Organ-on-a-chip (OoC) and microfluidic devices are conventionally produced using microfabrication procedures that require cleanrooms, silicon wafers, and photomasks. The prototyping stage often requires multiple iterations of design steps. A simplified prototyping process could therefore offer major advantages. Here, we describe a rapid and cleanroom-free microfabrication method using maskless photolithography. The approach utilizes a commercial digital micromirror device (DMD)-based setup using 375 nm UV light for backside exposure of an epoxy-based negative photoresist (SU-8) on glass coverslips. We show that microstructures of various geometries and dimensions, microgrooves, and microchannels of different heights can be fabricated. New SU-8 molds and soft lithography-based polydimethylsiloxane (PDMS) chips can thus be produced within hours. We further show that backside UV exposure and grayscale photolithography allow structures of different heights or structures with height gradients to be developed using a single-step fabrication process. Using this approach: (1) digital photomasks can be designed, projected, and quickly adjusted if needed; and (2) SU-8 molds can be fabricated without cleanroom availability, which in turn (3) reduces microfabrication time and costs and (4) expedites prototyping of new OoC devices@en

We present a wafer-scale fabricated, PDMS-based platform for culturing miniaturized engineered heart tissues (EHTs) which allows highly accurate measurements of the contractile properties of these tissues. The design of the platform is an anisometrically downscaled version of the Heart-Dyno system, consisting of two elastic micropillars inside an elliptic microwell with volume ranging from 3 down to 1μL which supports EHT formation. Size downscaling facilitates fabrication of the platform and makes it compatible with accurate and highly reproducible batch wafer-scale processing; furthermore, downscaling reduces the cost of cell cultures and increases assay throughput. After fabrication, the devices were characterized by nanoindentation to assess the mechanical properties of the pillars and transferred to 96-well plates for cell seeding. Regardless the size of the platform, cell seeding resulted in successful formation of EHTs and all tissues were functionally active (i.e. showed cyclic contractions). The precise characterization of the stiffness of the micropillars enabled accurate measurements of the contractile forces exerted by the cardiac tissues through optical tracking of micropillar displacement. The miniature EHT platforms described in this paper represent a proper microenvironment for culturing and studying EHTs.@en

Organ-on-chip (OoC) devices are in rising demand for high-throughput and low-cost development and toxico-logical screening of chemicals and pharmaceuticals, as they accurately mimic in vitro physiological conditions as in the human body. In particular, OoCs are urgently needed for screening cardiovascular drug toxicity. Physiological relevance of cardiovascular cell cultures requires moving substrates. To date cell culture substrates have been commonly actuated by pneumatic systems, which are bulky, expensive and non-user-friendly, and may thus limit the adoption of OoCs by researchers and industry. In this paper we propose the first actuating and sensing smart material-based OoC device and demonstrate its functionality by culturing human vascular smooth muscle cells (vSMC). Our device utilizes a single ionic polymer metal composite (IPMC)-based transducer to provide both actuation and sensing. The soft IPMC substrate allows to intermittently apply cyclic loading to tissues and to sense their spontaneous contractions. We integrated the transducer within a compact, easy-to-operate, economically affordable and scalable OoC prototype, which achieves an actuation range of 0.2 mm and 0.72 V/mm sensing resolution. The 0.1 % strain induced by actuation on cells accurately corresponds to in vitro strains for vSMCs. We successfully grew vSMCs on the IPMC substrate, and actuated them for 150 min at 1 Hz. Fluorescent staining showed no evidence of adverse effects. These results are a major step towards versatile OoCs for a wide variety of biological modelling of human tissues.@en

•Actuation has been succesfully performed for 2h30 with no side effects nor
delimination of the human tissue
•0.1 % strain has been achieved during the actutaion mode, close to the
strain experienced in vivo by vSMCs
•0.72 V/mm sensitivity has been shown on the sensing mode
•Batch fabrication and downscaling will be targetted in the near future
•Actual sensing of the cells’ contraction will be reserved for further work @en