A high-throughput microdialysis–parallel solid phase extraction–inductively coupled plasma mass spectrometry hyphenated system for continuous monitoring of extracellular metal ions in living rat brain

• The online segmentation and parallel solid phase extraction technique were combined.
• An online automatic MD/parallel PVC SPE/ICP-MS hyphenated system was developed.
• The sampling frequencies were highly improved to 180 h−1.
• The volume of microdialysates analyzed in this system was only 0.83 μL.
• After perfusing a high-K+ medium via MD probe, the Zn2+ was released into brain ECF.

To significantly improve the temporal resolving power of in vivo trace brain metal monitoring system, in this paper we describe a novel analytical configuration combining the dual functions of online segmentation of the rat brain microdialysate and parallel solid phase extraction (SPE) of multiple segmented samples. In contrast to traditional SPE procedures, in this study the three pumped media—the buffered rat brain microdialysate, the eluent, and the air stream—were converted to a series of segmented streams through the manipulation of a flow-through stream selector. After optimizing this online automatic MD/parallel poly(vinyl chloride) SPE/inductively coupled plasma mass spectrometry hyphenated system for the analysis of ultra-trace metal ions, the sample volume of the microdialysate was set at 0.83 μL, the analytical sequence was repeatable every 20 s, and the detection limits were in the range 0.03–0.24 μg L−1, with spike analyses of Mn, Co, Ni, Cu, and Zn in a rat brain ECF sample agreeing well with expected values (88–107%). To further examine the system's practicability, we also performed (i) in vivo dynamic monitoring of these trace metal ions in living rat brain extracellular fluid post-probe implantation (the basal values for Mn, Co, Ni, Cu, and Zn were 1.17 ± 0.18, 1.27 ± 0.36, 2.46 ± 0.62, 0.86 ± 0.37, and 2.35 ± 0.55 μg L−1, respectively) and (ii) real-time visualization of the physiological response to acute neural depolarization elicited upon perfusing a high-K+ medium through the MD probe.