ESR 8: Set-up and preliminary validation of a modular high-throughput microfluidic system for assessing drug toxicity and metabolism in the hepatobiliary environment.

ESR8

Project Title: Set-up and preliminary validation of a modular high-throughput microfluidic system for assessing drug toxicity and metabolism in the hepatobiliary environment.

Objectives: The ESR will be trained to develop a physiologically-relevant, long-term culture model system for assessing drug toxicity and metabolism in the hepatobiliary environment. The main objectives of the project will be to: a) develop an easy-to-use modular liver-on-chip, b) explore the liver-on-chip as a reliable drug toxicity and metabolism platform, c) integrate the liver-on-chip with other organ-on-chips developed by other ESRs (e.g. gut) to achieve a complete metabolic and PK model that reproduces the first-pass metabolism of drugs. The proposed model will be then compared to standardized in vitro drug toxicity and metabolism assays and next assessed against current in vivo model (rodent model). The ESR will be first trained to develop competence on lab-on-chip technologies. Moreover, the ESR will acquire competence in cell culture (standard 2D and 3D in vitro model), toxicity and metabolism profiling (using appropriate in vitro assays and analytical techniques-e.g. LC-MS/MS), method development and validation, and skills in vivo models (absorption, excretion and distribution studies in rodents).

Since compliance with Good Laboratory Practice (GLP) is generally expected for pivotal in vitro and in vivo testing, the ESR will learn how to conduct specific duties according to regulatory requirements and Standard Operating Procedures (SOPs).

Expected Results: Although some commercial liver-on-chip assays are already available, none of them take in account the hepatobiliary role in drug transport, and none of them have been so far fully validated. At the end of the project, after optimization and standardization, a modular high throughput microfluidic system that will help in drug discovery and development process will be generated.

Host: ACCELERA

Main Supervisor: Claudio Bernardi (Accelera)

Duration: 36 months

Planned Secondment: POLIMI (7 months total), in the first year (5 months) at POLIMI, the ESR will acquire skills on technical design and fabrication of microfluidics devices, while during the second year (2 months), the ESR will learn how to improve the design model and to bring advancements in term of throughput; FNUSA-ICRC (2 months), during the second year at FNUSA-IRCR, the ESR will acquire competence in liver cells differentiation and culture protocols.

Enrolment in Doctoral Degree: PhD in Bioengineering at Politecnico di Milano

For any specific requests on this project, please get in contact with Dr. Claudio Bernardi (Claudio.Bernardi@accelera.org)