Project acronym 3D-PXM
Project 3D Piezoresponse X-ray Microscopy
Researcher (PI) Hugh SIMONS
Host Institution (HI) DANMARKS TEKNISKE UNIVERSITET
Country Denmark
Call Details Starting Grant (StG), PE3, ERC-2018-STG
Summary Polar materials, such as piezoelectrics and ferroelectrics are essential to our modern life, yet they are mostly developed by trial-and-error. Their properties overwhelmingly depend on the defects within them, the majority of which are hidden in the bulk. The road to better materials is via mapping these defects, but our best tool for it – piezoresponse force microscopy (PFM) – is limited to surfaces. 3D-PXM aims to revolutionize our understanding by measuring the local structure-property correlations around individual defects buried deep in the bulk.
This is a completely new kind of microscopy enabling 3D maps of local strain and polarization (i.e. piezoresponse) with 10 nm resolution in mm-sized samples. It is novel, multi-scale and fast enough to capture defect dynamics in real time. Uniquely, it is a full-field method that uses a synthetic-aperture approach to improve both resolution and recover the image phase. This phase is then quantitatively correlated to local polarization and strain via a forward model. 3D-PXM combines advances in X-Ray optics, phase recovery and data analysis to create something transformative. In principle, it can achieve spatial resolution comparable to the best coherent X-Ray microscopy methods while being faster, used on larger samples, and without risk of radiation damage.
For the first time, this opens the door to solving how defects influence bulk properties under real-life conditions. 3D-PXM focuses on three types of defects prevalent in polar materials: grain boundaries, dislocations and polar nanoregions. Individually they address major gaps in the state-of-the-art, while together making great strides towards fully understanding defects. This understanding is expected to inform a new generation of multi-scale models that can account for a material’s full heterogeneity. These models are the first step towards abandoning our tradition of trial-and-error, and with this comes the potential for a new era of polar materials.
Summary
Polar materials, such as piezoelectrics and ferroelectrics are essential to our modern life, yet they are mostly developed by trial-and-error. Their properties overwhelmingly depend on the defects within them, the majority of which are hidden in the bulk. The road to better materials is via mapping these defects, but our best tool for it – piezoresponse force microscopy (PFM) – is limited to surfaces. 3D-PXM aims to revolutionize our understanding by measuring the local structure-property correlations around individual defects buried deep in the bulk.
This is a completely new kind of microscopy enabling 3D maps of local strain and polarization (i.e. piezoresponse) with 10 nm resolution in mm-sized samples. It is novel, multi-scale and fast enough to capture defect dynamics in real time. Uniquely, it is a full-field method that uses a synthetic-aperture approach to improve both resolution and recover the image phase. This phase is then quantitatively correlated to local polarization and strain via a forward model. 3D-PXM combines advances in X-Ray optics, phase recovery and data analysis to create something transformative. In principle, it can achieve spatial resolution comparable to the best coherent X-Ray microscopy methods while being faster, used on larger samples, and without risk of radiation damage.
For the first time, this opens the door to solving how defects influence bulk properties under real-life conditions. 3D-PXM focuses on three types of defects prevalent in polar materials: grain boundaries, dislocations and polar nanoregions. Individually they address major gaps in the state-of-the-art, while together making great strides towards fully understanding defects. This understanding is expected to inform a new generation of multi-scale models that can account for a material’s full heterogeneity. These models are the first step towards abandoning our tradition of trial-and-error, and with this comes the potential for a new era of polar materials.
Max ERC Funding
1 496 941 €
Duration
Start date: 2019-01-01, End date: 2023-12-31
Project acronym 3D-QUEST
Project 3D-Quantum Integrated Optical Simulation
Researcher (PI) Fabio Sciarrino
Host Institution (HI) UNIVERSITA DEGLI STUDI DI ROMA LA SAPIENZA
Country Italy
Call Details Starting Grant (StG), PE2, ERC-2012-StG_20111012
Summary "Quantum information was born from the merging of classical information and quantum physics. Its main objective consists of understanding the quantum nature of information and learning how to process it by using physical systems which operate by following quantum mechanics laws. Quantum simulation is a fundamental instrument to investigate phenomena of quantum systems dynamics, such as quantum transport, particle localizations and energy transfer, quantum-to-classical transition, and even quantum improved computation, all tasks that are hard to simulate with classical approaches. Within this framework integrated photonic circuits have a strong potential to realize quantum information processing by optical systems.
The aim of 3D-QUEST is to develop and implement quantum simulation by exploiting 3-dimensional integrated photonic circuits. 3D-QUEST is structured to demonstrate the potential of linear optics to implement a computational power beyond the one of a classical computer. Such ""hard-to-simulate"" scenario is disclosed when multiphoton-multimode platforms are realized. The 3D-QUEST research program will focus on three tasks of growing difficulty.
A-1. To simulate bosonic-fermionic dynamics with integrated optical systems acting on 2 photon entangled states.
A-2. To pave the way towards hard-to-simulate, scalable quantum linear optical circuits by investigating m-port interferometers acting on n-photon states with n>2.
A-3. To exploit 3-dimensional integrated structures for the observation of new quantum optical phenomena and for the quantum simulation of more complex scenarios.
3D-QUEST will exploit the potential of the femtosecond laser writing integrated waveguides. This technique will be adopted to realize 3-dimensional capabilities and high flexibility, bringing in this way the optical quantum simulation in to new regime."
Summary
"Quantum information was born from the merging of classical information and quantum physics. Its main objective consists of understanding the quantum nature of information and learning how to process it by using physical systems which operate by following quantum mechanics laws. Quantum simulation is a fundamental instrument to investigate phenomena of quantum systems dynamics, such as quantum transport, particle localizations and energy transfer, quantum-to-classical transition, and even quantum improved computation, all tasks that are hard to simulate with classical approaches. Within this framework integrated photonic circuits have a strong potential to realize quantum information processing by optical systems.
The aim of 3D-QUEST is to develop and implement quantum simulation by exploiting 3-dimensional integrated photonic circuits. 3D-QUEST is structured to demonstrate the potential of linear optics to implement a computational power beyond the one of a classical computer. Such ""hard-to-simulate"" scenario is disclosed when multiphoton-multimode platforms are realized. The 3D-QUEST research program will focus on three tasks of growing difficulty.
A-1. To simulate bosonic-fermionic dynamics with integrated optical systems acting on 2 photon entangled states.
A-2. To pave the way towards hard-to-simulate, scalable quantum linear optical circuits by investigating m-port interferometers acting on n-photon states with n>2.
A-3. To exploit 3-dimensional integrated structures for the observation of new quantum optical phenomena and for the quantum simulation of more complex scenarios.
3D-QUEST will exploit the potential of the femtosecond laser writing integrated waveguides. This technique will be adopted to realize 3-dimensional capabilities and high flexibility, bringing in this way the optical quantum simulation in to new regime."
Max ERC Funding
1 474 800 €
Duration
Start date: 2012-08-01, End date: 2017-07-31
Project acronym 3D-REPAIR
Project Spatial organization of DNA repair within the nucleus
Researcher (PI) Evanthia Soutoglou
Host Institution (HI) THE UNIVERSITY OF SUSSEX
Country United Kingdom
Call Details Consolidator Grant (CoG), LS2, ERC-2015-CoG
Summary Faithful repair of double stranded DNA breaks (DSBs) is essential, as they are at the origin of genome instability, chromosomal translocations and cancer. Cells repair DSBs through different pathways, which can be faithful or mutagenic, and the balance between them at a given locus must be tightly regulated to preserve genome integrity. Although, much is known about DSB repair factors, how the choice between pathways is controlled within the nuclear environment is not understood. We have shown that nuclear architecture and non-random genome organization determine the frequency of chromosomal translocations and that pathway choice is dictated by the spatial organization of DNA in the nucleus. Nevertheless, what determines which pathway is activated in response to DSBs at specific genomic locations is not understood. Furthermore, the impact of 3D-genome folding on the kinetics and efficiency of DSB repair is completely unknown.
Here we aim to understand how nuclear compartmentalization, chromatin structure and genome organization impact on the efficiency of detection, signaling and repair of DSBs. We will unravel what determines the DNA repair specificity within distinct nuclear compartments using protein tethering, promiscuous biotinylation and quantitative proteomics. We will determine how DNA repair is orchestrated at different heterochromatin structures using a CRISPR/Cas9-based system that allows, for the first time robust induction of DSBs at specific heterochromatin compartments. Finally, we will investigate the role of 3D-genome folding in the kinetics of DNA repair and pathway choice using single nucleotide resolution DSB-mapping coupled to 3D-topological maps.
This proposal has significant implications for understanding the mechanisms controlling DNA repair within the nuclear environment and will reveal the regions of the genome that are susceptible to genomic instability and help us understand why certain mutations and translocations are recurrent in cancer
Summary
Faithful repair of double stranded DNA breaks (DSBs) is essential, as they are at the origin of genome instability, chromosomal translocations and cancer. Cells repair DSBs through different pathways, which can be faithful or mutagenic, and the balance between them at a given locus must be tightly regulated to preserve genome integrity. Although, much is known about DSB repair factors, how the choice between pathways is controlled within the nuclear environment is not understood. We have shown that nuclear architecture and non-random genome organization determine the frequency of chromosomal translocations and that pathway choice is dictated by the spatial organization of DNA in the nucleus. Nevertheless, what determines which pathway is activated in response to DSBs at specific genomic locations is not understood. Furthermore, the impact of 3D-genome folding on the kinetics and efficiency of DSB repair is completely unknown.
Here we aim to understand how nuclear compartmentalization, chromatin structure and genome organization impact on the efficiency of detection, signaling and repair of DSBs. We will unravel what determines the DNA repair specificity within distinct nuclear compartments using protein tethering, promiscuous biotinylation and quantitative proteomics. We will determine how DNA repair is orchestrated at different heterochromatin structures using a CRISPR/Cas9-based system that allows, for the first time robust induction of DSBs at specific heterochromatin compartments. Finally, we will investigate the role of 3D-genome folding in the kinetics of DNA repair and pathway choice using single nucleotide resolution DSB-mapping coupled to 3D-topological maps.
This proposal has significant implications for understanding the mechanisms controlling DNA repair within the nuclear environment and will reveal the regions of the genome that are susceptible to genomic instability and help us understand why certain mutations and translocations are recurrent in cancer
Max ERC Funding
1 999 750 €
Duration
Start date: 2017-03-01, End date: 2022-02-28
Project acronym 3D-VIEW
Project Seeing the invisible: Light-based 3D imaging of opaque nanostructures
Researcher (PI) Stefan WITTE
Host Institution (HI) STICHTING NEDERLANDSE WETENSCHAPPELIJK ONDERZOEK INSTITUTEN
Country Netherlands
Call Details Consolidator Grant (CoG), PE7, ERC-2019-COG
Summary Nanostructures drive the world around us. Every modern electronic device contains integrated circuits and nano-electronics to provide its functionality. Advances in nanotechnology directly impact society by enabling smartphones, autonomous devices, the internet of things, data storage, and essentially all forms of advanced technology. Fabricating such nanostructures crucially depends on having the tools to make them visible without destroying them. Modern nanodevices often have complex three-dimensional architectures with small features in all dimensions. While imaging methods that achieve nanometer-scale resolution exist, there are currently no compact tools that can look inside 3D nanostructures made out of metals and semiconductors without damaging their delicate internal structure. I will address this challenge by developing compact tools to image 3D nanostructures in a non-invasive way. Even though most nanostructures are completely opaque to visible light, I will develop light-based methods, combined with computational imaging techniques developed in my previous ERC project, to look inside them with unprecedented resolution and contrast. Light-based imaging is unparalleled in speed and versatility, and allows contact-free detection. My proposal is to: 1) Use compact laser-produced soft-X-ray sources to image nanostructures with high 3D resolution and element-sensitive contrast; 2) Use laser-induced ultrasound pulses to image complex 3D nanostructures, even through strongly absorbing materials; 3) Employ computational imaging methods to reconstruct high-resolution 3D object images from the resulting complex diffraction signals. I will forge a coordinated research program to bring these concepts to reality. This program provides exciting prospects for fundamental science and industrial metrology. I will go beyond the state-of-the-art in nano-imaging, to extend our vision into the complex interior of the smallest structures found in science and technology.
Summary
Nanostructures drive the world around us. Every modern electronic device contains integrated circuits and nano-electronics to provide its functionality. Advances in nanotechnology directly impact society by enabling smartphones, autonomous devices, the internet of things, data storage, and essentially all forms of advanced technology. Fabricating such nanostructures crucially depends on having the tools to make them visible without destroying them. Modern nanodevices often have complex three-dimensional architectures with small features in all dimensions. While imaging methods that achieve nanometer-scale resolution exist, there are currently no compact tools that can look inside 3D nanostructures made out of metals and semiconductors without damaging their delicate internal structure. I will address this challenge by developing compact tools to image 3D nanostructures in a non-invasive way. Even though most nanostructures are completely opaque to visible light, I will develop light-based methods, combined with computational imaging techniques developed in my previous ERC project, to look inside them with unprecedented resolution and contrast. Light-based imaging is unparalleled in speed and versatility, and allows contact-free detection. My proposal is to: 1) Use compact laser-produced soft-X-ray sources to image nanostructures with high 3D resolution and element-sensitive contrast; 2) Use laser-induced ultrasound pulses to image complex 3D nanostructures, even through strongly absorbing materials; 3) Employ computational imaging methods to reconstruct high-resolution 3D object images from the resulting complex diffraction signals. I will forge a coordinated research program to bring these concepts to reality. This program provides exciting prospects for fundamental science and industrial metrology. I will go beyond the state-of-the-art in nano-imaging, to extend our vision into the complex interior of the smallest structures found in science and technology.
Max ERC Funding
2 000 000 €
Duration
Start date: 2020-10-01, End date: 2025-09-30
Project acronym 3D2DPrint
Project 3D Printing of Novel 2D Nanomaterials: Adding Advanced 2D Functionalities to Revolutionary Tailored 3D Manufacturing
Researcher (PI) Valeria Nicolosi
Host Institution (HI) THE PROVOST, FELLOWS, FOUNDATION SCHOLARS & THE OTHER MEMBERS OF BOARD, OF THE COLLEGE OF THE HOLY & UNDIVIDED TRINITY OF QUEEN ELIZABETH NEAR DUBLIN
Country Ireland
Call Details Consolidator Grant (CoG), PE8, ERC-2015-CoG
Summary My vision is to establish, within the framework of an ERC CoG, a multidisciplinary group which will work in concert towards pioneering the integration of novel 2-Dimensional nanomaterials with novel additive fabrication techniques to develop a unique class of energy storage devices.
Batteries and supercapacitors are two very complementary types of energy storage devices. Batteries store much higher energy densities; supercapacitors, on the other hand, hold one tenth of the electricity per unit of volume or weight as compared to batteries but can achieve much higher power densities. Technology is currently striving to improve the power density of batteries and the energy density of supercapacitors. To do so it is imperative to develop new materials, chemistries and manufacturing strategies.
3D2DPrint aims to develop micro-energy devices (both supercapacitors and batteries), technologies particularly relevant in the context of the emergent industry of micro-electro-mechanical systems and constantly downsized electronics. We plan to use novel two-dimensional (2D) nanomaterials obtained by liquid-phase exfoliation. This method offers a new, economic and easy way to prepare ink of a variety of 2D systems, allowing to produce wide device performance window through elegant and simple constituent control at the point of fabrication. 3D2DPrint will use our expertise and know-how to allow development of advanced AM methods to integrate dissimilar nanomaterial blends and/or “hybrids” into fully embedded 3D printed energy storage devices, with the ultimate objective to realise a range of products that contain the above described nanomaterials subcomponent devices, electrical connections and traditional micro-fabricated subcomponents (if needed) ideally using a single tool.
Summary
My vision is to establish, within the framework of an ERC CoG, a multidisciplinary group which will work in concert towards pioneering the integration of novel 2-Dimensional nanomaterials with novel additive fabrication techniques to develop a unique class of energy storage devices.
Batteries and supercapacitors are two very complementary types of energy storage devices. Batteries store much higher energy densities; supercapacitors, on the other hand, hold one tenth of the electricity per unit of volume or weight as compared to batteries but can achieve much higher power densities. Technology is currently striving to improve the power density of batteries and the energy density of supercapacitors. To do so it is imperative to develop new materials, chemistries and manufacturing strategies.
3D2DPrint aims to develop micro-energy devices (both supercapacitors and batteries), technologies particularly relevant in the context of the emergent industry of micro-electro-mechanical systems and constantly downsized electronics. We plan to use novel two-dimensional (2D) nanomaterials obtained by liquid-phase exfoliation. This method offers a new, economic and easy way to prepare ink of a variety of 2D systems, allowing to produce wide device performance window through elegant and simple constituent control at the point of fabrication. 3D2DPrint will use our expertise and know-how to allow development of advanced AM methods to integrate dissimilar nanomaterial blends and/or “hybrids” into fully embedded 3D printed energy storage devices, with the ultimate objective to realise a range of products that contain the above described nanomaterials subcomponent devices, electrical connections and traditional micro-fabricated subcomponents (if needed) ideally using a single tool.
Max ERC Funding
2 499 942 €
Duration
Start date: 2016-10-01, End date: 2021-09-30
Project acronym 3D_Tryps
Project The role of three-dimensional genome architecture in antigenic variation
Researcher (PI) Tim Nicolai SIEGEL
Host Institution (HI) LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN
Country Germany
Call Details Starting Grant (StG), LS6, ERC-2016-STG
Summary Antigenic variation is a widely employed strategy to evade the host immune response. It has similar functional requirements even in evolutionarily divergent pathogens. These include the mutually exclusive expression of antigens and the periodic, nonrandom switching in the expression of different antigens during the course of an infection. Despite decades of research the mechanisms of antigenic variation are not fully understood in any organism.
The recent development of high-throughput sequencing-based assays to probe the 3D genome architecture (Hi-C) has revealed the importance of the spatial organization of DNA inside the nucleus. 3D genome architecture plays a critical role in the regulation of mutually exclusive gene expression and the frequency of translocation between different genomic loci in many eukaryotes. Thus, genome architecture may also be a key regulator of antigenic variation, yet the causal links between genome architecture and the expression of antigens have not been studied systematically. In addition, the development of CRISPR-Cas9-based approaches to perform nucleotide-specific genome editing has opened unprecedented opportunities to study the influence of DNA sequence elements on the spatial organization of DNA and how this impacts antigen expression.
I have adapted both Hi-C and CRISPR-Cas9 technology to the protozoan parasite Trypanosoma brucei, one of the most important model organisms to study antigenic variation. These techniques will enable me to bridge the field of antigenic variation research with that of genome architecture. I will perform the first systematic analysis of the role of genome architecture in the mutually exclusive and hierarchical expression of antigens in any pathogen.
The experiments outlined in this proposal will provide new insight, facilitating a new view of antigenic variation and may eventually help medical intervention in T. brucei and in other pathogens relying on antigenic variation for their survival.
Summary
Antigenic variation is a widely employed strategy to evade the host immune response. It has similar functional requirements even in evolutionarily divergent pathogens. These include the mutually exclusive expression of antigens and the periodic, nonrandom switching in the expression of different antigens during the course of an infection. Despite decades of research the mechanisms of antigenic variation are not fully understood in any organism.
The recent development of high-throughput sequencing-based assays to probe the 3D genome architecture (Hi-C) has revealed the importance of the spatial organization of DNA inside the nucleus. 3D genome architecture plays a critical role in the regulation of mutually exclusive gene expression and the frequency of translocation between different genomic loci in many eukaryotes. Thus, genome architecture may also be a key regulator of antigenic variation, yet the causal links between genome architecture and the expression of antigens have not been studied systematically. In addition, the development of CRISPR-Cas9-based approaches to perform nucleotide-specific genome editing has opened unprecedented opportunities to study the influence of DNA sequence elements on the spatial organization of DNA and how this impacts antigen expression.
I have adapted both Hi-C and CRISPR-Cas9 technology to the protozoan parasite Trypanosoma brucei, one of the most important model organisms to study antigenic variation. These techniques will enable me to bridge the field of antigenic variation research with that of genome architecture. I will perform the first systematic analysis of the role of genome architecture in the mutually exclusive and hierarchical expression of antigens in any pathogen.
The experiments outlined in this proposal will provide new insight, facilitating a new view of antigenic variation and may eventually help medical intervention in T. brucei and in other pathogens relying on antigenic variation for their survival.
Max ERC Funding
1 498 175 €
Duration
Start date: 2017-04-01, End date: 2022-03-31
Project acronym 3DAddChip
Project Additive manufacturing of 2D nanomaterials for on-chip technologies
Researcher (PI) Cecilia Mattevi
Host Institution (HI) IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE
Country United Kingdom
Call Details Consolidator Grant (CoG), PE8, ERC-2018-COG
Summary The realization of “the internet of things” is inevitably constrained at the level of miniaturization that can be achieved in the electronic devices. A variety of technologies are now going through a process of miniaturization from micro-electromechanical systems (MEMS) to biomedical sensors, and actuators. The ultimate goal is to combine several components in an individual multifunctional platform, realizing on-chip technology. Devices have to be constrained to small footprints and exhibit high performance. Thus, the miniaturization process requires the introduction of new manufacturing processes to fabricate devices in the 3D space over small areas. 3D printing via robocasting is emerging as a new manufacturing technique, which allows shaping virtually any materials from polymers to ceramic and metals into complex architectures.
The goal of this research is to establish a 3D printing paradigm to produce miniaturized complex shape devices with diversified functions for on-chip technologies adaptable to “smart environment” such as flexible substrates, smart textiles and biomedical sensors. The elementary building blocks of the devices will be two-dimensional nanomaterials, which present unique optical, electrical, chemical and mechanical properties. The synergistic combination of the intrinsic characteristics of the 2D nanomaterials and the specific 3D architecture will enable advanced performance of the 3D printed objects. This research programme will demonstrate 3D miniaturized energy storage and energy conversion units fabricated with inks produced using a pilot plant. These units are essential components of any on-chip platform as they ensure energy autonomy via self-powering. Ultimately, this research will initiate new technologies based on miniaturized 3D devices.
Summary
The realization of “the internet of things” is inevitably constrained at the level of miniaturization that can be achieved in the electronic devices. A variety of technologies are now going through a process of miniaturization from micro-electromechanical systems (MEMS) to biomedical sensors, and actuators. The ultimate goal is to combine several components in an individual multifunctional platform, realizing on-chip technology. Devices have to be constrained to small footprints and exhibit high performance. Thus, the miniaturization process requires the introduction of new manufacturing processes to fabricate devices in the 3D space over small areas. 3D printing via robocasting is emerging as a new manufacturing technique, which allows shaping virtually any materials from polymers to ceramic and metals into complex architectures.
The goal of this research is to establish a 3D printing paradigm to produce miniaturized complex shape devices with diversified functions for on-chip technologies adaptable to “smart environment” such as flexible substrates, smart textiles and biomedical sensors. The elementary building blocks of the devices will be two-dimensional nanomaterials, which present unique optical, electrical, chemical and mechanical properties. The synergistic combination of the intrinsic characteristics of the 2D nanomaterials and the specific 3D architecture will enable advanced performance of the 3D printed objects. This research programme will demonstrate 3D miniaturized energy storage and energy conversion units fabricated with inks produced using a pilot plant. These units are essential components of any on-chip platform as they ensure energy autonomy via self-powering. Ultimately, this research will initiate new technologies based on miniaturized 3D devices.
Max ERC Funding
1 999 968 €
Duration
Start date: 2019-09-01, End date: 2024-08-31
Project acronym 3DALIGN
Project Enhancing the performance of 3D-printed organic thermoelectrics by electric field-assisted molecular alignment
Researcher (PI) Francisco Molina-Lopez
Host Institution (HI) KATHOLIEKE UNIVERSITEIT LEUVEN
Country Belgium
Call Details Starting Grant (StG), PE7, ERC-2020-STG
Summary Thermoelectrics (TEs) are important because they can convert heat directly into electrical energy and enable efficient heating/cooling. However, their popularization has been hindered by 1) their low efficiency (especially at room temperature), 2) the use of rare/toxic materials, and 3) the difficulty to process those materials. In 3DALIGN, I target a 3-in-1 solution to these challenges by using for the first time electric-field-assisted molecular alignment of 3D-printed TE polymers. High electrical/low thermal conductivity is required for efficient TEs, but both conductivities go hand in hand in traditional inorganic TE materials. This paradigm can shift for polymers, which possess complicated molecular structure. Despite their relatively low electrical conductivity, conducting polymers are appealing for TEs due to their much lower thermal conductivity than inorganic TE materials. Existing studies of organic TEs have focused on finding new materials, but no attention has been paid to molecular ordering, a known strategy to improve performance in organic transistors. I have recently developed a versatile method to induce molecular alignment in solution-processed polymers by using externally applied electric fields. In 3DALIGN, I propose to use this new method to boost the electrical conductivity of polymer TEs while inducing minimal alteration in their thermal conductivity. The high-risk of this goal is mitigated by other advantages of using polymer TEs: polymers are less toxic and more abundant than inorganic TE materials; and they are easy to 3D print, enabling a simple fabrication route for large-area through-plane TE structures that will lead to novel applications. In conclusion, this project will shed light in the relationship between molecular ordering and transport properties of organic electronic materials. If successful, it will also introduce a breakthrough in the performance and feasibility of TEs.
Summary
Thermoelectrics (TEs) are important because they can convert heat directly into electrical energy and enable efficient heating/cooling. However, their popularization has been hindered by 1) their low efficiency (especially at room temperature), 2) the use of rare/toxic materials, and 3) the difficulty to process those materials. In 3DALIGN, I target a 3-in-1 solution to these challenges by using for the first time electric-field-assisted molecular alignment of 3D-printed TE polymers. High electrical/low thermal conductivity is required for efficient TEs, but both conductivities go hand in hand in traditional inorganic TE materials. This paradigm can shift for polymers, which possess complicated molecular structure. Despite their relatively low electrical conductivity, conducting polymers are appealing for TEs due to their much lower thermal conductivity than inorganic TE materials. Existing studies of organic TEs have focused on finding new materials, but no attention has been paid to molecular ordering, a known strategy to improve performance in organic transistors. I have recently developed a versatile method to induce molecular alignment in solution-processed polymers by using externally applied electric fields. In 3DALIGN, I propose to use this new method to boost the electrical conductivity of polymer TEs while inducing minimal alteration in their thermal conductivity. The high-risk of this goal is mitigated by other advantages of using polymer TEs: polymers are less toxic and more abundant than inorganic TE materials; and they are easy to 3D print, enabling a simple fabrication route for large-area through-plane TE structures that will lead to novel applications. In conclusion, this project will shed light in the relationship between molecular ordering and transport properties of organic electronic materials. If successful, it will also introduce a breakthrough in the performance and feasibility of TEs.
Max ERC Funding
1 710 853 €
Duration
Start date: 2021-02-01, End date: 2026-01-31
Project acronym 3DBIOLUNG
Project Bioengineering lung tissue using extracellular matrix based 3D bioprinting
Researcher (PI) Darcy WAGNER
Host Institution (HI) LUNDS UNIVERSITET
Country Sweden
Call Details Starting Grant (StG), LS9, ERC-2018-STG
Summary Chronic lung diseases are increasing in prevalence with over 65 million patients worldwide. Lung transplantation remains the only potential option at end-stage disease. Around 4000 patients receive lung transplants annually with more awaiting transplantation, including 1000 patients in Europe. New options to increase available tissue for lung transplantation are desperately needed.
An exciting new research area focuses on generating lung tissue ex vivo using bioengineering approaches. Scaffolds can be generated from synthetic or biologically-derived (acellular) materials, seeded with cells and grown in a bioreactor prior to transplantation. Ideally, scaffolds would be seeded with cells derived from the transplant recipient, thus obviating the need for long-term immunosuppression. However, functional regeneration has yet to be achieved. New advances in 3D printing and 3D bioprinting (when cells are printed) indicate that this once thought of science-fiction concept might finally be mature enough for complex tissues, including lung. 3D bioprinting addresses a number of concerns identified in previous approaches, such as a) patient heterogeneity in acellular human scaffolds, b) anatomical differences in xenogeneic sources, c) lack of biological cues on synthetic materials and d) difficulty in manufacturing the complex lung architecture. 3D bioprinting could be a reproducible, scalable, and controllable approach for generating functional lung tissue.
The aim of this proposal is to use custom 3D bioprinters to generate constructs mimicking lung tissue using an innovative approach combining primary cells, the engineering reproducibility of synthetic materials, and the biologically conductive properties of acellular lung (hybrid). We will 3D bioprint hybrid murine and human lung tissue models and test gas exchange, angiogenesis and in vivo immune responses. This proposal will be a critical first step in demonstrating feasibility of 3D bioprinting lung tissue.
Summary
Chronic lung diseases are increasing in prevalence with over 65 million patients worldwide. Lung transplantation remains the only potential option at end-stage disease. Around 4000 patients receive lung transplants annually with more awaiting transplantation, including 1000 patients in Europe. New options to increase available tissue for lung transplantation are desperately needed.
An exciting new research area focuses on generating lung tissue ex vivo using bioengineering approaches. Scaffolds can be generated from synthetic or biologically-derived (acellular) materials, seeded with cells and grown in a bioreactor prior to transplantation. Ideally, scaffolds would be seeded with cells derived from the transplant recipient, thus obviating the need for long-term immunosuppression. However, functional regeneration has yet to be achieved. New advances in 3D printing and 3D bioprinting (when cells are printed) indicate that this once thought of science-fiction concept might finally be mature enough for complex tissues, including lung. 3D bioprinting addresses a number of concerns identified in previous approaches, such as a) patient heterogeneity in acellular human scaffolds, b) anatomical differences in xenogeneic sources, c) lack of biological cues on synthetic materials and d) difficulty in manufacturing the complex lung architecture. 3D bioprinting could be a reproducible, scalable, and controllable approach for generating functional lung tissue.
The aim of this proposal is to use custom 3D bioprinters to generate constructs mimicking lung tissue using an innovative approach combining primary cells, the engineering reproducibility of synthetic materials, and the biologically conductive properties of acellular lung (hybrid). We will 3D bioprint hybrid murine and human lung tissue models and test gas exchange, angiogenesis and in vivo immune responses. This proposal will be a critical first step in demonstrating feasibility of 3D bioprinting lung tissue.
Max ERC Funding
1 499 975 €
Duration
Start date: 2019-01-01, End date: 2023-12-31
Project acronym 3DBrainStrom
Project Brain metastases: Deciphering tumor-stroma interactions in three dimensions for the rational design of nanomedicines
Researcher (PI) Ronit Satchi Fainaro
Host Institution (HI) TEL AVIV UNIVERSITY
Country Israel
Call Details Advanced Grant (AdG), LS7, ERC-2018-ADG
Summary Brain metastases represent a major therapeutic challenge. Despite significant breakthroughs in targeted therapies, survival rates of patients with brain metastases remain poor. Nowadays, discovery, development and evaluation of new therapies are performed on human cancer cells grown in 2D on rigid plastic plates followed by in vivo testing in immunodeficient mice. These experimental settings are lacking and constitute a fundamental hurdle for the translation of preclinical discoveries into clinical practice. We propose to establish 3D-printed models of brain metastases (Aim 1), which include brain extracellular matrix, stroma and serum containing immune cells flowing in functional tumor vessels. Our unique models better capture the clinical physio-mechanical tissue properties, signaling pathways, hemodynamics and drug responsiveness. Using our 3D-printed models, we aim to develop two new fronts for identifying novel clinically-relevant molecular drivers (Aim 2) followed by the development of precision nanomedicines (Aim 3). We will exploit our vast experience in anticancer nanomedicines to design three therapeutic approaches that target various cellular compartments involved in brain metastases: 1) Prevention of brain metastatic colonization using targeted nano-vaccines, which elicit antitumor immune response; 2) Intervention of tumor-brain stroma cells crosstalk when brain micrometastases establish; 3) Regression of macrometastatic disease by selectively targeting tumor cells. These approaches will materialize using our libraries of polymeric nanocarriers that selectively accumulate in tumors.
This project will result in a paradigm shift by generating new preclinical cancer models that will bridge the translational gap in cancer therapeutics. The insights and tumor-stroma-targeted nanomedicines developed here will pave the way for prediction of patient outcome, revolutionizing our perception of tumor modelling and consequently the way we prevent and treat cancer.
Summary
Brain metastases represent a major therapeutic challenge. Despite significant breakthroughs in targeted therapies, survival rates of patients with brain metastases remain poor. Nowadays, discovery, development and evaluation of new therapies are performed on human cancer cells grown in 2D on rigid plastic plates followed by in vivo testing in immunodeficient mice. These experimental settings are lacking and constitute a fundamental hurdle for the translation of preclinical discoveries into clinical practice. We propose to establish 3D-printed models of brain metastases (Aim 1), which include brain extracellular matrix, stroma and serum containing immune cells flowing in functional tumor vessels. Our unique models better capture the clinical physio-mechanical tissue properties, signaling pathways, hemodynamics and drug responsiveness. Using our 3D-printed models, we aim to develop two new fronts for identifying novel clinically-relevant molecular drivers (Aim 2) followed by the development of precision nanomedicines (Aim 3). We will exploit our vast experience in anticancer nanomedicines to design three therapeutic approaches that target various cellular compartments involved in brain metastases: 1) Prevention of brain metastatic colonization using targeted nano-vaccines, which elicit antitumor immune response; 2) Intervention of tumor-brain stroma cells crosstalk when brain micrometastases establish; 3) Regression of macrometastatic disease by selectively targeting tumor cells. These approaches will materialize using our libraries of polymeric nanocarriers that selectively accumulate in tumors.
This project will result in a paradigm shift by generating new preclinical cancer models that will bridge the translational gap in cancer therapeutics. The insights and tumor-stroma-targeted nanomedicines developed here will pave the way for prediction of patient outcome, revolutionizing our perception of tumor modelling and consequently the way we prevent and treat cancer.
Max ERC Funding
2 353 125 €
Duration
Start date: 2019-04-01, End date: 2024-03-31
