells have since been attached to many other mass spectrometers, gas chromatographs and high-performance liquid chromatography setups. IMS is a widely used technique, and improvements and other uses are continually being developed.
Applications
Perhaps ion mobility spectrometry's greatest strength is the speed at which separations occur—typically on the order of tens of milliseconds. This feature combined with its ease of use, relatively high sensitivity, and highly compact design have allowed IMS as a commercial product to be used as a routine tool for the field detection of
explosives,
drugs, and
chemical weapons
A chemical weapon (CW) is a specialized munition that uses chemicals formulated to inflict death or harm on humans. According to the Organisation for the Prohibition of Chemical Weapons (OPCW), this can be any chemical compound intended as a ...
. Major manufacturers of IMS screening devices used in airports are Morpho and
Smiths Detection.
Smiths purchased Morpho Detection in 2017 and subsequently had to legally divest ownership of the Trace side of the business
miths have Trace Products which was sold on to Rapiscan Systems in mid 2017. The products are listed under ETD Itemisers. The latest model is a non-radiation 4DX.
In the pharmaceutical industry IMS is used in
cleaning validations, demonstrating that reaction vessels are sufficiently clean to proceed with the next batch of pharmaceutical product. IMS is much faster and more accurate than
HPLC and
total organic carbon
Total organic carbon (TOC) is the amount of carbon found in an organic compound and is often used as a non-specific indicator of water quality or cleanliness of pharmaceutical manufacturing equipment. TOC may also refer to the amount of organi ...
methods previously used. IMS is also used for analyzing the composition of drugs produced, thereby finding a place in quality assurance and control.
As a research tool ion mobility is becoming more widely used in the analysis of biological materials, specifically,
proteomics and
metabolomics
Metabolomics is the scientific study of chemical processes involving metabolites, the small molecule substrates, intermediates, and products of cell metabolism. Specifically, metabolomics is the "systematic study of the unique chemical fingerprin ...
. For example, IMS-MS using
MALDI
In mass spectrometry, matrix-assisted laser desorption/ionization (MALDI) is an ionization technique that uses a laser energy absorbing matrix to create ions from large molecules with minimal fragmentation. It has been applied to the analysis of b ...
as the ionization method has helped make advances in proteomics, providing faster high-resolution separations of protein pieces in analysis. Moreover, it is a really promising tool for
glycomics Glycomics is the comprehensive study of glycomes (the entire complement of sugars, whether free or present in more complex molecules of an organism), including genetic, physiologic, pathologic, and other aspects. Glycomics "is the systematic study ...
, as rotationally averaged collision cross section (CCS) values can be obtained. CCS values are important distinguishing characteristics of ions in the gas phase, and in addition to the empirical determinations it can also be calculated computationally when the 3D structure of the molecule is known. This way, adding CCS values of glycans and their fragments to databases will increase structural identification confidence and accuracy.
Outside of laboratory purposes, IMS has found great usage as a detection tool for hazardous substances. More than 10,000 IMS devices are in use worldwide in airports, and the US Army has more than 50,000 IMS devices. In industrial settings, uses of IMS include checking equipment cleanliness and detecting emission contents, such as determining the amount of hydrochloric and hydrofluoric acid in a stack gas from a process. It is also applied in industrial purposes to detect harmful substances in air.
In
metabolomics
Metabolomics is the scientific study of chemical processes involving metabolites, the small molecule substrates, intermediates, and products of cell metabolism. Specifically, metabolomics is the "systematic study of the unique chemical fingerprin ...
the IMS is used to detect
lung cancer
Lung cancer, also known as lung carcinoma (since about 98–99% of all lung cancers are carcinomas), is a malignant lung tumor characterized by uncontrolled cell growth in tissues of the lung. Lung carcinomas derive from transformed, malign ...
,
Chronic obstructive pulmonary disease
Chronic obstructive pulmonary disease (COPD) is a type of progressive lung disease characterized by long-term respiratory symptoms and airflow limitation. The main symptoms include shortness of breath and a cough, which may or may not produce ...
,
sarcoidosis
Sarcoidosis (also known as ''Besnier-Boeck-Schaumann disease'') is a disease involving abnormal collections of inflammatory cells that form lumps known as granulomata. The disease usually begins in the lungs, skin, or lymph nodes. Less commonly a ...
, potential rejections after
lung transplantation and relations to
bacteria
Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one Cell (biology), biological cell. They constitute a large domain (biology), domain of prokaryotic microorganisms. Typically a few micrometr ...
within the
lung (see
breath gas analysis
Breath gas analysis is a method for gaining information on the clinical state of an individual by monitoring volatile organic compounds (VOCs) present in the exhaled breath. Exhaled breath is naturally produced by the human body through expiration ...
).
Ion mobility
The
physical quantity ion mobility ''K'' is defined as the proportionality factor between an ion's drift velocity ''v
d'' in a gas and an electric field of strength ''E''.
:::
Ion mobilities are commonly reported as ''reduced mobilities'', correcting to standard gas density ''n
0'', which can be expressed in standard temperature ''T
0'' = 273 K and standard pressure ''p
0'' = 1013 hPa. This does not correct for other effects than the change in gas density and the reduced ion mobility is therefore still temperature dependent.
:::
The ion mobility ''K'' can, under a variety of assumptions, be calculated by the Mason-Schamp equation.
:::
where ''Q'' is the ion
charge
Charge or charged may refer to:
Arts, entertainment, and media Films
* '' Charge, Zero Emissions/Maximum Speed'', a 2011 documentary
Music
* ''Charge'' (David Ford album)
* ''Charge'' (Machel Montano album)
* ''Charge!!'', an album by The Aqu ...
, ''n'' is the drift gas
number density, ''μ'' is the
reduced mass
In physics, the reduced mass is the "effective" inertial mass appearing in the two-body problem of Newtonian mechanics. It is a quantity which allows the two-body problem to be solved as if it were a one-body problem. Note, however, that the mass ...
of the ion and the drift gas molecules, ''k'' is
Boltzmann constant
The Boltzmann constant ( or ) is the proportionality factor that relates the average relative kinetic energy of particles in a gas with the thermodynamic temperature of the gas. It occurs in the definitions of the kelvin and the gas constant, ...
, ''T'' is the drift gas
temperature
Temperature is a physical quantity that expresses quantitatively the perceptions of hotness and coldness. Temperature is measurement, measured with a thermometer.
Thermometers are calibrated in various Conversion of units of temperature, temp ...
, and ''σ'' is the
collision cross section between the ion and the drift gas molecules. Often, ''N'' is used instead of ''n'' for the drift gas number density and ''Ω'' instead ''σ'' for the ion-neutral collision cross section. This relation holds approximately at a low electric field limit, where the ratio of ''E/N'' is small and thus the thermal energy of the ions is much greater than the energy gained from the electric field between collisions. With these ions having similar energies as the buffer gas molecules, diffusion forces dominate ion motion in this case. The ratio ''E/N'' is typically given in
Townsends (Td) and the transition between low- and high-field conditions is typically estimated to occur between 2 Td and 10 Td. When low-field conditions no longer prevail, the ion mobility itself becomes a function of the electric field strength which is usually described empirically through the so-called alpha function.
:::
Ionization
The molecules of the sample need to be ionization, ionized, usually by corona discharge, atmospheric pressure photoionization (APPI), electrospray ionization (ESI), or
radioactive
Radioactive decay (also known as nuclear decay, radioactivity, radioactive disintegration, or nuclear disintegration) is the process by which an unstable atomic nucleus loses energy by radiation. A material containing unstable nuclei is consi ...
atmospheric-pressure chemical ionization
Atmospheric pressure chemical ionization (APCI) is an ionization method used in mass spectrometry which utilizes gas-phase ion-molecule reactions at atmospheric pressure (105 Pa), commonly coupled with high-performance liquid chromatography (HPLC ...
(R-APCI) source, e.g. a small piece of
63 Ni or
241 Am, similar to the one used in ionization
smoke detector
A smoke detector is a device that senses smoke, typically as an indicator of fire. Smoke detectors are usually housed in plastic enclosures, typically shaped like a disk about in diameter and thick, but shape and size vary. Smoke can be detecte ...
s. ESI and
MALDI
In mass spectrometry, matrix-assisted laser desorption/ionization (MALDI) is an ionization technique that uses a laser energy absorbing matrix to create ions from large molecules with minimal fragmentation. It has been applied to the analysis of b ...
techniques are commonly used when IMS is paired with mass spectrometry.
Doping materials are sometimes added to the drift gas for ionization selectivity. For example, acetone can be added for chemical warfare agent detection, chlorinated solvents added for explosives, and nicotinamide added for drugs detection.
Analyzers
Ion mobility spectrometers exist based on various principles, optimized for different applications. A review from 2014 lists eight different ion mobility spectrometry concepts.
Drift tube ion mobility spectrometry
500px, A drift tube ion mobility spectrometer.
Drift tube ion mobility spectrometry (DTIMS) measures how long a given ion takes to traverse a given length in a uniform
electric field through a given atmosphere. In specified intervals, a sample of the ions is let into the drift region; the gating mechanism is based on a charged electrode working in a similar way as the
control grid
The control grid is an electrode used in amplifying thermionic valves (vacuum tubes) such as the triode, tetrode and pentode, used to control the flow of electrons from the cathode to the anode (plate) electrode. The control grid usually consist ...
in
triode
A triode is an electronic amplifying vacuum tube (or ''valve'' in British English) consisting of three electrodes inside an evacuated glass envelope: a heated filament or cathode, a grid, and a plate (anode). Developed from Lee De Forest's ...
s works for electrons. For precise control of the ion pulse width admitted to the drift tube, more complex gating systems such as a
Bradbury-Nielsen or a Field Switching Shutter are employed. Once in the drift tube, ions are subjected to a homogeneous electric field ranging from a few volts per centimeter up to many hundreds of volts per centimeter. This electric field then drives the ions through the drift tube where they interact with the neutral drift molecules contained within the system and separate based on the
ion mobility, arriving at the detector for measurement. Ions are recorded at the detector in order from the fastest to the slowest, generating a response signal characteristic for the chemical composition of the measured sample.
The ion mobility ''K'' can then be experimentally determined from the drift time ''t
D'' of an ion traversing within a homogeneous electric field the potential difference ''U'' in the drift length ''L''.
:::
A drift tube's resolving power ''R
P'' can, when diffusion is assumed as the sole contributor to peak broadening, be calculated as
:::
where ''t
D'' is the ion drift time, ''Δt
D'' is the
Full width at half maximum
In a distribution, full width at half maximum (FWHM) is the difference between the two values of the independent variable at which the dependent variable is equal to half of its maximum value. In other words, it is the width of a spectrum curve mea ...
, L is the tube length, E is the electric field strength, Q is the ion charge, k is Boltzmann's constant, and T is the drift gas temperature. Ambient pressure methods allow for higher resolving power and greater separation selectivity due to a higher rate of ion-molecule interactions and is typically used for stand-alone devices, as well as for detectors for gas, liquid, and supercriticial fluid chromatography. As shown above, the resolving power depends on the total voltage drop the ion traverses. Using a drift voltage of 25 kV in a 15 cm long atmospheric pressure drift tube, a resolving power above 250 is achievable even for small, single charged ions. This is sufficient to achieve separation of some isotopologues based on their difference in
reduced mass
In physics, the reduced mass is the "effective" inertial mass appearing in the two-body problem of Newtonian mechanics. It is a quantity which allows the two-body problem to be solved as if it were a one-body problem. Note, however, that the mass ...
''μ.''
Low pressure drift tube
Reduced pressure drift tubes operate using the same principles as their atmospheric pressure counterparts, but at drift gas pressure of only a few torr. Due to the vastly reduced number of ion-neutral interactions, much longer drift tubes or much faster ion shutters are necessary to achieve the same resolving power. However, the reduced pressure operation offers several advantages. First, it eases interfacing the IMS with mass spectrometry.
Second, at lower pressures, ions can be stored for injection from an ion trap and re-focussed radially during and after the separation. Third, high values of ''E/N'' can be achieved, allowing for direct measurement of ''K''(''E/N'') over a wide range.
Travelling wave
Though drift electric fields are normally uniform, non-uniform drift fields can also be used. One example is the travelling wave IMS, which is a low pressure drift tube IMS where the electric field is only applied in a small region of the drift tube. This region then moves along the drift tube, creating a wave pushing the ions towards the detector, removing the need for a high total drift voltage. A direct determination of collision cross sections (CCS) is not possible, using TWIMS. Calibrants can help circumvent this major drawback, however, these should be matched for size, charge and chemical class of the given analyte. An especially noteworthy variant is the "SUPER" IMS, which combines ion trapping by the so-called structures for lossless ion manipulations (SLIM) with several passes through the same drift region to achieve extremely high resolving powers.
Trapped ion mobility spectrometry
In trapped ion mobility spectrometry (TIMS), ions are held stationary (or trapped) in a flowing buffer gas by an axial electric field gradient (EFG) profile while the application of radio frequency (rf) potentials results in trapping in the radial dimension. TIMS operates in the pressure range of 2 to 5 hPa and replaces the ion funnel found in the source region of modern mass spectrometers. It can be coupled with nearly any mass analyzer through either the standard mode of operation for beam-type instruments or selective accumulation mode (SA-TIMS) when used with trapping mass spectrometry (MS) instruments.
Effectively, the drift cell is prolonged by the ion motion created through the gas flow. Thus, TIMS devices do neither require large size nor high voltage in order to achieve high resolution, for instance achieving over 250 resolving power from a 4.7 cm device through the use of extended separation times.
However, the resolving power strongly depends on the ion mobility and decreases for more mobile ions. In addition, TIMS can be capable of higher sensitivity than other ion mobility systems because no grids or shutters exist in the ion path, improving ion transmission both during ion mobility experiments and while operating in a transparent MS only mode.
High-field asymmetric waveform ion mobility spectrometry
DMS (
differential mobility spectrometer) or FAIMS (
field asymmetric ion mobility spectrometer) make use of the dependence of the ion mobility ''K'' on the electric field strength ''E'' at high electric fields. Ions are transported through the device by the drift gas flow and subjected to different field strengths in orthogonal direction for different amounts of time. Ions are deflected towards the walls of the analyzer based on the change of their mobility. Thereby only ions with a certain mobility dependence can pass the thus created filter
Differential mobility analyzer
![Yuj](https://upload.wikimedia.org/wikipedia/commons/9/9f/Yuj.jpg)
A differential mobility analyzer (DMA) makes use of a fast gas stream perpendicular to the electric field. Thereby ions of different mobilities undergo different trajectories. This type of IMS corresponds to the
sector instruments
A sector instrument is a general term for a class of mass spectrometer that uses a static electric (E) or magnetic (B) sector or some combination of the two (separately in space) as a mass analyzer. Popular combinations of these sectors have been ...
in
mass spectrometry. They also work as a scannable filter. Examples include the differential mobility detector first commercialized by
Varian in the CP-4900 MicroGC. Aspiration IMS operates with open-loop circulation of sampled air. Sample flow is passed via ionization chamber and then enters to measurement area where the ions are deflected into one or more measuring electrodes by perpendicular
electric field which can be either static or varying. The output of the sensor is characteristic of the ion mobility distribution and can be used for detection and identification purposes.
![DEMC DMA](https://upload.wikimedia.org/wikipedia/commons/7/74/DEMC_DMA.PNG)
A DMA can separate charged
aerosol particles or
ion
An ion () is an atom or molecule with a net electrical charge.
The charge of an electron is considered to be negative by convention and this charge is equal and opposite to the charge of a proton, which is considered to be positive by conve ...
s according to their mobility in an
electric field prior to their detection, which can be done with several means, including electrometers or the more sophisticated mass spectrometers.
Drift gas
The drift gas composition is an important parameter for the IMS instrument design and resolution. Often, different drift gas compositions can allow for the separation of otherwise overlapping peaks. Elevated gas temperature assists in removing ion clusters that may distort experimental measurements.
[Bengt Nolting, ''Methods in Modern Biophysics'', Springer Verlag, 2005, ][Gary Eiceman & Zeev Karpas, ''Ion Mobility Spectrometry'', CRC Press, 2005, ]
Detector
Often the detector is a simple
Faraday plate coupled to a
transimpedance amplifier
In electronics, a transimpedance amplifier (TIA) is a current to voltage converter, almost exclusively implemented with one or more operational amplifiers. The TIA can be used to amplify the current output of Geiger–Müller tubes, photo multipli ...
, however, more advanced ion mobility instruments are
coupled
''Coupled'' is an American dating game show that aired on Fox from May 17 to August 2, 2016. It was hosted by television personality, Terrence J and created by Mark Burnett, of '' Survivor'', ''The Apprentice'', '' Are You Smarter Than a 5th G ...
with
mass spectrometer
Mass spectrometry (MS) is an analytical technique that is used to measure the mass-to-charge ratio of ions. The results are presented as a '' mass spectrum'', a plot of intensity as a function of the mass-to-charge ratio. Mass spectrometry is us ...
s in order to obtain both size and mass information simultaneously. It is noteworthy that the detector influences the optimum operating conditions for the ion mobility experiment.
Combined methods
IMS can be combined with other separation techniques.
Gas chromatography
When IMS is coupled with gas chromatography, common sample introduction is with the GC capillary column directly connected to the IMS setup, with molecules ionized as they elute from GC.
A similar technique is commonly used for
HPLC. A novel design for corona discharge ionization ion mobility spectrometry (CD–IMS) as a detector after capillary gas chromatography has been produced in 2012. In this design, a hollow needle was used for corona discharge creation and the effluent was entered into the ionization region on the upstream side of the corona source. In addition to the practical conveniences in coupling the capillary to IMS cell, this direct axial interfacing helps us to achieve a more efficient ionization, resulting in higher sensitivity.
When used with GC, a differential mobility analyzer is often called a differential mobility detector (DMD).
A DMD is often a type of
microelectromechanical system
Microelectromechanical systems (MEMS), also written as micro-electro-mechanical systems (or microelectronic and microelectromechanical systems) and the related micromechatronics and microsystems constitute the technology of microscopic devices, ...
, radio frequency modulated ion mobility spectrometry (MEMS RF-IMS) device.
Though small, it can fit into portable units, such as transferable gas chromatographs or drug/explosives sensors. For instance, it was incorporated by
Varian in its CP-4900 DMD MicroGC, and by
Thermo Fisher in its EGIS Defender system, designed to detect narcotics and explosives in transportation or other security applications.
Liquid chromatography
Coupled with LC and MS, IMS has become widely used to analyze biomolecules, a practice heavily developed by
David E. Clemmer, now at
Indiana University (Bloomington).
Mass spectrometry
When IMS is used with mass spectrometry, ion mobility spectrometry-mass spectrometry offers many advantages, including better signal to noise, isomer separation, and charge state identification.
IMS has commonly been attached to several mass spec analyzers, including quadropole, time-of-flight, and Fourier transform cyclotron resonance.
Dedicated software
Ion mobility mass spectrometry is a rather recently popularized gas phase ion analysis technique. As such there is not a large software offering to display and analyze ion mobility mass spectrometric data, apart from the software packages that are shipped along with the instruments. ProteoWizard,
OpenMS,
and msXpertSuite
are free software according to the OpenSourceInitiative definition. While ProteoWizard and OpenMS have features to allow spectrum scrutiny, those software packages do not provide combination features. In contrast, msXpertSuite features the ability to combine spectra according to various criteria: retention time, m/z range, drift time range, for example. msXpertSuite thus more closely mimicks the software that usually comes bundled with the mass spectrometer.
See also
*
Electrical mobility
*
Viehland-Mason Theory
*
Explosive detection
Explosive detection is a non-destructive inspection process to determine whether a container contains explosive material. Explosive detection is commonly used at airports, ports and for border control.
Detection tools
Colorimetrics & automated c ...
References
Bibliography
*
*
*
*
External links
*
{{Analytical chemistry
Mass spectrometry
Explosive detection