Jerome Wenger NanoBioPhotonics

Our recent publication in Small presents a new scalable way to fabricate zero-mode waveguides (ZMWs) which are metallic nanoapertures confining light into volumes 1000x smaller than the diffraction limit. These nanostructures enable single-molecule fluorescence detection at biologically relevant micromolar concentrations, something traditional microscopes cannot achieve.

By combining sol-gel nanoimprint lithography with hydrofluoric acid vapor etching, we developed a cost-effective, high-throughput process to produce high-performance ZMW arrays without expensive nanofabrication tools. Experiments with single fluorescent molecules demonstrated the effectivity and performance of our ZMWS for single molecule fluroescence detection, showing up to eightfold brightness enhancement and sub-millisecond temporal resolution across the visible spectrum.

This work opens the door to affordable, large-scale nanostructures devices, making nanophotonics techniques more accessible for applications in biophysics, biosensing, and advanced fluorescence microscopy.

Congratulations Hamza! Accessible freely through gold open access.

Two positions are open in our group for Master 2 internship in spring / first semester 2026 combined with a 3-years PhD fellowship starting in Fall 2026:

- Optical sequencing of digital polymers for molecular data storage: develop a groundbreaking optical sequencing platform that decodes fluorescently encoded polymers, paving the way for fast, high-throughput molecular data storage.

- Nanoplastics Detection Exploiting UV Autofluorescence for Enhanced Sensitivity: pioneer a groundbreaking UV autofluorescence approach that reveals and identifies nanoplastics as small as 30 nm—unlocking new frontiers in the fight against invisible plastic pollution.

Applications by email to Jerome Wenger with a CV, a letter of interest, academic transcripts and the name of a past supervisor serving as reference.

The optical detection of nanoparticles plays a pivotal role across many fields of nanoscience and nanotechnology, yet the weak optical response of single nanoparticles in the visible spectral range often challenges their detection. Dielectric materials such as polystyrene nanoparticles are especially difficult to detect as they remain nearly transparent across the visible domain.

In our recent Optics Express publication, we present a novel application of ultraviolet microscopy for detecting single nanoparticles with high sensitivity and versatility. By leveraging the strong absorption of both metallic and dielectric nanoparticles in the UV spectral range, we demonstrate robust detection capabilities, validated through correlative electron microscopy and Mie theory simulations. This work offers significant advancements for nanoparticle analysis, with potential applications spanning across material science, biotechnology, and environmental monitoring.

Following his success in winning the ED352 prize, Prithu Roy has been honored with the prestigious Prix de Thèse AMU 2024 at the official awards ceremony held on April 4th.

This annual distinction, presented by President Éric Berton during a major scientific event, recognizes outstanding doctoral research at Aix-Marseille University. Each year, the award celebrates 16 exceptional new PhDs accross all areas for science (only 1 or 2 per year in physics and engineering) and also pays tribute to eminent researchers named Doctor Honoris Causa of the university.

Prithu’s doctoral thesis, titled “Achieving Ultimate Sensitivity of Label-Free Autofluorescence Spectroscopy of Single Proteins with Deep Ultraviolet Nanophotonics,” is available for consultation on HAL repository.

Our article entitled “Breaking the low concentration barrier of single-molecule fluorescence quantitation to the sub-picomolar range” has recently been published in Small Methods.

Until now, the concentration range for effective single-molecule fluorescence detection was largely restricted to the concentrations above 50 pM, overlooking the immense potential of the single-molecule fluorescence for biosensing applications at sub-picomolar sensitivity.

In our work, we present a simple and effective modification to a confocal microscope setup that pushes the detection limit of fluorescence lifetime correlation spectroscopy (FLCS) down to 0.1 pM, overcoming the so-called low concentration barrier without the need for complex instrumentation or preconcentration techniques.

Main elements of significance:

• Adding a diaphragm on the laser excitation beam achieves a large detection volume together with a high fluorescence brightness per molecule. This is the key to push the sensitivity towards sub-picomolar concentrations.
• For the first time, we clearly discuss the physical parameters setting the lower the limit of quantification in FLCS and we introduce a universal figure of merit allowing to compare between experimental configurations.
• We demonstrate the effectiveness of our approach by monitoring the interaction dynamics of biotin-streptavidin binding, a highly relevant biochemical system yet challenging to measure on conventional systems due to its exceptionally high affinity.

These results open new avenues for applying single-molecule fluorescence detection to biosensing at sub-picomolar concentrations, with significant implications for biological and medical diagnostics.

Open access at Small Methods and available on the repository HAL 05043006.