Laser Ablation–Inductively Coupled Plasma Mass Spectrometry: An Emerging Technology for Detecting Rare Cells in Tissue Sections

Abstract

Administering immunoregulatory cells to patients as medicinal agents is a potentially revolutionary approach to the treatment of immunologically mediated diseases. Presently, there are no satisfactory, clinically applicable methods of tracking human cells in patients with adequate spatial resolution and target cell specificity over a sufficient period of time. Laser ablation–inductively coupled plasma mass spectrometry (LA-ICP-MS) represents a potential solution to the problem of detecting very rare cells in tissues. In this article, this exquisitely sensitive technique is applied to the tracking of gold-labeled human regulatory macrophages (Mregs) in immunodeficient mice. Optimal conditions for labeling Mregs with 50-nm gold particles were investigated by exposing Mregs in culture to variable concentrations of label: Mregs incubated with 3.5 × 109 particles/ml for 1 h incorporated an average of 3.39 × 108 Au atoms/cell without loss of cell viability. Analysis of single, gold-labeled Mregs by LA-ICP-MS registered an average of 1.9 × 105 counts/cell. Under these conditions, 100% labeling efficiency was achieved, and label was retained by Mregs for ≥36 h. Gold-labeled Mregs adhered to glass surfaces; after 24 h of culture, it was possible to colabel these cells with human-specific 154Sm-tagged anti–HLA-DR or 174Yb-tagged anti-CD45 mAbs. Following injection into immunodeficient mice, signals from gold-labeled human Mregs could be detected in mouse lung, liver, and spleen for at least 7 d by solution-based inductively coupled plasma mass spectrometry and LA-ICP-MS. These promising results indicate that LA-ICP-MS tissue imaging has great potential as an analytical technique in immunology.

High-throughput quantitation of inorganic nanoparticle biodistribution at the single-cell level using mass cytometry

“…Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) enables quantitation of metal contents at the single-cell level with additional insights on sub-cellular localization of NPs, however this image-based method also suffers from low throughput (tens to hundreds of cells typically analysed) and relatively low sensitivity (requiring millions of atoms per cell)151617. Single particle ICP-MS (SP-ICP-MS) is another ICP-based method that utilizes time-resolved mode to enable direct quantification of the number concentration, size distribution of NPs, and their state of agglomeration1819.…”

Multielemental bioimaging of tissues in children's environmental health research

“…Not only can metal-tagged antibodies be used to identify associations between metals and biologically-relevant proteins, they can also be used to identify rare yet important cell types in a number of chronic diseases [30], which may have implications for rare diseases in children. While most immunohistochemical approaches rely on secondary antibodies to amplify the signal for target detection, the sensitive nature of elemental imaging allows the direct use of metal-tagged primary antibodies, thus enabling the development of highly-multiplexed imaging methods.…”

High-Speed, Integrated Ablation Cell and Dual Concentric Injector Plasma Torch for Laser Ablation-Inductively Coupled Plasma Mass Spectrometry

“…Two important fields in which Laser Ablation-Inductively Coupled Plasma-Mass Spectrometry (LA-ICP-MS) is experiencing growing demand are those of imaging/mapping, notably of biological targets [1][2][3][4][5][6] and the analysis of discrete smallvolume samples such as single cells [7][8][9][10][11] or nanoparticulate [12][13][14] . For example this technique has been used to investigate the etiology and pathogenesis of disease states arising from imbalances in metal homeostasis.…”