Imaging mass spectrometry combines the chemical specificity and parallel detection of mass spectrometry with microscopic imaging capabilities. The ability to simultaneously obtain images from all analytes detected, from atomic to macromolecular ions, allows the analyst to probe the chemical organization of a sample and to correlate this with physical features. The sensitivity of the ionization step, sample preparation, the spatial resolution, and the speed of the technique are all important parameters that affect the type of information obtained. Recently, significant progress has been made in each of these steps for both secondary ion mass spectrometry (SIMS) and matrix-assisted laser desorption/ionization (MALDI) imaging of biological samples. Examples demonstrating localization of proteins in tumors, a reduction of lamellar phospholipids in the region binding two single celled organisms, and sub-cellular distributions of several biomolecules have all contributed to an increasing upsurge in interest in imaging mass spectrometry. Here we review many of the instrumental developments and methodological approaches responsible for this increased interest, compare and contrast the information provided by SIMS and MALDI imaging, and discuss future possibilities.

Imaging mass spectrometry

A mass spectrometer system which is capable of sampling ions directly from an atmospheric pressure source has been constructed and used to investigate ions which are evaporated from the surface of highly charged water droplets. Solutions of electrolytes are sprayed into the air, and a large charge imparted to the droplets by induction; an electric field applied across the plume of evaporating spray extracts small ions, probably already clustered with solvent molecules, which are drawn through a 25 μm orifice into the vacuum chamber. Differential pumping is applied and the ions are focused into a quadrupole mass filter. Approximately 30 univalent anions and cations of various sizes and structures have been tested, and almost all have been observed to evaporate; significant exceptions are Ag+, Tl+, and Cu+. Furthermore, certain molecules such as urea and acetanilide, when present as neutrals in the sprayed water, are observed to remain attached to the ions when these evaporate. The experimental results are ...

Field induced ion evaporation from liquid surfaces at atmospheric pressure

Micro- and nanoparticle production by electrospraying

Electrospraying utilises electrical forces for liquid atomisation. Droplets obtained by this method are highly charged to a fraction of the Rayleigh limit. The advantage of electrospraying is that the droplets can be extremely small, down to the order of 10’s nanometres, and the charge and size of the droplets can be controlled to some extent be electrical means. Motion of the charged droplets can be controlled by electric field. The deposition efficiency of the charged spray on an object is usually higher than that for uncharged droplets. Electrospray is, or potentially can be applied to many processes in industry and in scientific instruments manufacturing. The paper reviews electrospray methods and devices, including liquid metal ion sources, used for thin film deposition. This technique is applied in modern material technologies, microelectronics, micromachining, and nanotechnology.

Electrospray droplet sources for thin film deposition

A droplet pickup and other mechanisms have been suggested for the ionization of biomolecules like peptides and proteins by desorption electrospray ionization To verify this hypothesis phase Doppler particle analysis was used to study the sizes and velocities of droplets involved in DESI It was found that impacting droplets typically have velocities of 120 m/s and average diameters of 2−4 μm Small differences in sprayer construction influence the operating conditions at which droplets of these dimensions are produced Under these conditions, the kinetic energy per impacting water molecule is less than 06 meV and sputtering through momentum transfer during collisions or ionization by other electronic processes is unlikely Droplets arrive at the surface with velocities well below the speed of sound in common materials, thereby excluding the possibility of ionization by shockwave formation Some droplets appear to roll along the surface, increasing contact time and presumably the amount of material that 

Droplet Dynamics and Ionization Mechanisms in Desorption Electrospray Ionization Mass Spectrometry

An electrohydrodynamic (EHD) technique is used to generate ions from liquid metals. Liquid metal is fed to the tip of a capillary needle emitter with a voltage difference applied between the emitter and an extractor electrode to produce an intense electric field at the liquid surface. Electrostatic forces overcome surface tension forces to produce ions by field emission. When using liquid cesium, time‐of‐flight mass analysis showed the ion current to be primarily Cs+ with a small percentage of Cs2+ and Cs3+. Electron currents of over 1 mA have been produced by operating the emitter at 2 kV negative. Besides cesium, alkali ion beams have been generated using NaK/cesium alloy and sodium. Calculations show that liquid metals of low work functions appear more suitable for production of atomic ions while higher work functions metals may produce multiatomic ions and charged droplets in addition to atomic ions.

Electrohydrodynamic Ion Source

Amorphous or microcrystalline alloy powder is prepared by the rapid quenching of ultrafine metallic spheroids generated from the molten metal state. The molten metal droplets are formed when an intense electric field (10 5 V/cm) is applied to the surface of liquid metal held in a suitable container. The interactions between the intense electric field and liquid surface tension disrupts the metal surface, resulting in a beam of positively charged droplets. The liquid metal spheres generated by this electrohydrodynamic process are subsequently cooled by radiative heat transfer. Rapid cooling of the droplets may be accomplished by heat transfer to a low pressure gas by free molecular heat conductivity. Quenching rates exceeding 10 6 °K./sec are possible using this technique. Thin film coatings are prepared by electrohydrodynamically spraying a beam of charged droplets against a target (substrate). The target can be electrically controlled to effect the charged particles impact. The materials to be sprayed electrodynamically can be varied in both throughput and species such that a target can have multimaterial layers being deposited coincidentally or sequentially. The ultra small droplet size will enhance the physical properties by reducing skin stresses and enhance the optical properties by reducing the growth of crystallites in the film. Precise layers can be deposited from extremely thin films to thick filters for optical characteristics into the infrared. All materials that can be molten and contained can be electrohydrodynamically sprayed and controlled for depositions upon a substrate material.

Electrohydrodynamic spraying to produce ultrafine particles

https://link.springer.com/content/pdf/10.1016/1044-0305(92)87058-7.pdf

Shock wave model for sputtering biomolecules using massive cluster impacts

A process for producing ultrafine particles includes the steps of providing a consumable electrode having a rod or wire configuration, melting the tip of the electrode by means of electron bombardment, and applying an intense electric field to the molten tip to generate a beam of charged droplets. By heating the tip of the rod but avoiding melting of the tip and subsequently applying an electric field to the heated tip, an ion beam may be generated.

Method and apparatus for making submicrom powders

The Capillaritron is an ion source consisting of a very fine bore capillary and a concentric accelerating electrode. When a gas flows through the capillary and a potential difference of several kilovolts is maintained between the capillary and an accelerating electrode, current densities exceeding 100 A/cm2 with angular current densities greater than 6 mA/steradian are obtained from a source aperture only 2.5 × 10−3 cm in diameter. The source has been tested with hydrogen, helium, and argon and appears capable of operating with any gas. A tentative theory based on the existence of a plasma inside the capillary, which is sustained by a small flow of electrons to the capillary from the beam, and a relatively large current released from the walls by excited atoms, appears consistent with observations.

John F. Mahoney

Papers

Electrohydrodynamic Ion Source

Electrohydrodynamic spraying to produce ultrafine particles

Shock wave model for sputtering biomolecules using massive cluster impacts

Method and apparatus for making submicrom powders

Capillaritron: A new, versatile ion source