B-052 Automation of sample preparation workflow for trace elements testing by ICP-MS/MS

Abstract

Background Inductively coupled plasma–tandem mass spectrometry (ICP-MS/MS) is a gold standard for testing of trace elements. Despite its wide adoption within the clinical laboratories, sample preparation workflow is largely manual, time consuming, and prone to environmental contamination. Our clinical laboratory processes hundreds of serum samples daily and automation is needed for efficiency improvement. The objective of this study was to automate and validate a sample preparation procedure for quantitation of zinc (Zn), copper (Cu) and selenium (Se) in human serum by ICP-MS/MS. Methods We worked with the vendor to customize the Revvity Janus G3 expanded liquid handling workstation for trace elements testing to 1. scan barcodes on specimen collection (primary) tubes and sample preparation (secondary) tubes to verify sample matching; 2. add diluent with internal standards to secondary tubes; 3. aliquot blanks, calibrators, quality controls and human serum samples from the standard rack or primary tubes to secondary tubes. Zn, Cu and Se in human serum samples were quantified by an Agilent 8900 Triple Quadrupole ICP-MS/MS equipped with an SPS 4 autosampler. An in-house developed middleware was used to support sample preparation, automate data analysis and reporting. Results Linear regression results for the method comparison between the automated sample preparation method (y) and the manual sample preparation method (x) were y = 1.04x - 0.14 (R2=0.999, n=264) for serum Zn, y = 1.04x - 0.22 (R2=0.998, n=264) for serum Cu, and y = 1.03x + 0.00 (R2=0.994, n=264) for serum Se. A blank batch test with 96 blank samples was performed to determine environmental contamination during automated pipetting. It was demonstrated that the Janus workstation with enclosure, HEPA filter and a custom-made plastic cover on the barcode scanning arm are needed to minimize contamination. Additional control measures implemented to mitigate the risks of sample prep contamination include: a daily Janus deck cleaning, a weekly Janus workstation cleaning, and a monthly blank test. The results of other validation studies: calibration preparation verification, accuracy, precision, stability of standards (metal standards, QCs and 1% nitric acid), and storage caps for royal blue top tubes (without additive) all met the acceptable performance limits. Conclusion An automated sample preparation method using Revvity Janus G3 expanded liquid handling workstation has been successfully developed and validated for quantitation of Zn, Cu and Se in human serum samples by ICP-MS/MS. Since its implementation in February 2025, the automation method has resulted in 38%±9% (n=3) of hands-on time savings compared to the manual approach. Similar methods with minor modifications could be applied to other ICP-MS/MS applications for trace elements testing in human serum matrices.