Energy-Looping Nanoparticles: Harnessing Excited-State Absorption for Deep-Tissue Imaging.
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.
The Molecular Foundry, Lawrence Berkeley National Laboratory , Berkeley, California 94720, United States.
Elizabeth S
ES
Levy
The Molecular Foundry, Lawrence Berkeley National Laboratory , Berkeley, California 94720, United States.
Cheryl A
CA
Tajon
The Molecular Foundry, Lawrence Berkeley National Laboratory , Berkeley, California 94720, United States.
Thomas S
TS
Bischof
Department of Psychiatry, University of California , San Francisco, California 94143, United States.
Jillian
J
Iafrati
The Molecular Foundry, Lawrence Berkeley National Laboratory , Berkeley, California 94720, United States.
Angel
A
Fernandez-Bravo
The Molecular Foundry, Lawrence Berkeley National Laboratory , Berkeley, California 94720, United States.
David J
DJ
Garfield
Maysamreza
M
Chamanzar
Michel M
MM
Maharbiz
Department of Psychiatry, University of California , San Francisco, California 94143, United States.
Vikaas S
VS
Sohal
The Molecular Foundry, Lawrence Berkeley National Laboratory , Berkeley, California 94720, United States.
P James
PJ
Schuck
The Molecular Foundry, Lawrence Berkeley National Laboratory , Berkeley, California 94720, United States.
Bruce E
BE
Cohen
The Molecular Foundry, Lawrence Berkeley National Laboratory , Berkeley, California 94720, United States.
Emory M
EM
Chan
D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging; D002478:Cells, Cultured; D003952:Diagnostic Imaging / Q000379:methods*; D028581:Lanthanoid Series Elements; D053758:Nanoparticles; D055585:Physical Phenomena
D028581:Lanthanoid Series Elements
energy looping; imaging; nanocrystals; nanoparticles; near-infrared; photon avalanche; upconversion