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However, their 3D analysis using 2D\u2010 matrix\u2010assisted laser desorption\/ionization (MALDI) imaging\u2010based spatial metabolomics remains challenging, since end\u2010to\u2010end solutions for 3D\u2010enabling sample preparation, 3D\u2010data processing, 3D\u2010rendering, and 3D\u2010user interaction are lacking. Here, a 3D\u2010MALDI imaging platform and resource that advances each of three pillars is presented: i) the sample preparation introduces custom\u2010designed molds for precise and reproducible embedding and cryosectioning of multiple spheroids and organoids, a substantial improvement over ad hoc or single\u2010sample sectioning workflows; ii) the integrated computational framework that facilitates the generation of high\u2010fidelity volumetric datasets that enable voxel\u2010based analysis for feature discovery, surpassing traditional slice\u2010based 2D analysis; iii) the mixed reality tool enables immersive spatial exploration of molecular distributions in 3D, extending user engagement beyond static 3D renderings. The versatility of the platform is illustrated by its translation to a clinical framework for the molecular profiling of patient\u2010derived colon cancer organoids. Collectively, this integrated approach enables spatial metabolomic analysis in 3D, offers increased throughput, and paves the way for next\u2010generation molecular diagnostics and personalized medicine applications.<\/jats:p>","DOI":"10.1002\/advs.202516098","type":"journal-article","created":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T14:21:58Z","timestamp":1765981318000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["From Sample to Mixed Reality: A Translational 3D MALDI Imaging Platform for Advanced 3D Spatial Omics Analysis of 3D Cell Culture Disease Models"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4156-1942","authenticated-orcid":false,"given":"Stefania Alexandra","family":"Iakab","sequence":"first","affiliation":[{"name":"CeMOS Research and Transfer Center Mass Spectrometry and Optical Spectroscopy Technische Hochschule Mannheim  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