Smart membranes in barrier-on-chip systems

Many organ-on-a-chip systems (OOCs) utilize polydimethylsiloxane (PDMS) or other polymers as materials, creating porous membranes through methods such as soft lithography or track etching. This study, however, takes a markedly different approach by employing conventional semiconductor and microelectromechanical system (MEMS) materials, and utilizes wafer-level processes to fabricate barrier-on-a-chip systems (BOCs). This advanced BOCs platform features an ultra-thin SixNy nanoporous membrane with exceptional optical transparency and very low stress. The membrane supports various in-vitro tissues and co-cultures by enabling molecular passage while blocking cells. Utilizing two-photon polymerization (2pp) digital lithography for initial nanopore array design, followed by standard wafer-level photolithography to fabricate 500 nm nanopore arrays and co-planar electrodes via metal sputtering, enables the integration of an electric cell-substrate impedance sensing (ECIS) sensor. The synergy of ECIS and the novel BioMEMS design enhances real-time monitoring of cell behavior and barrier integrity, facilitating applications in micro physiological systems. The system design supports uniform cell seeding and dynamic cultivation, validated through live/dead assays, tight-junctions (TJs) modulators, and ECIS data, demonstrating cell growth and barrier formation dynamics. Neural network models enhance prediction accuracy for cellular layer morphological phases, offering automated, non-invasive monitoring of in-vitro barrier dynamics. This approach simplifies traditional cell monitoring techniques, promising scalable production in MEMS foundries and adaptability across various in-vitro testing scenarios. A low-cost multichannel impedance measurement system utilizing an 8×8 gold (Au) microelectrode array on 4-layer printed circuit board (PCB) maps cell distributions in liquid environments at 200 kHz. Deconvolution corrects parasitic currents, offering spatial impedance imaging ideal for integration into BOCs, potentially replacing traditional microscopy. Additionally, laser induced forward transfer (LIFT) technology produces porous 3D Au- electrodes, quadrupling the electrochemical surface area and enhancing 3D bio-impedance measurements for organoids.