Novel compact Quantum Dots for homogenous FRET-immunoassays and new approach for their structural characterization.

Karl David Wegner^a^,^b^,^c^,^d, Lucia Materra^a^,^b^,^d, Peter Reiss^a^,^b^,^d, Marie Carriere^a^,^c

^aUniversity Grenoble Alpes, INAC-SyMMES, Grenoble, 38000, France

^bCEA, INAC-SyMMES, Laboratoire STEP, 17 Rue des Martyrs, Grenoble Cedex 9, 38054, France

^cCEA, INAC-SyMMES, Laboratoire CIBEST, 17 Rue des Martyrs, Grenoble Cedex 9, 38054, France

^dCNRS, SPrAM-UMR5819, Grenoble, 38000, France

Materials for Sustainable Development Conference (MATSUS)
Proceedings of September Meeting 2016 (NFM16)

Berlin, Germany, 2016 September 5th - 13th

Organizers: Marin Alexe, Enrique Cánovas, Celso de Mello Donega, Ivan Infante, Thomas Kirchartz, Maksym Kovalenko, Federico Rosei, Lukas Schmidt-Mende, Laurens Siebbeles, Peter Strasser, Teodor K Todorov, Roel van de Krol and Ulrike Woggon

Poster, Karl David Wegner, 135
Publication date: 14th June 2016

In last decades the unique properties of semiconductor nanocrystals (QDs) were exploited in optoelectronic, photonic and biomedical applications. The essential requirement for the utilization of QDs within biological applications is their water solubility. A successful phase transfer from the organic phase to the water phase is characterized by maintaining a high quantum yield, colloidal stability over a wide pH range and a small overall size of the QD. Especially the last requirement is a critical parameter in biological applications and also in terms of toxicological effects.

One of the most popular signal transduction pathways in biomedical applications is the Förster resonance energy transfer (FRET). FRET is a non-radiative energy transfer from donor to an acceptor. It is one of the first super resolution methods as the working range is between 1 to 20 nm. Most popular is the utilization of QDs as donors, but they also have a great potential as acceptors in combination with lanthanide terbium complexes (LTCs). Due to its strong distance sensitivity in the nanometer range one of the popular applications for FRET are fluorescent homogenous sandwich immunoassays. Thereby the combination of QDs and LTCs has several advantages in terms of the detection limit and multiplexing capabilities compared to classical fluorophore combinations. One striking advantage of FRET was given too little attention, which is the use as spectroscopic ruler. It allows the structural characterization of QDs in the aqueous phase and offers advantages compared to common structural analysis methods like transmission electron microscopy or dynamic light scattering.

In this contribution we will present a novel approach to render in house and commercial QDs water soluble, which enabled the preparation of the smallest antibody-functionalized QD probe ever reported. In a direct comparison to commercial QDs we will show the advantages of this preparation for the quantification of the prostate cancer marker inside homogenous FRET immunoassays with LTCs as donors. Furthermore, we will demonstrate the strength of FRET for the structural analysis of the QDs by using time-resolved analysis of the decay times of LTC-QD FRET systems. This approach allows for the first time the simultaneous estimation of size and shape at the same concentration (nanomolar) and in the same biological environment as used for the biological application. A detailed time-resolved study of 11 QDs with different sizes, shapes and surface coatings will confirm the large potential of the new nano-tool for the structural analysis of QDs.

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