Towards increased throughput and automated workflows for organs- on-a-chip, a novel high-definition electrophysiology multiwell plate is developed in the Moore4Medical project [1]. It consists of an advanced CMOS microelectrode array (MEA) chip with 16 sampling areas, each featuring 1024 electrodes [2], and of a polymeric fluidic cartridge with 16 corresponding microchambers, each connected to an integrated pneumatic peristaltic pump [3]. It can perform 16-well assays with single-cell-resolution electrical recording and integrated microfluidics. Building on an earlier prototype, we present recent developments showing a scalable integration route and excellent fluidic and electrical functionalities of the plate in an easy-to-use system. Direct bonding of the MEA chip and the cartridge was achieved using accurate glue deposition and a high-precision pick-&-place procedure, resulting in 16 well-aligned, sealed microchambers on top of the MEA. This method is developed for high-volume production. To run the plate, a user-friendly toolbox, which can be placed inside an incubator, is made together with a data acquisition unit, a pneumatic control unit, and custom software. The plate can be clamped directly inside the toolbox, ensuring communication of the MEA with the data acquisition unit by a pogo-pin connection. The pneumatic control unit actuates the 16 integrated pumps simultaneously via three pressure lines. Hence, 16 assays can run in parallel, with simple pipetting steps for cell seeding and media perfusion. To demonstrate the plate’s functions, all the 16 microchambers were primed and filled with water and 1% PBS buffer sequentially. No liquid leakage or bubble entrapment was observed. The voltage scan of the 16 MEA areas showed uniform signals and a clear difference between the two liquids (0.08 mVrms for water; 0.02 mVrms for PBS). Plate biological-validation is currently on-going to study the effect of drugs on electrical and contractile properties of human stem-cell derived cardiomyocytes and to demonstrate the plate potential for OoC standardization and workflow streamlining. @en

Organs-on-Chip (OoC) have been a promise of microfluidics since their early days, leading to a widespread use in research. OoC adoption by industry conversely has so far been slow, resulting in a big gap between what is developed by elite pioneers and what can be offered to a broad audience. A way to bridge this gap is the consolidation of standards for design, manufacturing and qualification of OoC, making it easier for experts in different fields to combine their expertise and creating integrated systems with higher value than the sum of the parts. To this end, here we present the Smart Multi-Well Plate (SMWP), a device based on an open technology platform and the standardized 96-well plate format. Within this format, the SMWP integrates 16 OoC devices and piezoelectric micropumps, connected by a microfluidic network and controlled by integrated electronics. Results and discussion: The SMWP allows for high modularity, with design and interfacing rules according to guidelines defined by experts from industry and academia [1]. With the SMWP, OoC devices, sensors and piezoelectric micropumps can be integrated using industrial workflows exploiting automated pick-and-placing and wire-bonding machines. The modules are fluidically connected by means of a polymeric fluidic circuit board and electrically connected by reusable and disposable printed circuits boards. These take care of both control of micropumps and sensors and transfer of power and data to the outside world. Fluidic and electric performance of the plate, including piezoelectric micropumps from Fraunhofer EMFT, were tested in combination with barrier model OoC devices from BEOnChip and Bi/ond and multi electrode array chips from MultiChannel Systems. Preliminary results of the biological validation of the three embodiments of the SMWP will also be presented. Conclusions: An autonomous standardized OoC platform based on an open technology was realized by leveraging industrially upscalable processes and integrating OoC devices. @en