A MultiOrgan-on-a-chip platform for real-time assessment of efficacy, toxicity, and the discovery of novel nanocarrier systems

Objective and technology breakthrough The major scientific challenge addressed in this project is to develop a robust preclinical advanced tool (the Discover@MOChip) able to perform in-situ and long-term monitoring key physicochemical biomarkers related to the interaction of new nanocarriers at the cellular level. This tool will play a crucial role to accelerate the discovery and clinical translation of novel nanomedicine products. The lack of functional continuous and long-term redouts are crucial for accurate acquisition of dynamic cellular responses and specifically quantify key biomarkers of the efficacy and toxicity of theranostic nanocarriers, such as magnetic nanoparticles (MNPs). Thus, Discover@MOChip main objectives (OBJ) are: OBJ1- the development of multi-biosensing technology for real-time and continuous long-term cells response quantification within a microfluidic multiorgan-on-a-chip platform (MOoCp); OBJ2- the integration of temperature and pH microsensors, and biosensing microneedles-based technology, capable to assess the efficacy of novel drug nanocarrier systems designed for cancer therapy by aids of numerical simulations and live imaging. As such, the major technological goals (TG) to accomplish the main project objectives are: TG1.Microfluidic PDMS Multiorgan-on-chip cell-based platform; TG2.Continuously microenvironment variables monitoring, pH and Temperature; TG3.Continuously in situ optical quantification of key-biomarkers of cells toxicity and drug efficiency; TG4. Real-time 3D biomodels imaging monitoring system; TG5. New insights about novel nanocarrier systems for drug delivery; Disruptive technological approach The project will take advantage of pH and Temperature biosensors under development at the CMEMS research group [9E,18] for the quantification of physical parameters, pH and T, for long-term experiments control (TG2). By doing so, this approach offer the unique advantage to precisely monitor and predict the therapeutic effect, within a MOoCp with 3 healthy bioprinting organoid models (liver, heart, kidney) and liver tumor model, mimicking the in vivo drugs pharmacokinetics to assess safety and toxicity (metabolism, distribution and excretion). Herein, numerical simulations will be of utmost importance to optimize and improve the microfluidic MOoCp design and integration of the proposed MOoCp at different scale levels of the: fluid flow, heat transfer phenomena, therapeutic effects of the NPs and biosensors integration (T1&2, TG1). The innovative add-in to the MOoCp and, microneedles-based technology, will increase the biosensing Low detection limit, a major challenge find in MOoCp applications (T3&4, TG3). Yet, porous microneedles will be used for in situ delivery system as achieved by CMEMS [10F]. An imaging monitoring system, ongoing work within the collaboration with Carlos Ortiz [19] (consultant), will be integrated for deeper insight on cell growth and organoids behavior (T5, TG4). Therefore, real-time evaluation of the performance of the novel nanocarriers graphene-based (GBMNPs) pH dependent (TG2), designed as intelligent drug delivery systems by CMEMS Researchers [14, 15H] will be attained (T6, TG5). In doing so, the ambitious yet attainable technological goals will effectively achieve the main project objective – the Discover@MOChip – with the long-term vision, of shift the industry paradigm and provide a gold standard technology for industry-led acceptance of in vitro models.