One of the most basic components of a typical MS systems is its ion source—a chamber where the sample becomes negatively or positively charged, a necessary step that allows the sample to be properly separated, manipulated and analyzed by the mass analyzer. Among the most common ionization methods are chemical ionization, electron ionization and MALDI, all of which function within the vacuum chamber of the instrument and require various modes of sample preparation.

Although such ionization methods form the basis of classical MS, there continues to emerge an alternative strategy of ionizing samples, one that seeks to eliminate sample preparation completely and permit samples to be analyzed in their native states at atmospheric pressure. In fact, over the past couple decades this strategy has yielded not one, but dozens of methods collectively belonging to a family of techniques known as ambient ionization.

Ambient ionization methods for MS can generally be placed into two categories. The first category encompasses methods related to atmospheric pressure chemical ionization (APCI). In APCI, analyte flowing into the ion source is exposed to heat and high-pressure gas (usually nitrogen). This forms a gas stream that sweeps past high voltage from a corona discharge pin, creating a plasma where both positive solvent ions and electrons ionize the analyte. These sample ions are then directed through a narrow ion path with a vacuum where they are sent to the mass analyzer.

The most common form of APCI-based technique is known as Direct Analysis in Real Time (DART). DART typically uses helium gas to flow through the corona discharge, where it either ionizes or forms excited atoms. When the excited atoms are directed onto the sample to form positive sample ions, a competing process that ionizes oxygen leads to the creation of negative sample ions. The heat from the helium flow, along with the like-charge repulsion of the ionized sample, evaporates the analyte ions, allowing them to enter the mass analyzer through a skimmer cone. DART technology is primarily offered through JEOL, having developed it in 2005. It is also sold by IonSense, which often collaborates with Waters to integrate the company’s MS systems with a DART ionization source.

The second category of ambient ionization methods encompasses those that are related to electrospray ionization (ESI). In ESI, analytes flowing into the ion source are subjected to a high voltage that removes ions with the opposite polarity. A solution with only one charge type remains and is directed through a narrow steel tube. When exposed to nitrogen, the solution is nebulized into a spray of charged droplets, which are quickly dried with a secondary flow of heated nitrogen gas. As the ions are released into the vapor phase, they form progressively smaller droplets that distort and develop an extension with a concave surface (a Taylor cone) from which the ions are released. Influenced by a voltage gradient and vacuum source, the ions are then directed through an ion path toward the mass analyzer.

By far the most conventional form of ambient ionization technique related to ESI is desorption electrospray ionization (DESI). Developed in 2004 by Graham Cook, PhD, at Purdue University, DESI is very similar to ESI except it lacks a secondary flow of heated nitrogen to dry the charged droplets. Instead, a mixture of methanol and water is subjected to a high voltage and nebulized with nitrogen. This stream of charged droplets is directed at the surface of solid samples, from which the analyte is ejected as ions. These ions are then directed through a collection tube to enter the mass analyzer. DESI is commonly used in cancer research, with the first instrument of its kind launched commercially in 2008 by Prosolia, which currently owns the technology. Prosolia also offers PaperSpray ionization, another variant of ESI.

Ambient ionization techniques are useful for a wide variety of applications, including forensics, food safety, petroleum analysis, environmental studies, pharmaceuticals and clinical research. The appeal of these techniques is that they require no sample pretreatment, are able to perform rapid analysis on-site and are relatively low-cost. The technique also allows for the development of miniaturized instruments.

However, their main drawbacks are that they cannot ionize all of the sample types they comes across, and the techniques are usually not validated. Also, there is also more susceptibility to increased noise within the spectrum. Despite its limitations, the market for the technology is expected to post high single digit growth over the next few years, driven by applications in drug analysis and point-of-care testing.

Ambient Ionization MS at a Glance:

Leading Vendors

• JEOL
• Prosolia
• IonSense

Largest Markets

• Forensics
• Pharmaceuticals
• Agriculture and Food

Instrument Cost:

• $40,000–$90,000