Method and Device for Performing Quantitative Spatially Resolved Local and Distribution Analysis of Chemical Elements and In-Situ Characterization of Ablated Surface Regions

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This invention describes a system and method for highly precise, spatially resolved, quantitative analysis of chemical elements in a sample at the nanometer scale. By combining laser ablation (inductively coupled plasma mass spectrometry, LA-ICP-MS), atomic force microscopy (AFM), and laser microdissection (LMD), it enables both the mapping of element distribution and the characterization (imaging and topography) of sample surfaces before and after laser ablation. The system features enhanced spatial resolution (down to tens of nanometers) by leveraging near-field laser effects with a metallic tip, allowing for detailed chemical and morphological analysis of very small structures such as single cells or nanomaterials.

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• High-resolution chemical mapping of biological tissue sections, such as studying neurodegenerative diseases at the cellular or even subcellular level.
• Elemental analysis and distribution mapping in nanomaterials, thin films, micro- and nanoelectronic components for material science and electronics research.
• In-situ surface characterization and elemental analysis of individual cells, cell organelles (e.g., mitochondria), or other small biological structures.
• Forensics, environmental analysis, and geoscience: investigating trace elements and inhomogeneities in minerals, inclusions, bones, teeth, or hair.
• Development and validation of micro- and nanostructured devices, enabling quantitative, spatially-resolved chemical and morphological studies.

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• Combines high-resolution microscopy (AFM) with quantitative chemical analysis (ICP-MS) for correlated morphological and elemental information.
• Near-field laser ablation using a metallic tip enables true nanometer-scale spatial resolution, surpassing limitations of conventional laser ablation methods.
• Provides both pre- and post-ablation surface characterization without moving or disturbing the sample, ensuring accurate correlation of data.
• Allows for precise selection and analysis of regions of interest within complex samples, using the optical advantages and precise positioning of LMD systems.
• Applicable to a wide variety of sample types, including biological, medical, geological, and material science samples.
• Enables new insights into nanoscale distribution of essential and toxic elements, critical for healthcare, nanotechnology, and advanced materials research.

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Patent Abstract

The invention relates to an apparatus which can be used to carry out both a quantitative spatially resolved nanolocal and distribution analysis of element concentrations of a specimen and a microscopic detection of the surface topography in the nanometer range of said specimen. For this purpose, the specimen is introduced into a laser ablation chamber on a microscope slide, and said chamber is arranged on a scanning table of a laser micro-dissection system (LMD). A partial region of the specimen is selected for examination using an enlarged object lens of the LMD. The object lens is removed without changing the x-y position of the specimen, the defocused laser beam of the LMD is intensified in the vicinity of the selected surface of the sample irradiated by the laser on a tip comprising a metal in the near field, wherein the tip comprising the metal is positioned in the vicinity of the spot of the laser beam focused on the surface of the specimen by a positioning device not coupled to the LMD. Part of the specimen is ablated and analyzed by way of ICP-MS. The topography of the specimen surface is captured before and/or after the laser ablation using the same tip comprising the metal as part of the AFM.