Energy-Looping Nanoparticles: Harnessing Excited-State Absorption for Deep-Tissue Imaging

Abstract

Near infrared (NIR) microscopy enables noninvasive imaging in tissue, particularly in the NIR-II spectral range (1000-1400 nm) where attenuation due to tissue scattering and absorption is minimized. Lanthanide-doped upconverting nanocrystals are promising deep-tissue imaging probes due to their photostable emission in the visible and NIR, but these materials are not efficiently excited at NIR-II wavelengths due to the dearth of lanthanide ground-state absorption transitions in this window. Here, we develop a class of lanthanide-doped imaging probes that harness an energy-looping mechanism that facilitates excitation at NIR-II wavelengths, such as 1064 nm, that are resonant with excited-state absorption transitions but not ground-state absorption. Using computational methods and combinatorial screening, we have identified Tm(3+)-doped NaYF4 nanoparticles as efficient looping systems that emit at 800 nm under continuous-wave excitation at 1064 nm. Using this benign excitation with standard confocal microscopy, energy-looping nanoparticles (ELNPs) are imaged in cultured mammalian cells and through brain tissue without autofluorescence. The 1 mm imaging depths and 2 μm feature sizes are comparable to those demonstrated by state-of-the-art multiphoton techniques, illustrating that ELNPs are a promising class of NIR probes for high-fidelity visualization in cells and tissue.

Non-obstructive intracellular nanolasers

“…the functionality of molecular dyes in biomedical optics [1][2][3][4][5][6][7] . However, their operation is usually governed by spontaneous processes, which results in broad spectral features and limited signalto-noise ratio, thus restricting opportunities for spectral multiplexing and sensing.…”

Optimal Sensitizer Concentration in Single Upconversion Nanocrystals

“…This gap is becoming pronounced when the UCNCs shrink smaller than 30 nm, where the upconversion brightness proportionally drops as the number of dopants per crystal reduces and the ratio of surface quenchers increases. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 For bio-labeling applications, both the excitation IR wavelength and 800 nm emission wavelength of Tm 3+ doped UCNCs are attractive as they are within a "window of optical transparency" for imaging biological tissues 36 . Strategies to enhance the upconversion luminescence at 800 nm are accordingly of particular interest for in vivo bio-imaging 37,38 .…”

Photon Upconversion Kinetic Nanosystems and Their Optical Response

“…Benefiting from ample energy levels of the lanthanide ions, many excitation wavelengths that can produce efficient upconversion luminescence have been identified for different systems, e.g., ∼980 nm for Yb 3 + sensitized systems, ∼808 nm for Nd 3 + sensitized systems, and ∼808 nm and ∼1500 nm for Er 3 + solely doped nanoparticles . Interestingly, with adequate assistance of interionic energy transfer, the above mentioned excitation‐wavelength selection rule for efficient upconversion luminescence can be broken, as in the cases of energy‐looping and photon avalanche induced upconversion processes . In such circumstances, the excitation wavelength is allowed to be only resonant with excited state absorption transitions but not the ground state absorption.…”

“…Due to the ample energy levels of rare earth ions, often with ladder‐like arrangement, and efficient interionic energy transfer, upconversion luminescence can be generated in singly‐doped UCNPs by many single excitation wavelengths, spanning from NIR to visible range ‐ for instance, 532 nm, 808 nm and 1490 nm for Er 3 + ions, 532 nm for Ho 3 + ions, 800 nm and 1064 nm for Tm 3 + ions, and 473 nm and 609 nm for Pr 3 + ions . However, these upconversion systems generally have low efficiency due to the relatively small absorption cross‐sections of the rare earth ions at these wavelengths.…”