Periodic Reporting for period 3 - DynAMic (Dynamic adaptive microscopy for label-free multi-parametric imaging in biology and medicine)
Okres sprawozdawczy: 2023-07-01 do 2024-12-31
Optical microscopy constitutes one of the most fundamental paradigms in biological and medical imaging. However, significant challenges remain regarding the application of optical microscopy to in vivo interrogations. First, the diffusing nature of light propagation in tissue due to random variations of the refractive index limits in vivo microscopy to superficial depths; within only a few mean free paths (<1mm). Second, the invasive nature of fluorescent proteins and probes allows monitoring of only 1-5 events by spectrally multiplexing different fluorochromes, i.e. performance that is highly incompatible with functional genomics and proteomics targets.
The long-term vision and ambition of DynAMic is to revolutionize microscopic imaging by breaking i) the depth-to-resolution ratio and ii) the limited number of labels visualized, offering non-invasive, real-time, high resolution, multiparametric in vivo imaging, across length scales, deep in biological complex media.
The new optical imaging ability delivered in DynAMic will be applied to a first target application of ophthalmic imaging, also used as a window to the brain and nervous disease detection, defining the next generation ophthalmology and neurology sensing of devastating diseases, disrupting the modus operandi of retinal and neuronal imaging without disturbing the modus agendi of the end-users.
The long-term vision and ambition of DynAMic is to revolutionize microscopic imaging by breaking i) the depth-to-resolution ratio and ii) the limited number of labels visualized, offering non-invasive, real-time, high resolution, multiparametric in vivo imaging, across length scales, deep in biological complex media.
The new optical imaging ability delivered in DynAMic will be applied to a first target application of ophthalmic imaging, also used as a window to the brain and nervous disease detection, defining the next generation ophthalmology and neurology sensing of devastating diseases, disrupting the modus operandi of retinal and neuronal imaging without disturbing the modus agendi of the end-users.
Within the 1st reporting period, several research tracks were followed in parallel and in conjunction with specific goals within the overall timeline and targets of the project.
A highly significant initial effort was dedicated synergistically by all partners to define the user needs, and the most appropriate technologies within the consortium to target the most relevant, significant, and feasible to detect biomarkers. An exhaustive literature research was performed and from this, a subset of the most relevant, significant, and feasible to detect markers was selected as our prime targets. We believe that this effort and the produced detailed, concentrated and filtered information can be beneficial for the consortium but also for the greater scientific community.
To facilitate a smooth operation and efficiency in progressing the work, despite the pandemic effects, the consortium defined Technical Task Groups per WP that continued meeting regularly over virtual meetings to advance common research and development in a focused, problem solving, and monitoring fashion. This has led to the definition of strategies and tasks for the development, implementation and testing of our technologies. This effort provided the developments that made it possible to complete all deliverables on time and produce some new publications and conference presentations by the partners.
In addition, the project partners outlined and defined the strategy for achieving effective communication, dissemination, and exploitation of DynAMic foreground results with an evolving Exploitation Plan.
Within the 2nd Reporting Period significant progress has been achieved with accelerated development of technologies, integration of systems and proof of concept studies. All Partners have contributed immensely to achieve the current state of the project, with a large number of publications, conference presentations, exploitation of products, strong synergies and technologies that are ready to proceed to the next stage of implementation towards the objectives of the project.
This second period marks the achievement of significant milestones in terms of joint efforts and synergies towards common development of technologies and research studies, as well as research visits for knowledge exchange and common work, as well as focused research meetings.
In terms of the contractual obligations, all deliverables have been completed successfully and all milestones achieved on time.
The 3rd reporting period signifies the closure of the Dynamic project. In this last reporting period the microscopes in FORTH and TUM have reached a final stage where all technologies have been integrated and several studies have concluded. The combined efforts of all the partners have produced several high impact publications, numerous presentations and forged strong collaborations that will extend beyond the Dynamic project.
In the 3rd reporting period multiple milestones have been achieved promoting the synergies already established in the previous reporting period. Technology and protocol sharing along with intense knowledge exchange was achieved in focused meetings but also in the organized summer school.
Finally, three amendments to the GA were completed to include Linked Third Partied to CNRS and extend the duration of the project by 18 months due to the pandemic and equipment acquiring delays.
A highly significant initial effort was dedicated synergistically by all partners to define the user needs, and the most appropriate technologies within the consortium to target the most relevant, significant, and feasible to detect biomarkers. An exhaustive literature research was performed and from this, a subset of the most relevant, significant, and feasible to detect markers was selected as our prime targets. We believe that this effort and the produced detailed, concentrated and filtered information can be beneficial for the consortium but also for the greater scientific community.
To facilitate a smooth operation and efficiency in progressing the work, despite the pandemic effects, the consortium defined Technical Task Groups per WP that continued meeting regularly over virtual meetings to advance common research and development in a focused, problem solving, and monitoring fashion. This has led to the definition of strategies and tasks for the development, implementation and testing of our technologies. This effort provided the developments that made it possible to complete all deliverables on time and produce some new publications and conference presentations by the partners.
In addition, the project partners outlined and defined the strategy for achieving effective communication, dissemination, and exploitation of DynAMic foreground results with an evolving Exploitation Plan.
Within the 2nd Reporting Period significant progress has been achieved with accelerated development of technologies, integration of systems and proof of concept studies. All Partners have contributed immensely to achieve the current state of the project, with a large number of publications, conference presentations, exploitation of products, strong synergies and technologies that are ready to proceed to the next stage of implementation towards the objectives of the project.
This second period marks the achievement of significant milestones in terms of joint efforts and synergies towards common development of technologies and research studies, as well as research visits for knowledge exchange and common work, as well as focused research meetings.
In terms of the contractual obligations, all deliverables have been completed successfully and all milestones achieved on time.
The 3rd reporting period signifies the closure of the Dynamic project. In this last reporting period the microscopes in FORTH and TUM have reached a final stage where all technologies have been integrated and several studies have concluded. The combined efforts of all the partners have produced several high impact publications, numerous presentations and forged strong collaborations that will extend beyond the Dynamic project.
In the 3rd reporting period multiple milestones have been achieved promoting the synergies already established in the previous reporting period. Technology and protocol sharing along with intense knowledge exchange was achieved in focused meetings but also in the organized summer school.
Finally, three amendments to the GA were completed to include Linked Third Partied to CNRS and extend the duration of the project by 18 months due to the pandemic and equipment acquiring delays.
The long-term vision and ambition of DynAMic is to revolutionize microscopic imaging by breaking i) the depth-to-resolution ratio and ii) the limited number of labels visualized, offering non-invasive, real-time, high resolution, multiparametric in vivo imaging, across length scales, deep in biological complex media.
DynAMic proposes a radically new concept for optical imaging of tissue based on:
• Developing real-time wavefront-shaping adaptive optics to enhance microscopic imaging performance and for the first time in coherent Raman microscopy.
• Reaching tenfold deeper in tissue than conventional optical microscopy by compensating for the refractive index variations and retrieving scrambled coherent properties of transmitted light
• Utilizing advanced image formation to improve the sensitivity and utilization of Raman scattering for multi-parametric label-free contrast that radically expands at least tenfold the number of labels concurrently retrieved from living systems, linking optical observation to functional proteomic requirements.
To achieve this we are working on producing some new line of research and technology with a wider impact on science and society. Even at this early stage of the project timeline, we have identified innovations that potentially can impact the field of microscopy with spillover effects in many areas of biology research and clinical practice.
A prime goal is of course the complete DynAMic microscope that will create a totally new microscopy environment, but in the process of navigating towards that unified achievement we have identifies the following innovations that synergistically between partners can create impactful new technology:
- A new deformable mirror with operational and commercial characteristics suitable for microscopy systems routinely used in biology. This is now commercially available from 2022.
- A next generation “Wavesim” platform again optimised for microscopic imaging with wavefront shaping and optimised operational characteristics
- A k-vector engineering and adaptive optics Light Sheet Fluorescence Microscopy system. The system is now a prototype and the new spin-off is coordinating its exploitation.
- A frequency domain optoacoustic microscopy modality that can be transferred to the DynAMic microscope, reducing costs and bill of materials as well as enhancing and widening applicability.
- Engineering of model scattering media to control light diffusion
- A wavefront shaping digital microscope objective lens (Wavelens) for precision light control. A patent applicaiton was submitted and waiting the granting form the EPO and a new spin-off company was created to comercialise the rechnology.
DynAMic proposes a radically new concept for optical imaging of tissue based on:
• Developing real-time wavefront-shaping adaptive optics to enhance microscopic imaging performance and for the first time in coherent Raman microscopy.
• Reaching tenfold deeper in tissue than conventional optical microscopy by compensating for the refractive index variations and retrieving scrambled coherent properties of transmitted light
• Utilizing advanced image formation to improve the sensitivity and utilization of Raman scattering for multi-parametric label-free contrast that radically expands at least tenfold the number of labels concurrently retrieved from living systems, linking optical observation to functional proteomic requirements.
To achieve this we are working on producing some new line of research and technology with a wider impact on science and society. Even at this early stage of the project timeline, we have identified innovations that potentially can impact the field of microscopy with spillover effects in many areas of biology research and clinical practice.
A prime goal is of course the complete DynAMic microscope that will create a totally new microscopy environment, but in the process of navigating towards that unified achievement we have identifies the following innovations that synergistically between partners can create impactful new technology:
- A new deformable mirror with operational and commercial characteristics suitable for microscopy systems routinely used in biology. This is now commercially available from 2022.
- A next generation “Wavesim” platform again optimised for microscopic imaging with wavefront shaping and optimised operational characteristics
- A k-vector engineering and adaptive optics Light Sheet Fluorescence Microscopy system. The system is now a prototype and the new spin-off is coordinating its exploitation.
- A frequency domain optoacoustic microscopy modality that can be transferred to the DynAMic microscope, reducing costs and bill of materials as well as enhancing and widening applicability.
- Engineering of model scattering media to control light diffusion
- A wavefront shaping digital microscope objective lens (Wavelens) for precision light control. A patent applicaiton was submitted and waiting the granting form the EPO and a new spin-off company was created to comercialise the rechnology.