Periodic Reporting for period 1 - BRIGHT (Best-in-class canceR dIaGnostic cHip for patient sTratification.)
Berichtszeitraum: 2022-08-01 bis 2023-07-31
Circulating tumour cells (CTCs) are a rare population of cancer cells that have detached from the primary tumour or metastatic sites and circulates in the blood. CTCs are considered valuable biomarkers by potentially providing information regarding diagnosis, prognosis and follow-up of treatment. However, CTC scarcity has posed a particular challenge to their detection. Funded by the European Innovation Council (EIC), the BRIGHT project brings a proprietary technology for the detection of CTCs which is based on the size and aberrant shape of these cells compared to other cells in the blood. The microfluidic chip supports the isolation and retention of CTCs for further investigation of phenotype and drug resistance.
Through advanced microengineering and nanotechnology, we have developed a proprietary microfluidic-based liquid biopsy device, the RUBYchip™ (PCT/EP2016/078406). This technology allows for the isolation of all types of CTCs, keeping them viable and enabling the analysis of their phenotypic, genetic and functional characteristics, enabling unprecedented frequent monitoring of cancer progression in a minimally invasive and cost-efficient way. Our chip isolates 70% of the very scarce CTCs from a 7.5mL blood sample of a cancer patient in less than 3 h and without the need of sample pre‐processing. This dramatic improvement in the sensitivity compared to competition is enabled by a unique microfilter network embedded in a microfluidic device that separates the CTCs from the healthy cells based on their size and deformability. Furthermore, the RUBYchip enables automation reducing inter-laboratory and inter-user dependence and ensuring reproducible analysis of CTCs.
Through advanced microengineering and nanotechnology, we have developed a proprietary microfluidic-based liquid biopsy device, the RUBYchip™ (PCT/EP2016/078406). This technology allows for the isolation of all types of CTCs, keeping them viable and enabling the analysis of their phenotypic, genetic and functional characteristics, enabling unprecedented frequent monitoring of cancer progression in a minimally invasive and cost-efficient way. Our chip isolates 70% of the very scarce CTCs from a 7.5mL blood sample of a cancer patient in less than 3 h and without the need of sample pre‐processing. This dramatic improvement in the sensitivity compared to competition is enabled by a unique microfilter network embedded in a microfluidic device that separates the CTCs from the healthy cells based on their size and deformability. Furthermore, the RUBYchip enables automation reducing inter-laboratory and inter-user dependence and ensuring reproducible analysis of CTCs.
During the first year of the project, RUBYnanomed has worked in the development of a new version of its technology platform towards achieving Milestone MM1 “Beta prototype and pre-series ready for clinical validation”.
The industrialization work done towards a production-ready device for full industrialisation of the RUBYchip and its automated analysis has been the main focus. The team worked on setting up the requirements for industrialization altogether with key partners (foundries, subcontractors, service providers), with wide experience in the IVD sector will ensure not only the robustness of the individual parts of the technology and their performance but also the compliance with ISO13485 regulations. After the definition of requirements, the implementation of large-scale manufacturing process for the RUBYchip was set up, in which several geometries were tested. Within this period two units of the first alpha prototype of the industrialised automated unit, the software components and the reagent kit were developed achieving a TRL7. Finally, once the alpha prototypes were tested and demonstrated to be fully functional, the company is working in the pre-production units (1100 RUBYchipTM units, 1100 reagent kits, and 2 automated units) in compliance with regulatory requirements to start the clinical trials.
Before launching the clinical trials, it was critical to define the regulatory strategy focused on the entry in two main markets, in EU and the US; as well as stablishing the Quality Management System (QMS) of the company. The company is currently implementing ISO13485 and expects to finalise certification at the end of 2023. In parallel, RUBYnanomed expects to use Parsortix as a predicate device to follow the 510k certification process in the FDA. A similar strategy will be followed to achieve CE-IVD. The clinical trial to fulfil this objective is being designed and expects to run in parallel in selected sites in Europe and the US.
The industrialization work done towards a production-ready device for full industrialisation of the RUBYchip and its automated analysis has been the main focus. The team worked on setting up the requirements for industrialization altogether with key partners (foundries, subcontractors, service providers), with wide experience in the IVD sector will ensure not only the robustness of the individual parts of the technology and their performance but also the compliance with ISO13485 regulations. After the definition of requirements, the implementation of large-scale manufacturing process for the RUBYchip was set up, in which several geometries were tested. Within this period two units of the first alpha prototype of the industrialised automated unit, the software components and the reagent kit were developed achieving a TRL7. Finally, once the alpha prototypes were tested and demonstrated to be fully functional, the company is working in the pre-production units (1100 RUBYchipTM units, 1100 reagent kits, and 2 automated units) in compliance with regulatory requirements to start the clinical trials.
Before launching the clinical trials, it was critical to define the regulatory strategy focused on the entry in two main markets, in EU and the US; as well as stablishing the Quality Management System (QMS) of the company. The company is currently implementing ISO13485 and expects to finalise certification at the end of 2023. In parallel, RUBYnanomed expects to use Parsortix as a predicate device to follow the 510k certification process in the FDA. A similar strategy will be followed to achieve CE-IVD. The clinical trial to fulfil this objective is being designed and expects to run in parallel in selected sites in Europe and the US.
A plethora of methods are emerging, analysing different (cancer) biomarkers in body fluids, such as circulating tumour cells (CTCs), circulating tumour DNA (ctDNA), and exosomes. The most frequently targeted analyte is ctDNA, small fragments of cancer DNA released into circulation, capable of reflecting tumour burden and evolution over time. ctDNA has taken over CTCs, as it can be routinely implemented using standard clinical laboratory equipment. However, ctDNA derives from those cancer cells that died, and not from those that are actively proliferating.
The innovation of the BRIGHT project relies on providing a solution that simultaneously answers to the recent understanding of cancer as a dynamic and heterogeneous disease and meets the needs of precision medicine. The progress beyond the state of the art of this project provides a source of novel information for clinical decision-making such as early detection of cancer recurrence and monitoring treatment response. We aim to unlock the accessibility of CTC technology by enabling a straightforward implementation in clinics with unprecedented sensitivity, cost-efficiency, automation and reliability to position the technology as the new gold standard.
The outcomes will transform current long-standing value chain models within cancer diagnostics to successfully include automated CTC counting as a companion diagnostic tool. RUBYchip is creating a market segment not covered by any competitor.
The innovation of the BRIGHT project relies on providing a solution that simultaneously answers to the recent understanding of cancer as a dynamic and heterogeneous disease and meets the needs of precision medicine. The progress beyond the state of the art of this project provides a source of novel information for clinical decision-making such as early detection of cancer recurrence and monitoring treatment response. We aim to unlock the accessibility of CTC technology by enabling a straightforward implementation in clinics with unprecedented sensitivity, cost-efficiency, automation and reliability to position the technology as the new gold standard.
The outcomes will transform current long-standing value chain models within cancer diagnostics to successfully include automated CTC counting as a companion diagnostic tool. RUBYchip is creating a market segment not covered by any competitor.