Open multi-organ communication device for easy interrogation of tissue slices

Abstract

Here, we have developed an open multi-organ communication device that facilitates cellular and molecular communication between ex vivo organ slices. Measuring communication between organs is vital for understanding the mechanisms of health regulation yet remains difficult with current technology. Communication between organs along the gut–brain-immune axis is a key regulator of gut homeostasis. As a novel application of the device, we have used tissue slices from the Peyer's patch (PP) and mesenteric lymph node (MLN) due to their importance in gut immunity; however, any organ slices could be used here. The device was designed and fabricated using a combination of 3D printed molds for polydimethylsiloxane (PDMS) soft lithography, PDMS membranes, and track-etch porous membranes. To validate cellular and protein transfer between organs on-chip, we used fluorescence microscopy to quantitate movement of fluorescent proteins and cells from the PP to the MLN, replicating the initial response to immune stimuli in the gut. IFN-γ secretion during perfusion from a naïve vs. inflamed PP to a healthy MLN was quantitated to demonstrate soluble signaling molecules are moving on-chip. Finally, transient catecholamine release was measured during perfusion from PP to MLN using fast-scan cyclic voltammetry at carbon-fiber microelectrodes to demonstrate a novel application of the device for real-time sensing during communication. Overall, we show an open-well multi-organ device capable of facilitating transfer of soluble factors and cells with the added benefit of being available for external analysis techniques like electrochemical sensing which will advance abilities to probe communication in real-time across multiple organs ex vivo.