Periodic Reporting for period 2 - SuperCol (SuperCol: Rational design of super-selective and responsive colloidal particles for biomedical applications)
Período documentado: 2022-01-01 hasta 2023-12-31
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.
The conclusions of the action are:
- super-resolution localisation can be effectively used on colloidal particles, provided that the deformations of the point-spread-function are properly accounted for. SuperCol has created and published software, methods, and experimental results to achieve this, thereby extending the application potential of localization microscopy to colloids.
- rational design of colloidal particles for biomedical applications requires knowledge of the chemical interface of the colloid at the molecular level. SuperCol has developed methods to quantify the surface chemical properties of colloids at the single-particle level. These methods combine chemical protocols for chemical functionalization, numerical modeling of the chemical interface, and single-molecule microscopy.
- SuperCol has trained the next generation of creative researchers that are trained in novel super-resolution microscopies and are capable of molecular thinking. This has been achieved by providing a training program at the interface of microscopy, surface chemistry, and applications that focused on both scientific and soft skills.
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.
The conclusions of the action are:
- super-resolution localisation can be effectively used on colloidal particles, provided that the deformations of the point-spread-function are properly accounted for. SuperCol has created and published software, methods, and experimental results to achieve this, thereby extending the application potential of localization microscopy to colloids.
- rational design of colloidal particles for biomedical applications requires knowledge of the chemical interface of the colloid at the molecular level. SuperCol has developed methods to quantify the surface chemical properties of colloids at the single-particle level. These methods combine chemical protocols for chemical functionalization, numerical modeling of the chemical interface, and single-molecule microscopy.
- SuperCol has trained the next generation of creative researchers that are trained in novel super-resolution microscopies and are capable of molecular thinking. This has been achieved by providing a training program at the interface of microscopy, surface chemistry, and applications that focused on both scientific and soft skills.
- the training program was completed
- the first ESRs have obtained their PhD degree, the degrees of the other ESRs are on track
- our partner HiQ-Nano has several new products on the market that are a direct result of SuperCol
- an invention disclosure was filed
- the outreach program was concluded, with several highlights: a winning entry in the Science Slam, a highly visited exhibit at the Dutch Design Week
- we generated several promotional video's for a broad audience that can be found on our Youtube channel: https://www.youtube.com/@supercol_itn(se abrirá en una nueva ventana)
- new and lasting collaborations were created due to collaborations between industrial and academic partners in SuperCol.
- the research was disseminated in journal publications, conference presentations, and posters.
Scientific achievements WP1-3:
- 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 have developed models that ensure accurate 3D localisation of fluorophores on/in model particles. This has extended the applicability of optical super-resolution microscopy from the biological domain to materials science.
- Current protocols for the synthesis and functionalisation of particles optimise the ensemble-averaged density and distribution 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 have for the first time combined 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. This work has shown highly promising results and will continue in the future.
- Responsive and multivalent particles have been designed exhibiting receptors whose accessibility and/or orientation can be controlled. We have integrated responsive ligands that can be switched on demand. Application of the multivalent particles in biosensing and drug delivery has resulted in microsecond biosensors and multifunctional drug delivery vehicles.
- the first ESRs have obtained their PhD degree, the degrees of the other ESRs are on track
- our partner HiQ-Nano has several new products on the market that are a direct result of SuperCol
- an invention disclosure was filed
- the outreach program was concluded, with several highlights: a winning entry in the Science Slam, a highly visited exhibit at the Dutch Design Week
- we generated several promotional video's for a broad audience that can be found on our Youtube channel: https://www.youtube.com/@supercol_itn(se abrirá en una nueva ventana)
- new and lasting collaborations were created due to collaborations between industrial and academic partners in SuperCol.
- the research was disseminated in journal publications, conference presentations, and posters.
Scientific achievements WP1-3:
- 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 have developed models that ensure accurate 3D localisation of fluorophores on/in model particles. This has extended the applicability of optical super-resolution microscopy from the biological domain to materials science.
- Current protocols for the synthesis and functionalisation of particles optimise the ensemble-averaged density and distribution 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 have for the first time combined 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. This work has shown highly promising results and will continue in the future.
- Responsive and multivalent particles have been designed exhibiting receptors whose accessibility and/or orientation can be controlled. We have integrated responsive ligands that can be switched on demand. Application of the multivalent particles in biosensing and drug delivery has resulted in microsecond biosensors and multifunctional drug delivery vehicles.
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.