Periodic Reporting for period 4 - Cell-Lasers (Intracellular lasers: Coupling of optical resonances with biological processes)
Berichtszeitraum: 2024-11-01 bis 2025-10-31
The Cell-Lasers project addresses the challenge of obtaining high-precision, quantitative measurements of biochemical and biophysical parameters within live cells, where tissue scattering and the limitations of traditional fluorescent labels often hinder deep-tissue imaging. This work is vital for society as it advances the understanding of human health processes and introduces new technologies for food safety, laboratory diagnostics, and quantum computing. The project's primary objectives are to develop functional microlasers for three-dimensional cell tracking and environmental sensing, and to explore innovative applications such as edible lasers for food monitoring and organic quantum light sources.
We showed that intracellular optical microcavity probes enable three-dimensional localization, long-term tracking of individual cells, and environmental sensing at depths far beyond the light transport length [1]. This capability relies on the distinctive spectral signatures of whispering-gallery modes, which are robust against tissue scattering, absorption, and autofluorescence (Fig. 1). Moreover, functionalized microcavities allow simultaneous sensing of parameters such as temperature or pH, exceeding the capabilities of conventional fluorescent labels.
Light–matter coupling in complex soft-matter structures placed inside laser cavities was investigated experimentally and through simulations. Tunable microlasers emitting structured light were realized using self-assembled topological liquid-crystal superstructures embedded in Fabry–Pérot microcavities [2]. The topology and geometry of these structures govern the emitted light by introducing three-dimensionally varying optical axes and singularities, thereby shaping the polarization topology (Fig. 2).
Interfacial tension plays a key role in many biological processes, motivating the development of precise in situ measurement techniques. We demonstrated a simple and highly accurate optical-resonance-based method to measure interfacial tension between immiscible liquids [3]. Micron-scale droplets formed at the tip of a glass microcapillary were monitored with nanometer precision while applying controlled pressure, allowing interfacial tension to be extracted from equilibrium conditions using minimal sample volumes (Fig. 3).
We developed microlasers made entirely out of edible materials [4]. Microlasers that can be embedded directly into edible products were designed as barcodes or as sensors/indicators for various food-related parameters. Illuminating a food product, containing such microlaser(s), with a laser pulse, and measuring the emission spectrum enables remote measuring of pH, sugar concentration, etc. or reading encoded information e.g. on expiry dates and the food origin (Fig. 4). The microlasers are entirely safe for consumption and do not alter the appearance or taste of food. The research on edible microlasers could significantly enhance traceability, security and freshness monitoring of food.
One of the goals of this project was to use the cell lasers to barcode the cells. The lasers are, however, relatively large, so we looked into other possibilities. Specifically, we have used color centers in hexagonal boron nitride as nanometer-sized barcodes [5]. These barcodes are also single-photon sources, so they emit quantum light. With this, we started looking into whether we could generate other sources of quantum light from biological or other organic materials. We have, for the first time, demonstrated the generation of entangled photons in liquid crystals and, with this, in any organic material (Fig. 5) [6]. In addition to the fact that the efficiency of entangled photon generation in liquid crystals is comparable to the best existing sources, their main advantage lies in the tunability of the state of photon pairs. This tunability can be achieved by applying an electric field or by arranging the liquid crystal molecules into the appropriate configuration. The ability to tune the quantum state indicates significant practical potential for numerous quantum technologies. The work was published in Nature [6].
Following the work in [3], we investigated making microlasers even more sensitive to forces and pressure. We demonstrated for the first time that smectic and soap bubbles can be used as lasers [7]. We doped the bubbles with a fluorescent dye and pumped them with an external laser to induce whispering-gallery-mode optical lasing (Fig. 6). Bubbles made of smectic liquid crystals have a very thin and uniform wall and are extremely stable. Shifts in lasing wavelengths in the emitted light's spectrum, which contained hundreds of regularly spaced, sharp peaks, enabled the measurement of subtle size changes of just 10 nanometers in a millimeter-sized bubble. This incredible precision enabled the bubbles to serve as one of the best pressure and electric-field sensors developed to date.
1. Peer reviewed article: Aljaž Kavčič, Maja Garvas, Matevž Marinčič, Katrin Unger, Anna Maria Coclite, Boris Majaron, Matjaž Humar, Deep tissue localization and sensing using optical microcavity probes, Nature Communications 13, 1269 (2022), DOI: 10.1038/s41467-022-28904-6
2. Peer reviewed article: Miha Papič, Urban Mur, Kottoli Poyil Zuhail, Miha Ravnik, Igor Muševič, and Matjaž Humar, Topological liquid crystal superstructures as structured light lasers, Proceedings of the National Academy of Sciences 118, e2110839118 (2021), DOI: 10.1073/pnas.2110839118
3. Peer reviewed article: Gregor Pirnat, and Matjaž Humar, Whispering Gallery-Mode Microdroplet Tensiometry, Advanced Photonics Research 2, 2100129 (2021), DOI: 10.1002/adpr.202100129
4. Peer reviewed article: Abdur Rehman Anwar, Maruša Mur, Georgia Michailidou, Dimitrios N. Bikiaris, Matjaž Humar, Microlasers Made Entirely from Edible Substances, Advanced Optical Materials 13, 2500497 (2025), DOI: 10.1002/adom.202500497.
5. Aljaž Kavčič, Rok Podlipec, Ana Krišelj, Andreja Jelen, Daniele Vella, Matjaž Humar, Intracellular biocompatible hexagonal boron nitride quantum emitters as single-photon sources and barcodes, Nanoscale 16, 4691-4702 (2024), DOI: doi.org/10.1039/D3NR05305A
6. V. Sultanov, A. Kavčič, E. Kokkinakis, N. Sebastián, M. V. Chekhova, M. Humar, Tunable entangled photon-pair generation in a liquid crystal, Nature 631 (8020), 294-299 (2024), DOI: 10.1038/s41586-024-07543-5
7. Z. Korenjak, M. Humar, Smectic and soap bubble optofluidic lasers, Physical Review X 14, 011002 (2024), DOI: 10.1103/PhysRevX.14.011002
Light–matter coupling in complex soft-matter structures placed inside laser cavities was investigated experimentally and through simulations. Tunable microlasers emitting structured light were realized using self-assembled topological liquid-crystal superstructures embedded in Fabry–Pérot microcavities [2]. The topology and geometry of these structures govern the emitted light by introducing three-dimensionally varying optical axes and singularities, thereby shaping the polarization topology (Fig. 2).
Interfacial tension plays a key role in many biological processes, motivating the development of precise in situ measurement techniques. We demonstrated a simple and highly accurate optical-resonance-based method to measure interfacial tension between immiscible liquids [3]. Micron-scale droplets formed at the tip of a glass microcapillary were monitored with nanometer precision while applying controlled pressure, allowing interfacial tension to be extracted from equilibrium conditions using minimal sample volumes (Fig. 3).
We developed microlasers made entirely out of edible materials [4]. Microlasers that can be embedded directly into edible products were designed as barcodes or as sensors/indicators for various food-related parameters. Illuminating a food product, containing such microlaser(s), with a laser pulse, and measuring the emission spectrum enables remote measuring of pH, sugar concentration, etc. or reading encoded information e.g. on expiry dates and the food origin (Fig. 4). The microlasers are entirely safe for consumption and do not alter the appearance or taste of food. The research on edible microlasers could significantly enhance traceability, security and freshness monitoring of food.
One of the goals of this project was to use the cell lasers to barcode the cells. The lasers are, however, relatively large, so we looked into other possibilities. Specifically, we have used color centers in hexagonal boron nitride as nanometer-sized barcodes [5]. These barcodes are also single-photon sources, so they emit quantum light. With this, we started looking into whether we could generate other sources of quantum light from biological or other organic materials. We have, for the first time, demonstrated the generation of entangled photons in liquid crystals and, with this, in any organic material (Fig. 5) [6]. In addition to the fact that the efficiency of entangled photon generation in liquid crystals is comparable to the best existing sources, their main advantage lies in the tunability of the state of photon pairs. This tunability can be achieved by applying an electric field or by arranging the liquid crystal molecules into the appropriate configuration. The ability to tune the quantum state indicates significant practical potential for numerous quantum technologies. The work was published in Nature [6].
Following the work in [3], we investigated making microlasers even more sensitive to forces and pressure. We demonstrated for the first time that smectic and soap bubbles can be used as lasers [7]. We doped the bubbles with a fluorescent dye and pumped them with an external laser to induce whispering-gallery-mode optical lasing (Fig. 6). Bubbles made of smectic liquid crystals have a very thin and uniform wall and are extremely stable. Shifts in lasing wavelengths in the emitted light's spectrum, which contained hundreds of regularly spaced, sharp peaks, enabled the measurement of subtle size changes of just 10 nanometers in a millimeter-sized bubble. This incredible precision enabled the bubbles to serve as one of the best pressure and electric-field sensors developed to date.
1. Peer reviewed article: Aljaž Kavčič, Maja Garvas, Matevž Marinčič, Katrin Unger, Anna Maria Coclite, Boris Majaron, Matjaž Humar, Deep tissue localization and sensing using optical microcavity probes, Nature Communications 13, 1269 (2022), DOI: 10.1038/s41467-022-28904-6
2. Peer reviewed article: Miha Papič, Urban Mur, Kottoli Poyil Zuhail, Miha Ravnik, Igor Muševič, and Matjaž Humar, Topological liquid crystal superstructures as structured light lasers, Proceedings of the National Academy of Sciences 118, e2110839118 (2021), DOI: 10.1073/pnas.2110839118
3. Peer reviewed article: Gregor Pirnat, and Matjaž Humar, Whispering Gallery-Mode Microdroplet Tensiometry, Advanced Photonics Research 2, 2100129 (2021), DOI: 10.1002/adpr.202100129
4. Peer reviewed article: Abdur Rehman Anwar, Maruša Mur, Georgia Michailidou, Dimitrios N. Bikiaris, Matjaž Humar, Microlasers Made Entirely from Edible Substances, Advanced Optical Materials 13, 2500497 (2025), DOI: 10.1002/adom.202500497.
5. Aljaž Kavčič, Rok Podlipec, Ana Krišelj, Andreja Jelen, Daniele Vella, Matjaž Humar, Intracellular biocompatible hexagonal boron nitride quantum emitters as single-photon sources and barcodes, Nanoscale 16, 4691-4702 (2024), DOI: doi.org/10.1039/D3NR05305A
6. V. Sultanov, A. Kavčič, E. Kokkinakis, N. Sebastián, M. V. Chekhova, M. Humar, Tunable entangled photon-pair generation in a liquid crystal, Nature 631 (8020), 294-299 (2024), DOI: 10.1038/s41586-024-07543-5
7. Z. Korenjak, M. Humar, Smectic and soap bubble optofluidic lasers, Physical Review X 14, 011002 (2024), DOI: 10.1103/PhysRevX.14.011002
Practically all the research within this grant has led to developments well beyond the state of the art, since we showed some completely new concepts:
• First demonstration that microcavities can be used for deep tissue imaging
• We have demonstrated a new concept where a topological soft matter is inserted into a micro laser cavity to generate a very rich array of laser beams
• Entirely new way of measuring forces and mechanical properties of biological tissues via microlasers
• We developed for the first time microlasers made entirely out of edible materials
• We showed for the first time that soap bubbles can be used as a laser source
• First demonstration of color centers being used as barcodes
• First demonstration of the generation of entangled photons from organic material
• First demonstration that microcavities can be used for deep tissue imaging
• We have demonstrated a new concept where a topological soft matter is inserted into a micro laser cavity to generate a very rich array of laser beams
• Entirely new way of measuring forces and mechanical properties of biological tissues via microlasers
• We developed for the first time microlasers made entirely out of edible materials
• We showed for the first time that soap bubbles can be used as a laser source
• First demonstration of color centers being used as barcodes
• First demonstration of the generation of entangled photons from organic material