Aurélian Michel John-Herpin

Infrared nanoplasmonic metasurfaces augmented by artificial intelligence for universal biosensing

Nanoplasmonic metasurfaces have shown outstanding light-matter interaction enhancement capabilities, leading to their emergence as powerful platforms for highly sensitive biospectroscopy. Metasurface-enhanced biospectroscopy offers unprecedented opportunities for biological studies, and its full potential remains to be unleashed. Mid-IR metasurfaces, in particular, are very promising because they can act as amplifiers of fingerprint-like molecule vibrations, which are plentiful in this rich spectral range. In this thesis, we develop novel nanoplasmonic designs coupled with custom microfluidics and artificial intelligence-based data analysis models to demonstrate real-time, label-free, chemically-specific, and non-destructive monitoring of biomolecules and their interactions in aqueous media. Our first nanoplasmonic design combines optimized grating order-coupled nanoantenna arrays with protein-accessible nanogaps to enable the high sensitivity monitoring of proteins and their three-dimensional structures in aqueous media. The engineered nanoantennas reach electric field intensity enhancements of up to five orders of magnitude and provide chemically specific detection of proteins and their secondary structures down to picograms and nanograms per milliliter, respectively.In the next part of the thesis, we develop multiresonant metasurfaces to monitor interactions between biomolecules with vibrational fingerprints in different parts of the mid-IR range. Our first effort focuses on developing a nanoplasmonic design for simultaneous monitoring of both proteins and lipid molecules. Lipids are another important class of biomolecules as they are the building blocks of biological membranes, and lipid-protein interactions are at the core of many cellular processes. New analytical tools for their study in water and at the monolayer level are of fundamental importance. Therefore, we introduce a dual-resonant nanoplasmonic design coupled to machine learning-based data analysis to overcome current sensor challenges. We apply our technology to a dynamic system involving synaptic vesicle mimics and demonstrate that we can resolve complex mass-preserving biological interactions in real-time. This is a remarkable feat that traditional non-chemically specific analytical measurement tools such as surface plasmon resonance or quartz crystal microbalance spectroscopy could not achieve. In the final part of the thesis, we develop yet another multiresonant design for broadband coverage of the whole mid-IR range. We couple our sensor to a deep learning model to resolve a dynamic biological system including all major classes of biomolecules simultaneously. Specifically, we resolve the toxic peptide-induced release of carbohydrates and nucleotides from exosome-like bionanoparticles.

EPFL2022

Metasurface-Enhanced Infrared Spectroscopy: An Abundance of Materials and Functionalities

Hatice Altug, Aurélian Michel John-Herpin, Felix Ulrich Richter, Andreas Tittl

Infrared spectroscopy provides unique information on the composition and dynamics of biochemical systems by resolving the characteristic absorption fingerprints of their constituent molecules. Based on this inherent chemical specificity and the capability for label-free, noninvasive, and real-time detection, infrared spectroscopy approaches have unlocked a plethora of breakthrough applications for fields ranging from environmental monitoring and defense to chemical analysis and medical diagnostics. Nanophotonics has played a crucial role for pushing the sensitivity limits of traditional far-field spectroscopy by using resonant nanostructures to focus the incident light into nanoscale hot-spots of the electromagnetic field, greatly enhancing light-matter interaction. Metasurfaces composed of regular arrangements of such resonators further increase the design space for tailoring this nanoscale light control both spectrally and spatially, which has established them as an invaluable toolkit for surface-enhanced spectroscopy. Starting from the fundamental concepts of metasurface-enhanced infrared spectroscopy, a broad palette of resonator geometries, materials, and arrangements for realizing highly sensitive metadevices is showcased, with a special focus on emerging systems such as phononic and 2D van der Waals materials, and integration with waveguides for lab-on-a-chip devices. Furthermore, advanced sensor functionalities of metasurface-based infrared spectroscopy, including multiresonance, tunability, dielectrophoresis, live cell sensing, and machine-learning-aided analysis are highlighted.

WILEY-V C H VERLAG GMBH2022

Infrared Metasurface Augmented by Deep Learning for Monitoring Dynamics between All Major Classes of Biomolecules

Hatice Altug, Aurélian Michel John-Herpin, Deepthy Kavungal, Lea Katharina Von Mücke

Insights into the fascinating molecular world of biological processes are crucial for understanding diseases, developing diagnostics, and effective therapeutics. These processes are complex as they involve interactions between four major classes of biomolecules, i.e., proteins, nucleic acids, carbohydrates, and lipids, which makes it important to be able to discriminate between all these different biomolecular species. In this work, a deep learning-augmented, chemically-specific nanoplasmonic technique that enables such a feat in a label-free manner to not disrupt native processes is presented. The method uses a highly sensitive multiresonant plasmonic metasurface in a microfluidic device, which enhances infrared absorption across a broadband mid-IR spectrum and in water, despite its strongly overlapping absorption bands. The real-time format of the optofluidic method enables the collection of a vast amount of spectrotemporal data, which allows the construction of a deep neural network to discriminate accurately between all major classes of biomolecules. The capabilities of the new method are demonstrated by monitoring of a multistep bioassay containing sucrose- and nucleotides-loaded liposomes interacting with a small, lipid membrane-perforating peptide. It is envisioned that the presented technology will impact the fields of biology, bioanalytics, and pharmacology from fundamental research and disease diagnostics to drug development.

WILEY-V C H VERLAG GMBH2021

Wafer‐Scale Functional Metasurfaces for Mid‐Infrared Photonics and Biosensing

Hatice Altug, Aurélian Michel John-Herpin, Aleksandrs Leitis

Metasurfaces have emerged as a breakthrough platform for manipulating light at the nanoscale and enabling on-demand optical functionalities for next-generation biosensing, imaging, and light-generating photonic devices. However, translating this technology to practical applications requires low-cost and high-throughput fabrication methods. Due to the limited choice of materials with suitable optical properties, it is particularly challenging to produce metasurfaces for the technologically relevant mid-infrared spectral range. These constraints are overcome by realizing functional metasurfaces on almost completely transparent free-standing metal-oxide membranes. A versatile nanofabrication process is developed and implemented for highly efficient dielectric and plasmonic mid-infrared metasurfaces with wafer-scale and complementary metal–oxide–semiconductor (CMOS)-compatible manufacturing techniques. The advantages of this method are revealed by demonstrating highly uniform and functional metasurfaces, including high-Q structures enabling fine spectral selectivity, large-area metalenses with diffraction-limited focusing capabilities, and birefringent metasurfaces providing polarization control at record-high conversion efficiencies. Aluminum plasmonic devices and their integration into microfluidics for real-time and label-free mid-infrared biosensing of proteins and lipid vesicles are further demonstrated. The versatility of this approach and its compatibility with mass-production processes bring infrared metasurfaces markedly closer to commercial applications, such as thermal imaging, spectroscopy, and biosensing.

2021

Metasurface-Based Molecular Biosensing Aided by Artificial Intelligence

Hatice Altug, Aurélian Michel John-Herpin, Aleksandrs Leitis, Eduardo Romero Arvelo, Andreas Tittl

Molecular spectroscopy provides unique information on the internal structure of biological materials by detecting the characteristic vibrational signatures of their constituent chemical bonds at infrared frequencies. Nanophotonic antennas and metasurfaces have driven this concept towards few-molecule sensitivity by confining incident light into intense hot spots of the electromagnetic fields, providing strongly enhanced light-matter interaction. In this Minireview, recently developed molecular biosensing approaches based on the combination of dielectric metasurfaces and imaging detection are highlighted in comparison to traditional plasmonic geometries, and the unique potential of artificial intelligence techniques for nanophotonic sensor design and data analysis is emphasized. Because of their spectrometer-less operation principle, such imaging-based approaches hold great promise for miniaturized biosensors in practical point-of-care or field-deployable applications.

WILEY-V C H VERLAG GMBH2019

Metasurface‐based molecular biosensing aided by artificial intelligence

Hatice Altug, Aurélian Michel John-Herpin, Aleksandrs Leitis, Eduardo Romero Arvelo, Andreas Tittl

Molecular spectroscopy provides unique information on the internal structure of biological materials by detecting the characteristic vibrational signatures of their constituent chemical bonds at infrared frequencies. Nanophotonic antennas and metasurfaces have driven this concept towards few‐molecule sensitivities by confining incident light into intense hot spots of the electromagnetic fields, providing strongly enhanced light‐matter interaction. In this Minireview, recently developed molecular biosensing approaches based on the combination of dielectric metasurfaces and imaging detection are highlighted in comparison to traditional plasmonic geometries, and the unique potential of artificial intelligence techniques for nanophotonic sensor design and data analysis is emphasized. Because of their spectrometer‐less operation principle, such imaging‐based approaches hold great promise for miniaturized biosensors in practical point‐of‐care or field‐deployable applications.

2019

High-Contrast Infrared Absorption Spectroscopy via Mass-Produced Coaxial Zero-Mode Resonators with Sub-10 nm Gaps

Hatice Altug, Aurélian Michel John-Herpin, Sunghwan Kim

We present a wafer-scale array of resonant coaxial nanoapertures as a practical platform for surface-enhanced infrared absorption spectroscopy (SEIRA). Coaxial nanoapertures with sub-10 nm gaps are fabricated via photolithography, atomic layer deposition of a sacrificial Al2O3 layer to define the nanogaps, and planarization via glancing-angle ion milling. At the zeroth-order Fabry-Pérot resonance condition, our coaxial apertures act as a “zero-mode resonator (ZMR)”, efficiently funneling as much as 34% of incident infrared (IR) light along 10 nm annular gaps. After removing Al2O3 in the gaps and inserting silk protein, we can couple the intense optical fields of the annular nanogap into the vibrational modes of protein molecules. From 7 nm gap ZMR devices coated with a 5 nm thick silk protein film, we observe high-contrast IR absorbance signals drastically suppressing 58% of the transmitted light and infer a strong IR absorption enhancement factor of 10^4∼10^5. These single nanometer gap ZMR devices can be mass-produced via batch processing and offer promising routes for broad applications of SEIRA.

2018

Quantifying the Limits of Detection of Surface-Enhanced Infrared Spectroscopy with Grating Order-Coupled Nanogap Antennas

Hatice Altug, Aurélian Michel John-Herpin, Andreas Tittl

Infrared spectroscopy is widely used for biomolecular studies, but struggles when investigating minute quantities of analytes due to the mismatch between vibrational cross sections and IR wavelengths. It is therefore beneficial to enhance absorption signals by confining the infrared light to deeply subwavelength volumes comparable in size to the biomolecules of interest. This can be achieved with surface-enhanced infrared absorption spectroscopy, for which plasmonic nanorod antennas represent the predominant implementation. However, unifying design guidelines for such systems are still lacking. Here, we introduce an experimentally verified framework for designing antenna-based molecular IR spectroscopy sensors. Specifically, we find that in order to maximize the sensing performance, it is essential to combine the signal enhancement originating from nanoscale gaps between the antenna elements with the enhancement obtained from coupling to the grating order modes of the unit cell. Using an optimized grating order-coupled nanogap design, our experiments and numerical simulations show a hotspot limit of detection of two proteins per nanogap. Furthermore, we introduce and analyze additional limit of detection parameters, specifically for deposited surface mass, in-solution concentration, and secondary structure determination. These limits of detection provide valuable reference points for performance metrics of surface-enhanced infrared absorption spectroscopy in practical applications, such as the characterization of biological samples in aqueous solution.

2018

Aurélian Michel John-Herpin

Infrared nanoplasmonic metasurfaces augmented by artificial intelligence for universal biosensing

Metasurface-Enhanced Infrared Spectroscopy: An Abundance of Materials and Functionalities

Infrared Metasurface Augmented by Deep Learning for Monitoring Dynamics between All Major Classes of Biomolecules

Infrared Metasurfaces Augmented by Artificial Intelligence for Monitoring Dynamics between All Major Classes of Biomolecules

Wafer‐Scale Functional Metasurfaces for Mid‐Infrared Photonics and Biosensing

Metasurface-Based Molecular Biosensing Aided by Artificial Intelligence

Metasurface‐based molecular biosensing aided by artificial intelligence

High-Contrast Infrared Absorption Spectroscopy via Mass-Produced Coaxial Zero-Mode Resonators with Sub-10 nm Gaps

High-Contrast Infrared Absorption Spectroscopy via Mass-Produced Coaxial Zero-Mode Resonators with Sub-10 nm Gaps

Quantifying the Limits of Detection of Surface-Enhanced Infrared Spectroscopy with Grating Order-Coupled Nanogap Antennas

Infrared Metasurfaces Augmented by Artificial Intelligence for Monitoring Dynamics between All Major Classes of Biomolecules

Infrared nanoplasmonic metasurfaces augmented by artificial intelligence for universal biosensing

Metasurface-Enhanced Infrared Spectroscopy: An Abundance of Materials and Functionalities

High-Contrast Infrared Absorption Spectroscopy via Mass-Produced Coaxial Zero-Mode Resonators with Sub-10 nm Gaps

Infrared Metasurface Augmented by Deep Learning for Monitoring Dynamics between All Major Classes of Biomolecules

Quantifying the Limits of Detection of Surface-Enhanced Infrared Spectroscopy with Grating Order-Coupled Nanogap Antennas

Wafer‐Scale Functional Metasurfaces for Mid‐Infrared Photonics and Biosensing

Metasurface-Based Molecular Biosensing Aided by Artificial Intelligence

High-Contrast Infrared Absorption Spectroscopy via Mass-Produced Coaxial Zero-Mode Resonators with Sub-10 nm Gaps

Metasurface‐based molecular biosensing aided by artificial intelligence