“White and Clear” (WaC): A tunable hydrophilic tissue clearing strategy for multi‐species 3D imaging
6 affiliations
- 1Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM) Madrid Spain
- 2Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC) Madrid Spain
- 3Unidad de Cirugía Cardiaca Infantil. Hospital General Universitario Gregorio Marañón Madrid Spain
- 4Instituto de Ciencia de Materiales de Madrid (ICMM) Madrid Spain
- 5Departamento de Química en Ciencias Farmacéuticas Facultad de Farmacia Universidad Complutense de Madrid Madrid Spain
- 6Departamento de Bioingeniería Universidad Carlos III de Madrid Leganés Spain
Abstract
Optical tissue clearing (OTC) techniques have transformed three‐dimensional (3D) biological imaging, yet existing protocols often face limitations related to pigment persistence, reagent viscosity, or restricted applicability across tissues and species. Here, we introduce White and Clear (WaC), a tunable hydrophilic tissue clearing strategy developed from the CUBIC (clear, unobstructed brain imaging cocktails) workflow that integrates efficient delipidation, hydrogen peroxide‐based pigment removal, and customizable refractive index matching using 2,2′‐thiodiethanol (TDE). WaC provides rapid, versatile, and reproducible clearing across multiple organs and species while preserving morphology and immunoreactivity, and enabling deep 3D imaging with confocal and light‐sheet microscopy. WaC improves ease of use, versatility and clearing efficiency across samples from multiple species, including rodents, pigs, and humans; it also includes the capability for whole‐body clearing of small animals like mice; compatibility with 3D imaging techniques such as selective plane illumination microscopy (SPIM)/light‐sheet fluorescence microscopy (LSFM); the possibility of fine‐tuning clearing parameters for optimal results in different situations; and the avoidance of cumbersome synthesis or application procedures as well as the use of toxic reagents.
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BibTeX
@article{llorente2026white,
title = {{“White and Clear” (WaC): A tunable hydrophilic tissue clearing strategy for multi‐species 3D imaging}},
author = {Vicente Llorente and Elena Fernández‐Cortés and Daniel Sanderson and Julia Carolina Salazar Romero and Juan Miguel Gil‐Jaurena and Esther Bernaldo‐de‐Quirós and Rafael J. Jiménez‐Riobóo and Rafael Correa‐Rocha and Isabel Izquierdo‐Barba and Rafael Samaniego and Jorge Ripoll and Manuel Desco and María Victoria Gómez‐Gaviro},
journal = {View},
year = {2026},
month = oct,
doi = {10.1002/viw.20260029},
url = {https://doi.org/10.1002/viw.20260029},
note = {CC BY},
}
RIS
TY - JOUR
TI - “White and Clear” (WaC): A tunable hydrophilic tissue clearing strategy for multi‐species 3D imaging
AU - Vicente Llorente
AU - Elena Fernández‐Cortés
AU - Daniel Sanderson
AU - Julia Carolina Salazar Romero
AU - Juan Miguel Gil‐Jaurena
AU - Esther Bernaldo‐de‐Quirós
AU - Rafael J. Jiménez‐Riobóo
AU - Rafael Correa‐Rocha
AU - Isabel Izquierdo‐Barba
AU - Rafael Samaniego
AU - Jorge Ripoll
AU - Manuel Desco
AU - María Victoria Gómez‐Gaviro
PY - 2026
DA - 2026/10/26
JO - View
DO - 10.1002/viw.20260029
UR - https://doi.org/10.1002/viw.20260029
AB - Optical tissue clearing (OTC) techniques have transformed three‐dimensional (3D) biological imaging, yet existing protocols often face limitations related to pigment persistence, reagent viscosity, or restricted applicability across tissues and species. Here, we introduce White and Clear (WaC), a tunable hydrophilic tissue clearing strategy developed from the CUBIC (clear, unobstructed brain imaging cocktails) workflow that integrates efficient delipidation, hydrogen peroxide‐based pigment removal, and customizable refractive index matching using 2,2′‐thiodiethanol (TDE). WaC provides rapid, versatile, and reproducible clearing across multiple organs and species while preserving morphology and immunoreactivity, and enabling deep 3D imaging with confocal and light‐sheet microscopy. WaC improves ease of use, versatility and clearing efficiency across samples from multiple species, including rodents, pigs, and humans; it also includes the capability for whole‐body clearing of small animals like mice; compatibility with 3D imaging techniques such as selective plane illumination microscopy (SPIM)/light‐sheet fluorescence microscopy (LSFM); the possibility of fine‐tuning clearing parameters for optimal results in different situations; and the avoidance of cumbersome synthesis or application procedures as well as the use of toxic reagents.
SN - 2688-268X
SN - 2688-3988
ER -