In Vivo Spectral Distortions of Infrared Luminescent Nanothermometers Compromise Their Reliability

Abstract

Luminescence nanothermometry has emerged over the past decade as an exciting field of research due to its potential applications where conventional methods have demonstrated to be ineffective. Preclinical research has been one of the areas that have benefited the most from the innovations proposed in the field. Nevertheless, certain questions concerning the reliability of the technique under in vivo conditions have been continuously overlooked by most of the scientific community. In this proof-of-concept, hyperspectral in vivo imaging is used to explain how unverified assumptions about the thermal dependence of the optical transmittance of biological tissues in the so-called biological windows can lead to erroneous measurements of temperature. Furthermore, the natural steps that should be taken in the future for a reliable in vivo luminescence nanothermometry are discussed together with a perspective view of the field after the findings here reported.

A Theoretical Framework for Ratiometric Single Ion Luminescent Thermometers—Thermodynamic and Kinetic Guidelines for Optimized Performance

“…Given the large number of possible electronic 4f n microstates of lanthanides, the flexibility in choice of a potential luminescent probe for luminescence thermometry appears unlimited if ∆E 21 is in the order of several k B T. Any inappropriate choice of a lanthanide ion for luminescence thermometry at a temperature of interest may in principle work, but at the cost of a low temperature sensitivity and thus, high temperature uncertainty. Critical reviews stressing the various experimental difficulties in achieving high precision and accuracy in luminescence thermometry have been recently published by the group of Jaque, [199,200] Dramićanin's book [201] and perspective [202] or by Bednarkiewicz et al [203] Despite the enormous amount of experimental data available in the literature of luminescence thermometry, a governing unifying theory that allows for a systematically driven search towards effective thermometers is still virtually non-existent. Only in the last few years, some progress towards this direction is recordable, which also resulted in the availability of applets and programs.…”

Accurate In Vivo Nanothermometry through NIR‐II Lanthanide Luminescence Lifetime

“…Spectral profile deformation demands complicated calibration procedures in order to attain an accurate temperature in vivo. [27] Alongside spectral profile, lifetime is a temporal parameter that characterizes the decay process of nanoprobe luminescence, and is independent of nanoprobe concentration and laser irradiance. [29][30][31] Importantly, luminescence lifetime of nanoprobes remains unaltered after passing through varying thicknesses of biological tissues (Figure 1c), providing possibilities to implement accurate luminescence nanothermometry in vivo in the biological windows.…”

Erbium Single‐Band Nanothermometry in the Third Biological Imaging Window: Potential and Limitations

“…However, it is even more so pertinent to appreciate the reliability of the photoluminescence nanothermometers, which can be affected by factors such as laser excitation power, self-absorption, or solvent (tissue) attenuation. [16,60] The reliability of temperature sensing via the thermometric parameter Δ DS was evaluated at different excitation powers (100-900 mW) of the 793 nm laser. The Δ DS and corresponding temperature values of the water dispersion containing LiErF 4 /LiYF 4 RENPs were measured after several 15 min laser irradiation intervals, increasing the excitation power by 200 mW each time.…”