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Multi-cellular hybrid bio-MEMS

Final Report Summary - PHANES (Multi-cellular hybrid bio-MEMS)

Summary of the project objectives

The main goal of the project PHANES is the fabrication and assembly of multi-cellular hybrid bio-MEMS aiming to produce highly biocompatible and autonomous microsystems.

PHANES plays at the interface between microfabrication and cell biology. It aims to take advantage of the recent advances in assembling microelectromechanical systems (MEMS) by optical tweezers to combine cellular and silicon-based intelligence into novel smart systems. The outcome of the project will contribute to advance the state of the art in emerging technologies as well as to enable novel applications. The project is an essential part of the long-term development of active and implantable biomedical MEMS, i.e. functional micro-prostheses such as inner ear replacements or iris reconstructions.

Description of the work performed and main results

In order to assemble bio-hybrid micro devices, it was necessary to first investigate cell growth conditions as well as design and biocompatibility of the MEMS. The project successfully addressed this challenge by answering the following three related scientific questions:
• What are the cell growth conditions and co-culture protocols for multi-cell patterns in order to keep the initially induced order during growth?
For this purpose, a novel method for the optical positioning and long-term co-culture of multicellular bio-hybrid microsystems was established. The initially induced order could be kept by geometrically containing the cell migration.
• How can we induce a material-independent bio-compatibility of polymeric MEMS?
The intrinsic biocompatibility of the microstructures has been achieved by developing a novel hydrogel-based photopolymer. When microstructuring this novel material, toxic agents such as polymerization radicals and solvents were completely removed.
• What is the simplest design that offers the highest flexibility for manufacturing hybrid bio-MEMS containing multiple cell types?
Based on the knowledge gained from addressing the two previous questions, we succeeded in designing mechanical microstructures capable of guiding the migration of cells of different types into a predefined arrangement. In particular, we grew muscle and neuron cells on a mechanical microstructure which could be actuated by electrical stimulation.

Future devices based on the method developed by us might enable the fabrication of a multitude of functional devices, i.e. micro finger/hand, simple micro robot, iris etc.

Potential impact

Combining the functional advantages of cells with the robustness of MEMS will result in an unprecedented kind of hybrid system. For the first time the fabrication of micrometer-sized, autonomous hybrid and multi-cellular bio-MEMS is foreseen.

In the field of cell culturing the concept of optical manipulation will open new and promising possibilities to position and co-culture multiple types of cells. Even without considering the combination with MEMS, this ability goes beyond what has been reported so far. In the long-term, the ability of positioning and co-culturing multiple types of cells in 3D opens a wide range of applications in the field of biotechnologies and biomedical technologies. In fact, advances in this field will create timely relevant opportunity for the development of active micro-prostheses:
• Self-powered, micrometer-sized hybrid bio-MEMS may considerably contribute to the down-scaling of implantable sensors, due to the combination of self-powered, actuating and sensing cells with intelligent MEMS.
• The combination of patient cells with implantable devices may increase the body acceptance of the devices and so reduce the fibrotic rejections necessitating the frequent exchange of the devices.
• Interfacing hybrid devices with neurons can contribute to advances in neuroplastic surgery as well as to body replacements such as cochlea and iris.
• The design of a universal intelligent MEMS bricks for cell assembly will doubtlessly set the basis for unprecedented combinations of cells and MEMS and set a milestone in the development of hybrid bio-MEMS.
The outcomes of this project represent a unique opportunity for European Research Community to fortify its scientific excellence by developing a new kind of hybrid microsystems that can become a revolution in bio-technological and potentially in bio-medical related research and industry.

Contact information

Prof. Oliver Paul, University of Freiburg, Department of Microsystems Engineering (IMTEK), Georges-Koehler-Allee 103, 79110 Freiburg, Germany
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