Periodic Reporting for period 1 - SuperCol (SuperCol: Rational design of super-selective and responsive colloidal particles for biomedical applications)
Periodo di rendicontazione: 2020-01-01 al 2021-12-31
The advent of super-resolution microscopy and novel modelling approaches provides us with a timely and unique opportunity to quantify and control the sensory response of particle-surfaces at the single-molecule level. Specifically, the emerging ability to quantify the particle’s chemical interface using super-resolution microscopy will open the window to rationally design sensitive, responsive, and selective sensors with quantitative functionality that can be compared to models, see the infographic on the front page. However, the field lacks the human capital that can oversee and bridge disciplines to effectively (a) control, (b) visualise and quantify, and (c) rationally design surface-functionality to advance particle-based biomedical applications. SuperCol will train the next generation of researchers to overcome this barrier and will develop e.g. super-selective biosensors for dengue and cholera, and responsive particles that allow biomolecules to be captured (e.g. inflammation markers)
and released (e.g. doxorubicin) on demand.
SuperCol will pursue the following 3 research objectives:
1. To extend super-resolution localisation to colloidal particles with different degrees of optically distorting properties (e.g. shape, size, and materials). We will develop data-driven models to retrieve the accurate position of a fluorescent label (WP-1).
2. Guided by super-resolution microscopy we will design protocols to control different surface chemistries and unravel how the chemical organisation on the interface can be controlled (WP-2).
3. To use our ability to image and control a particle’s chemical interface to develop particle-based biological assays with novel functionalities including high responsiveness and super-selectivity (WP-3).
The impact of SuperCol will be:
- There is an enormous demand for creative researchers that can design and develop materials for use in our everyday lives.
- By providing the missing link between structure and function SuperCol will enable the rational design of colloidal systems with tailored functionality.
- A major goal of this ETN is to serve as a spring-board to translate and commercialise the findings generated by the ESRs involved.
- A communication and dissemination plan is in place to increase publica awareness and introduce SuperCol research/innovation to students from secondary schools/universities to inspire a new generation.
and released (e.g. doxorubicin) on demand.
SuperCol will pursue the following 3 research objectives:
1. To extend super-resolution localisation to colloidal particles with different degrees of optically distorting properties (e.g. shape, size, and materials). We will develop data-driven models to retrieve the accurate position of a fluorescent label (WP-1).
2. Guided by super-resolution microscopy we will design protocols to control different surface chemistries and unravel how the chemical organisation on the interface can be controlled (WP-2).
3. To use our ability to image and control a particle’s chemical interface to develop particle-based biological assays with novel functionalities including high responsiveness and super-selectivity (WP-3).
The impact of SuperCol will be:
- There is an enormous demand for creative researchers that can design and develop materials for use in our everyday lives.
- By providing the missing link between structure and function SuperCol will enable the rational design of colloidal systems with tailored functionality.
- A major goal of this ETN is to serve as a spring-board to translate and commercialise the findings generated by the ESRs involved.
- A communication and dissemination plan is in place to increase publica awareness and introduce SuperCol research/innovation to students from secondary schools/universities to inspire a new generation.
During the first reporting project the following general results were obtained (WP4-7):
- all ESRs were recruited and wrote a first version of their personal development plan
- the website has gone live, and social media accounts on linkedin and instagram are maintained.
- the training program has started and courses regarding super-resolution microscopy, colloidal synthesis, and modelling were completed by all ESRs
- the first publications were accepted
Regarding the scientific results, the work in WP1 has focused on the use use of correlative microscopy and modelling to understand the mis-localizations induced by metallic and dielectric particles. To achieve this we have established a tool for modelling images of single emitters placed near a particle for arbitrary orientations. The software has been made available in the consortium and will be available to the wider community once published. Experimentally the work in WP1 has focused on obtaining experimental data (microscopy images) of emitters near particles that can be used to validate the model. Here we take a correlative approach, i.e. we use different imaging methods to obtain both optical images and the "ground truth" from e.g. electron microscopy that reveals the location of the emitter with respect to the particle. In WP2 we focus on synthesizing and functionalizing particles with novel functionalities and their characterization using super-resolution microscopy. In the first reporting period we have successfully synthesized and characterized Janus (two-faced) nanoparticles and a variety of DNA-grafted polystyrene particles that will be distributed to other labs in the consortium for super-resolution imaging and application in cell-models. We have achieved a library of uniform silica nanoparticles dispersed over an extensive size range from 25 to 300 nm and fluorescently labelled. In WP3 we focus on biosensing applications and structure-function correlations. Dengue Virus and DNA nanoparticle sensors were developed and are currently being quantified for sensitivity and specificity. Nanoparticles for photo-thermal anti-cancer therapies are synthetized and tested in cell systems. WP3 also consists of modelling of swelling of microparticles with potential use for drug delivery and are synthetized in WP2.
- all ESRs were recruited and wrote a first version of their personal development plan
- the website has gone live, and social media accounts on linkedin and instagram are maintained.
- the training program has started and courses regarding super-resolution microscopy, colloidal synthesis, and modelling were completed by all ESRs
- the first publications were accepted
Regarding the scientific results, the work in WP1 has focused on the use use of correlative microscopy and modelling to understand the mis-localizations induced by metallic and dielectric particles. To achieve this we have established a tool for modelling images of single emitters placed near a particle for arbitrary orientations. The software has been made available in the consortium and will be available to the wider community once published. Experimentally the work in WP1 has focused on obtaining experimental data (microscopy images) of emitters near particles that can be used to validate the model. Here we take a correlative approach, i.e. we use different imaging methods to obtain both optical images and the "ground truth" from e.g. electron microscopy that reveals the location of the emitter with respect to the particle. In WP2 we focus on synthesizing and functionalizing particles with novel functionalities and their characterization using super-resolution microscopy. In the first reporting period we have successfully synthesized and characterized Janus (two-faced) nanoparticles and a variety of DNA-grafted polystyrene particles that will be distributed to other labs in the consortium for super-resolution imaging and application in cell-models. We have achieved a library of uniform silica nanoparticles dispersed over an extensive size range from 25 to 300 nm and fluorescently labelled. In WP3 we focus on biosensing applications and structure-function correlations. Dengue Virus and DNA nanoparticle sensors were developed and are currently being quantified for sensitivity and specificity. Nanoparticles for photo-thermal anti-cancer therapies are synthetized and tested in cell systems. WP3 also consists of modelling of swelling of microparticles with potential use for drug delivery and are synthetized in WP2.
Quantitative understanding of the structure-function relationship of colloidal systems is key towards rational design of colloids with emergent functionalities. Until the end of the project we will for the first time employ super-resolution microscopy in a quantitative way, e.g. characterise heterogeneity and particle-to-particle differences, use the direct visualisation of molecular organisation to iteratively adapt chemical protocols to achieve emergent properties such as super-selective and responsive particles. By combining super-resolution microscopy with advanced modelling and colloid chemistry SuperCol will deliver revolutionary insights into structure-function relationships in the application area of particle-based sensors. In addition, the results obtained will for the first time bridge the gap between experiments and modelling, where nanoscale chemical heterogeneity will be used to generate predictive value. Research and Development activities regarding colloidal chemistry are world-class in Europe, and we can benefit from world-wide unique expertise in super-resolution imaging. Regarding the progress beyond state-of-the-art, and the anticipated results:
- (partially complete in the form of MS1) Currently no theoretical framework exists to accurately localise molecules (fluorophores) on/in a colloidal particle using super-resolution microscopy. By combining experiments and theory we will develop models that ensure accurate 3D localisation of fluorophores on/in model particles. This will extend the applicability of optical super-resolution microscopy from the biological domain to materials science.
- (ongoing) Current protocols for the synthesis and functionalisation of particles optimise the ensemble-averaged density of functional groups using spectroscopy and diffraction. These approaches do not reveal particle-to-particle differences, let alone heterogeneity on the interface of a single particle. We will for the first time combine super-resolution microscopy and numerical modelling to obtain nanoscale (~10 nm), quantitative information of the number and distribution of bio-active groups on single particles. Guided by this combination we will develop novel synthesis and functionalisation protocols with quantitative molecular information and controlled particle-to-particle differences.
- (ongoing) Responsive and multivalent particles have been designed exhibiting receptors whose density can be controlled. In the coming period we will integrate responsive ligands that can be switched on demand. Application of the multivalent particles in biosensing and drug delivery has commenced.
- (partially complete in the form of MS1) Currently no theoretical framework exists to accurately localise molecules (fluorophores) on/in a colloidal particle using super-resolution microscopy. By combining experiments and theory we will develop models that ensure accurate 3D localisation of fluorophores on/in model particles. This will extend the applicability of optical super-resolution microscopy from the biological domain to materials science.
- (ongoing) Current protocols for the synthesis and functionalisation of particles optimise the ensemble-averaged density of functional groups using spectroscopy and diffraction. These approaches do not reveal particle-to-particle differences, let alone heterogeneity on the interface of a single particle. We will for the first time combine super-resolution microscopy and numerical modelling to obtain nanoscale (~10 nm), quantitative information of the number and distribution of bio-active groups on single particles. Guided by this combination we will develop novel synthesis and functionalisation protocols with quantitative molecular information and controlled particle-to-particle differences.
- (ongoing) Responsive and multivalent particles have been designed exhibiting receptors whose density can be controlled. In the coming period we will integrate responsive ligands that can be switched on demand. Application of the multivalent particles in biosensing and drug delivery has commenced.