Periodic Reporting for period 3 - M3DLoC (Additive Manufacturing of 3D Microfluidic MEMS for Lab-on-a-Chip applications) Reporting period: 2021-01-01 to 2022-06-30 Summary of the context and overall objectives of the project There is a clear and urgent need for the development, provision and widespread use of affordable, portable, reliable and rapid Point-of-Care (PoC) diagnostic devices, especially for early diagnosis of diseases, so as to enable time-sensitive, life-saving therapeutic interventions. The intrinsic advantages of miniaturization and integration from microfluidics and Lab-on-a-Chip (LoC) devices has seldom been translated into commercial products due to various challenges. M3DLoC has established a hybrid manufacturing pilot production line, to link flexible micro-fabrication and multi-material use, aiming to address challenges in PoC diagnostics. This hybrid manufacturing process enables the fabrication of high aspect ratio microfluidic features on polymer substrates with high accuracy and repeatability, while conductive functional components of micro-structured carbon-based electrodes by inkjet printing technology with pico-litre dispensing capabilities. The conclusions of M3DLoC include:- An innovative pilot line for advanced manufacturing of affordable and scalable microfluidic MEMS for LoC and sensing applications was established.The modules are: - Industrial extrusion-based 3D printer with multi-material capabilities a four times production capacity, utilising synchronised printing heads. - Micro-milling system with a high-precision positioner for the high-speed spindle for small-scale fabrication and low surface roughness. - Inkjet deposition system with multi-material capability using 8 distinct nozzles, utilizing a proprietary non-contact acoustic technology. - Laser modules, for polishing and surface texturing through ablation, employed for reduction of surface roughness and the creation of high-resolution features, for structures down to 11μm. - In-line X-ray laminography and radioscopy platform for inspection and QA, utilising a novel image analysis algorithms. - Microwave probe microscopy for nanoscale material evaluation. - System integration through bespoke automated transport system, together with tailored software with scheduling capabilities.- Demonstration of a low-cost alternative to ultra-precision machine tools for micro-machining and multi-material use.- Demonstration of cutting-edge technologies and functional (nano)materials in industry-relevant applications. - Clinical sample measurements showcasing the performance of devices produced using the pilot line, with detection protocols and assay processes that were developed in the project for viral (HIV, SARS-CoV-2), bacterial (drug resistant Tuberculosis bacterial strains) and cancer biomarker (epidermal growth factor receptor mutations).The case studies demonstrated the feasibility of the design, materials and manufacturing technologies and their relevancy for the PoC diagnostic market. The pilot line is available for end-users requiring a microfabrication facility in an industrial setting for the pilot fabrication of medical devices, allowing the development and validation of new products, filling the gap between R&D and pre-commercial production, which can subsequently be transferred to mass production technologies. Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far During the project timeline, the M3DLoC pilot line was designed, built and tested, utilising the capabilities of the individual integrated modules. The pilot line architecture and device-manufacturing sequence were studied and designed, demonstrating the production line capability to meet end-users’ requirements and targeted quality characteristics. A two-phase material development was undertaken, focusing on material processability and application-specific requirements for the project’s test cases. Biodegradable thermoplastic materials have been tailored by melt-mixing and (nano)additive incorporation, in order to form the main BioMEMS matrix that hosts and interconnects all functional elements. In parallel carbon-based inks were developed, with formulations optimized for ink-jet printing and improved interaction with substrate materials, with the aim to decrease surface resistivity and improve electrochemical performance. Microfluidic prototypes related to the 3 test cases have been manufactured and evaluated, and clinical samples measurements demonstrated the performance of devices produced using project-developed detection protocols and assay processes. A detailed business and exploitation plan for the M3DLoC pilot line and services was developed and updated, and a strategy on innovation management and technology transfer was defined, resulting in one patent application. Dissemination and communication activities were extensively carried out throughout the duration of the action, focused to present M3DLoC’s results to the scientific community and key industrial stakeholders. The project website and social media shared the latest news, newsletters were prepared and distributed, scientific articles have been published and open day events were organized to approach industrial and academic relevant stakeholders. Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far) The impact of the project can be summarised in the following:- Contribution to maintain EU competitiveness in a high-technology environment, in developing advanced microfluidic devices through Additive Manufacturing technologies, nanotechnology and material functionalization, automation and in-line monitoring, with wide range of biomedical applications.- Sustainable material solutions with low environmental impact, utilising low cost and low toxicity materials, capable of replacing high environmental impact industry standards, focusing on polymer materials for microfluidic devices, shifting from silicon and glass materials.- A prototype pilot line capable of fully digital and rapid prototyping for BioMEMS, providing a low-cost alternative to ultra-precision micro-machining and flexible multi-material integration.- Development and testing of novel detection technologies for viral and bacterial infections and early cancer diagnosis.- Demonstration of clinical sample measurements showcasing the capabilities of the pilot line to produce devices suitable for clinical diagnostic use.- Contribution to current diagnostics market trends, towards integrated sample-to-result workflows within a cartridge, reducing labour costs, requirements for staff training and lowering error rates, moving from centralized labs to PoC in low-resource contexts.The open access pilot line is available for end-users who require a microfabrication facility in an industrial setting, for the development and demonstration of new products, linking concept creation and high-volume manufacturing and bridging R&D and pre-commercial production. A wider impact of the advanced LoC applications is the potential to shorten time-to-result due to rapid on-device processing times and ability to test individual samples efficiently, without extended logistics and batching delays. This provides a key advantage for disease diagnosis, monitoring, and management, leading to improved health outcomes for patients. logo.jpg
