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MEETING NEWS Katie Cottingham reports from the American Society for Mass Spectrometry 54th Conference on Mass Spectrometry—Seattle
Ionization of complex biological mixtures by ESI is a bit like musical chairs. The trick to the game is that for n participants, only n – 1 chairs are available; whoever doesn’t get a chair is out. Likewise, there may not be enough charge to go around when droplets of complex mixtures are electrosprayed. “Competition [can exist] between the analytes in solution for the amount of available charge” in ESI, explains Ryan Hilger. Analyte molecules at the surface of a droplet are more likely to be ionized than molecules buried deep within the droplet. To overcome this ionization suppression, many researchers incorporate separation steps so that fewer analytes are present in each droplet to compete for charge. But Hilger, Mike Westphall, Lloyd Smith, and colleagues at the University of Wisconsin are developing a different approach, which Smith describes as “milking the droplets for all they’re worth.” The researchers use a piezoelectric dispenser to create a droplet that is trapped by single-axis acoustic levitation. The droplet, which levitates between a planar emitter and a curved reflector, is then bombarded with charged solvent droplets. If the levitating droplet and the incoming droplets are of the same polarity, then the incoming droplets will simply hover near the trapped droplet. But if the droplets are of opposite charge, then the incoming droplets will be attracted to the levitating droplet, and the droplets will fuse. Initially, this process neutralizes the charge of the trapped droplet. Additional incoming droplets charge up the levitating droplet. “Eventually, the levitating droplet is so charged that the repulsive force prevents the incoming droplets from adding again,” says Hilger. The researchers
allow the trapped droplet to “desolvate until the surface charge builds up and then it will [undergo] fission,” he explains. The researchers then recharge the trapped droplet and repeat the process until all of the analytes have been ejected.
RYAN HILGER AND LLOYD SMITH
Overcoming ionization suppression in electrospray
Researchers trap a droplet, charge it, then recharge it to overcome ionization suppression and analyze all of the molecules.
The next step is to devise a way to direct the resulting analyte droplets to a mass spectrometer. “We think we should be able to use an electric field to kick the smaller progeny droplets out of the trap [because] the acoustic force on them is small,” says Hilger. After that, the researchers plan to apply the method to the study of complex biological mixtures, such as serum.
New DESI-like ionization sources Variations on desorption ESI (DESI) have been developed by Zoltán Takáts, Graham Cooks, and colleagues at Purdue University and Semmelweis University (Hungary). The three new ambient methods are ideal for different types of molecules and matrixes. In desorption atmospheric-pressure
chemical ionization (DAPCI), ions are produced by corona discharge of a nebulizing gas and a reagent vapor. The ions hit a solid target containing a sample, which undergoes ion/molecule reactions with the reagent ions. Sample ions are desorbed and then analyzed by MS. Unlike for DESI, in DAPCI liquid is not sprayed onto the sample, and only low-molecular-weight nonpolar molecules, such as steroids and explosives, are ionized. To obtain in-depth analyses of tissue, the researchers developed jet desorption ionization (JeDI). In JeDI, a high-velocity, electrically charged water jet is directed onto a sample. Charged droplets are generated upon the impact of the water jet, and these droplets produce sample ions, which are analyzed by MS. “DESI is a surface analysis technique, [but in] jet desorption, the high-velocity water intrudes into the sample,” says Takáts. Because the water jet is confined to a small point, researchers can obtain much better spatial resolution with JeDI than with DESI. Takáts explains that these features should make 3D imaging with JeDI MS a real possibility. Almost any molecule that can be ionized by ESI can be ionized with this method. The researchers plan to use JeDI MS to analyze tumors in vivo. The newest of the three techniques, extractive ESI (EESI), is ideal for studying complex liquid samples. “Usually, liquid-phase samples are a problem for DESI because when you put [a liquid sample] on a surface, the high-velocity nitrogen from the DESI just blows it away,” explains Takáts. In EESI, charged solvent droplets are sprayed into the path of sample droplets. According to Takáts, the droplets probably fuse before continuing on their journey to a mass spectrometer. He says that, so far, only small molecules and those molecules that readily undergo ESI can be analyzed by EESI MS.
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