Microfluidic chip for peptide analysis with an integrated HPLC column, sample enrichment column, and nanoelectrospray tip

Anal Chem. 2005 Jan 15;77(2):527-33. doi: 10.1021/ac049068d.

Abstract

Current nano-LC/MS systems require the use of an enrichment column, a separation column, a nanospray tip, and the fittings needed to connect these parts together. In this paper, we present a microfabricated approach to nano-LC, which integrates these components on a single LC chip, eliminating the need for conventional LC connections. The chip was fabricated by laminating polyimide films with laser-ablated channels, ports, and frit structures. The enrichment and separation columns were packed using conventional reversed-phase chromatography particles. A face-seal rotary valve provided a means for switching between sample loading and separation configurations with minimum dead and delay volumes while allowing high-pressure operation. The LC chip and valve assembly were mounted within a custom electrospray source on an ion-trap mass spectrometer. The overall system performance was demonstrated through reversed-phase gradient separations of tryptic protein digests at flow rates between 100 and 400 nL/min. Microfluidic integration of the nano-LC components enabled separations with subfemtomole detection sensitivity, minimal carryover, and robust and stable electrospray throughout the LC solvent gradient.

MeSH terms

  • Chromatography, High Pressure Liquid / instrumentation*
  • Chromatography, High Pressure Liquid / methods
  • Microfluidic Analytical Techniques / instrumentation*
  • Microfluidic Analytical Techniques / methods
  • Nanotechnology
  • Peptides / analysis*
  • Sensitivity and Specificity
  • Serum Albumin, Bovine / analysis
  • Spectrometry, Mass, Electrospray Ionization / instrumentation*
  • Spectrometry, Mass, Electrospray Ionization / methods

Substances

  • Peptides
  • Serum Albumin, Bovine