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Vivas, A.

Publications and source records attributed to Vivas, A..

2 recordsLinked to original sources

Fluidic Circuit Board with Modular Sensor and Valves Enables Stand-Alone, Tubeless Microfluidic Flow Control in Organs-on-Chips

Organs-on-chips are a unique class of microfluidic in vitro cell culture models, in which the in vivo tissue microenvironment is mimicked. Unfortunately, its widespread use is hampered by their operation complexity and incompatibility with end-user research settings. To address these issues, many commercial and non-commercial platforms have been developed for semi-automated culture of organs-on-chips. However, these organ-on-chip culture platforms each represent a closed ecosystem, with very little opportunity to interchange and integrate components from different platforms or to develop new ones. The Translational Organ-on-Chip Platform (TOP) is a multi-institutional effort to develop an open platform for automated organ-on-chip culture and integration of components from various developers. Central to TOP is the fluidic circuit board (FCB), a microfluidic plate with the form factor of a typical well plate. The FCB enables microfluidic control of multiple components like sensors or organ-on-chip devices through an interface based on openly available standards. Here, we report an FCB to integrate commercial and in-house developed components forming a stand-alone flow control system for organs-on-chips. The control system is able to achieve constant and pulsatile flow recirculation through a connected organ-on-chip device. We demonstrate that this system is able to automatically perfuse a heart-on-chip device containing co-cultures of cardiac tissues derived from human pluripotent stem cell-derived cardiomyocytes and monolayers of endothelial cells for five days. Altogether, we conclude that open technology platforms allow the integration of components from different sources to form functional and fit-for-purpose organ-on-chip systems. We anticipate that open platforms will play a central role in catalysing and maturing further technological development of organ-on-chip culture systems.

bioengineering↗

Generation and Culture of Cardiac Microtissues in a Microfluidic Chip with a Reversible Open Top Enables Electrical Pacing, Dynamic Drug Dosing and Endothelial Cell Co-Culture

Cardiovascular disease morbidity has increased worldwide in recent years while drug development has been affected by failures in clinical trials and lack of physiologically relevant models. Organs-on-chips and human pluripotent stem cell technologies aid to overcome some of the limitations in cardiac in vitro models. Here, a bi-compartmental, monolithic heart-on-chip device that facilitates porous membrane integration in a single fabrication step is presented. Moreover, the device includes open-top compartments that allow facile co-culture of human pluripotent stem cell-derived cardiomyocytes and human adult cardiac fibroblast into geometrically defined cardiac microtissues. The device can be reversibly closed with a glass seal or a lid with fully customized 3D-printed pyrolytic carbon electrodes allowing electrical stimulation of cardiac microtissues. A subjacent microfluidic channel allowed localized and dynamic drug administration to the cardiac microtissues, as demonstrated by a chronotropic response to isoprenaline. Moreover, the microfluidic channel could also be populated with human induced pluripotent stem-derived endothelial cells allowing co-culture of heterotypic cardiac cells in one device. Overall, this study demonstrates a unique heart-on-chip model that systematically integrates the structure and electromechanical microenvironment of cardiac tissues in a device that enables active perfusion and dynamic drug dosing. Advances in the engineering of human heart-on-chip models represent an important step towards making organ-on-a-chip technology a routine aspect of preclinical cardiac drug development.

bioengineering↗