Microfluidic high performance liquid chromatography-chip hyphenation to inductively coupled plasma-mass spectrometry

•Coupling of a microfluidic chip HPLC to ICP-MS.•New low flow (300 nL min−1) nebulizer.•Simple and sensitive analysis of cobalamin in horse plasma.

The Agilent Chip Cube Interface is a microfluidic chip-based technology originally designed for nanospray molecular mass spectrometry in which the sample enrichment, nano-column, tubing, connectors and spray tip were integrated into a single biocompatible chip. Here we describe the hyphenation of the Chip Cube Interface to ICP-MS via modification of the standard HPLC chip design and a new total consumption nebuliser suitable for flow rates as low as 300 nL min−1. The potential of the instrument to eliminate common nanoLC - ICP-MS shortcomings such as leaks, blockages and band-broadening was demonstrated via analysis of cyanocobalamin in equine plasma. The method was linear over three orders of magnitude with an r2 of 0.9999, the peak area repeatability was 1.9% (n = 7), and the detection limit was 14 ng mL−1. This novel configuration of the Chip Cube Interface coupled to ICP-MS is a suitable platform for the analysis of biomolecules associated with trace metals and speciation applications.