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Advanced and versatile PRInting platform for the next generation of active Microfluidic dEvices

Periodic Reporting for period 3 - PRIME (Advanced and versatile PRInting platform for the next generation of active Microfluidic dEvices)

Periodo di rendicontazione: 2022-05-01 al 2023-10-31

Microfluidic devices manipulate small amounts of fluid enabling cost-effective and high throughput analytical assays. Progress in Microfluidics has impact in areas such as biomedicine, biological studies or diagnostics. Despite this potential, the microfluidics market growth is limited by the complexity and elevated prices of the large-scale off-chip equipment needed and its operational cost. PRIME has implemented and integrated smart materials-based valves in a microfluidic chip. Besides PRIME has produced new ultra-sensitive and selective sensors embedded in the chip and readable with light. The final devices can be remotely addressed and read using simple photonic elements.

PRIME has gone beyond the state-of-the-art generating a platform to create a new generation of active microfluidic chips effectively changing the established paradigm. PRIME has set the basis to create a radically new platform that: i) integrates all the required responsive materials and elements in the chip, effectively providing it with all the fluidic and sensing functions, ii) uses compatible materials and manufacturing technologies making future industrial production viable and cost-effective, iii) allows to implement with extensive freedom of design a plethora of new smart-integrated and easy-to-operate microfluidic chips.

PRIME objectives have been successfully achieved to a large extent, setting new advanced smart materials, processing and modeling tools leading to the implementation of an unprecedented functional microfluidic valve actuated by light and novel ultra-sensitive and selective sensors. These elements have been successfully integrated in a microfluidic chip and the feasibility of the technology in real application cases, including in vitro diagnostic (IVD) and Organ on Chip (OoC), has been validated.
PRIME contributions leave a notable scientific and technological impact, with potential implications across scientific and industrial sectors. This summary highlights some of our achievements and outlines future directions.

- Advanced smart materials and their processing: A set of smart responsive materials have been successfully prepared showing large mechanical photoresponse, previously unreported in 4D printing of LCEs, and comparable to LCE materials processed by conventional non-digital methods. Remarkably, PRIME has led to the development of thermoplastic liquid crystal soft actuators. This new class of smart materials demonstrates both temperature and light-driven deformations and afforded sustainable soft actuators exhibiting melt-processable and recyclable functionalities compatible with large-scale industrial processing methods. It is envisioned that these thermoplastic materials will serve as a starting point for industrially-relevant smart materials that are applicable in our society for a myriad of applications including deployable soft actuating and microfluidic devices.

- Modelling and simulation of active matter: The modelling and simulation tools set up within PRIME have allowed us to push the envelope on LCE shape programmable design techniques, simulation approaches, and even underlying theoretical questions. We have developed a robust simulation framework for active, shape-programmed LCE mechanics that led to optimal design parameters for both the conical and hybrid type valves and can be employed in the future similarly to improve and optimize the designs of many other classes of LCE shape shifting devices.

- Photoactive valve technology: One major project accomplishment has been the successful development of a functional microfluidic valve actuated by light. This valve enables fluid control functions without the need for physical contact, making it suitable for integration into disposable devices, thereby eliminating the need for maintenance or complex cleaning protocols. Within the project, we have successfully developed and validated light-actuated valves, thereby expanding the scope of potential applications. As a future direction, we aim to further develop these concepts into real products in the framework of a spin-off company we are launching.

- IVD technology: A novel fluidic chip analysis technique has been developed using plasmonic nanoparticles as a transduction system. These nanoparticles and supports have been functionalized with capture and developer antibodies for the development of a thermal immunosensor. A thermochromic material has been used as a readout system. This immunoassay works in such a way that in the presence of the analyte to be detected, a sandwich is formed, and the particle is retained on the support. After irradiation with laser light in the NIR, these particles generate heat that is transmitted through the chip and provides a colour signal on the thermal paper. Using this technology, it has been possible to detect the tumour marker CEA.

- New horizons in OoC: The achievement of an integrated valve and organ-on-chip system on the same platform has been a promising first step in obtaining complex but easy-to-use systems. Automation in liquid handling in organ-on-chip represents a decrease in human error, which is a step forward in the widespread use of technology for more complex systems. As an additional tangible result, a new generation of barrier-free OoC devices has been developed during the project, leading to a new commercial product.

- A small consortium with significant impact: Out of a consortium of only 6 partners, the PRIME project partners have seized numerous opportunities to disseminate our results. The PRIME team published 18 peer-reviewed publications in scientific journals. Over the course of the project, consortium members gave 28 conference presentations, either oral presentations or posters, as well as presented the project at 17 public Science events, ending with our own final dissemination event. We took advantage of webinars, created videos and graphics, and engaged on social media to communicate the project consistently throughout its lifetime – and our materials will be available well after the end of the project. Protection of the intellectual property of the identified exploitable results has been undertaken and paths of exploitation have been explored for each of them in a continuous fashion along the project duration. An efficient management, has facilitated a smooth running of project activities ensuring timely achievement of objectives and deliverables.
The standard in microfluidics is a passive microfluidic chip using bulky external equipment to perform liquid control and manipulation functions. For detection, also external complex and expensive equipment, making the cost of microfluidics platforms expensive and operation complex.

The vision of the PRIME technology overcomes all these limitations through the use of smart and nano- materials, advanced manufacturing as well as concepts that will enable integration of all the fluidic and sensing functions into a single device, leading to a radically new generation of microfluidic systems.

PRIME has pursued to narrow the gap between microfluidic technology and non-specialized end-users favouring spreading and penetration of microfluidics to diverse application fields ranging from biological basic research and drug testing studies in the biomedical field to environmental, food and water assays.
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