The identification and quantification of biomolecules play a crucial role in understanding cellular functions and disease mechanisms. The detection of trace biomolecules is particularly important for early disease diagnosis, as even minute molecular changes can influence biological processes. Traditional methods, such as fluorescence and radiolabeling techniques, have been widely used but suffer from spectral overlap and safety concerns, respectively. Metal stable isotope tagging, coupled with inductively coupled plasma mass spectrometry (ICP-MS), has emerged as a powerful approach for biomolecular detection due to its high sensitivity, accuracy, and multiplexing capabilities.
Metal Stable Isotope Detection Tool
ICP-MS is the primary analytical tool for detecting metal stable isotopes. This technique, developed in the early 1980s, provides ultra-trace level detection (pg/mL range), low matrix interference, a broad dynamic range, and high isotopic resolution. The working principle involves introducing a sample into an argon plasma, where it is ionized at temperatures between 6000 and 8000 K. The generated ions are then separated based on their mass-to-charge ratio, enabling the precise detection of metal isotopes [1]. ICP-MS is widely used for the quantification of metal-tagged biomolecules due to its superior detection capabilities.
Fig.1. The metal isotopes that can be detected using ICP-MS, along with their approximate detection limits.
Applications of Metal Stable Isotope Tagging in Bioanalysis
Metal Stable Isotope Tagging Based Simultaneous Analysis of Multiple Components
One of the key advantages of metal stable isotope tagging is the ability to simultaneously analyze multiple biomolecules. Traditional fluorescence-based methods suffer from overlapping emission spectra, limiting the number of detectable targets in a single assay. In contrast, metal stable isotope tagging based on ICP-MS allows for the simultaneous detection of over 100 different isotopes, making it ideal for multiplexed analysis. Several studies have demonstrated the potential of multiplexed bioanalysis using metal isotopes. For example, researchers have used europium and samarium-labeled antibodies to simultaneously detect alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG) in serum samples. The combination of different isotopic labels enables the concurrent quantification of multiple disease biomarkers, providing valuable information for disease diagnosis and monitoring. Additionally, DNA analysis using lanthanide-labeled probes has facilitated the simultaneous detection of multiple nucleic acid targets with high precision.
Metal Stable Isotope Tagging Based Single-Cell Analysis
Single-cell analysis is a rapidly growing field that aims to understand cellular heterogeneity and its implications for health and disease. Traditional flow cytometry techniques rely on fluorescence labeling, which is limited by spectral overlap and autofluorescence. In contrast, mass cytometry, also known as CyTOF (cytometry by time-of-flight), leverages metal stable isotope tagging to analyze single cells with unprecedented resolution. By using ICP-MS, mass cytometry enables the simultaneous quantification of dozens of cellular parameters. Researchers have used this approach to profile immune cell populations, study cancer heterogeneity, and investigate drug responses at the single-cell level. The ability to detect multiple markers in individual cells provides a comprehensive view of cellular functions and interactions, advancing our understanding of complex biological systems.
Future Perspectives and Conclusions
Metal stable isotope tagging has revolutionized bioanalysis by providing high sensitivity, multiplexing capability, and accurate quantification. The integration of signal amplification techniques and advanced mass spectrometry instrumentation will further enhance the detection limits and analytical performance of this approach. Future research will focus on:
- Improving assay efficiency and reproducibility by the development of novel metal stable isotope -labeled probes and automation of ICP-MS workflows.
- Combining metal stable isotope tagging with emerging technologies such as artificial intelligence and machine learning to facilitate data interpretation and biomarker discovery.
In summary, metal stable isotope tagging is a powerful tool for bioanalysis, offering unique advantages over conventional detection methods. Continued advancements in this field will drive new discoveries and innovations in biomedical research and healthcare.
Reference
- Liu R., et al. Metal Stable Isotope Tagging-Based Bioassay[J]. Spectroscopy and Spectral Analysis, 2019, 39(5): 1346-1353.
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