![SESI-MS](https://upload.wikimedia.org/wikipedia/commons/2/26/SESI-MS.png)
Secondary electro-spray ionization (SESI) is an
ambient ionization
Ambient ionization is a form of ionization in which ions are formed in an ion source outside the mass spectrometer without sample preparation or separation. Ions can be formed by extraction into charged electrospray droplets, thermally desorbed a ...
technique for the analysis of trace concentrations of vapors, where a
nano-electrospray produces charging agents that collide with the analyte molecules directly in gas-phase. In the subsequent reaction, the charge is transferred and vapors get ionized, most molecules get protonated (in positive mode) and deprotonated (in negative mode). SESI works in combination with
mass spectrometry
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 use ...
or
ion-mobility spectrometry
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 detect ...
.
History
The fact that trace concentrations of gases in contact with an electrospray plume were efficiently ionized was first observed by
Fenn and colleagues when they noted that tiny concentrations of plasticizers produced intense peaks in their mass spectra. However, it was not until 2000 when this problem was reframed as a solution, when Hill and coworkers used an electrospray to ionize molecules in the gas phase, and named the technique Secondary Electrospray Ionization. In 2007, the almost simultaneous works of Zenobi
and
Pablo Sinues applied SESI to breath analysis for the first time, marking the beginning of a fruitful field or research. With sensitivities in the low ppt
v range (10
−12), SESI has been used in other applications, where the detection of low volatility vapors is important.
Detecting low volatility species in the gas phase is important because larger molecules tend to have higher biological significance. Low volatility species have been overlooked because it is technically difficult to detect them, as they are in very low concentration, and they tend to condensate in the inner piping of instruments. However, as this problem is solved, and new instruments are able to handle larger and more specific molecules, the ability to perform on-line, real time analysis of molecules naturally released in the air, even at minute concentrations, is attracting attention to this ionization technique.
Principle of operation
![Secondary electrospray ionization mechanisim diagram](https://upload.wikimedia.org/wikipedia/commons/4/4c/Secondary_electrospray_ionization_mechanisim_diagram.png)
In the early days of SESI, two ionization mechanisms were under debate.: the droplet-vapor interaction model postulates that vapors are adsorbed in the
electrospray ionization
Electrospray ionization (ESI) is a technique used in mass spectrometry to produce ions using an electrospray in which a high voltage is applied to a liquid to create an aerosol. It is especially useful in producing ions from macromolecules becaus ...
(ESI) droplets, and then reemitted as the droplet shrinks, just as regular liquid phase analytes are produced in electrospray ionization; on the other hand, the ion-vapor interaction model postulates that molecules and ions or small clusters collide, and the charge is transferred in this collision. Currently available commercial SESI sources operate at high temperature so as to better handle low volatility species. In this regime, nanodroplets from the electrospray evaporate very quickly to form ion clusters in equilibrium. This results in ion-vapor reactions dominating the majority of the ionization region. As charging ions originate from nano-droplets, and no high energy ions are involved at any point of the ionization process nor the creation of ionizing agents,
fragmentation in SESI is remarkably low, and the resulting spectra are very clean. This allows for a very high dynamic range, where low intensity peaks are not affected by more abundant species.
Some related techniques are
laser ablation electrospray ionization
Laser ablation electrospray ionization (LAESI) is an ambient ionization method for mass spectrometry that combines laser ablation from a mid-infrared (mid-IR) laser with a secondary electrospray ionization (ESI) process. The mid-IR laser is used t ...
,
proton-transfer-reaction mass spectrometry
Proton-transfer-reaction mass spectrometry (PTR-MS) is an analytical chemistry technique that uses gas phase hydronium reagent ions which are produced in an ion source. PTR-MS is used for online monitoring of volatile organic compounds (VOCs) in a ...
and
selected-ion flow-tube mass spectrometry
Selected-ion flow-tube mass spectrometry (SIFT-MS) is a quantitative mass spectrometry technique for trace gas analysis which involves the chemical ionization of trace volatile compounds by selected positive precursor ions during a well-defined ...
.
Applications
![SESI_and_the_analysis_of_relevant_metabolites](https://upload.wikimedia.org/wikipedia/commons/6/66/SESI_and_the_analysis_of_relevant_metabolites.png)
The main feature of SESI is that it can detect minuscule concentrations of low
volatility species in real time, with molecular masses as high as 700 Da, falling in the realm of
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 ...
. These molecules are naturally released by living organisms, and are commonly detected as odors, which means that they can be analyzed
non-invasively. SESI, combined with High Resolution Mass Spectrometry, provides time-resolved, biologically relevant information of living systems, where the system does not need to be interfered with. This allows to seamlessly capture the time
evolution of their metabolism and their response to controlled stimuli.
SESI has been widely used for
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 ...
for
biomarker
In biomedical contexts, a biomarker, or biological marker, is a measurable indicator of some biological state or condition. Biomarkers are often measured and evaluated using blood, urine, or soft tissues to examine normal biological processes, ...
discovery, and ''in vivo''
pharmacokinetic
Pharmacokinetics (from Ancient Greek ''pharmakon'' "drug" and ''kinetikos'' "moving, putting in motion"; see chemical kinetics), sometimes abbreviated as PK, is a branch of pharmacology dedicated to determining the fate of substances administered ...
studies:
Biomarker discovery
Bacterial infection
It has been widely reported the identification of bacteria by their
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 ...
fingerprint. SESI-MS has proven to be a robust technique for the identification of bacteria from cell cultures and infections ''in vivo'' from breath samples, after the development of libraries of vapor profiles. Other studies include: ''In vivo'' differentiation between critical pathogens ''Staphylococcus aureus'' and ''Pseudomonas aeruginosa''. or differential detection among antibiotic resistant ''S. aureus'' and its non-resistant strains. Bacterial infection detection from other fluids such as saliva have also been reported.
Respiratory diseases
Many chronic respiratory diseases lack of an appropriate method of monitoring and differentiation among disease stages. SESI-MS has been used to diagnose and distinguish exacerbations from breath samples in
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 ...
. Metabolic profiling of breath samples has accurately differentiated healthy individuals from
idiopathic pulmonary fibrosis
Idiopathic pulmonary fibrosis (IPF), or (formerly) fibrosing alveolitis, is a rare, progressive illness of the respiratory system, characterized by the thickening and stiffening of lung tissue, associated with the formation of scar tissue. It is ...
or
obstructive sleep apnea
Obstructive sleep apnea (OSA) is the most common sleep-related breathing disorder and is characterized by recurrent episodes of complete or partial obstruction of the upper airway leading to reduced or absent breathing during sleep. These episod ...
patients.
Cancer
SESI-MS is being studied as a non-invasive detection system of cancer biomarkers in breath. A preliminary study differentiates patients suffering from breast neoplasia.
Skin
Volatiles released from the skin can be detected by sampling the ambient gas surrounding it, providing a fast method for detecting metabolic changes in fatty acids composition patterns.
Pharmacokinetics
To study pharmacokinetics, it is necessary a robust technique because of the complex nature of the samples' matrix, be it plasma, urine, or breath. Recent studies show that secondary electrospray ionization (SESI) is a powerful technique to monitor drug kinetics via breath analysis.
Because breath is naturally produced, several datapoints can be readily collected. This allows for the number of collected data-points to be greatly increased.
In animal studies, this approach SESI can reduce animal sacrifice while yielding pharmacokinetic curves with unmatched time resolutions.
In humans, SESI-MS non-invasive analysis of breath can help study the kinetics of drugs at a personalized level.
Monitoring exogenously introduced species allows tracking their specific metabolic pathway, which reduces the risk of picking
confounding factors
In statistics, a confounder (also confounding variable, confounding factor, extraneous determinant or lurking variable) is a variable that influences both the dependent variable and independent variable, causing a spurious association. Con ...
.
Time-resolved metabolic analysis
Introducing known stimuli, such as specific metabolites isotopically labeled compounds, or other sources of stress triggers metabolic changes which can be easily monitored with SESI-MS. Some examples if this include: cell culture volatile compounds profiling; and metabolic studies for plant or trace human metabolic pathways.
Other applications
Other applications developed with SESI-MS include:
* Detection of illicit drugs;
* Detection of explosives;
* Food quality control monitoring.
References
{{DEFAULTSORT:Secondary electrospray Ionization (SESI)
Mass spectrometry
External links
Deep Breath InitiativeFossiliontechSinueslab Breath Research
Breath tests
Mathematical and theoretical biology
Mathematical modeling