High-precision K Isotopic Analysis of Cerebrospinal Fluid and Blood Serum Microsamples via Multicollector Inductively Coupled Plasma-Mass Spectrometry Equipped with 1013 Ω Faraday Cup Amplifier Resistors

Background Potassium isotopic analysis is increasingly performed in both geological and biological contexts as a result of the introduction of MC-ICP-MS instrumentation equipped with either a collision/reaction cell or having the capability of working at “extra-high” mass resolution in order to deal with spectral interference caused by argon hydride (ArH+) ions. Potassium plays an important role in the central nervous system, and its isotopic analysis could provide an enhanced insight into the corresponding processes, but K isotopic analysis of cerebrospinal fluid is challenging due to the small volume, a few microliter only, typically available. This work aimed at developing a method for determining the K isotopic signature of serum and cerebrospinal fluid at a final K concentration of 25 ng mL-1 using Faraday cup amplifiers equipped with a 1013 Ω resistor. Results Potassium isotope ratios obtained for reference materials measured at a final K concentration of 25 ng mL-1 were in excellent agreement with the corresponding reference values and the internal and external precision for the δ41K value were 0.11 ‰ (2SE, N = 50) and 0.10 ‰ (2SD, N = 6), respectively. The robustness against the presence of matrix elements and concentration mismatch between sample and standard observed at higher K concentrations is preserved at low K concentration. Finally, K isotopic analysis of serum and cerebrospinal fluid (3 to 12 μL of sample) of healthy mice of both sexes was performed, revealing a trend towards an isotopically lighter signature for female serum and cerebrospinal fluid, however being significant for serum only. Significance This work provides a robust method for high-precision K isotopic analysis at a concentration of 25 ng mL-1. By monitoring both K isotopes, 39K and 41K, with Faraday cups connected to amplifiers with 1013 Ω resistors, accurate K isotope ratio results are obtained with a two-fold improvement in internal and external precision compared to those obtained with the set-up with traditional 1011 Ω resistors. The difference in the K isotope ratio in CSF and serum between the sexes, is possibly indicating sex-based fractionation effects during cellular uptake/release or might be affected by the hormonal effects.