Probe electrospray ionization

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Probe electrospray ionization (PESI) is an electrospray-based ambient ionization technique which is coupled with mass spectrometry for sample analysis. [1] [2] Unlike traditional mass spectrometry ion sources which must be maintained in a vacuum, ambient ionization techniques permit sample ionization under ambient conditions, allowing for the high-throughput analysis of samples in their native state, often with minimal or no sample pre-treatment. [3] The PESI ion source simply consists of a needle to which a high voltage is applied following sample pick-up, initiating electrospray directly from the solid needle.

Contents

History

Probe electrospray ionization is an ambient ionization mass spectrometry technique developed by Kenzo Hiraoka et al. at the University of Yamanashi, Japan. [4] The technique was developed to address some of the issues associated with traditional electrospray ionization (ESI), including clogging of the capillary and contamination, whilst providing a means of rapid and direct sample analysis. Since its initial conception, various modified forms of the PESI ion source have been developed, and the PESI-MS system has been commercialized by instrument manufacturing company Shimadzu.

Principle of operation

The PESI ion source consists of a solid needle or wire which acts as both the sampling probe and electrospray emitter. [5] The needle is moved up and down along a vertical axis, a process which can be either automated or manual. When the needle is lowered to the sampling stage, the tip of the needle briefly touches the surface of a typical liquid sample. During this stage, the needle is held at ground potential. The needle is then raised to be level with the mass spectrometer inlet where a high voltage of 2–3 kV is applied. Electrospray is induced at the tip of the needle, producing analyte ions which are drawn into the mass spectrometer for analysis. The mechanism by which ions are formed is believed to be identical to traditional electrospray ionization. As a result, in positive ion mode analytes are often observed as the protonated, sodiated and potentiated ions, depending on the sample and analyte type.

Probe electrospray ionization (PESI) schematic Probe electrospray ionization (schematic).png
Probe electrospray ionization (PESI) schematic

Although the amount of sample picked up by the needle is largely dependent on sample viscosity, it has been estimated that just a few picolitres of the sample solution are typically used. [6]

Because of this, the technique can be applied to small sample sizes, particularly ideal when limited sample amounts are available. As such a small sample amount is picked up and completely exhausted during the ionization process, issues of contamination are severely reduced. Furthermore, the process of sampling and ionization takes just a few seconds, so PESI-MS is suitable for high-throughput analysis.

Sequential ionization

A phenomenon observed with probe electrospray ionization is the sequential and exhaustive ionization of analytes with different surface activities. During the development of PESI, it was discovered that analytes could be sequentially ionized throughout the electrospray, thus enabling a temporal separation of components within a sample. [7] In normal ESI, the sample solution is typically continuously supplied through a capillary and the charged droplets contain all sample components, with more surface-active analytes being constantly preferentially ionized. In PESI, surface-active analytes are also preferentially ionized. However, as a finite droplet exists on the tip of the needle, following the depletion of surface-active analytes, the remaining components in the droplet can then be ionized and observed. This can result in the production of distinctively different mass spectra from a single sample over the application of the high voltage for just a few seconds.

This effect offers a particular advantage in the analysis of analytes suffering from ion suppression effects. The presence of surface-active analytes or charged solvent additives can result in the suppressed ionization of analytes of interest, resulting in low sensitivity or the complete absence of the analyte. [7] The effects of ion suppression can be minimized by reducing the complexity of the sample, for instance through sample extraction techniques such as solid phase extraction, or by separation of analytes of interest using chromatographic separation. However, these sample preparation steps can be laborious, time-consuming and expensive. PESI enables a reduction in ion suppression without the need for sample pre-treatment. By separating the ionization of different analytes, components causing ion suppression can be exhausted before enabling the ionization of components of interest. This has been demonstrated in a number of scenarios, including in the analysis of raw urine, with concentrated components such as creatinine ionization initially, followed by the appearance of previously undetected metabolites. [8]

Sheath-flow PESI

As the PESI needle is only applicable to liquid or penetrable solid samples, it cannot be used for the analysis of the majority of dry solid materials. To circumvent this limitation, sheath-flow probe electrospray ionization (sfPESI) was developed, a modification of the traditional PESI technique. The sfPESI ion source consists of a solid needle housed within a plastic sheath (typically a gel-loading tip) filled with a small amount of solvent. The needle protrudes from the base of the sheath by approximately 0.1 mm, where a minute solvent droplet is held. The based of[ clarification needed ] based the probe is briefly touched to the sample surface, where a convex solvent meniscus forms between the probe and the sample, wetting the sample and enabling analyte extraction. [9] The chemistry of the solvent can be modified to induce the extraction of particular analytes of interest. After application to the sample, the sfPESI probe is then raised to be level with the mass spectrometer inlet, with solubilised analytes held in the droplet at the tip of the needle, and a high voltage applied. sfPESI offers the same advantages as standard PESI, including the sequential and exhaustive ionization phenomenon, whilst enabling the direct analysis of dry samples.

Applications

PESI-MS has proven to be particularly effective in the metabolic analysis of biological materials, having been applied to the analysis of cancerous and non-cancerous breast tissue, [10] as well as brain and liver tissue removed from mice. [11] [12] Interestingly, PESI-MS has recently been applied to the direct analysis of living animals for real-time metabolic profiling. [13] [14] Due to the narrow diameter of the PESI needle and brief sample introduction time, PESI is reasonably non-invasive. As a result, the technique has been used to sample from the organs of living anaesthetized animals, specifically to analyse metabolites in the brain, spleen, liver and kidney of a living mouse. In addition to this, PESI-MS has been applied to the on-site analysis of food products for the purpose of quality control, to the detection of herbicides in body fluids to demonstrate exposure, and finally to the detection of illicit drugs in bodily fluids to indicate drug use. Several groups have also harnessed the small size of the PESI probe to achieve single-cell analysis, demonstrating the capability of rapidly detecting metabolites at cellular and subcellular levels. [15] [16] [17]

The PESI modification known as sheath-flow PESI has been applied to the analysis of various solid samples in their native state, including pharmaceutical tablets, [9] illicit drugs, [5] food and agricultural products, [18] and pesticides. [19] In addition, sfPESI has been utilised in the field of forensic science for the analysis and identification of fresh and dried body fluids of forensic interest. [8] In this work, sfPESI was also coupled with tandem mass spectrometry (MS/MS), demonstrating the capability of ion fragmentation for identification of unknown components.

See also

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<span class="mw-page-title-main">Liquid chromatography–mass spectrometry</span> Analytical chemistry technique

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<span class="mw-page-title-main">Laser spray ionization</span>

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<span class="mw-page-title-main">Capillary electrophoresis–mass spectrometry</span>

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<span class="mw-page-title-main">Laser ablation electrospray ionization</span>

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 to generate gas phase particles which are then ionized through interactions with charged droplets from the ESI source. LAESI was developed in Professor Akos Vertes lab by Dr. Peter Nemes in 2007 and it was marketed commercially by Protea Biosciences, Inc until 2017. Fiber-LAESI for single-cell analysis approach was developed by Dr. Bindesh Shrestha in Professor Vertes lab in 2009. LAESI is a novel ionization source for mass spectrometry (MS) that has been used to perform MS imaging of plants, tissues, cell pellets, and even single cells. In addition, LAESI has been used to analyze historic documents and untreated biofluids such as urine and blood. The technique of LAESI is performed at atmospheric pressure and therefore overcomes many of the obstacles of traditional MS techniques, including extensive and invasive sample preparation steps and the use of high vacuum. Because molecules and aerosols are ionized by interacting with an electrospray plume, LAESI's ionization mechanism is similar to SESI and EESI techniques.

<span class="mw-page-title-main">Surface-assisted laser desorption/ionization</span>

Surface-assisted laser desorption/ionization (SALDI) is a soft laser desorption technique used for mass spectrometry analysis of biomolecules, polymers, and small organic molecules. In its first embodiment Koichi Tanaka used a cobalt/glycerol liquid matrix and subsequent applications included a graphite/glycerol liquid matrix as well as a solid surface of porous silicon. The porous silicon represents the first matrix-free SALDI surface analysis allowing for facile detection of intact molecular ions, these porous silicon surfaces also facilitated the analysis of small molecules at the yoctomole level. At present laser desorption/ionization methods using other inorganic matrices such as nanomaterials are often regarded as SALDI variants. As an example, silicon nanowires as well as Titania nanotube arrays (NTA) have been used as substrates to detect small molecules. SALDI is used to detect proteins and protein-protein complexes. A related method named "ambient SALDI" - which is a combination of conventional SALDI with ambient mass spectrometry incorporating the direct analysis real time (DART) ion source has also been demonstrated. SALDI is considered one of the most important techniques in MS and has many applications.

<span class="mw-page-title-main">Extractive electrospray ionization</span>

Extractive electrospray ionization (EESI) is a spray-type, ambient ionization source in mass spectrometry that uses two colliding aerosols, one of which is generated by electrospray. In standard EESI, syringe pumps provide the liquids for both an electrospray and a sample spray. In neutral desorption EESI (ND-EESI), the liquid for the sample aerosol is provided by a flow of nitrogen.

<span class="mw-page-title-main">Nanospray desorption electrospray ionization</span>

Nanospray desorption electrospray ionization (nano-DESI) is an ambient pressure ionization technique used in mass spectrometry (MS) for chemical analysis of organic molecules. In this technique, analytes are desorbed into a liquid bridge formed between two capillaries and the sampling surface. Unlike desorption electrospray ionization (DESI), from which nano-DESI is derived, nano-DESI makes use of a secondary capillary, which improves the sampling efficiency.

<span class="mw-page-title-main">Atmospheric pressure photoionization</span> Soft ionization method

Atmospheric pressure photoionization (APPI) is a soft ionization method used in mass spectrometry (MS) usually coupled to liquid chromatography (LC). Molecules are ionized using a vacuum ultraviolet (VUV) light source operating at atmospheric pressure, either by direct absorption followed by electron ejection or through ionization of a dopant molecule that leads to chemical ionization of target molecules. The sample is usually a solvent spray that is vaporized by nebulization and heat. The benefit of APPI is that it ionizes molecules across a broad range of polarity and is particularly useful for ionization of low polarity molecules for which other popular ionization methods such as electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI) are less suitable. It is also less prone to ion suppression and matrix effects compared to ESI and APCI and typically has a wide linear dynamic range. The application of APPI with LC/MS is commonly used for analysis of petroleum compounds, pesticides, steroids, and drug metabolites lacking polar functional groups and is being extensively deployed for ambient ionization particularly for explosives detection in security applications.

<span class="mw-page-title-main">Secondary electrospray ionization</span>

Secondary electro-spray ionization (SESI) is an ambient ionization 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 and deprotonated. SESI works in combination with mass spectrometry or ion-mobility spectrometry.

References

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  9. 1 2 Usmanov, Dilshadbek T.; Ashurov, Khatam B.; Ninomiya, Satoshi; Hiraoka, Kenzo; Wada, Hiroshi; Nakano, Hiroshi; Matsumura, Masaya; Sanada-Morimura, Sachiyo; Nonami, Hiroshi (2018-03-15). "Remote sampling mass spectrometry for dry samples: Sheath-flow probe electrospray ionization (PESI) using a gel-loading tip inserted with an acupuncture needle". Rapid Communications in Mass Spectrometry. 32 (5): 407–413. Bibcode:2018RCMS...32..407U. doi:10.1002/rcm.8045. PMID   29235697.
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