A High-Throughput Method To Measure Relative Quantum Yield of Lanthanide Complexes for Bioimaging

Abstract

Luminescent lanthanides provide a promising alternative to organic chromophores for cellular bioimaging and bioassay applications; efficacy is closely governed by their respective quantum yields. Conventionally utilized quantum-yield measurements for lanthanides are laborious and not amenable to rapid relative comparison of compound performance. Here, we introduce a highthroughput optical imaging method to determine and directly compare relative quantum yield using Cherenkov-radiation-mediated excitation of luminescent lanthanide complexes.

Accessing lanthanide-based, in situ illuminated optical turn-on probes by modulation of the antenna triplet state energy

“…Quantum yield measurements were carried out as described previously, using [Tb( L1 )] − ( Φ Ln = 0.47) as the reference compound. 16 Quantum yield was 0.0002 for Tb( L3 ), which corresponds well to diminished efficiency of transfer from the corresponding T 1 state. Substitution of the electron-withdrawing nitro-substituent ( L3 ) with an amine ( L4 ), increased the quantum yield of Tb( L4 ) 500-fold, to 0.10.…”

“…2 ). 16 We attributed this increase to the 1330 cm −1 blue-shift of the triplet excited state energy for [Tb( L2 )] − relative to [Tb( L1 )] − , which decreases the likelihood of a back energy transfer to the antenna. The high quantum yield of [Tb( L2 )] − motivated the design of an antenna that possessed a poor triplet energy match and could be transformed into the para -NH 2 -picolinate for a particularly efficient luminescence turn-on.…”

“…As we have previously shown, Cherenkov radiation (CR) provides a convenient in situ excitation source for luminescent Tb( iii ) complexes. 16 CR-imaging was carried out with complexes Tb( L3 ), Tb( L4 ), and Tb( L5 ), imaging phantoms containing 1–150 nmol probe (as measured by ICP-OES). Based on our previous CRET studies, Tb( iii ) complexes with Φ Tb of 0.10 possess a limit of detection of 5 nmol (25 μM), which corresponds to 1–2 orders of magnitude greater sensitivity than clinically administered, T 1 -based MRI contrast agents in phantoms and small animal imaging experiments.…”

Versatile Macrocyclic Platform for the Complexation of [natY/90Y]Yttrium and Lanthanide Ions

“…Furthermore, the (long) lifetime of the 5 D 4 excited state of Tb (2.41 ms) is also close to the values reported for highly luminescent Tb III complexes that lack water molecules in the inner coordination sphere. 31 , 70 − 74 …”

Multiplex and In Vivo Optical Imaging of Discrete Luminescent Lanthanide Complexes Enabled by In Situ Cherenkov Radiation Mediated Energy Transfer

“…12−14 We have successfully established CRET as a means to excite discrete luminescent lanthanide complexes and employ CRET excitation to estimate quantum yields of Tb(III) complexes in a high-throughput manner. 15,16 Motivated by our results, we posited that functionalized, high quantum yield Tb(III) and Eu(III) complexes bore potential for multiplexed and even targeted in vivo optical imaging when combined with a CR-emissive positron emission tomography (PET) radiopharmaceutical (Figure 1). The latter has been widely regarded as not feasible without specialized means of excitation such as two-photon excitation/upconver-sion and custom-built laser photon sources 6,17 and even if enabled, is further complicated by the need of exceedingly large quantities of lanthanide ion to produce a detectable luminescence signal.…”