Microfluidic oxygen tolerability screening of nanocarriers for triplet fusion photon upconversion

The full potential of triplet fusion photon upconversion (TF-UC) of providing high-energy photons locally with low-energy excitation is limited in biomedicine and life sciences by its oxygen sensitivity. This hampers the applicability of TF-UC systems in sensors, imaging, optogenetics and drug release. Despite the advances in improving the oxygen tolerability of TF-UC systems, the evaluation of oxygen tolerability is based on comparing the performance at completely deoxygenated (0% oxygen) and ambient (20-21%) conditions, leaving the physiological oxygen levels (0.3-13.5%) neglected. This oversight is not deliberate and is only the result of the lack of simple and predictable methods to obtain and maintain these physiological oxygen levels in an optical setup. Herein, we demonstrate the use of microfluidic chips made of oxygen depleting materials to study the oxygen tolerability of four different micellar nanocarriers made of FDA-approved materials with various oxygen scavenging capabilities by screening their TF-UC performance over physiological oxygen levels. All nanocarriers were capable of efficient TF-UC even in ambient conditions. However, utilizing oxygen scavengers in the oil phase of the nanocarrier improves the oxygen tolerability considerably. For example, at the mean tumour oxygen level (1.4%), nanocarriers made of surfactants and oil phase both capable of oxygen scavenging retained remarkably 80% of their TF-UC emission. This microfluidic concept enables faster, simpler and more realistic evaluation of, not only TF-UC, but any micro or nanoscale oxygen-sensitive system and facilitates their development and implementation in biomedical and life science applications. A new microfluidic approach was used to screen the oxygen tolerability of photon upconverting nanocarriers and to quantify their performance at oxygen levels ranging from severely hypoxic tumours to healthy peripheral tissue.