Periodic Reporting for period 2 - CoDaFlight (Colouring the Dark in Fluorescence Light)
Período documentado: 2023-10-01 hasta 2025-03-31
CoDaFlight aims to advance time-domain fluorescence lifetime imaging (tdFLI) for real-time, non-invasive assessment of novel (patho)physiological and molecular processes. Compared to conventional fluorescence imaging, tdFLI offers superior contrast, distinguishing true fluorescence from background signals.We aim to impact in situ planning of resection lines, potentially reducing surgical margins, enhancing detection of small or deep-seated malignancies, identifying invaded lymph nodes, and enabling multiplexed imaging for colocalization with vital organs. tdFLI can be applied in endoscopic or intravascular procedures, with or without contrast agents, for improved diagnosis, staging, and characterization of tumors or atherosclerotic lesions.
A key strength of tdFLI is its ability to monitor real-time tissue parameters—such as pH, oxygenation, and metabolic changes—offering powerful insights into tissue viability during surgery. Early detection of reduced oxygenation can guide timely restoration of blood flow and help prevent tissue damage. tdFLI also aids in the precise removal of non-viable tissue and enables deep-tissue monitoring in challenging conditions like diabetes or burns.
Figure 1. Our project follows two development cycles and three key phases: assessment, adjustment, and breakthrough.
In the assessment phase, we begin developing core technologies and explore their capabilities using in vitro and in vivo models to understand the system’s strengths and limitations.
The adjustment phase refines our approach based on initial results, aligning development with clinical needs.
Finally, the breakthrough phase integrates and fine-tunes all advancements, culminating in proof-of-concept demonstrations for medical applications.
A key strength of tdFLI is its ability to monitor real-time tissue parameters—such as pH, oxygenation, and metabolic changes—offering powerful insights into tissue viability during surgery. Early detection of reduced oxygenation can guide timely restoration of blood flow and help prevent tissue damage. tdFLI also aids in the precise removal of non-viable tissue and enables deep-tissue monitoring in challenging conditions like diabetes or burns.
Figure 1. Our project follows two development cycles and three key phases: assessment, adjustment, and breakthrough.
In the assessment phase, we begin developing core technologies and explore their capabilities using in vitro and in vivo models to understand the system’s strengths and limitations.
The adjustment phase refines our approach based on initial results, aligning development with clinical needs.
Finally, the breakthrough phase integrates and fine-tunes all advancements, culminating in proof-of-concept demonstrations for medical applications.
We have developed biocompatible azaBODIPY fluorescent contrast agents with extended lifetimes, alongside two time-domain camera technologies: the CAPS tauCAM and CA-SPAD sensor and camera, and advanced supporting tdFLI models and algorithms. The CAPS sensor offers excellent NIR sensitivity, essential for medical fluorescence imaging, and is available at 128×128 resolution. The CA-SPAD camera, with a higher QVGA resolution (320×240), introduces fast and efficient photon-to-lifetime conversion, though it has limited NIR efficiency. Achieving high resolution combined with strong NIR performance remains a key challenge.
We have engineered a preclinical time-domain fluorescence imaging instrument, pioneering tdFLI in mesoscopic preclinical research. Additional research has focused on identifying optimal illumination sources. With the systems and contrast agents in place, we now have a validated preclinical proof-of-concept (PoC) instrument and have begun showcasing tdFLI’s transformative potential. Feedback from early users confirmed the system’s suitability for specific applications, while other use cases require adaptation—these are now pursued in secondary development tracks.
Each CoDaFlight sensors have unique strengths, enabling us to tailor different systems to different needs. While a single sensor combining all advantages remains our ultimate goal, a major bottleneck is the limited availability of high-power pulsed lasers, especially for azaBODIPY dyes. We are currently working around this with medium-powered lasers and are also exploring the development or acquisition of suitable high-power laser systems.
In parallel, based on feedback from our External Advisory Board, we have begun exploring specimen imaging, aligning better with clinical needs and increasing the technology’s impact. This too has become a dedicated secondary track. We need to spin this towards 775 nm excitation because of the laser power, and the current clinically approved fluorescent molecualr tracers.
Our aim is to demonstrate tdFLI's capabilities through in vivo PoC studies to build acceptance in the biomedical field and pave the way for adoption in new markets. We have shown that the CoDaFlight system and azaBODIPY dyes can clearly distinguish tumor fluorescence from background based on large lifetime differences—enabled by the novel dye chemistry. Upcoming efforts include real-time surgical demonstrations and showcasing our new pH-sensitive dyes.
Feedback from molecular imaging centers is increasingly shaping project priorities, prompting engineers to develop application-specific instrument versions—a key step for broader adoption.
We are also building visibility within the scientific community, independently and with US collaborators. Notably, we are organizing dedicated tdFLI sessions at EMIM 2024 and 2025, covering the full spectrum from microscopy to clinical translation, featuring key European and US experts.
Though still at a relatively low TRL, our technology is steadily moving toward market readiness. Encouragingly, there is growing interest in our minimum viable product from the life sciences sector, with clinicians and researchers exploring how tdFLI could expand the potential of fluorescence imaging in practice.
We have engineered a preclinical time-domain fluorescence imaging instrument, pioneering tdFLI in mesoscopic preclinical research. Additional research has focused on identifying optimal illumination sources. With the systems and contrast agents in place, we now have a validated preclinical proof-of-concept (PoC) instrument and have begun showcasing tdFLI’s transformative potential. Feedback from early users confirmed the system’s suitability for specific applications, while other use cases require adaptation—these are now pursued in secondary development tracks.
Each CoDaFlight sensors have unique strengths, enabling us to tailor different systems to different needs. While a single sensor combining all advantages remains our ultimate goal, a major bottleneck is the limited availability of high-power pulsed lasers, especially for azaBODIPY dyes. We are currently working around this with medium-powered lasers and are also exploring the development or acquisition of suitable high-power laser systems.
In parallel, based on feedback from our External Advisory Board, we have begun exploring specimen imaging, aligning better with clinical needs and increasing the technology’s impact. This too has become a dedicated secondary track. We need to spin this towards 775 nm excitation because of the laser power, and the current clinically approved fluorescent molecualr tracers.
Our aim is to demonstrate tdFLI's capabilities through in vivo PoC studies to build acceptance in the biomedical field and pave the way for adoption in new markets. We have shown that the CoDaFlight system and azaBODIPY dyes can clearly distinguish tumor fluorescence from background based on large lifetime differences—enabled by the novel dye chemistry. Upcoming efforts include real-time surgical demonstrations and showcasing our new pH-sensitive dyes.
Feedback from molecular imaging centers is increasingly shaping project priorities, prompting engineers to develop application-specific instrument versions—a key step for broader adoption.
We are also building visibility within the scientific community, independently and with US collaborators. Notably, we are organizing dedicated tdFLI sessions at EMIM 2024 and 2025, covering the full spectrum from microscopy to clinical translation, featuring key European and US experts.
Though still at a relatively low TRL, our technology is steadily moving toward market readiness. Encouragingly, there is growing interest in our minimum viable product from the life sciences sector, with clinicians and researchers exploring how tdFLI could expand the potential of fluorescence imaging in practice.
The project is poised to propel fluorescence intensity imaging to new heights in sensitivity and specificity. As is customary with pioneering advancements, our initial focus lies in demonstrating the concept and tangible results, laying the foundation before committing substantial investments, and then accelerating the team, business idea, and technology within the challenges of a highly regulated landscape. This step is crucial in establishing the credibility and potential of our innovation. We then will need to find investments and team acceleration.
In this project, we are committed to showcasing the viability and efficacy of our technology through a comprehensive proof-of-concept demonstration.
Our commitment extends beyond the initial breakthrough, but in this project, we aim for the following
1.) Design, develop, and deliver the tdFLI instrument for the PoC with the right illumination from the developed models, translated into the right algorithms and user software.
2.) Show in a PoC a better, real-time contrast in fluorescence-guided surgery that can in time increase surgical precision and patient safety.
3.) Show in a PoC, that measuring the sub-nanosecond decay of the lifetime of responsive fluorescence tracers can sense differences in tissue pH and oxygenation, and that can kickstart the utilization of these parameters for diagnostic use.
4.) Provide a PoC for the tissue analysis (fingerprinting) capability of tdFLI, by utilizing the natural auto-fluorescence of different types of tissues, e.g. detecting cancer or wound healing, possibly in combination with artificial intelligence (ai) and deep learning capabilities.
In this project, we are committed to showcasing the viability and efficacy of our technology through a comprehensive proof-of-concept demonstration.
Our commitment extends beyond the initial breakthrough, but in this project, we aim for the following
1.) Design, develop, and deliver the tdFLI instrument for the PoC with the right illumination from the developed models, translated into the right algorithms and user software.
2.) Show in a PoC a better, real-time contrast in fluorescence-guided surgery that can in time increase surgical precision and patient safety.
3.) Show in a PoC, that measuring the sub-nanosecond decay of the lifetime of responsive fluorescence tracers can sense differences in tissue pH and oxygenation, and that can kickstart the utilization of these parameters for diagnostic use.
4.) Provide a PoC for the tissue analysis (fingerprinting) capability of tdFLI, by utilizing the natural auto-fluorescence of different types of tissues, e.g. detecting cancer or wound healing, possibly in combination with artificial intelligence (ai) and deep learning capabilities.