On-line reverse isotope dilution analysis for spatial quantification of elemental labels used in immunohistochemical assisted imaging mass spectrometry via LA-ICP-MS

Abstract

We present a novel on-line isotope dilution analysis (IDA) approach for the quantification of isotopically enriched metal labels used in immunohistochemical assisted imaging mass spectrometry.

Laser Ablation–Inductively Coupled Plasma–Mass Spectrometry Imaging in Biology

“…164 Douglas et al 165 investigated the uncertainty for the analysis of biological tissue and developed a method to directly determine mass flows for ID. Clases et al 166 used a gelatin-based standard material for the calculation of mass fractions and applied online ID for the spatial quantification of tyrosine hydroxylase (TH) in the substantia nigra of murine brains and compared it with external calibration. Metal-coded antibodies (anti-TH) were used as proxy for TH, repurposed from the isotopically enriched lanthanides used as metal tags for mass cytometry.…”

“…As such, online isotope dilution was performed with conventional standards for ICP-MS in a reverse ID approach. 166…”

Preparation of ashless cellulose paper standards for rapid determination of multi-element concentrations in airborne fine particulate matter using laser ablation inductively coupled plasma mass spectrometry

“…[17][18][19] In recent years, multiple quantitative analysis methods have been reported, including external calibration with or without internal standardization, solution-based calibration, and isotope dilution. [20][21][22][23] In general, external calibration strategy using solid certied materials (CRMs) that match the composition of an actual sample is the most reliable quantitative analysis method for LA-ICP-MS. There are several commercial solid CRMs for different types of materials such as glass and ceramics; unfortunately, they cannot cover every type of sample (e.g., biological tissues or mineral compositions).…”

Low background mould-prepared gelatine standards for reproducible quantification in elemental bio-imaging

“…Recent advances in immunohistochemistry have expanded the applicability of LA-ICP-MS to the qualitative and quantitative investigation of biomolecule distributions 2,3 . Internal standardisation approaches 5,6 to overcome instrumental drifts as well as progress in sampling techniques 4 have contributed to improved precision and accuracy and rapid analyses 7 . LA-ICP-MS is often considered the gold standard for spatial quantification of elements in biological tissues due to its high dynamic range and species-and matrix-independent ionisation and detection.…”

“…However, consistent ablation with a pulsed laser is dependent on the matrix of the standard and specimen, and internal standardisation is difficult. Instrumental drift also influences quantification, which becomes particularly pronounced when long acquisition times are required 6,8 . The quantification of biomolecules is even more challenging and requires careful characterisation of the labelled bio-probes 9 .…”