Miniaturization of electrospray ionization mass spectrometry

The development of electrospray ionization (ESI) has proved an enormous breakthrough in structural biology because it provides a means for transferring large biological molecules into the gas-phase as intact charged ions. In the post-genomics era, increased attention has been focused on mass spectrometry techniques capable of providing structural information for biological molecules-especially proteins-with minimal sample consumption. Miniaturized ESI, known as either microspray or nanospray, is of keen interest in structural biology because of its low sample consumption requirements, low flow rates (nL/min), and improved ion transfer efficiency from source to detector vs. conventional ESI sources. Here, the principles of ESI are detailed, followed by a discussion on the development, advantages, and applications of miniaturized ESI, especially as applied in structural biology. Along the way, we also highlight some of our own research aimed at producing high-durability nanospray emitters for utility in coupling capillary separations techniques with miniaturized ESI sources.