High-precision K isotopic analysis of cerebrospinal fluid and blood serum microsamples via multicollector inductively coupled plasma-mass spectrometry equipped with 10 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 either equipped with 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 using Faraday cup amplifiers equipped with a 10 Ω resistor.

Results: Potassium isotope ratios obtained for reference materials measured at a final K concentration of 25 ng mL were in excellent agreement with the corresponding reference values and the internal and external precision for the δK value was 0.11 ‰ (2SE, N = 50) and 0.10 ‰ (2SD, N = 6), respectively. The robustness against the presence of matrix elements and the 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 (3-12 μL of sample) of healthy mice of both sexes was performed, revealing a trend towards an isotopically lighter signature for serum and cerebrospinal fluid from female individuals, 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. By monitoring both K isotopes, K and K, with Faraday cups connected to amplifiers with 10 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 10 Ω resistors. The difference in the K isotope ratio in CSF and serum between the sexes, is possibly indicating an influence of the sex or hormones on the fractionation effects accompanying cellular uptake/release.