New mass spectrometry method achieves single-molecule resolution

David L. Shenkenberg

Although conventional mass spectrometers can occupy a room, researchers have developed a method that may lead to a device about the size of a cell phone. They have demonstrated that the technique can discriminate between the tiniest of molecules.

The researchers were from National Institute of Standards and Technology in Gaithersburg, Md., Universidade Federal de Pernambuco in Recife, Brazil, and Wright State University in Dayton, Ohio.

In their experiment, they used a voltage applied to a buffer solution to drive poly(ethylene glycol) molecules through a channel protein, α-hemolysin from Staphylococcus aureus. As molecules of various sizes passed through the protein, a patch-clamp amplifier measured corresponding current changes. The experiment occurred within a Teflon chamber with two reservoirs that hold between 100 μl and 2 ml.

The researchers found that a decrease and a subsequent increase in the current coincided with a single poly(ethylene glycol) molecule entering and exiting the channel, respectively. Furthermore, the time that the molecule spent in the pore corresponded to its size, and the technique could discriminate among all of the poly(ethylene glycol) molecules (about 24) used in the study.

A resolution of approximately 10 to 15 g/mol was achieved. Finally, a histogram of the data corresponded well to a mass spectrogram obtained with Maldi-Tof.

Complementary technique

Senior scientist John J. Kasianowicz said that the method is complementary to Maldi-Tof. It can be done in aqueous solution and without labels, and it could be performed with a relatively low-cost instrument. He also said that the team has already improved the resolution of the technique and that the device eventually will be a lab on a chip with microfluidics portals and embedded electrodes, perhaps with signal processing electronics and a microprocessor.

PNAS, May 15, 2007, pp. 8207-8211.