DataVXAdvanced SciencePaper
journal article·2026-02Open access

From Sample to Mixed Reality: A Translational 3D MALDI Imaging Platform for Advanced 3D Spatial Omics Analysis of 3D Cell Culture Disease Models

Stefania Alexandra Iakab, Jonas Cordes, Thomas Enzlein, Florian Keller, Kevin Kastner, Theresa Mulholland, Björn Christian Fröhlich, Lars Gruber, James Lucas Cairns, Stefan Schmidt, Mathias Hafner, Richard Schneider, Johannes Betge, Frank Fischer, Julian Reichwald, Rüdiger Rudolf, Carsten Hopf

Advanced Science· Volume 13· Issue 12
Publisher pageOpen full text
Source abstract

Abstract

Abstract Human 3D cell cultures, including spheroids and organoids, are essential biological models for translational pharmaceutical and biomedical research. However, their 3D analysis using 2D‐ matrix‐assisted laser desorption/ionization (MALDI) imaging‐based spatial metabolomics remains challenging, since end‐to‐end solutions for 3D‐enabling sample preparation, 3D‐data processing, 3D‐rendering, and 3D‐user interaction are lacking. Here, a 3D‐MALDI imaging platform and resource that advances each of three pillars is presented: i) the sample preparation introduces custom‐designed molds for precise and reproducible embedding and cryosectioning of multiple spheroids and organoids, a substantial improvement over ad hoc or single‐sample sectioning workflows; ii) the integrated computational framework that facilitates the generation of high‐fidelity volumetric datasets that enable voxel‐based analysis for feature discovery, surpassing traditional slice‐based 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‐derived colon cancer organoids. Collectively, this integrated approach enables spatial metabolomic analysis in 3D, offers increased throughput, and paves the way for next‐generation molecular diagnostics and personalized medicine applications.
Source: crossref · Quality: baseline

Research context

OpenAlex topics: Mass Spectrometry Techniques and Applications · Metabolomics and Mass Spectrometry Studies · Cell Image Analysis Techniques

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

CeMOS Research and Transfer Center Mass Spectrometry and Optical Spectroscopy Technische Hochschule Mannheim Paul‐Wittsack‐Str. 10 68163 Mannheim Germany

CeMOS Research and Transfer Center 3D‐Models and Imaging Technische Hochschule Mannheim Paul‐Wittsack‐Str. 10 68163 Mannheim Germany

CeMOS Research and Transfer Center Virtual Engineering Technische Hochschule Mannheim Paul‐Wittsack‐Str. 10 68163 Mannheim Germany

Junior Clinical Cooperation Unit Translational Gastrointestinal Oncology and Preclinical Models German Cancer Research Center (DKFZ) Im Neuenheimer Feld 280 69120 Heidelberg Germany

Department of Medicine II University Medical Center Mannheim Medical Faculty Mannheim Heidelberg University Theodor‐Kutzer‐Ufer 1‐3 68167 Mannheim Germany

DKFZ Hector Cancer Institute at University Medical Center Mannheim Theodor‐Kutzer‐Ufer 1‐3 68167 Mannheim Germany

German Cancer Consortium (DKTK) Im Neuenheimer Feld 280 69120 Heidelberg Germany

Medical Faculty Heidelberg University Im Neuenheimer Feld 672 69120 Heidelberg Germany

Merck Healthcare KGaA Frankfurter Str. 250 64293 Darmstadt Germany

Merck KGaA Frankfurter Str. 250 64293 Darmstadt Germany

Mannheim Center for Translational Neuroscience (MCTN) Medical Faculty Mannheim Heidelberg University Theodor‐Kutzer‐Ufer 1‐3 68167 Mannheim Germany

Funding

Deutsche Forschungsgemeinschaft

References (60)

Show source-provided references
1. 10.3390/ph1508092610.3390/ph15080926 ↗
2. 10.1245/s10434-021-10829-x10.1245/s10434-021-10829-x ↗
3. 10.1080/14789450.2021.187656810.1080/14789450.2021.1876568 ↗
4. 10.1038/s41392-024-02097-410.1038/s41392-024-02097-4 ↗
5. 10.1038/s41467-022-30722-910.1038/s41467-022-30722-9 ↗
6. 10.3390/cells908190010.3390/cells9081900 ↗
7. 10.1021/ac202356g10.1021/ac202356g ↗
8. 10.1021/acs.analchem.9b0246210.1021/acs.analchem.9b02462 ↗
9. 10.1002/adhm.20230249910.1002/adhm.202302499 ↗
10. 10.1146/annurev-anchem-061424-09054710.1146/annurev-anchem-061424-090547 ↗
11. 10.1016/j.jbc.2021.10113910.1016/j.jbc.2021.101139 ↗
12. 10.1016/j.copbio.2018.08.00310.1016/j.copbio.2018.08.003 ↗
13. 10.1177/247255522094184310.1177/2472555220941843 ↗
14. 10.1002/mas.2180410.1002/mas.21804 ↗
15. 10.1021/acs.analchem.9b0066110.1021/acs.analchem.9b00661 ↗
16. 10.1038/s41596-021-00661-810.1038/s41596-021-00661-8 ↗
17. 10.1002/jms.446110.1002/jms.4461 ↗
18. 10.1016/j.heliyon.2024.e4081310.1016/j.heliyon.2024.e40813 ↗
19. Ahlf Wheatcraft D. R. · J. Vis. Exp. · 2014
20. 10.1016/j.bbapap.2013.01.04010.1016/j.bbapap.2013.01.040 ↗
21. 10.1021/acs.analchem.0c0082610.1021/acs.analchem.0c00826 ↗
22. 10.1016/j.jmsacl.2021.12.00610.1016/j.jmsacl.2021.12.006 ↗
23. 10.1021/ac504604g10.1021/ac504604g ↗
24. 10.1038/s41598-017-14949-x10.1038/s41598-017-14949-x ↗
25. 10.1038/s41598-018-38257-010.1038/s41598-018-38257-0 ↗
26. 10.1093/gigascience/giab04910.1093/gigascience/giab049 ↗
27. 10.3390/su1705231810.3390/su17052318 ↗
28. 10.1016/j.xcrm.2021.10034810.1016/j.xcrm.2021.100348 ↗
29. 10.1186/s12909-024-05777-510.1186/s12909-024-05777-5 ↗
30. 10.1021/acs.analchem.0c0258510.1021/acs.analchem.0c02585 ↗
31. 10.1002/jms.490410.1002/jms.4904 ↗
32. 10.3390/cancers1510267610.3390/cancers15102676 ↗
33. 10.1038/s41598-022-13987-410.1038/s41598-022-13987-4 ↗
34. 10.1186/s13045-020-00931-010.1186/s13045-020-00931-0 ↗
35. 10.1002/mco2.27410.1002/mco2.274 ↗
36. 10.1093/nar/gkl92310.1093/nar/gkl923 ↗
37. 10.1038/s42255-021-00480-x10.1038/s42255-021-00480-x ↗
38. 10.1038/s41592-023-02070-z10.1038/s41592-023-02070-z ↗
39. 10.1093/gigascience/giz14310.1093/gigascience/giz143 ↗
40. 10.1038/s41467-025-64603-810.1038/s41467-025-64603-8 ↗
41. 10.1038/s41467-025-59839-310.1038/s41467-025-59839-3 ↗
42. 10.3390/curroncol2911064210.3390/curroncol29110642 ↗
43. 10.3892/ijo.2022.535710.3892/ijo.2022.5357 ↗
44. 10.7150/thno.6237810.7150/thno.62378 ↗
45. 10.1038/s41419-020-2434-z10.1038/s41419-020-2434-z ↗
46. 10.1186/s40170-024-00345-310.1186/s40170-024-00345-3 ↗
47. 10.3389/frobt.2016.0007410.3389/frobt.2016.00074 ↗
48. 10.1038/nature0793510.1038/nature07935 ↗
49. 10.1016/j.cell.2015.03.05310.1016/j.cell.2015.03.053 ↗
50. 10.1021/acs.analchem.3c0354310.1021/acs.analchem.3c03543 ↗
51. 10.3389/fendo.2021.69428410.3389/fendo.2021.694284 ↗
52. 10.1038/s41467-019-09045-910.1038/s41467-019-09045-9 ↗
53. 10.1016/j.celrep.2021.10930710.1016/j.celrep.2021.109307 ↗
54. 10.1007/s00441-017-2618-810.1007/s00441-017-2618-8 ↗
55. 10.1186/s12944-019-0977-810.1186/s12944-019-0977-8 ↗
56. 10.1016/j.jcmgh.2023.02.01410.1016/j.jcmgh.2023.02.014 ↗
57. 10.1093/nar/gkad89610.1093/nar/gkad896 ↗
58. 10.1002/jms.177710.1002/jms.1777 ↗
59. 10.1038/s41592-019-0344-810.1038/s41592-019-0344-8 ↗
60. 10.1021/acs.analchem.3c0555710.1021/acs.analchem.3c05557 ↗