Periodic Reporting for period 1 - Cellularity (The critical shift to single-cell formats in functional analyses of living cells)
Reporting period: 2023-08-01 to 2024-07-31
Researchers and CIT (cell-based immunotherapy) manufacturers face significant challenges with current technologies for single-cell analysis and sorting. Xplore aims to revolutionize this space by offering high-throughput, cost-effective, and easy-to-use solutions for functional single-cell analysis and sorting.
Current technologies face several challenges in both potency analysis and manufacturing. Commonly used formats where millions of cells are analysed together lack the resolution to identify sub-populations of cells, and frequently applied staining procedures to obtain single-cell resolution often impair cell viability. Additionally, existing methods are complex, low throughput, and expensive. Xplore addresses these issues by enabling high-throughput live single-cell functional analysis and sorting. It also increases usability through single-use sterile cartridges. In CIT manufacturing, current processes are expensive and time-consuming with high failure rates and lengthy, complex quality control procedures. Xplore improves the quality and reduces costs by employing single-cell functional analysis to choose the best cells, thereby reducing failures and increasing yield.
Accelerating CIT research is another critical area where improvements are needed. Current processes are limited in capacity, suffer from high costs, and are time-consuming. Xplore offers the needed capacity as millions of single cells can be analysed per day. The primary goal of this project is to develop a cell analysis platform that enables comprehensive analysis of individual cells. This capability is crucial in immunology, where cell diversity and functionality are highly complex. Our aim is to create an accessible product by ensuring the system is affordable and easy to use, with minimal training required. The platform will feature advanced software for sophisticated data analysis and presentation.
We anticipate that Xplore will accelerate the development of new treatments and reduce associated costs. Additionally, it is expected to decrease reliance on animal models in immunotherapy research. In the long run, the platform may facilitate patient stratification based on individual immune profiles, leading to more personalized treatment strategies and potential breakthroughs in treatment options including treatments tailored to individual patients. The impact and key pain points addressed by Xplore can be summarized as follows:
• Overcomes limitations in current immune cell analyses, enhancing the development of new treatments and improving quality assessments of immune cells produced for therapeutic use.
• Enables ultra-deep screening of novel therapeutic antibodies.
• Offers single-cell analysis to evaluate the functional diversity of immune cells.
These advancements will have a positive impact on a range of diseases, including cancer.
Current technologies face several challenges in both potency analysis and manufacturing. Commonly used formats where millions of cells are analysed together lack the resolution to identify sub-populations of cells, and frequently applied staining procedures to obtain single-cell resolution often impair cell viability. Additionally, existing methods are complex, low throughput, and expensive. Xplore addresses these issues by enabling high-throughput live single-cell functional analysis and sorting. It also increases usability through single-use sterile cartridges. In CIT manufacturing, current processes are expensive and time-consuming with high failure rates and lengthy, complex quality control procedures. Xplore improves the quality and reduces costs by employing single-cell functional analysis to choose the best cells, thereby reducing failures and increasing yield.
Accelerating CIT research is another critical area where improvements are needed. Current processes are limited in capacity, suffer from high costs, and are time-consuming. Xplore offers the needed capacity as millions of single cells can be analysed per day. The primary goal of this project is to develop a cell analysis platform that enables comprehensive analysis of individual cells. This capability is crucial in immunology, where cell diversity and functionality are highly complex. Our aim is to create an accessible product by ensuring the system is affordable and easy to use, with minimal training required. The platform will feature advanced software for sophisticated data analysis and presentation.
We anticipate that Xplore will accelerate the development of new treatments and reduce associated costs. Additionally, it is expected to decrease reliance on animal models in immunotherapy research. In the long run, the platform may facilitate patient stratification based on individual immune profiles, leading to more personalized treatment strategies and potential breakthroughs in treatment options including treatments tailored to individual patients. The impact and key pain points addressed by Xplore can be summarized as follows:
• Overcomes limitations in current immune cell analyses, enhancing the development of new treatments and improving quality assessments of immune cells produced for therapeutic use.
• Enables ultra-deep screening of novel therapeutic antibodies.
• Offers single-cell analysis to evaluate the functional diversity of immune cells.
These advancements will have a positive impact on a range of diseases, including cancer.
A key advantage of Xplore is its compatibility with existing workflows and its ability to expand the range of analyses that can be performed on equipment already installed at customer sites.
We have developed a technology that encapsulates single cells in tiny droplets, which act as individual vessels or reaction chambers to assess the functionality of specific immune cells. This innovation enables a variety of analyses that are currently not democratized, including screening for new therapeutic antibodies from primary immune cells and measuring immune cell potency. Determining the potency or cell-mediated cytotoxicity of immune cells is highly complex. It involves evaluating their ability to, for example, kill cancer cells and release key immune signalling molecules, such as cytokines.
In the first year, we successfully demonstrated proof of concept for Xplore’s ability to monitor the potency of individual immune cells. We have documented detailed single-cell immune profiling, monitoring the release of cytokines and granzyme B (one of the components released by immune cells to kill cancer cells), as well as the immune-mediated activation of “self-destructive” mechanisms in cancer cells, such as caspase 3/7.
Key technical progress includes the following prototypes:
• An Xplore instrument, which ensures 100% analysis of the precious immune sample
• Integration of barcodes for improved traceability
• Software that automates data analysis, partially using AI
• Automated report generation to streamline data documentation and dissimilation
• Development of protocols and reagents for single-cell analysis, including cytokine detection, granzyme B, antibody screening, cell identification, and immune-mediated cancer cell killing
We have developed a technology that encapsulates single cells in tiny droplets, which act as individual vessels or reaction chambers to assess the functionality of specific immune cells. This innovation enables a variety of analyses that are currently not democratized, including screening for new therapeutic antibodies from primary immune cells and measuring immune cell potency. Determining the potency or cell-mediated cytotoxicity of immune cells is highly complex. It involves evaluating their ability to, for example, kill cancer cells and release key immune signalling molecules, such as cytokines.
In the first year, we successfully demonstrated proof of concept for Xplore’s ability to monitor the potency of individual immune cells. We have documented detailed single-cell immune profiling, monitoring the release of cytokines and granzyme B (one of the components released by immune cells to kill cancer cells), as well as the immune-mediated activation of “self-destructive” mechanisms in cancer cells, such as caspase 3/7.
Key technical progress includes the following prototypes:
• An Xplore instrument, which ensures 100% analysis of the precious immune sample
• Integration of barcodes for improved traceability
• Software that automates data analysis, partially using AI
• Automated report generation to streamline data documentation and dissimilation
• Development of protocols and reagents for single-cell analysis, including cytokine detection, granzyme B, antibody screening, cell identification, and immune-mediated cancer cell killing
We have identified three key steps to successfully commercialize our products:
1. Documenting the Complete Workflow: We need to establish comprehensive protocols for every stage of the workflow. To address this, we have partnered with multiple commercial collaborators to demonstrate integrated workflows. These workflows include droplet sorting, droplet analysis via flow cytometry and imaging techniques, and integration with single-cell sequencing.
2. Validating Our Value Proposition in Scientific Literature: It’s crucial to document the value of our technology in peer-reviewed scientific journals. To this end, we have engaged six application development partners within immunology. Additionally, we’ve launched a grant program that provides early access to our technology. Grant recipients are applying our platform in diverse areas, including CAR T therapy for solid tumours, AI-driven cell therapy design, and antibiotic resistance monitoring, with the goal of securing early scientific publications.
3. Expanding Market Presence, Particularly in the US: Strengthening our market presence, especially in the US, is essential. To build a robust commercial organization, we are in the process of raising at least €15 million in equity, with support from EIC/EIB. We are also in discussions with potential distribution partners to cover specific geographic regions.
All these initiatives will remain ongoing for years. While the first suite of products will be completed during the Cellularity project, product development, partner and customer engagements will continue beyond project completion.
1. Documenting the Complete Workflow: We need to establish comprehensive protocols for every stage of the workflow. To address this, we have partnered with multiple commercial collaborators to demonstrate integrated workflows. These workflows include droplet sorting, droplet analysis via flow cytometry and imaging techniques, and integration with single-cell sequencing.
2. Validating Our Value Proposition in Scientific Literature: It’s crucial to document the value of our technology in peer-reviewed scientific journals. To this end, we have engaged six application development partners within immunology. Additionally, we’ve launched a grant program that provides early access to our technology. Grant recipients are applying our platform in diverse areas, including CAR T therapy for solid tumours, AI-driven cell therapy design, and antibiotic resistance monitoring, with the goal of securing early scientific publications.
3. Expanding Market Presence, Particularly in the US: Strengthening our market presence, especially in the US, is essential. To build a robust commercial organization, we are in the process of raising at least €15 million in equity, with support from EIC/EIB. We are also in discussions with potential distribution partners to cover specific geographic regions.
All these initiatives will remain ongoing for years. While the first suite of products will be completed during the Cellularity project, product development, partner and customer engagements will continue beyond project completion.