Project acronym 3D-nanoMorph
Project Label-free 3D morphological nanoscopy for studying sub-cellular dynamics in live cancer cells with high spatio-temporal resolution
Researcher (PI) Krishna AGARWAL
Host Institution (HI) UNIVERSITETET I TROMSOE - NORGES ARKTISKE UNIVERSITET
Call Details Starting Grant (StG), PE7, ERC-2018-STG
Summary Label-free optical nanoscopy, free from photobleaching and photochemical toxicity of fluorescence labels and yielding 3D morphological resolution of <50 nm, is the future of live cell imaging. 3D-nanoMorph breaks the diffraction barrier and shifts the paradigm in label-free nanoscopy, providing isotropic 3D resolution of <50 nm. To achieve this, 3D-nanoMorph performs non-linear inverse scattering for the first time in nanoscopy and decodes scattering between sub-cellular structures (organelles).
3D-nanoMorph innovatively devises complementary roles of light measurement system and computational nanoscopy algorithm. A novel illumination system and a novel light collection system together enable measurement of only the most relevant intensity component and create a fresh perspective about label-free measurements. A new computational nanoscopy approach employs non-linear inverse scattering. Harnessing non-linear inverse scattering for resolution enhancement in nanoscopy opens new possibilities in label-free 3D nanoscopy.
I will apply 3D-nanoMorph to study organelle degradation (autophagy) in live cancer cells over extended duration with high spatial and temporal resolution, presently limited by the lack of high-resolution label-free 3D morphological nanoscopy. Successful 3D mapping of nanoscale biological process of autophagy will open new avenues for cancer treatment and showcase 3D-nanoMorph for wider applications.
My cross-disciplinary expertise of 14 years spanning inverse problems, electromagnetism, optical microscopy, integrated optics and live cell nanoscopy paves path for successful implementation of 3D-nanoMorph.
Summary
Label-free optical nanoscopy, free from photobleaching and photochemical toxicity of fluorescence labels and yielding 3D morphological resolution of <50 nm, is the future of live cell imaging. 3D-nanoMorph breaks the diffraction barrier and shifts the paradigm in label-free nanoscopy, providing isotropic 3D resolution of <50 nm. To achieve this, 3D-nanoMorph performs non-linear inverse scattering for the first time in nanoscopy and decodes scattering between sub-cellular structures (organelles).
3D-nanoMorph innovatively devises complementary roles of light measurement system and computational nanoscopy algorithm. A novel illumination system and a novel light collection system together enable measurement of only the most relevant intensity component and create a fresh perspective about label-free measurements. A new computational nanoscopy approach employs non-linear inverse scattering. Harnessing non-linear inverse scattering for resolution enhancement in nanoscopy opens new possibilities in label-free 3D nanoscopy.
I will apply 3D-nanoMorph to study organelle degradation (autophagy) in live cancer cells over extended duration with high spatial and temporal resolution, presently limited by the lack of high-resolution label-free 3D morphological nanoscopy. Successful 3D mapping of nanoscale biological process of autophagy will open new avenues for cancer treatment and showcase 3D-nanoMorph for wider applications.
My cross-disciplinary expertise of 14 years spanning inverse problems, electromagnetism, optical microscopy, integrated optics and live cell nanoscopy paves path for successful implementation of 3D-nanoMorph.
Max ERC Funding
1 499 999 €
Duration
Start date: 2019-07-01, End date: 2024-06-30
Project acronym NANOSCOPY
Project High-speed chip-based nanoscopy to discover real-time sub-cellular dynamics
Researcher (PI) Balpreet Singh Ahluwalia
Host Institution (HI) UNIVERSITETET I TROMSOE - NORGES ARKTISKE UNIVERSITET
Call Details Starting Grant (StG), PE7, ERC-2013-StG
Summary Optical nanoscopy has given a glimpse of the impact it may have on medical care in the future. Slow imaging speed and the complexity of the current nanoscope limits its use for living cells. The imaging speed is limited by the bulk optics that is used in present nanoscopy. In this project, I propose a paradigm-shift in the field of advanced microscopy by developing optical nanoscopy based on a photonic integrated circuit. The project will take advantage of nanotechnology to fabricate an advance waveguide-chip, while fast telecom optical devices will provide switching of light to the chip, enhancing the speed of imaging. This unconventional route will change the field of optical microscopy, as a simple chip-based system can be added to a normal microscope. In this project, I will build a waveguide-based structured-illumination microscope (W-SIM) to acquire fast images (25 Hz or better) from a living cell with an optical resolution of 50-100 nm. I will use W-SIM to discover the dynamics (opening and closing) of fenestrations (100 nm) present in the membrane of a living liver sinusoidal scavenger endothelial cell. It is believed among the Hepatology community that these fenestrations open and close dynamically, however there is no scientific evidence to support this hypothesis because of the lack of suitable tools. The successful imaging of fenestration kinetics in a live cell during this project will provide new fundamental knowledge and benefit human health with improved diagnoses and drug discovery for liver. Chip-based nanoscopy is a new research field, inherently making this a high-risk project, but the possible gains are also high. The W-SIM will be the first of its kind, which may open a new era of simple, integrated nanoscopy. The proposed multiple-disciplinary project requires a near-unique expertise in the field of laser physics, integrated optics, advanced microscopy and cell-biology that I have acquired at leading research centers on three continents.
Summary
Optical nanoscopy has given a glimpse of the impact it may have on medical care in the future. Slow imaging speed and the complexity of the current nanoscope limits its use for living cells. The imaging speed is limited by the bulk optics that is used in present nanoscopy. In this project, I propose a paradigm-shift in the field of advanced microscopy by developing optical nanoscopy based on a photonic integrated circuit. The project will take advantage of nanotechnology to fabricate an advance waveguide-chip, while fast telecom optical devices will provide switching of light to the chip, enhancing the speed of imaging. This unconventional route will change the field of optical microscopy, as a simple chip-based system can be added to a normal microscope. In this project, I will build a waveguide-based structured-illumination microscope (W-SIM) to acquire fast images (25 Hz or better) from a living cell with an optical resolution of 50-100 nm. I will use W-SIM to discover the dynamics (opening and closing) of fenestrations (100 nm) present in the membrane of a living liver sinusoidal scavenger endothelial cell. It is believed among the Hepatology community that these fenestrations open and close dynamically, however there is no scientific evidence to support this hypothesis because of the lack of suitable tools. The successful imaging of fenestration kinetics in a live cell during this project will provide new fundamental knowledge and benefit human health with improved diagnoses and drug discovery for liver. Chip-based nanoscopy is a new research field, inherently making this a high-risk project, but the possible gains are also high. The W-SIM will be the first of its kind, which may open a new era of simple, integrated nanoscopy. The proposed multiple-disciplinary project requires a near-unique expertise in the field of laser physics, integrated optics, advanced microscopy and cell-biology that I have acquired at leading research centers on three continents.
Max ERC Funding
1 490 976 €
Duration
Start date: 2014-02-01, End date: 2019-01-31
Project acronym sCENT
Project Cryptophane-Enhanced Trace Gas Spectroscopy for On-Chip Methane Detection
Researcher (PI) Jana JAGERSKA
Host Institution (HI) UNIVERSITETET I TROMSOE - NORGES ARKTISKE UNIVERSITET
Call Details Starting Grant (StG), PE7, ERC-2017-STG
Summary Sensitivity of on-chip gas sensors is still at least 2-3 orders of magnitude lower than what is needed for applications in atmospheric monitoring and climate research. For optical sensors, this comes as a natural consequence of miniaturization: sensitivity scales with interaction length, which is directly related to instrument size. The aim of this project is to explore a new concept of combined chemical and spectroscopic detection for on-chip sensing of methane, the principal component of natural gas and a potent climate forcer.
The sought-after sensitivity will be achieved by pre-concentrating gas molecules directly on a chip surface using cryptophanes, and subsequently detecting them using slow-light waveguides and mid-infrared laser absorption spectroscopy. Cryptophanes are macromolecular structures that can bind and thus pre-concentrate different small molecules, including methane. Spectroscopic detection of methane in a cryptophane host is an absolute novelty, and, if successful, it will not only contribute to unprecedented sensitivity enhancement, but will also address fundamental questions about the dynamics of small molecules upon encapsulation. The actual gas sensing will be realized using evanescent field interaction in photonic crystal waveguides, which exhibit both large evanescent field confinement and long effective interaction pathlengths due to the slow-light effect. The waveguide design alone is expected to improve the per-length sensitivity up to 10 times, while another 10 to 100-fold sensitivity enhancement is expected from the pre-concentration.
The targeted detection limit of 10 ppb will revolutionize current methods of atmospheric monitoring, enabling large-scale networks of integrated sensors for better quantification of global methane emissions. Beyond that, this method can be extended to the detection of other gases, e.g. CO2 and different volatile organic compounds with equally relevant applications in the medical domain.
Summary
Sensitivity of on-chip gas sensors is still at least 2-3 orders of magnitude lower than what is needed for applications in atmospheric monitoring and climate research. For optical sensors, this comes as a natural consequence of miniaturization: sensitivity scales with interaction length, which is directly related to instrument size. The aim of this project is to explore a new concept of combined chemical and spectroscopic detection for on-chip sensing of methane, the principal component of natural gas and a potent climate forcer.
The sought-after sensitivity will be achieved by pre-concentrating gas molecules directly on a chip surface using cryptophanes, and subsequently detecting them using slow-light waveguides and mid-infrared laser absorption spectroscopy. Cryptophanes are macromolecular structures that can bind and thus pre-concentrate different small molecules, including methane. Spectroscopic detection of methane in a cryptophane host is an absolute novelty, and, if successful, it will not only contribute to unprecedented sensitivity enhancement, but will also address fundamental questions about the dynamics of small molecules upon encapsulation. The actual gas sensing will be realized using evanescent field interaction in photonic crystal waveguides, which exhibit both large evanescent field confinement and long effective interaction pathlengths due to the slow-light effect. The waveguide design alone is expected to improve the per-length sensitivity up to 10 times, while another 10 to 100-fold sensitivity enhancement is expected from the pre-concentration.
The targeted detection limit of 10 ppb will revolutionize current methods of atmospheric monitoring, enabling large-scale networks of integrated sensors for better quantification of global methane emissions. Beyond that, this method can be extended to the detection of other gases, e.g. CO2 and different volatile organic compounds with equally relevant applications in the medical domain.
Max ERC Funding
1 499 749 €
Duration
Start date: 2018-01-01, End date: 2022-12-31
