Project acronym DROPCELLARRAY
Project DropletMicroarrays: Ultra High-Throughput Screening of Cells in 3D Microenvironments
Researcher (PI) Pavel Levkin
Host Institution (HI) KARLSRUHER INSTITUT FUER TECHNOLOGIE
Country Germany
Call Details Starting Grant (StG), PE8, ERC-2013-StG
Summary High-throughput (HT) screening of live cells is crucial to accelerate both fundamental biological research and discovery of new drugs. Current methods for HT cell screenings, however, either require a large number of microplates, are prone to cross-contaminations and are limited to adherent cells (cell microarrays), or are not compatible with adherent cells as well as with spatial indexing (droplet microfluidics). We recently demonstrated the use of superhydrophobic-superhydrophilic microarrays to create high-density arrays of microdroplets or hydrogel micropads. We propose here to develop a new platform for HT cell screening experiments using the unique properties of the superhydrophilic microarrays separated by superhydrophobic thin barriers. The new technology will allow us to perform up to 300K cell experiments in parallel using a single chip. Individual cell experiments will be performed in thousands of completely isolated microdroplet at defined locations on the chip. This will enable spatial indexing, time-lapse measurements and screening of either adherent or non-adherent cells. Parallel manipulations within individual microreservoirs, such as washing, addition of chemical libraries, or staining will be developed to open new possibilities in the field of live cell studies. Superhydrophobic barriers will allow complete isolation of the microreservoirs, thus preventing cross-contamination and cell migration. We will also develop a technology for the HT screening of cells in 3D hydrogel micropads. We will use these methods to gain better understanding of how different parameters of the 3D cell microenvironment influence various aspects of cell behavior. The project will require the development of new technological tools which can later be applied to a wide range of cell screening experiments and biological problems. Our long term aim is to replace the outdated microplate technology with a more powerful and convenient method for cell screening experiments.
Summary
High-throughput (HT) screening of live cells is crucial to accelerate both fundamental biological research and discovery of new drugs. Current methods for HT cell screenings, however, either require a large number of microplates, are prone to cross-contaminations and are limited to adherent cells (cell microarrays), or are not compatible with adherent cells as well as with spatial indexing (droplet microfluidics). We recently demonstrated the use of superhydrophobic-superhydrophilic microarrays to create high-density arrays of microdroplets or hydrogel micropads. We propose here to develop a new platform for HT cell screening experiments using the unique properties of the superhydrophilic microarrays separated by superhydrophobic thin barriers. The new technology will allow us to perform up to 300K cell experiments in parallel using a single chip. Individual cell experiments will be performed in thousands of completely isolated microdroplet at defined locations on the chip. This will enable spatial indexing, time-lapse measurements and screening of either adherent or non-adherent cells. Parallel manipulations within individual microreservoirs, such as washing, addition of chemical libraries, or staining will be developed to open new possibilities in the field of live cell studies. Superhydrophobic barriers will allow complete isolation of the microreservoirs, thus preventing cross-contamination and cell migration. We will also develop a technology for the HT screening of cells in 3D hydrogel micropads. We will use these methods to gain better understanding of how different parameters of the 3D cell microenvironment influence various aspects of cell behavior. The project will require the development of new technological tools which can later be applied to a wide range of cell screening experiments and biological problems. Our long term aim is to replace the outdated microplate technology with a more powerful and convenient method for cell screening experiments.
Max ERC Funding
1 499 820 €
Duration
Start date: 2014-02-01, End date: 2019-01-31
Project acronym GeopolyConc
Project Durability of geopolymers as 21st century concretes
Researcher (PI) John Lloyd Provis
Host Institution (HI) THE UNIVERSITY OF SHEFFIELD
Country United Kingdom
Call Details Starting Grant (StG), PE8, ERC-2013-StG
Summary GeopolyConc will provide the necessary scientific basis for the prediction of the long-term durability performance of alkali-activated ‘geopolymer’ concretes. These materials can be synthesised from industrial by-products and widely-available natural resources, and provide the opportunity for a highly significant reduction in the environmental footprint of the global construction materials industry, as it expands to meet the infrastructure needs of 21st century society. Experimental and modelling approaches will be coupled to provide major advances in the state of the art in the science and engineering of geopolymer concretes. The key scientific focus areas will be: (a) the development of the first ever rigorous mathematical description of the factors influencing the transport properties of alkali-activated concretes, and (b) ground-breaking work in understanding and controlling the factors which lead to the onset of corrosion of steel reinforcing embedded in alkali-activated concretes. This project will generate confidence in geopolymer concrete durability, which is essential to the application of these materials in reducing EU and global CO2 emissions. The GeopolyConc project will also be integrated with leading multinational collaborative test programmes coordinated through a RILEM Technical Committee (TC DTA) which is chaired by the PI, providing a route to direct international utilisation of the project outcomes.
Summary
GeopolyConc will provide the necessary scientific basis for the prediction of the long-term durability performance of alkali-activated ‘geopolymer’ concretes. These materials can be synthesised from industrial by-products and widely-available natural resources, and provide the opportunity for a highly significant reduction in the environmental footprint of the global construction materials industry, as it expands to meet the infrastructure needs of 21st century society. Experimental and modelling approaches will be coupled to provide major advances in the state of the art in the science and engineering of geopolymer concretes. The key scientific focus areas will be: (a) the development of the first ever rigorous mathematical description of the factors influencing the transport properties of alkali-activated concretes, and (b) ground-breaking work in understanding and controlling the factors which lead to the onset of corrosion of steel reinforcing embedded in alkali-activated concretes. This project will generate confidence in geopolymer concrete durability, which is essential to the application of these materials in reducing EU and global CO2 emissions. The GeopolyConc project will also be integrated with leading multinational collaborative test programmes coordinated through a RILEM Technical Committee (TC DTA) which is chaired by the PI, providing a route to direct international utilisation of the project outcomes.
Max ERC Funding
1 495 458 €
Duration
Start date: 2013-09-01, End date: 2018-08-31
Project acronym HIENA
Project Hierarchical Carbon Nanomaterials
Researcher (PI) Michael Franciscus Lucas De Volder
Host Institution (HI) THE CHANCELLOR MASTERS AND SCHOLARSOF THE UNIVERSITY OF CAMBRIDGE
Country United Kingdom
Call Details Starting Grant (StG), PE8, ERC-2013-StG
Summary "Over the past years, carbon nanomaterial such as graphene and carbon nanotubes (CNTs) have attracted the interest of scientists, because some of their properties are unlike any other engineering material. Individual graphene sheets and CNTs have shown a Youngs Modulus of 1 TPa and a tensile strength of 100 GPa, hereby exceeding steel at only a fraction of its weight. Further, they offer high currents carrying capacities of 10^9 A/cm², and thermal conductivities up to 3500 W/mK, exceeding diamond. Importantly, these off-the-chart properties are only valid for high quality individualized nanotubes or sheets. However, most engineering applications require the assembly of tens to millions of these nanoparticles into one device. Unfortunately, the mechanical and electronic figures of merit of such assembled materials typically drop by at least an order of magnitude in comparison to the constituent nanoparticles.
In this ERC project, we aim at the development of new techniques to create structured assemblies of carbon nanoparticles. Herein we emphasize the importance of controlling hierarchical arrangement at different length scales in order to engineer the properties of the final device. The project will follow a methodical approach, bringing together different fields of expertise ranging from macro- and microscale manufacturing, to nanoscale material synthesis and mesoscale chemical surface modification. For instance, we will pursue combined top-down microfabrication and bottom-up self-assembly, accompanied with surface modification through hydrothermal processing.
This research will impact scientific understanding of how nanotubes and nanosheets interact, and will create new hierarchical assembly techniques for nanomaterials. Further, this ERC project pursues applications with high societal impact, including energy storage and water filtration. Finally, HIENA will tie relations with EU’s rich CNT industry to disseminate its technologic achievements."
Summary
"Over the past years, carbon nanomaterial such as graphene and carbon nanotubes (CNTs) have attracted the interest of scientists, because some of their properties are unlike any other engineering material. Individual graphene sheets and CNTs have shown a Youngs Modulus of 1 TPa and a tensile strength of 100 GPa, hereby exceeding steel at only a fraction of its weight. Further, they offer high currents carrying capacities of 10^9 A/cm², and thermal conductivities up to 3500 W/mK, exceeding diamond. Importantly, these off-the-chart properties are only valid for high quality individualized nanotubes or sheets. However, most engineering applications require the assembly of tens to millions of these nanoparticles into one device. Unfortunately, the mechanical and electronic figures of merit of such assembled materials typically drop by at least an order of magnitude in comparison to the constituent nanoparticles.
In this ERC project, we aim at the development of new techniques to create structured assemblies of carbon nanoparticles. Herein we emphasize the importance of controlling hierarchical arrangement at different length scales in order to engineer the properties of the final device. The project will follow a methodical approach, bringing together different fields of expertise ranging from macro- and microscale manufacturing, to nanoscale material synthesis and mesoscale chemical surface modification. For instance, we will pursue combined top-down microfabrication and bottom-up self-assembly, accompanied with surface modification through hydrothermal processing.
This research will impact scientific understanding of how nanotubes and nanosheets interact, and will create new hierarchical assembly techniques for nanomaterials. Further, this ERC project pursues applications with high societal impact, including energy storage and water filtration. Finally, HIENA will tie relations with EU’s rich CNT industry to disseminate its technologic achievements."
Max ERC Funding
1 496 379 €
Duration
Start date: 2014-01-01, End date: 2018-12-31
Project acronym IgYPurTech
Project IgY Technology: A Purification Platform using Ionic-Liquid-Based Aqueous Biphasic Systems
Researcher (PI) Mara Guadalupe Freire Martins
Host Institution (HI) UNIVERSIDADE DE AVEIRO
Country Portugal
Call Details Starting Grant (StG), PE8, ERC-2013-StG
Summary With the emergence of antibiotic-resistant pathogens the development of antigen-specific antibodies for use in passive immunotherapy is, nowadays, a major concern in human society. Despite the most focused mammal antibodies, antibodies obtained from egg yolk of immunized hens, immunoglobulin Y (IgY), are an alternative option that can be obtained in higher titres by non-stressful and non-invasive methods. This large amount of available antibodies opens the door for a new kind of cheaper biopharmaceuticals. However, the production cost of high-quality IgY for large-scale applications remains higher than other drug therapies due to the lack of an efficient purification method. The search of new purification platforms is thus a vital demand to which liquid-liquid extraction using aqueous biphasic systems (ABS) could be the answer. Besides the conventional polymer-based systems, highly viscous and with a limited polarity/affinity range, a recent type of ABS composed of ionic liquids (ILs) may be employed. ILs are usually classified as “green solvents” due to their negligible vapour pressure. Yet, the major advantage of IL-based ABS relies on the possibility of tailoring their phases’ polarities aiming at extracting a target biomolecule. A proper manipulation of the system constituents and respective composition allows the pre-concentration, complete extraction, or purification of the most diverse biomolecules.
This research project addresses the development of a new technique for the extraction and purification of IgY from egg yolk using IL-based ABS. The proposed plan contemplates the optimization of purification systems at the laboratory scale and their use in countercurrent chromatography to achieve a simple, cost-effective and scalable process. The success of this project and its scalability to an industrial level certainly will allow the production of cheaper antibodies with a long-term impact in human healthcare.
Summary
With the emergence of antibiotic-resistant pathogens the development of antigen-specific antibodies for use in passive immunotherapy is, nowadays, a major concern in human society. Despite the most focused mammal antibodies, antibodies obtained from egg yolk of immunized hens, immunoglobulin Y (IgY), are an alternative option that can be obtained in higher titres by non-stressful and non-invasive methods. This large amount of available antibodies opens the door for a new kind of cheaper biopharmaceuticals. However, the production cost of high-quality IgY for large-scale applications remains higher than other drug therapies due to the lack of an efficient purification method. The search of new purification platforms is thus a vital demand to which liquid-liquid extraction using aqueous biphasic systems (ABS) could be the answer. Besides the conventional polymer-based systems, highly viscous and with a limited polarity/affinity range, a recent type of ABS composed of ionic liquids (ILs) may be employed. ILs are usually classified as “green solvents” due to their negligible vapour pressure. Yet, the major advantage of IL-based ABS relies on the possibility of tailoring their phases’ polarities aiming at extracting a target biomolecule. A proper manipulation of the system constituents and respective composition allows the pre-concentration, complete extraction, or purification of the most diverse biomolecules.
This research project addresses the development of a new technique for the extraction and purification of IgY from egg yolk using IL-based ABS. The proposed plan contemplates the optimization of purification systems at the laboratory scale and their use in countercurrent chromatography to achieve a simple, cost-effective and scalable process. The success of this project and its scalability to an industrial level certainly will allow the production of cheaper antibodies with a long-term impact in human healthcare.
Max ERC Funding
1 386 020 €
Duration
Start date: 2014-02-01, End date: 2019-01-31
Project acronym MechJointMorph
Project The role of mechanical forces induced by prenatal movements in joint morphogenesis
Researcher (PI) Niamh Catherine Nowlan
Host Institution (HI) IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE
Country United Kingdom
Call Details Starting Grant (StG), PE8, ERC-2013-StG
Summary Most joints start off the same during embryonic development, as two opposing cartilage surfaces, and are moulded into the diverse range of shapes seen in the adult in a process known as morphogenesis. While we understand very little of the biological or mechanobiological processes driving joint morphogenesis, there is evidence to suggest that fetal movements play a critical role in joint shape development. Developmental Dysplasia of the Hip (DDH), where the hip is partly or fully dislocated, is much more common when the baby’s movement is restricted or prevented. This proposal will determine how mechanical forces influence joint shape morphogenesis, which is of key relevance to neonatal joint conditions such as DDH, to adult joint health and disease, and to tissue engineering of cartilage. A mouse line in which mutant embryos have no skeletal muscle will be studied, providing the first in depth analysis of mammalian joint shape development for normal and abnormal mechanical environments. The mouse line could provide the first mammalian model system for prenatal onset DDH. ‘Passive’ movements of these mutant embryos will then be induced by massage of the mother, and the effects on the joints measured. If the effects on joint shape of absent spontaneous movement are mitigated by the treatment, this technique could eventually be used as a preventative treatment for DDH. Next, an in vitro approach will be used to quantify how much movement is needed for joint shape development. This research will provide an optimised protocol for applying biophysical stimuli to promote cartilage growth and morphogenesis in culture, providing valuable cues to cartilage tissue engineers. Finally, a computational simulation of joint shape morphogenesis will be created, which will integrate the new understanding gained from the experimental research in order to predict how different joints shapes develop in normal and abnormal mechanical environments.
Summary
Most joints start off the same during embryonic development, as two opposing cartilage surfaces, and are moulded into the diverse range of shapes seen in the adult in a process known as morphogenesis. While we understand very little of the biological or mechanobiological processes driving joint morphogenesis, there is evidence to suggest that fetal movements play a critical role in joint shape development. Developmental Dysplasia of the Hip (DDH), where the hip is partly or fully dislocated, is much more common when the baby’s movement is restricted or prevented. This proposal will determine how mechanical forces influence joint shape morphogenesis, which is of key relevance to neonatal joint conditions such as DDH, to adult joint health and disease, and to tissue engineering of cartilage. A mouse line in which mutant embryos have no skeletal muscle will be studied, providing the first in depth analysis of mammalian joint shape development for normal and abnormal mechanical environments. The mouse line could provide the first mammalian model system for prenatal onset DDH. ‘Passive’ movements of these mutant embryos will then be induced by massage of the mother, and the effects on the joints measured. If the effects on joint shape of absent spontaneous movement are mitigated by the treatment, this technique could eventually be used as a preventative treatment for DDH. Next, an in vitro approach will be used to quantify how much movement is needed for joint shape development. This research will provide an optimised protocol for applying biophysical stimuli to promote cartilage growth and morphogenesis in culture, providing valuable cues to cartilage tissue engineers. Finally, a computational simulation of joint shape morphogenesis will be created, which will integrate the new understanding gained from the experimental research in order to predict how different joints shapes develop in normal and abnormal mechanical environments.
Max ERC Funding
1 499 501 €
Duration
Start date: 2014-01-01, End date: 2018-12-31
Project acronym UrbanWaves
Project Urban Waves: evaluating structure vulnerability to tsunami and earthquakes
Researcher (PI) Tiziana Rossetto
Host Institution (HI) University College London
Country United Kingdom
Call Details Starting Grant (StG), PE8, ERC-2013-StG
Summary Exposure to coastal floods across the world is forecast to increase to 150 million people and £20 trillion in assets by 2070 (>9% of projected annual global GDP). In addition to cities, potentially vulnerable assets include key infrastructure such as nuclear power plants and ports: the recent Japan earthquake and tsunami demonstrating this. Urban Waves will fill the gap in the engineering design and assessment of buildings in coastal areas subjected to onshore flow from tsunami preceded (or not) by earthquake ground shaking.
In Aim 1 the unique experimental capability developed by the PI to reproduce flows on shorelines from tsunami will be used to provide information for fundamental research into tsunami flows onshore as well as the forces and pressures they exert on model buildings and coastal protection structures. In Aim 2 the experimentally measured force/pressure time-histories will be used to calibrate advanced finite element models of the structures that will then be used to further investigate the influence of bathymetry, topography, tsunami and structure characteristics on the structure forces/pressures. The study findings will be used to propose simplified relationships for tsunami forces/pressures suitable for inclusion in codes of practice (for buildings and coastal defences). In Aim 3, the FE models built will be used to generate fragility functions for buildings that can be used for the assessment of risk to urban areas. The first analytical tsunami fragility functions to be derived, these will also account for the effect of preceding earthquake ground shaking. These will also be compared to data collected after past tsunami events using advanced statistical methods.
Urban Waves capitalises on the PI's recognised expertise in large-scale experiments, structural dynamics, analytical and empirical fragility function derivation and ability to carry out high quality multi-disciplinary research..
Summary
Exposure to coastal floods across the world is forecast to increase to 150 million people and £20 trillion in assets by 2070 (>9% of projected annual global GDP). In addition to cities, potentially vulnerable assets include key infrastructure such as nuclear power plants and ports: the recent Japan earthquake and tsunami demonstrating this. Urban Waves will fill the gap in the engineering design and assessment of buildings in coastal areas subjected to onshore flow from tsunami preceded (or not) by earthquake ground shaking.
In Aim 1 the unique experimental capability developed by the PI to reproduce flows on shorelines from tsunami will be used to provide information for fundamental research into tsunami flows onshore as well as the forces and pressures they exert on model buildings and coastal protection structures. In Aim 2 the experimentally measured force/pressure time-histories will be used to calibrate advanced finite element models of the structures that will then be used to further investigate the influence of bathymetry, topography, tsunami and structure characteristics on the structure forces/pressures. The study findings will be used to propose simplified relationships for tsunami forces/pressures suitable for inclusion in codes of practice (for buildings and coastal defences). In Aim 3, the FE models built will be used to generate fragility functions for buildings that can be used for the assessment of risk to urban areas. The first analytical tsunami fragility functions to be derived, these will also account for the effect of preceding earthquake ground shaking. These will also be compared to data collected after past tsunami events using advanced statistical methods.
Urban Waves capitalises on the PI's recognised expertise in large-scale experiments, structural dynamics, analytical and empirical fragility function derivation and ability to carry out high quality multi-disciplinary research..
Max ERC Funding
1 911 315 €
Duration
Start date: 2014-01-01, End date: 2018-12-31
