Tartrazine Clears Live Cells while Preserving Viability at High Refractive Indices and Osmolality
Year: 2026
Type: article
Abstract: Tissue-clearing techniques have transformed optical imaging of fixed specimens, yet their application to living systems remains limited by toxicity and removal of key tissue components. We recently demonstrated that absorbing molecules such as tartrazine can reversibly render live mouse skin transparent. Subsequently, it was reported that isotonic protein solutions can achieve ex vivo and in vivo cellular clearing. However, discrepancies remain regarding the optimal refractive index (RI) for live-cell clearing and the impact of elevated osmolality on cell viability. Here, using cultured mammalian cells, we systematically examine the dependence of optical contrast on medium RI and the effects of hyperosmolality. We find that, contrary to the recent report of an optimal RI of 1.36∼1.37 for suspended cells, densely-packed adherent cells exhibit a monotonic decrease in phase contrast up to an RI of 1.41 with tartrazine. Moreover, even under highly hyperosmotic conditions (∼1200 mOsm/kg), cultured cells exhibit minimal deformation and negligible loss of viability for up to 30 min in the clearing solution. These results demonstrate that tartrazine enables effective live-cell clearing at RI up to 1.41 while preserving viability under elevated osmolality, and motivate future studies to define optimal conditions for in vivo optical clearing. Graphical Abstract
Source: Bioconjugate Chemistry
Institution: Stanford University
Language: English
Subfield: Biophysics
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,500
Funders: National Science Foundation, Spinal Muscular Atrophy Foundation, Camille and Henry Dreyfus Foundation, Focused Ultrasound Foundation, National Institutes of Health, Stanford Bio-X, Wu Tsai Neurosciences Institute, Stanford University, National Institute on Aging, Air Force Office of Scientific Research
Awards: Mesh electronics for understanding space encoding in the amphibian brain, Brain Aging Studies with Single-Neuron Resolution Using Syringe-Injectable Electronics, CAREER: Sculpting light in biological tissue: an ultrasound-mediated traveling light source for spatiotemporally precise in vivo gene editing, EAGER: Neuromodulation in the second near-infrared window, Rapid brain-wide optogenetic screening with a noninvasive, dynamically programmable in vivo light source, G6671297155, G999900475
OpenAlex ID: W7164300793
