Final Report Summary - IN TIME (In Vitro Tissue Model with Integrated Micro-fluidics and Electronics)
1. Work progress and achievements
IN TIME was aimed at investigating a new strategy for developing in vitro two-dimensional (2D) and three-dimensional (3D) living tissue models using micro-fluidic devices to deliver cues required for differentiation and growth, and additionally, using state-of the art technologies based on organic electrochemical transistors (OECTs) to realise in-line monitoring systems. Developing such multi-sensing devices requires the combination of expertise in biology, micro-fabrication, and organic electronics. This project focused on the design, the fabrication and the integration of organic electronic devices within an ‘organ-on-a-chip’ in order to perform in-line measurement of living cell tissues.
The fellow trained on the fabrication and operation of organic electronic devices as well as on the seeding and maintenance of in vitro cell culture. He visited the laboratory of Prof. Nacho Romero at the Open University, United Kingdom, where he learned about a technique for the fabrication of 3D cell cultures based on the use of collagen biopolymer. He also visited the laboratory of Dr. Ying Zheng at the University of Washington where he learnt the fabrication and operation of in vitro 3D microfluidics models.
The fellow developed a facile microfluidic fabrication process for a simple and straightforward integration with OECTs. The microfluidic channel is used to flow cell culture media in order to apply mechanical shear stress to the cell tissue layer. The transistors, based on the use of a conducting polymer poly(3,4-ethylenedioxythiophene) doped with poly(styrene sulfonate), are in direct contact with the cells and capable of monitoring in realtime both changes in the resistance and capacitance of the cell barrier. Also the microfluidics are used for the perfusion of drugs and cytotoxicity while the cell barrier is monitored with an OECTs. The fellow had proved the long-term operation of the device and its potential use for drug testing.
The fellow has also developed proof-of-concept devices that can be used for testing of 3D cell models. In particular he realized a microfluidic trapping device to position 3D cell spheroids inside microfluidic channels and assess the spheroid electrical resistance using OECT. The trapping device can operate without the need of any pumping system and it has also shown minimal impact on the viability of the cells. Finally, in collaboration with Dr. Zheng (UW) he has also engineered a novel platform for the integration of multi-electrode arrays with 3D tubular structures made of collagen hydrogels.
With these individual components in place, the fellow participated in various efforts to make possible the integration of electronic devices inside microfluidic chips to be used for in vitro applications, such as in vitro toxicology.
2. Project management
The project is organized in 3 tasks:
Task1 Interfacing cell culture with in-line monitoring systems
Task2 Micro-fluidics integration of multi live cell tissues in vitro
Task3 3D cell culture
Deliverables and Milestones:
M1:
• Hold official project kick-off meeting. Accomplished
• Task1 commences with training of the fellow on device fabrication and characterization. Accomplished
M5-8:
• Fellow learns basic technique for cell culture biology and OECTs operation when interfaced with cell barrier. Accomplished
M9-11
• First microfluidic platform integrating OECTs for simultaneous optical and electronic monitoring of in vitro kidney epithelium. Accomplished
M10-13:
• Design of fully integrated microfluidics platform for testing of 3D cell cultures Accomplished.
M14-24
• Development of novel fabrication protocol for integration of PDMS based microfluidic device with planar electronic sensors Accomplished
• Validation of a microfluidic trapping device for impedance sensing of 3D cell culture spheroids Accomplished
• Integration of multi-electrode arrays with 3D tubular cell culture models Accomplished
IN TIME was aimed at investigating a new strategy for developing in vitro two-dimensional (2D) and three-dimensional (3D) living tissue models using micro-fluidic devices to deliver cues required for differentiation and growth, and additionally, using state-of the art technologies based on organic electrochemical transistors (OECTs) to realise in-line monitoring systems. Developing such multi-sensing devices requires the combination of expertise in biology, micro-fabrication, and organic electronics. This project focused on the design, the fabrication and the integration of organic electronic devices within an ‘organ-on-a-chip’ in order to perform in-line measurement of living cell tissues.
The fellow trained on the fabrication and operation of organic electronic devices as well as on the seeding and maintenance of in vitro cell culture. He visited the laboratory of Prof. Nacho Romero at the Open University, United Kingdom, where he learned about a technique for the fabrication of 3D cell cultures based on the use of collagen biopolymer. He also visited the laboratory of Dr. Ying Zheng at the University of Washington where he learnt the fabrication and operation of in vitro 3D microfluidics models.
The fellow developed a facile microfluidic fabrication process for a simple and straightforward integration with OECTs. The microfluidic channel is used to flow cell culture media in order to apply mechanical shear stress to the cell tissue layer. The transistors, based on the use of a conducting polymer poly(3,4-ethylenedioxythiophene) doped with poly(styrene sulfonate), are in direct contact with the cells and capable of monitoring in realtime both changes in the resistance and capacitance of the cell barrier. Also the microfluidics are used for the perfusion of drugs and cytotoxicity while the cell barrier is monitored with an OECTs. The fellow had proved the long-term operation of the device and its potential use for drug testing.
The fellow has also developed proof-of-concept devices that can be used for testing of 3D cell models. In particular he realized a microfluidic trapping device to position 3D cell spheroids inside microfluidic channels and assess the spheroid electrical resistance using OECT. The trapping device can operate without the need of any pumping system and it has also shown minimal impact on the viability of the cells. Finally, in collaboration with Dr. Zheng (UW) he has also engineered a novel platform for the integration of multi-electrode arrays with 3D tubular structures made of collagen hydrogels.
With these individual components in place, the fellow participated in various efforts to make possible the integration of electronic devices inside microfluidic chips to be used for in vitro applications, such as in vitro toxicology.
2. Project management
The project is organized in 3 tasks:
Task1 Interfacing cell culture with in-line monitoring systems
Task2 Micro-fluidics integration of multi live cell tissues in vitro
Task3 3D cell culture
Deliverables and Milestones:
M1:
• Hold official project kick-off meeting. Accomplished
• Task1 commences with training of the fellow on device fabrication and characterization. Accomplished
M5-8:
• Fellow learns basic technique for cell culture biology and OECTs operation when interfaced with cell barrier. Accomplished
M9-11
• First microfluidic platform integrating OECTs for simultaneous optical and electronic monitoring of in vitro kidney epithelium. Accomplished
M10-13:
• Design of fully integrated microfluidics platform for testing of 3D cell cultures Accomplished.
M14-24
• Development of novel fabrication protocol for integration of PDMS based microfluidic device with planar electronic sensors Accomplished
• Validation of a microfluidic trapping device for impedance sensing of 3D cell culture spheroids Accomplished
• Integration of multi-electrode arrays with 3D tubular cell culture models Accomplished