Expanding the boundaries of atomic spectroscopy at the single-cell level: critical review of SP-ICP-MS, LIBS and LA-ICP-MS advances for the elemental analysis of tissues and single cells

Abstract

Metals have a fundamental role in microbiology, and accurate methods are needed for their identification and quantification. The inability to assess cellular heterogeneity is considered an impediment to the successful treatment of different diseases. Unlike bulk approaches, single-cell analysis allows elemental heterogeneity across genetically identical populations to be related to specific biological events and to the effectiveness of drugs. Single particle-inductively coupled plasma-mass spectrometry (SP-ICP-MS) can analyse single cells in suspension and measure this heterogeneity. Here we explore advances in instrumental design, compare mass analysers and discuss key parameters requiring optimisation. This review has identified that the effect of pre-treatment of cell suspensions and cell fixation approaches require further study and novel validation methods are needed as using bulk measurements is unsatisfactory. SP-ICP-MS has the advantage that a large number of cells can be analysed; however, it does not provide spatial information. Techniques based on laser ablation (LA) enable elemental mapping at the single-cell level, such as laser-induced breakdown spectroscopy (LIBS) and laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS). The sensitivity of commercial LIBS instruments restricts its use for sub-tissue applications; however, the capacity to analyse endogenous bulk components paired with developments in nano-LIBS technology shows great potential for cellular research. LA-ICP-MS offers high sensitivity for the direct analysis of single cells, but standardisation requires further development. The hyphenation of these trace elemental analysis techniques and their coupling with multi-omic technologies for single-cell analysis have enormous potential in answering fundamental biological questions.

Assessment of the Electrolyte Heterogeneity of Tissues in Mandibular Bone-Infiltrating Head and Neck Cancer Using Laser-Induced Breakdown Spectroscopy

“…While Wang et al [ 30 ] recently showed that the heterogeneity of elements within tumor cells can be used for LIBS-based discrimination of different tumor cell lines, our study proves that the distribution of elements is also significantly different between different areas within mandibular bone-infiltrating head and neck tumors. Further development of nano-LIBS systems is expected to have great potential for cellular research in the future [ 31 ], which could also contribute to addressing current challenges in the diagnosis and treatment of head and neck cancers.…”

Atomic spectrometry update: review of advances in the analysis of clinical and biological materials, foods and beverages

“…Two review papers cover the use of atomic spectrometry techniques for imaging of biological samples (Section 6.2). Davison et al 19 discussed the state-of-the-art and perspectives of single cell analysis using spICP-MS, LIBS and LA-ICP-MS, whereas the work of Peng et al 20 was devoted to explore the use of multiple laser imaging techniques and nanomaterials to improve cancer diagnosis in vivo .…”

“…1 Additionally, two review papers have covered the use of spectroscopy-based imaging for biological research . Davison et al 19 provided an evaluation of single cell analysis utilising spICP-MS, LIBS and LA-ICP-MS. The advantages and limitations were assessed, concluding that more than one technique was required to fully elucidate processes and that calibration and standardisation still require further development.…”

Research progress of the detection and analysis methods of heavy metals in plants

“…LA-ICP-MS can perform in situ analyses rapidly and in real-time on a micro-scale. It offers several advantages, including easy sample preparation, minimal contamination levels, high spatial resolution, sensitivity, low detection limits, provides relatively simple spectra while allowing for simultaneous determination of multiple elements and information about isotope ratio ( Trejos and Almirall, 2005 ; López-Fernández et al., 2016 ; Nunes et al., 2016 ; Davison et al., 2023 ; Janovszky et al., 2023 ).…”