Simplifying CE-MS operation. 2. Interfacing low-flow separation techniques to mass spectrometry using a porous tip.

Area of Science:

• Analytical Chemistry
• Separation Science
• Mass Spectrometry

Background:

• Interfacing low flow rate separation techniques like capillary electrophoresis (CE) and nanoliquid chromatography (nLC) with mass spectrometry (MS) using electrospray ionization (ESI) presents challenges in achieving robust and reproducible electrical connections.
• Existing methods often involve complex setups or introduce dead volume, impacting separation efficiency and MS sensitivity, particularly for narrow-bore capillaries and low flow rates (<100 nL/min).

Purpose of the Study:

• To introduce a novel, single-step interface design for sheathless CE-MS and nLC-MS that overcomes the limitations of current interfacing techniques.
• To provide a robust, reproducible, and easily fabricated interface suitable for narrow capillaries (<30 µm i.d.) and low flow rates, enhancing analytical performance.

Main Methods:

• A porous tip was fabricated at the capillary outlet by removing polyimide coating and etching with hydrofluoric acid (HF).
• This porous tip facilitates electrical connection by inserting into the ESI needle, with background electrolyte enabling ion transport for ESI and CE outlet electrode function.
• The etching process thins the capillary wall (5-10 µm) and reduces outer diameter, enabling stable electrospray at ~1.5 kV.

Main Results:

• The porous tip design ensures stable electrospray for narrow capillaries (20-30 µm i.d.) at low voltages (~1.5 kV).
• The interface is versatile, supporting both nLC-MS and CE-MS applications with a wide range of capillary sizes and flow rates.
• Key advantages include reproducible fabrication, automation potential, no added dead volume, and externalized bubble formation, ensuring uninterrupted separation and MS performance.

Conclusions:

• The developed porous tip interface offers a significant advancement for sheathless CE-MS and nLC-MS, particularly for low flow rate and narrow-bore capillary applications.
• Its simple, robust, and reproducible design enhances analytical capabilities and simplifies the interfacing process.
• The demonstrated performance with amino acids, peptides, and proteins highlights its utility in complex mixture analysis.