DS0305 -

Nanoparticle-Enhanced Ultrasensitive Tracking of Biological Interactions by Optical Sensing – NEUTRINOS

Submission summary

Photoluminescence (PL) sensing is a standard technique in biological and chemical analysis, and its advantages of user friendliness, speed, low cost, very high sensitivity, and unrivalled versatility have opened a broad scope of sensing applications, including the use of consumer electronic devices and point-of-care diagnostics. Driven by the ever demanding requirements of sensitivity, specificity, accuracy, reproducibility, and multiparametric detection (multiplexing) for the quantification of extremely low concentrations of various biological targets (e.g., proteins, peptides, and nucleic acids) as well as the monitoring of their interactions, luminescent nanoparticles (NPs) and FRET (Förster resonance energy transfer) have appeared as very promising technologies to further increase the versatility of biosensing.
The combination of luminescent lanthanide (Ln) complexes and semiconductor quantum dots (QDs) in FRET can provide extraordinary photophysical and photochemical properties with many advantages for multiplexed, sensitive, and versatile biosensing. The main drawback of the Ln-based probes is their limited brightness due to extremely low absorption cross sections of Ln ions. This can only partly be overcome by the design of supramolecular Ln-complexes with antenna ligands or the doping of many Ln ions into NPs, and Ln-based PL probes with very high brightness (>50,000 M-1cm-1) do not exist to date. Another disadvantage of Ln-NPs is particular for the strongly distance-dependent FRET process. Due to the limited FRET distance (up to max. 20 nm), only the Ln-ions close to the NP surface can be used for FRET, whereas the ions in the center contribute to PL but not to FRET. Another current limitation of PL biosensing is the unavailability of bright and stable NIR emitters. The NIR range is highly important for biosensing because it allows for higher penetration depths due to the low absorption cross section of tissues and significantly reduced autofluorescence background (compared to UV/Vis excitation and Vis detection) from endogenous biological components. NIR dyes and QDs are mainly limited by their relatively low PL quantum yields. Moreover, QDs often contain Cd, which is highly toxic and can therefore be very problematic for biosensing, in particular in live cells or in-vivo. An aspect that is probably even more important is the lack of ratiometric NIR PL probes. Ratiometric detection, in which the PL ratio of an analyte-specific and an analyte-unspecific probe is measured, is of paramount importance for biosensing to be independent of PL intensity variations within different environments (e.g., in different cells) or due to altered excitation or detection conditions.
The NEUTRINOS project will go significantly beyond the state-of-the art by proposing two novel types of advanced PL nanomaterials. These new nanoparticles combine Ln and QDs for advanced FRET biosensing and ratiometric imaging. Attachment of surface photo-sensitizing antennas on Ln-NPs will lead to efficient excitation of only surface-near Ln ions, which will overcome the limited absorption cross sections of Ln NPs and the strong PL background of Ln ions inside the NPs and allow for highly efficient FRET from the surfaces of the Ln NPs. The additional attachment of biological recognition molecules, such as antibodies, peptides, or DNA/RNA, and the use of QD acceptors will lead to highly improved ultrasensitive multiplexing for clinical diagnostics. The second material approach consists of QD/Ln core/shell NPs, in which the NIR-emitting QD core will be protected from the environment by a Ln-doped shell, which will be in contact to the environment. The NIR PL of the Ln-shell can be used for analyte-specific sensing, whereas the unaffected PL of Cd-free QDs can be used for highly reproducible ratiometric detection in live cell and in-vivo imaging.

Project coordination

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

IPHC Institut Pluridisciplinaire Hubert Curien
I2BC Institut de Biologie Intégrative de la Cellule
INAC-SPrAM Commissariat à l'Energie Atomique et aux Energies Alternatives

Help of the ANR 465,787 euros
Beginning and duration of the scientific project: October 2016 - 42 Months

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