■ Biodetection with whispering quantum dots

Description of the PhD project

Quantification of specific biomarkers is an important diagnostic tool. Many biodetection schemes require extensive washing steps and signal amplification, which limit portability, cost effectiveness and make these schemes prone to false positives and lack of reproducibility, in particular when the biomarker of interest is only present at very low concentrations. Non radiative energy transfer (or FRET) has been used to design one-step bioassays which do not require washing steps, where the biomarker enables the formation of a “sandwich” complex involving donor-labeled and acceptor-labeled antibodies. FRET then provides an optical signature of the complex formation, hence of the biomarker of interest. However the large size of this complexes limits the efficiency of energy transfer, preventing sensitive detection. Recent improvements in energy transfer efficiencies have been reported using plasmonic nanostructures but these structures remain ill adapted to the design of a simple and portable device. In this project we propose to improve the efficiency of energy transfer through the use of solution-phase optical microcavities.

To this aim we will first design structures in which fluorescent colloidal quantum dots are precisely located within dielectric microspheres to enable strong coupling of their fluorescence emission with the whispering gallery modes of the microspheres. Quantum dots are semiconductor nanocrystals with unique optical properties due to strong confinement of their charge carriers. These include high brightness and photostability, as well as narrow emission spectra that can be tuned thoughout the UV, visible and near infrared range. All these properties make them valuable energy transfer donors. Coupling these nanocrystals to whispering gallery modes will provide solution-phase light sources with novel intrinsic properties, including low-threshold lasing and confined light propagation at the microsphere interface.

We will then characterize the coupling and energy transfer between these confined optical modes and acceptor molecules present in the evanescent field, within the solution at a few 10s-100s nms of the interface. In this configuration energy transfer will occur over distances much larger and more efficiently than with standard FRET. We will take benefit of this strong coupling to design novel biodetection schemes presenting the advantages of simplicity (no washing steps), portability and sensitivity. We will impart biospecificity to the microspheres with a surface chemistry recently developed in our group. We will in particular design a novel diagnostic tool for Chagas disease, a widespread tropical parasitic disease causing severe damage to the heart, nervous and digestive systems. Since only early treatment can lead to complete cure, patients would strongly benefit from more sensitive diagnostic tools.

Keywords

Quantum dots ; whispering gallery modes ; biodetection ; energy transfer

Research unit

UMR7636
Physics & Materials

Description of the research Unit/subunit

The LPEM main research themes are nanostructures, nanophysics and nanomaterials ; low dimensionality and correlated electronic systems ; technical instrumentation. The quantum dot (QD) team at LPEM specializes in the synthesis, characterization and application of semiconductor colloidal quantum dots. During the last years, it has pioneered many important development in the field, including thick shell non-blinking QDs (Mahler et al, Nat Mater 2008), atomically flat nanoplatelets (Ithurria et al JACS 2008), heavy-metal free near infrared emitting QDs (Pons et al, ACS Nano 2010), or QD-plasmonic shell nanohybrids (Ji et al, Nat Nanotech 2015). The team also develops applications of these nanocrystals for optoelectronic applications as well as for cellular and in vivo bioimaging. It has in particular developed novel performant surface chemistries enabling specific targeting of biomolecules in complex environments (Tasso et al, ACS Nano 2015).

Name of the supervisor
Thomas Pons

3i Aspects of the proposal

This project involves the use of fluorescent semiconductor nanocrystals (QDs) coupled to optical microcavities. These novel emitters involves two KETs: nanotechnology and photonics. The versatility of QDs coupled to optical microcavities will likely generate interesting opportunities for various applications involving sensing and lasing. The aim of the project is the development of novel biomedical diagnostic tools. Therefore, the project has a strong potential for innovation, which could lead to patents. This is a truly multidisciplinary project involving chemistry, physics and biology. Indeed, it will require the synthesis of inorganic particles and their incorporation into dielectric microspheres through sol-gel chemistry. Furthermore, surface functionalization of the microspheres will use a novel copolymer-based surface chemistry developed in our group. The spectroscopic characterization of these fluorescent emitters located within optical micro-cavities, the modeling and characterization of energy transfer processes will represent an important area of study during the project and a strong physics component. Finally, the goal of the project lies in the realization of novel biodetection tools, and will involve functionalization with biomolecules and application to model biological samples. The project will include a collaboration with Dr Mariana Tasso, a CONICET researcher at the Soft Matter Laboratory in Buenos Aires, Argentina, working on the development of novel diagnostic tools for Chagas disease. The collaboration will include immobilization of biomolecules at the surface of the microspheres and tests of materials developed at LPEM on model and patient serum samples for diagnostics. Regular online meetings will occur to follow project development, and one or several visit of the PhD student to Buenos Aires could be programmed to develop our detection scheme for this specific application.

Expected Profile of the candidate

• Speciality : Materials chemistry and/or physics
• Knowledge : Optics and/or colloidal chemistry
• Soft skills : communication, curiosity, interest for interdisciplinarity

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