Periodic Reporting for period 1 - FADEQ (Fully automated cell-free DNA extraction and quantification - liquid biopsies safely from Patient to Lab)
Reporting period: 2022-04-01 to 2023-03-31
Liquid biopsy (e.g. blood) is an established tool for cancer diagnostics and prenatal screening with highly significant potential for future applications. However, the approach is not yet integrated into the daily clinical routine, and one reason is the lack of standardized solutions for pre-analytical and analytical workflows. The project FADEQ (36 month duration) builds on a previous ERC-PoC project to develop a fully automated, disposable cartridge for use in the point-of-care settings for liquid biopsy sample preparation, quantification and stabilization. The technology can support high-precision liquid biopsy diagnostics by standardizing and simplifying the sample processing and logistics. The objective is to demonstrate and validate the automated cell-free DNA extraction technology in its intended use. Industrial and service design is applied to create a technology that is ready for marketing and IVD validation after the project.
The liquid biopsy extraction market is estimated to reach $500M by 2028. Aim of the FADEQ project is to develop a product that can capture 10-20% of the global market potential of oncology and prenatal screening segments in the next 5 years. The technology can also be further extended to process other liquid biopsy biomarkers (proteins, RNA and exosomes) and fill additional diagnostic needs.
The liquid biopsy extraction market is estimated to reach $500M by 2028. Aim of the FADEQ project is to develop a product that can capture 10-20% of the global market potential of oncology and prenatal screening segments in the next 5 years. The technology can also be further extended to process other liquid biopsy biomarkers (proteins, RNA and exosomes) and fill additional diagnostic needs.
During the Reporting Period 1, the project has had 8 full-time and 12 part-time or temporary employees. Project started with a kick-off meeting (Milestone 1) with the external advisory board and publication of the website. Project logo and Data Management Plan were also developed. The main dissemination channel for FADEQ/BiopSense is the website and BiopSense LinkedIn page. Development of the cartridge technology has been proceeding as originally planned. Altogether 13 000 blood and plasma samples have been processed for the fluidic technology and chemistry optimization. Most of the key parameters are now set for the disposable cartridge prototype. New 3D printing techniques combined with the traditional CNC and vacuum forming methods have enabled efficient and rapid prototype construction. The technology has advanced to a stage where table-top (macro scale) prototypes provide the two main functions of the solution (filtration and purification) and the design model of the combined cartridge has been compiled (Milestone 2). Optimal solution for room-temperature stabilization of the extracted sample has also been developed. Process yield and sample purity have been compared against the reference methods for cell-free DNA and optimized to provide a comparable or improved performance.
Latest freedom to operate (FTO) review for the overall solution has been performed in late March 2022. Further IP protection actions for the technical solutions are planned for 2023. Quotations for the supporting Controller Device development have also been collected and initial contract with a designer office has been signed.
New manufacturing workflow has been implemented for prototyping the disposable cartridge in WP3. Component designs for both the plasma separation and the DNA extraction phases have been conceptualized. First discussions and quotations related to the scalable, future manufacturing (injection moulding) are in progress. Actuators and sensors solutions for the instrument are being developed. Mechanical solutions for interfacing with a blood sample in a standard blood collection tube and with the extraction product container have been developed.
WP4, focusing on the clinical verification and service design, will officially start in full during M13. However, the ethical approval for the first clinical tests was already applied for in autumn 2022 and approved (Milestone 5) in January 2023. Device IVD requirements and the overall regulatory pathway has been updated and further designed with consultants. Quality management system is also being updated to meet the requirements of the ISO 13485 standard.
In WP5 a first comprehensive Dissemination and Exploitation Plan has been compiled. The plan includes setting the key performance indicators. By end of the RP1, most indicators are progressing well, except public communications as articles and conference presentations. However, 13 pitching and presentation actions were done to attract investors and partners.
Latest freedom to operate (FTO) review for the overall solution has been performed in late March 2022. Further IP protection actions for the technical solutions are planned for 2023. Quotations for the supporting Controller Device development have also been collected and initial contract with a designer office has been signed.
New manufacturing workflow has been implemented for prototyping the disposable cartridge in WP3. Component designs for both the plasma separation and the DNA extraction phases have been conceptualized. First discussions and quotations related to the scalable, future manufacturing (injection moulding) are in progress. Actuators and sensors solutions for the instrument are being developed. Mechanical solutions for interfacing with a blood sample in a standard blood collection tube and with the extraction product container have been developed.
WP4, focusing on the clinical verification and service design, will officially start in full during M13. However, the ethical approval for the first clinical tests was already applied for in autumn 2022 and approved (Milestone 5) in January 2023. Device IVD requirements and the overall regulatory pathway has been updated and further designed with consultants. Quality management system is also being updated to meet the requirements of the ISO 13485 standard.
In WP5 a first comprehensive Dissemination and Exploitation Plan has been compiled. The plan includes setting the key performance indicators. By end of the RP1, most indicators are progressing well, except public communications as articles and conference presentations. However, 13 pitching and presentation actions were done to attract investors and partners.
• We made an internal study of 150 liquid biopsy review articles. In 61% of these articles, sample processing was mentioned as critical step in the liquid biopsy diagnostics (reviewed by Dr. Satu Pekkala, 2023)
• In another study, it was discovered that immediate plasma separation could yield ~4X lower hemolysis levels, ~10X lower genomic contamination, and ~20X higher cfDNA signal-to-noise when compared to a stabilizing cfDNA collection tube after 7 days of storage at room temperature (https://ascopubs.org/doi/abs/10.1200/JCO.2019.37.15_suppl.e14529 ). These results are not peer-reviewed, but our own work has also demonstrated that extended sample storage time reduces the yield and quality of cfDNA.
• Our technology can provide standardization of the pre-analytical steps of liquid biopsy. When combined with quantification, it can be scaled to any biomarker present in plasma as a point-of-care solution, which can simplify diagnostics outside hospitals and in remote areas, where manual sample processing is not feasible.
Next steps include 1) prototype evaluation by potential hospital/company partners (hospital collaborator, potential distributors and subcontractors), 2) finding international KOLs and information spreading, 3) setting up the plan and actions for clinical validation. Risk factors have significantly decreased during the project. Mitigation plan of the identified risks include new technology patent filings and attraction of venture capital during the year 2023.
• In another study, it was discovered that immediate plasma separation could yield ~4X lower hemolysis levels, ~10X lower genomic contamination, and ~20X higher cfDNA signal-to-noise when compared to a stabilizing cfDNA collection tube after 7 days of storage at room temperature (https://ascopubs.org/doi/abs/10.1200/JCO.2019.37.15_suppl.e14529 ). These results are not peer-reviewed, but our own work has also demonstrated that extended sample storage time reduces the yield and quality of cfDNA.
• Our technology can provide standardization of the pre-analytical steps of liquid biopsy. When combined with quantification, it can be scaled to any biomarker present in plasma as a point-of-care solution, which can simplify diagnostics outside hospitals and in remote areas, where manual sample processing is not feasible.
Next steps include 1) prototype evaluation by potential hospital/company partners (hospital collaborator, potential distributors and subcontractors), 2) finding international KOLs and information spreading, 3) setting up the plan and actions for clinical validation. Risk factors have significantly decreased during the project. Mitigation plan of the identified risks include new technology patent filings and attraction of venture capital during the year 2023.