Ion mobility spectrometer
Encyclopedia
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, recently being coupled with mass spectrometry
and high-performance liquid chromatography
. IMS devices come in a wide range of sizes (often tailored for a specific application) and are capable of operating under a broad range of conditions. Systems operated at higher pressure (i.e. atmospheric conditions, 1 atm or 1013 mbar) are also accompanied by elevated temperature (above 100°C), while lower pressure systems (1-20 mbar) do not require heating.
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 and high-performance liquid chromatography setups. Currently IMS is a widely-used technique implemented by many, and improvements and other uses are continually being developed.
Outside of laboratory purposes, IMS has found great usage as a detection tool. 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.
The physical quantity
ion mobility K is defined as the proportionality factor of an ion's drift velocity vd in a gas and an electric field of strength E,
Ion mobilities are commonly reported as a reduced mobilities, correcting to standard gas density n0, which can be expressed in standard temperature T0 = 273 K and standard pressure p0 = 1013 mbar:
The ion mobility K can be experimentally determined by measuring the drift time tD of an ion traversing within a homogeneous electric field the potential difference U in the drift length L:
The ion mobility K can also be calculated by the Mason equation:
where Q is the ion charge
, n is the drift gas number density
, μ is the reduced mass
of the ion and the drift gas molecules, k is Boltzmann constant, T is the drift gas temperature
, and σ is the ion’s collision cross section
with the drift gas. This relation holds approximately at a low electric field limit, where the ratio of E/n is small, at ≤ 2 x 10-17 J•C-1•cm2
A drift tube’s resolving power R can be calculated as
where 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.
With a low electric field applied, the thermal energy of the ions is 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.
, usually by corona discharge
, atmospheric pressure photoionization (APPI), electrospray ionization
(ESI), or a radioactive source, eg. a small piece of 63Ni
or 241Am
, similar to the one used in ionization smoke detector
s. ESI and MALDI techniques are commonly used when IMS is paired with mass spec.
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.
through a given atmosphere.
In specified intervals, a sample of the ions is let into the drift chamber; the gating mechanism is based on a charged electrode working in a similar way as the control grid
in triode
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
design 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.
In the drift tube, chemical species 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.
For drift-time IMS, two main methods are used – either reduced pressure or ambient pressure. A reduced pressure is where the applied pressure gas is at a few torr, commonly used to measure ion collision cross-sections. Ambient pressure is what is used for stand-alone detector devices, as well as detection for gas, liquid, and supercriticial fluid chromatographies. The higher pressures of ambient pressure methods allow for higher resolving power and greater separation selectivity due to a higher rate of ion-molecule interactions. Reduced pressure IMS allows for ion-focusing and an easier interface with mass spec.
Though drift electric fields are normally uniform, non-uniform drift fields are also used. These non-uniform field IMS results are often calibrated to uniform field instrumentation. Non-uniform field usage is still in a relatively early developing stage.
. They also work as a scanable filter. Examples include DMD (Differential Mobility Detector
), first commercialized in Varian
CP-4900 MicroGC.
Elevated gas temperature assists in removing ion clusters that may distort experimental measurements.
with mass spectrometers where both size and mass information may be obtained simultaneously.
s through homogeneous electric field
. It is a version of ion mobility spectrometry. ITMS provides a substantial performance improvement over IMS, as the shutter grid is eliminated together with the associated loss of sensitivity.
, and chemical weapons. Major manufacturers of IMS screening devices used in airports are Morpho and Smiths Detection
.
In the pharmaceutical industry IMS is used in cleaning validation
s, 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 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
. For example, IMS-MS using MALDI as the ionization method has helped make advances in proteomics, providing faster high-resolution separations of protein pieces in analysis.
Aspirating IMS is an ion mobility spectrometry technology used to detect low or trace quantities of chemicals in the surrounding atmosphere. It is applied in industrial and military purposes to detect harmful substances in air. 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.
In metabolomics
the IMS is used to detect lung cancer
, Chronic obstructive pulmonary disease
, Sarcoidosis
, potential rejections after Lung transplantation
and relations to bacteria
within the lung
.
Mass spectrometry
Mass spectrometry is an analytical technique that measures the mass-to-charge ratio of charged particles.It is used for determining masses of particles, for determining the elemental composition of a sample or molecule, and for elucidating the chemical structures of molecules, such as peptides and...
and high-performance liquid chromatography
High-performance liquid chromatography
High-performance liquid chromatography , HPLC, is a chromatographic technique that can separate a mixture of compounds and is used in biochemistry and analytical chemistry to identify, quantify and purify the individual components of the mixture.HPLC typically utilizes different types of stationary...
. IMS devices come in a wide range of sizes (often tailored for a specific application) and are capable of operating under a broad range of conditions. Systems operated at higher pressure (i.e. atmospheric conditions, 1 atm or 1013 mbar) are also accompanied by elevated temperature (above 100°C), while lower pressure systems (1-20 mbar) do not require heating.
History
IMS was first developed primarily by Earl W. McDanielEarl W. McDaniel
Earl W. McDaniel was a Regents Professor of Physics at the Georgia Institute of Technology and the Georgia Tech Research Institute and is most noted for his contributions to the field of ion mobility spectrometry....
of Georgia Institute of Technology
Georgia Institute of Technology
The Georgia Institute of Technology is a public research university in Atlanta, Georgia, in the United States...
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 and high-performance liquid chromatography setups. Currently IMS is a widely-used technique implemented by many, and improvements and other uses are continually being developed.
Outside of laboratory purposes, IMS has found great usage as a detection tool. 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.
Ion Mobility
In the traditional method of drift-time IMS, commonly referred to as just IMS, produced ions travel through a drift tube which has an applied electric field and a carrier buffer gas that opposes the ion motion. At the end of the tube is a detector. Based on an ion’s mass, charge, size and shape (the ion mobility), the migration time through the tube is characteristic of different ions, leading to the ability to distinguish different analyte species. The area of an ion that gas molecules strike is an ion’s collision cross-section, related to the ion size and shape. The greater this collision cross-section is, meaning the larger the ion size, the more area available for buffer gas to collide and impede the ion’s drift – the ion then requires a longer time to migrate through the drift tube.The physical quantity
Physical quantity
A physical quantity is a physical property of a phenomenon, body, or substance, that can be quantified by measurement.-Definition of a physical quantity:Formally, the International Vocabulary of Metrology, 3rd edition defines quantity as:...
ion mobility K is defined as the proportionality factor of an ion's drift velocity vd in a gas and an electric field of strength E,
Ion mobilities are commonly reported as a reduced mobilities, correcting to standard gas density n0, which can be expressed in standard temperature T0 = 273 K and standard pressure p0 = 1013 mbar:
The ion mobility K can be experimentally determined by measuring the drift time tD of an ion traversing within a homogeneous electric field the potential difference U in the drift length L:
The ion mobility K can also be calculated by the Mason equation:
where Q is the ion charge
Charge (physics)
In physics, a charge may refer to one of many different quantities, such as the electric charge in electromagnetism or the color charge in quantum chromodynamics. Charges are associated with conserved quantum numbers.-Formal definition:...
, n is the drift gas number density
Number density
In physics, astronomy, and chemistry, number density is an intensive quantity used to describe the degree of concentration of countable objects in the three-dimensional physical space...
, μ is the reduced mass
Reduced mass
Reduced mass is the "effective" inertial mass appearing in the two-body problem of Newtonian mechanics. This is a quantity with the unit of mass, which allows the two-body problem to be solved as if it were a one-body problem. Note however that the mass determining the gravitational force is not...
of the ion and the drift gas molecules, k is Boltzmann constant, T is the drift gas temperature
Temperature
Temperature is a physical property of matter that quantitatively expresses the common notions of hot and cold. Objects of low temperature are cold, while various degrees of higher temperatures are referred to as warm or hot...
, and σ is the ion’s collision cross section
Cross section (physics)
A cross section is the effective area which governs the probability of some scattering or absorption event. Together with particle density and path length, it can be used to predict the total scattering probability via the Beer-Lambert law....
with the drift gas. This relation holds approximately at a low electric field limit, where the ratio of E/n is small, at ≤ 2 x 10-17 J•C-1•cm2
A drift tube’s resolving power R can be calculated as
where 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.
With a low electric field applied, the thermal energy of the ions is 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.
Ionization
The molecules of the sample need to be ionizedIonization
Ionization is the process of converting an atom or molecule into an ion by adding or removing charged particles such as electrons or other ions. This is often confused with dissociation. A substance may dissociate without necessarily producing ions. As an example, the molecules of table sugar...
, usually by corona discharge
Corona discharge
In electricity, a corona discharge is an electrical discharge brought on by the ionization of a fluid surrounding a conductor that is electrically energized...
, atmospheric pressure photoionization (APPI), electrospray ionization
Electrospray ionization
Electrospray ionization is a technique used in mass spectrometry to produce ions. It is especially useful in producing ions from macromolecules because it overcomes the propensity of these molecules to fragment when ionized...
(ESI), or a radioactive source, eg. a small piece of 63Ni
Nickel
Nickel is a chemical element with the chemical symbol Ni and atomic number 28. It is a silvery-white lustrous metal with a slight golden tinge. Nickel belongs to the transition metals and is hard and ductile...
or 241Am
Americium
Americium is a synthetic element that has the symbol Am and atomic number 95. This transuranic element of the actinide series is located in the periodic table below the lanthanide element europium, and thus by analogy was named after another continent, America.Americium was first produced in 1944...
, similar to the one used in ionization smoke detector
Smoke detector
A smoke detector is a device that detects smoke, typically as an indicator of fire. Commercial, industrial, and mass residential devices issue a signal to a fire alarm system, while household detectors, known as smoke alarms, generally issue a local audible and/or visual alarm from the detector...
s. ESI and MALDI techniques are commonly used when IMS is paired with mass spec.
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.
TOFIMS
In its simplest form an IMS system measures how fast a given ion moves in a uniform electric fieldElectric field
In physics, an electric field surrounds electrically charged particles and time-varying magnetic fields. The electric field depicts the force exerted on other electrically charged objects by the electrically charged particle the field is surrounding...
through a given atmosphere.
Control grid
The control grid is an electrode used in thermionic valves used to modulate the flow of electrons in the cathode to anode or plate circuit.- Operation :...
in triode
Triode
A triode is an electronic amplification device having three active electrodes. The term most commonly applies to a vacuum tube with three elements: the filament or cathode, the grid, and the plate or anode. The triode vacuum tube was the first electronic amplification device...
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
Bradbury-Nielsen shutter
A Bradbury-Nielsen shutter is a type of electrical ion gate, which was first proposed in an article by Norris Bradbury and Russel A. Nielsen, where they used it as an electron filter...
design 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.
In the drift tube, chemical species 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.
For drift-time IMS, two main methods are used – either reduced pressure or ambient pressure. A reduced pressure is where the applied pressure gas is at a few torr, commonly used to measure ion collision cross-sections. Ambient pressure is what is used for stand-alone detector devices, as well as detection for gas, liquid, and supercriticial fluid chromatographies. The higher pressures of ambient pressure methods allow for higher resolving power and greater separation selectivity due to a higher rate of ion-molecule interactions. Reduced pressure IMS allows for ion-focusing and an easier interface with mass spec.
Though drift electric fields are normally uniform, non-uniform drift fields are also used. These non-uniform field IMS results are often calibrated to uniform field instrumentation. Non-uniform field usage is still in a relatively early developing stage.
DMS
DMS (differential mobility spectrometer) make use of the dependence of ion mobility K on electric field strength E at high electric fields. Ions are subjected to different field strengths for different amounts of time. Thereby only ions with certain mobility dependence survive. These types of IMS work as a scanable filter. They are also called FAIMSHigh-field asymmetric waveform ion mobility spectrometry
High-field asymmetric-waveform ion-mobility spectrometry is a mass spectrometry technique in which ions at atmospheric pressure are separated by the application of a high-voltage asymmetric waveform at radio frequency combined with a static waveform applied between two electrodes...
DMA
DMA differential mobility analyzer make 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 in mass spectrometryMass spectrometry
Mass spectrometry is an analytical technique that measures the mass-to-charge ratio of charged particles.It is used for determining masses of particles, for determining the elemental composition of a sample or molecule, and for elucidating the chemical structures of molecules, such as peptides and...
. They also work as a scanable filter. Examples include DMD (Differential Mobility Detector
Differential mobility detector
Differential Mobility Detector is a type of microelectromechanical system, radio frequency modulated IMS device.Due its small size, it easily fits into portable units, such as transferable gas chromatographs or drug/explosives sensors...
), first commercialized in Varian
Varian
Varian may refer to:People:* Varian Fry , American journalist who helped thousands escape from Nazi-occupied Europe during World War II...
CP-4900 MicroGC.
Drift Gas
The drift gas pressure is an important parameter for the IMS instrument design and resolution. Most drift gases have a greater potential to break down at pressures higher than a few mbar, with the potential to break down increasing as the pressure increases. As an example, high drift voltages of about 10-30 kV can be used with tubes of 1 m length and high gas pressures of 100-1000 mbar to obtain high resolutions. At higher pressures than 10 mbar, ions become more difficult to store. At lower pressures, ions can be stored more easily to obtain an accumulated continuous signal, with the trade-off of lower electric fields (around 10-30 V/cm).Elevated gas temperature assists in removing ion clusters that may distort experimental measurements.
Detector
Often the detector is a simple Faraday plate, however, more advanced ion mobility instruments are coupledIon mobility spectrometry-mass spectrometry
Ion-mobility spectrometry–mass spectrometry is a method that combines ion-mobility spectrometry and mass spectrometry to identify different substances within a test sample.-History:...
with mass spectrometers where both size and mass information may be obtained simultaneously.
Ion traps
Ion trap mobility spectrometry is an instrumental analytical method for detection and analysis of chemical substances, able to detect very low concentrations of chemicals based upon the differential migration of ionIon
An ion is an atom or molecule in which the total number of electrons is not equal to the total number of protons, giving it a net positive or negative electrical charge. The name was given by physicist Michael Faraday for the substances that allow a current to pass between electrodes in a...
s through homogeneous electric field
Electric field
In physics, an electric field surrounds electrically charged particles and time-varying magnetic fields. The electric field depicts the force exerted on other electrically charged objects by the electrically charged particle the field is surrounding...
. It is a version of ion mobility spectrometry. ITMS provides a substantial performance improvement over IMS, as the shutter grid is eliminated together with the associated loss of sensitivity.
GC-IMS : Gas Chromatography - Ion Mobility Spectrometry
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.IMS-MS : Ion Mobility Spectrometry - 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.LC-IMS-MS : Liquid Chromatography - Ion Mobility Spectrometry - Mass spectrometry
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).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, drugsIllegal drug trade
The illegal drug trade is a global black market, dedicated to cultivation, manufacture, distribution and sale of those substances which are subject to drug prohibition laws. Most jurisdictions prohibit trade, except under license, of many types of drugs by drug prohibition laws.A UN report said the...
, and chemical weapons. Major manufacturers of IMS screening devices used in airports are Morpho and Smiths Detection
Smiths Group
Smiths Group plc is a global engineering company headquartered in London, United Kingdom. It has operations in over 50 countries and employs around 23,550 staff....
.
In the pharmaceutical industry IMS is used in cleaning validation
Cleaning validation
Cleaning validation for is the methodology used to assure that a cleaning process removes residues of the active pharmaceutical ingredients of the product manufactured in a piece of equipment, the cleaning aids utilized in the cleaning process and the microbial attributes...
s, 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 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
Proteomics
Proteomics is the large-scale study of proteins, particularly their structures and functions. Proteins are vital parts of living organisms, as they are the main components of the physiological metabolic pathways of cells. The term "proteomics" was first coined in 1997 to make an analogy with...
and metabolomics
Metabolomics
Metabolomics is the scientific study of chemical processes involving metabolites. Specifically, metabolomics is the "systematic study of the unique chemical fingerprints that specific cellular processes leave behind", the study of their small-molecule metabolite profiles...
. For example, IMS-MS using MALDI as the ionization method has helped make advances in proteomics, providing faster high-resolution separations of protein pieces in analysis.
Aspirating IMS is an ion mobility spectrometry technology used to detect low or trace quantities of chemicals in the surrounding atmosphere. It is applied in industrial and military purposes to detect harmful substances in air. 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
Electric field
In physics, an electric field surrounds electrically charged particles and time-varying magnetic fields. The electric field depicts the force exerted on other electrically charged objects by the electrically charged particle the field is surrounding...
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.
In metabolomics
Metabolomics
Metabolomics is the scientific study of chemical processes involving metabolites. Specifically, metabolomics is the "systematic study of the unique chemical fingerprints that specific cellular processes leave behind", the study of their small-molecule metabolite profiles...
the IMS is used to detect lung cancer
Lung cancer
Lung cancer is a disease characterized by uncontrolled cell growth in tissues of the lung. If left untreated, this growth can spread beyond the lung in a process called metastasis into nearby tissue and, eventually, into other parts of the body. Most cancers that start in lung, known as primary...
, Chronic obstructive pulmonary disease
Chronic obstructive pulmonary disease
Chronic obstructive pulmonary disease , also known as chronic obstructive lung disease , chronic obstructive airway disease , chronic airflow limitation and chronic obstructive respiratory disease , is the co-occurrence of chronic bronchitis and emphysema, a pair of commonly co-existing diseases...
, Sarcoidosis
Sarcoidosis
Sarcoidosis , also called sarcoid, Besnier-Boeck disease or Besnier-Boeck-Schaumann disease, is a disease in which abnormal collections of chronic inflammatory cells form as nodules in multiple organs. The cause of sarcoidosis is unknown...
, potential rejections after Lung transplantation
Lung transplantation
Lung transplantation, or pulmonary transplantation is a surgical procedure in which a patient's diseased lungs are partially or totally replaced by lungs which come from a donor...
and relations to bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
within the lung
Lung
The lung is the essential respiration organ in many air-breathing animals, including most tetrapods, a few fish and a few snails. In mammals and the more complex life forms, the two lungs are located near the backbone on either side of the heart...
.
External links
- Ion mobility spectrometry method and apparatus - Patent 7071465
- White paper: The science behind ion trap mobility spectrometry
- International Society for Ion Mobility Spectrometry
- International Journal for Ion Mobility Spectrometry uo to 2007
- International Journal for Ion Mobility Spectrometry since 2008 with SPRINGER