Developing an inflammation on a chip device with integrated electrodes

Short description: Patients with altered inflammatory response, due to metabolic diseases (e.g., diabetes mellitus), chronic inflammation, autoimmune diseases and pharmaceutical treatments often experience delayed or incomplete tissue repair, including poor bone healing.1 Current therapeutic strategies rely on controlling stem cell differentiation and macrophage polarization towards pro-/anti-inflammatory cells, by using soluble factors and bio-instructive materials.  However, cells are also guided by biochemical cues. They also respond to physical cues (e.g., mechanical and vibration, bioelectricity), regulating their fate and function. Therefore the use of biophysical cues has been increasingly investigated, at both laboratory and biobank scales for clinical applications and represents an emerging field in regenerative medicine, offering potentially safer, tunable and more precise approaches. 

In particular, the endogenous bioelectric signalling that is orchestrated by ion channels and ion pumps, referred to as the bioelectric code, has gained growing interest. Externally applied electric fields (EFs) can alter this code, influencing cell membrane potential, directing cell migration, and modulating cell function (e.g., stem cell differentiation, change in cytokine secretion in T-cells).2–5 Yet, there remains a critical knowledge gap on how EFs influence monocyte commitment towards pro-/anti-inflammatory macrophages. This lack of understanding slows down the point of translation to reach immune response regulation and tissue repair in clinical settings driven by electrical cues.

PhD Project: the proposed PhD project will develop an “inflammation on a chip” device, designed to host, monitor and electrically guide monocytes to macrophage differentiation. This device will take advantage of a multidisciplinary approach, by integrating microelectrodes to deliver precise electrical stimulation protocols to drive monocytes to differentiate into macrophages, and a real time monitoring of inflammatory biomarkers to evaluate their commitment towards either pro- or anti-inflammatory cells within a microfluidic system integration.

This innovative model will provide first insights into bioelectric regulation of inflammatory cells, opening new therapeutic avenues for tissue engineering, regenerative medicine and inflammation disorders. This inflammation on a chip device is expected to become an essential model for studying immune cells in controlled microenvironments, opening the way to investigate patient specific responses, ultimately contributing to personalised medicine.

 The main tasks of the PhD student will be:

microfabrication and characterization of the chip in a cleanroom environment

In vitro cell culture of inflammatory cells

development of an on-chip imaging technique

Collaborations. This project is in collaboration between two different laboratories of Mines Saint-Etienne (Bioelectronics department, Gardanne (13) and Biomaterials department, Saint Priest en Jarez (42)). Additionally, a period abroad is envisioned for the PhD student to acquire knowledge on the design, manufacturing and modelling of microfluidic chips.

Required skills: Applicants must hold a Master’s degree or equivalent in Cell biology/Biomedical sciences/Biomedical Engineering. Preference will be given to candidates with experience in microfabrication and/or cell biology.

Expertise in electrical engineering will be a plus.

The project is highly experimental, therefore we are seeking candidates with a keen interest in experimental work.

Candidates must be curious and intellectually ambitious.

The successful candidate will be expected to work independently, while also collaborating with several lab members and external partners, and to contribute effectively to team efforts.

She/he will need to communicate well in English (orally and in writing).

Basic knowledge of French (or willingness to learn) is a plus.

The Ecole des Mines de Saint-Étienne is part of the INSTITUT MINES-TELECOM (IMT) and is the French oldest elite engineering school outside Paris. IMT mission is to support the economy by educating highly qualified managers with strong technical and scientific skills, developing applied research to meet the needs of industry, and contributing to companies’ innovation and competitiveness.

The Centre of Microelectronics in Provence's mission is to explore new microelectronics Technology and devices for innovative applications. The Bioelectronics department combines expertise in organic electronics and biology. Our research aims to elucidate the fundamentals of the electronic materials/biology interface and to launch new bioelectronic technologies.

The Centre for Biomedical and Healthcare Engineering focuses on improving health through science and develops applications in healthcare engineering, soft tissue biomechanics, surface bioengineering and biomaterial engineering. The Biomaterials Engineering (BioMat) department  focuses on the synthesis and manufacturing of bioceramics, In vitro bone tissue models as well as on the development of bioinstructive materials for understanding mechanisms. We also study the behavior and aging of orthopedic implants (Fatigue testing).

Required skills: Applicants must hold a Master’s degree or equivalent in Cell biology/Biomedical sciences/Biomedical Engineering. Preference will be given to candidates with experience in microfabrication and/or cell biology.

Expertise in electrical engineering will be a plus.

The project is highly experimental, therefore we are seeking candidates with a keen interest in experimental work.

Candidates must be curious and intellectually ambitious.

The successful candidate will be expected to work independently, while also collaborating with several lab members and external partners, and to contribute effectively to team efforts.

She/he will need to communicate well in English (orally and in writing).

Basic knowledge of French (or willingness to learn) is a plus.