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Oxalis features: independent control of pO2, pH and the liquid flowrate. pO2 equilibration time in the medium: 3 minutes. pO2 accuracy: 3 mmHg. Flowrate as low as 1 μL min−1 to avoid shear stress.

Correction for ‘Developing an advanced gut on chip model enabling the study of epithelial cell/fibroblast interactions’ by Marine Verhulsel et al., Lab Chip, 2021, 21, 365–377, https://doi.org/10.1039/d0lc00672f.

Currently, fluidic control in microdevices is mainly achieved either by external pumps and valves, which are expensive and bulky, or by valves integrated in the chip. Numerous types of internal valves or actuation methods have been proposed, but they generally impose difficult compromises between performance and fabrication complexity. We propose here a new paradigm for actuation in microfluidic devices based on rigid or semi-rigid walls with transversal dimensions of hundreds of micrometres that are able to slide within a microfluidic chip and to intersect microchannels with hand-driven or translation stage-based actuation. With this new concept for reconfigurable microfluidics, the implementation of a wide range of functionalities was facilitated and allowed for no or limited dead volume, low cost and low footprint. We demonstrate here several fluidic operations, including on/off or switch valving, where channels are blocked or reconfigured depending on the sliding wall geometry. The valves sustain pressures up to 30 kPa. Pumping and reversible compartmentalisation of large microfluidic chambers were also demonstrated. This last possibility was applied to a “4D” migration assay of dendritic cells in a collagen gel. Finally, sliding walls containing a hydrogel-based membrane were developed and used to concentrate, purify and transport biomolecules from one channel to another, such functionality involving complex fluidic transport patterns not possible in earlier microfluidic devices. Overall, this toolbox is compatible with “soft lithography” technology, allowing easy implementation within usual fabrication workflows for polydimethylsiloxane chips. This new technology opens the route to a variety of microfluidic applications, with a focus on simple, hand-driven devices for point-of-care or biological laboratories with low or limited equipment and resources. A new technology, termed “sliding walls,” has been developed for operating microfluidic devices (which function at sub-millimetre scales), whereby rigid or semi-rigid walls, hundreds of micrometres thick, slide within a microfluidic chip. Fluid control in micro-devices is currently achieved largely by expensive, bulky external valves and pumps or by valves integrated in the chip. Such internal valves or actuation methods generally have shortcomings related to performance and complex fabrication. A team headed by Stephanie Descroix and Jean-Louis Viovy at the Institut Curie—Institut Pierre Gilles de Gennes, Paris applied its sliding wall technique and was able to execute several fluidic operations in which channels could be blocked or reconfigured through the sliding wall geometry. The authors believe that their technology has the potential for various microfluidic operations in biological laboratories with limited equipment and resources.

s In vitro models, cell culture models, microtissue, organ-on-a-chip, microfabrication, micropumps, membrane, manufacturing, filtration, vascularization, perfusion, microfluidics, channels, cleanroom, silicon, glass, polydimethylsiloxane, additive manufacturing, bioprinting, bioprinter, three-dimensional printing, bioreactor, stimulation, biointerfaces, scaffold, barrier, junction, sterilization, biodegradable, polymers, functionalization, hydrogels, coatings, etching, photolithography, microinjection, fluid control, automation, disposable, autoclavable, media exchange, sampling, pipetting, viscous drag pump, peristaltic pump, capillary pump, valves, bubble traps, flow sensor, pressure sensor, noninvasive monitoring, oxygen sensor, pH sensor, mechanotransduction, shear stress, compression, tensile stress, gauge sensor, TEER, electrochemical sensor, biosensor, calibration, immunosensor, ion-sensitive field-effect transistor, electrical impedance spectroscopy, label-free sensor, lactate sensor, glucose sensor, temperature sensor.

International audience; Tumor initiation and growth is associated with significant changes in the surrounding tissue. During carcinoma progression, a global stiffening of the extracellular matrix is observed and is interpreted as a signature of aggressive invasive tumors. However, it is still unknown whether this increase in matrix rigidity promotes invasion and whether this effect is constant along the course of invasion. Here we have developed a biomimetic in vitro assay that enabled us to address the question of the importance of tissue rigidity in the chronology of tumor invasion. Using low concentrations of the sugar threose, we can effectively stiffen reconstituted collagen I matrices and control the stiffening in time with no direct effect on residing cells. Our findings demonstrate that, depending on the timing of its stiffening, the extracellular matrix could either inhibit or promote cancer cell invasion and subsequent me-tastasis: while matrix stiffening after the onset of invasion promotes cancer cell migration and tumor spreading, stiff matrices encapsulate the tumor at an early stage and prevent cancer cell invasion. Our study suggests that adding a temporal dimension in in vitro models to analyze biological processes in four dimensions is necessary to fully capture their complexity.

International audience; We report here a simple yet robust transient compartmentalization system for microfluidic platforms. Cylindrical microfilaments made of commercially available fishing lines are embedded in a microfluidic chamber and employed as removable walls, dividing the chamber into several compartments. These partitions allow tight sealing for hours, and can be removed at any time by longitudinal sliding with minimal hydrodynamic perturbation. This allows the easy implementation of various functions, previously impossible or requiring more complex instrumentation. In this study, we demonstrate the applications of our strategy, firstly to trigger chemical diffusion, then to make surface co-coating or cell co-culture on a two-dimensional substrate, and finally to form multiple cell-laden hydrogel compartments for three-dimensional cell co-culture in a microfluidic device. This technology provides easy and low-cost solutions, without the use of pneumatic valves or external equipment, for constructing well-controlled microenvironments for biochemical and cellular assays.

International audience; Organoids are widely used as a model system to study gut pathophysiology; however, they fail to fully reproduce the complex, multi-component structure of the intestinal wall. We present here a new gut on chip model that allows the co-culture of primary epithelial and stromal cells. The device has the topography and dimensions of the mouse gut and is based on a 3D collagen I scaffold. The scaffold is coated with a thin layer of laminin to mimic the basement membrane. To maintain the scaffold structure while preserving its cytocompatibility, the collagen scaffold was rigidified by threose-based postpolymerization treatment. This treatment being cytocompatible enabled the incorporation of primary intestinal fibroblasts inside the scaffold, reproducing the gut stromal compartment. We observed that mouse organoids, when deposited into crypts, opened up and epithelialized the scaffold, generating a polarized epithelial monolayer. Proper segregation of dividing and differentiated cells along the crypt-villus axis was achieved under these conditions. Finally, we show that the application of fluid shear stress allows the long-term culture of this intestinal epithelium. Our device represents a new biomimetic tool that captures key features of the gut complexity and could be used to study gut pathophysiology.