3D Pathology-Guided Tissue Micromachining for Targeted Molecular and Spatial Multi-Omics Analysis

Researchers at Stanford have developed TRIM3D (Tissue-Referenced Integrated Micromachining in 3D), a precision tissue extraction platform that couples 3D pathology imaging with guided physical retrieval of specific tissue regions.

Modern 3D pathology methods can generate detailed, high-resolution volumetric images of intact biological tissues. However, no reliable method currently exists to extract specific volumes of interest or 2D tissue sections from defined depths and angles within a 3D specimen. A common workaround is to serially section thick specimens prior to identifying the best regions for molecular analysis, but this approach makes it impossible to obtain continuous-depth 3D pathology data and requires exhaustive sectioning before any region of interest can be identified.

TRIM3D solves this problem by leveraging the physical properties of a standard tissue-clearing agent to stabilize and immobilize specimens during precision micromachining. This enables accurate retrieval of user-defined 3D tissue volumes for downstream molecular profiling. Critically, the platform also supports extraction of thin, slide-ready 2D sections at any prescribed depth or angle within a specimen, making them directly compatible with spatial multi-omics platforms such as spatial transcriptomics and proteomics.

Stage of development: Proof of Concept