Fraunhofer Institute for Ceramic Technologies and Systems IKTS
Fraunhofer Institute for Ceramic Technologies and Systems IKTS

Organ-on-chip systems

Topic

Use of stacking machines to manufacture organ-on-chip systems with integrated TEER electrodes and membranes for barrier models

Organ-on-chip (OoC) systems are microfluidic devices that cultivate living cells in a 3D environment to simulate the physiology and functions of human organs. These systems are used to study biological processes, carry out drug tests and research diseases.

The success of OoC technology depends not only on the integration of various functions, but also on the scalability of the manufacturing processes. As OoC devices move from laboratory prototypes to industrial research, their production in high volumes becomes critical. Scalability in OoC manufacturing goes beyond device replication; it is about maintaining model accuracy while meeting increasing production demands. Due to its simple implementation and integration, stacking several structured layers - as is standard in the production of LTCC ceramics – could be a suitable manufacturing method. In this manufacturing process, the individual polymer layers are structured, functionalized, aligned and bonded into an integrated system. Thus, the most complex manufacturing steps, namely assembly and integration, have been transferred to semi-automatic stacking machines, which are used for the production of Low Temperature Cofired Ceramics (LTCC) and enable the integration of the individual layers.

 

Illustration of the project approach.

To demonstrate the functionality of the new approach, a simple membrane design for barrier models was realized using an LTCC stacking machine. For this purpose, electrodes for measuring the transepithelial/transendothelial electrical resistance (TEER) of the endothelial barrier were applied to PMMA films using a screen printing process and functionalized at max. 90 °C.

TEER demonstrator manufactured on an LTCC stacking machine and cell test.

For proof of concept, human umbilical vein endothelial cells (HUVECs) were seeded into the channels and onto the integrated membrane. The cells were cultured in the chip for 7-10 days, fixed and stained for the endothelial surface marker CD31. The cell nuclei were also stained for visibility. No signs of cell death were observed. The novel manufacturing process significantly shortened the manufacturing time while ensuring excellent positioning accuracy. The conductivity of the screen-printed TEER electrodes was investigated by measuring the impedance of solutions with different ionic strengths. The results confirmed the ability of the integrated TEER electrodes to measure the impedance of solutions on the chip.

Technical characteristics

  • Stacking and laminating of PMMA and COC polymers at temperatures of 70°C to 80°C
  • Alignment accuracy of less than 20 µm determined
  • Sizes from 4-inch (101.6 mm x 101.6 mm) to 8-inch (203.2 mm x 203.2 mm)

Services offered

  • Requirement-specific development of multilayer microfluidic systems for organ-on-chip or diagnostic applications
  • Scaling of multilayer microfluidic systems with the aid of the LTCC stacking machine

 

Project title: FermiSys - Use of automatic stacking machines for the production of organ-on-chip systems with integrated TEER electrodes and membranes for barrier models

Funding: IGF No: 22703 BR / 2

Project partners:

  • TU Dresden, Institute for Semiconductor and Microsystems Technology (Layout and Characterization)
  • FILK Freiberg Institute gGmbH (Optimization of joining processes)