Development of micromachined hollow tips for protein analysis based on nanoelectrospray ionization mass spectrometry

Abstract

Two novel types of micromachined nanoelectrospray emitter tips have been designed, fabricated and tested. The fabrication method of the hollow tips is based on a self-aligning deep reactive ion etch process. The tips consist of either silicon dioxide or silicon and feature orifice diameters of 10 and 18 μm, respectively. The geometrical characteristics of both emitter types are favorable for the generation of stable electrospray ionization, i.e. wetting of the tip shaft is avoided and the base of the Taylor cone is limited to the diameter of the orifice. A silicon dioxide tip was operated in a bench top setup to visually evaluate the electrospray. Both types of tips were also successfully used for the analysis of an insulin sample in an ion trap mass spectrometer.

Why the move to microfluidics for protein analysis?

“…These devices are now being microfabricated with technologies imported from the microelectronics industry to improve reproducibility and robustness of the system. Many technological approaches have been based on polymer [10][11][12][13] and glass or silicon [14,15] microfabrication, among them are mature devices working either with robotic stations such as the Nanomate TM system from Advion Biosciences [16 ] or stand-alone disposable devices [17]. This kind of micro-or nanospray microfabricated emitter is appearing at a time when exciting developments in mass spectrometry are starting to emerge, such as new methodologies based on the capabilities of MS for the structural elucidation of protein complexes or complex mixture analysis.…”

An open design microfabricated nib-like nanoelectrospray emitter tip on a conducting silicon substrate for the application of the ionization voltage

“…Microfabrication of ESI emitter tips follows two main approaches: (1) a "needle-like" ap-proach or (2) a "channel-like" approach consisting of a sharpened interface at the outlet of a microchannel. "Needle-like" approaches were reported using silicon nitride [11], parylene [12], silicon [13][14][15], as well as polycarbonate [16] or polymethyl methacrylate (PMMA) [17]. The reported "channel-like" approaches include PMMA starshaped systems [18], polydimethyl siloxane (PDMS) devices having a triangular shape [19], devices based on a groove feature [20], machined point-like structures [21], polyimide-based triangular systems [22], and triangular parylene sheet-based devices [23].…”

Microfabricated out-of-plane arrays of integrated capillary nano-electrospray emitters

“…The process flow for the capillaries is summarized in Figure 5. The shape of the tip of the capillaries is based on a design by Griss et al [8]. A key step is the use of a silicon nitride layer that serves as a mask during oxidation, preventing the top of the capillaries from being oxidized (Fig 5d-e), thus making a self-aligned oxide mask for the DRIE of the inside of the capillaries.…”