Understanding how oxygen is delivered and used in the brain is essential for uncovering the mechanisms behind stroke, dementia, traumatic brain injury, and many other neurological conditions. Yet measuring oxygen levels deep within living tissue has historically been extremely challenging. Traditional imaging tools either can’t reach deep enough, damage tissue during delivery, or are too slow to capture rapid physiological changes.
A new research breakthrough, Oxyphor 2P, a high-performance oxygen-sensing probe, may finally change that. Developed by Esipova, Barrett, Erlebach, Masunov, Weber, and Vinogradov, this innovative phosphorescent probe represents a major step forward in neuroscience and biomedical imaging. Their findings demonstrate that Oxyphor 2P makes oxygen imaging deeper, faster, and more stable than previously possible, opening the door to new insights into brain function and disease.
The authors introduce Oxyphor 2P as a high-performance phosphorescent probe designed specifically for measuring oxygen in biological systems. Unlike earlier probes, Oxyphor 2P is optimized for two-photon phosphorescence lifetime microscopy, a technique that allows scientists to visualize oxygen levels deep inside tissue using minimally invasive infrared light.
The researchers report several major advancements including two-photon imaging up to 600 micrometers deep, imaging speeds nearly 60 times faster than previous methods, delivery method that avoids local tissue damage, and reliable multi-day longitudinal oxygen measurements. These innovations make Oxyphor 2P one of the most promising tools for studying oxygen dynamics in living brains.
Oxygen is the primary fuel of the brain. Even slight disruptions can influence cognition and behavior and may contribute to conditions such as stroke, Alzheimer’s disease, Parkinson’s disease, and age-related cognitive decline. Historically, limited imaging tools have prevented scientists from monitoring oxygen levels at depth or over extended periods.
With Oxyphor 2P, researchers can achieve a multitude of things, including, observing oxygen levels across deeper cortical layers, tracking how oxygen changes during neural activity, studying chronic vascular and metabolic changes after injury, monitoring oxygen dynamics over days instead of minutes, and investigating early biomarkers of neurological disorders. The ability to perform multi-day, deep-tissue imaging without damaging the brain allows for more accurate and biologically realistic studies.
At a recent Loyola Neuroscience seminar, Dr. Tatiana V. Esipova, one of the lead authors of the Oxyphor 2P study, shared her experiences and scientific goals behind developing this probe. Dr. Esipova is a faculty member in the Department of Chemistry and Biochemistry at Loyola University Chicago, where she is now an Associate Professor. Her career has included research positions at the University of Pennsylvania and EPFL in Switzerland, building deep expertise in chemical probe design and biophysics.
During the seminar, Dr. Esipova emphasized the importance of designing oxygen probes that can reach deep brain layers without disrupting normal tissue architecture. She also highlighted how long-term tracking of oxygen levels can help researchers understand how the brain adjusts during learning, recovery, injury, and disease progression. Her work demonstrates how chemistry and neuroscience can intersect to create transformative tools.
The development of Oxyphor 2P shows how advancements in chemical probe design can reshape what neuroscientists are capable of studying. Just as multi-ancestry genetics has expanded our understanding of Parkinson’s disease, advanced oxygen imaging tools have the potential to unlock new insights into brain health.
Oxyphor 2P represents a major leap forward in deep-tissue oxygen imaging. With deeper penetration, faster imaging speeds, and multi-day stability, this probe allows researchers to view the brain’s oxygen landscape with an unprecedented level of detail. The work of Dr. Esipova and her collaborators highlights how innovation at the intersection of chemistry and neuroscience can drive meaningful progress in understanding human health and disease.
References
Esipova, T. V., Barrett, M. J. P., Erlebach, E., Masunov, A. E., Weber, B., & Vinogradov, S. A. (2024). Oxyphor 2P: A high-performance probe for deep-tissue longitudinal oxygen imaging. Cell Reports Methods.
Vinogradov, S. A., Wilson, D. F., & Lebedev, A. Y. (2020). Phosphorescent probes for oxygen imaging in vivo: Principles and applications. Progress in Molecular Biology and Translational Science.
Weber, B., & Helmchen, F. (2019). Imaging oxygen in the brain: Methods and applications. Annual Review of Neuroscience.
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