Proof-of-concept: Interfacing the liquid sampling-atmospheric pressure glow discharge ion source with a miniature quadrupole mass spectrometer towards trace metal analysis in cell culture media

Abstract

In an effort to provide a mass spectrometry system capable of at-reactor trace metal analysis of bioprocess media and clarified cell culture fluid, the liquid sampling-atmospheric pressure glow discharge (LS-APGD) ion source was interfaced with a Waters QDa mass spectrometer. The LS-APGD is capable of elemental analysis, as well as organic compound determinations. The Waters QDa is a compact, rack-mounted single quadrupole mass analyzer commonly employed in an integrated liquid chromatography system. By replacing the QDa's standard electrospray ionization (ESI) source with the LS-APGD, trace metal analysis of bioprocess stock media samples can be performed, alleviating use of high-end, inductively coupled plasma (ICP-MS) instruments. Presented here is a proof-of-concept effort, interfacing the microplasma to this platform for the first time. Preliminary optimization of the LS-APGD operating parameters and the QDa's in-source collision induced dissociation (CID) conditions was performed, yielding signal intensities of >6 × 10⁷ AU for a multi-element test solution containing 25 μg mL⁻¹ of Cu, Ag, and Tl. As further proof-of-concept, Chinese hamster ovary (CHO) cell culture medium was spiked with the same elemental concentrations and analyzed on the LS-APGD/QDa system. Stable plasma response allows spectral background subtraction of the media components, yielding analytically-relevant elemental signals. These results suggest that the LS-APGD/QDa coupling may be a viable approach for at-bioreactor, elemental analysis.