PIEZO-dependent mechanosensing is essential for intestinal stem cell fate decision and maintenance.

Stem cells perceive and respond to biochemical and physical signals to maintain homeostasis. Yet, it remains unclear how stem cells sense mechanical signals from their niche in vivo. In this work, we investigated the roles of PIEZO mechanosensitive channels in the intestinal stem cell (ISC) niche.

Intercellular fluid dynamics in tissue morphogenesis.

During embryonic development, cells shape our body, which is mostly made up of water. It is often forgotten that some of this water is found in intercellular fluid, which, for example, immerses the cells of developing embryos. Intercellular fluid contributes to the properties of tissues and influences cell behaviour, thereby participating in tissue morphogenesis.

Decoupling shear stress and pressure effects in the biomechanics of autosomal dominant polycystic kidney disease using a perfused kidney-on-chip.

Kidney tubular cells are submitted to two distinct mechanical forces generated by the urine flow: shear stress and hydrostatic pressure. In addition, the mechanical properties of the surrounding extracellular matrix modulate tubule deformation under constraints. These mechanical factors likely play a role in the pathophysiology of kidney diseases as exemplified by autosomal dominant polycystic kidney disease, in which pressure, flow and matrix stiffness have been proposed to modulate the cystic dilation of tubules with mutations.

Acoustic detection of a mutation-specific Ligase Chain Reaction based on liposome amplification.

Single nucleotide variants (SNVs) play a crucial role in understanding genetic diseases, cancer development, and personalized medicine. However, existing ligase-based amplification and detection techniques, such as Rolling Circle Amplification and Ligase Detection Reaction, suffer from low efficiency and difficulties in product detection. To address these limitations, we propose a novel approach that combines Ligase Chain Reaction (LCR) with acoustic detection using highly dissipative liposomes.

Magnetic Microtweezers for High-Throughput Bioseparation in Sub-Nanoliter Droplets.

Multiomics studies at single-cell level require small volume manipulation, high throughput analysis, and multiplexed detection, characteristics that droplet microfluidics can tackle. However, the initial step of molecule bioseparation remains challenging. Here, we describe a unique magnetic device to trap and extract magnetic particles in sub-nanoliter droplets, for compartmentalisation of detection steps.

On-Chip Magnetic Extraction of Circulating Cell-Free DNA from Biological Samples.

In recent years, the analysis of circulating cell-free DNA (cfDNA) containing tumor-derived DNA has emerged as a noninvasive means for cancer monitoring and personalized medicine. However, the isolation of cfDNA from peripheral blood has remained a challenge due to the low abundance and high fragmentation of these molecules. Here, we present a dynamic Magnetic ExTRactiOn (METRO) protocol using microfluidic fluidized bed technology to isolate circulating cfDNA from raw biological materials such as undiluted serum.

Assessing personalized responses to anti-PD-1 treatment using patient-derived lung tumor-on-chip.

There is a compelling need for approaches to predict the efficacy of immunotherapy drugs. Tumor-on-chip technology exploits microfluidics to generate 3D cell co-cultures embedded in hydrogels that recapitulate simplified tumor ecosystems. Here, we present the development and validation of lung tumor-on-chip platforms to quickly and precisely measure ex vivo the effects of immune checkpoint inhibitors on T cell-mediated cancer cell death by exploiting the power of live imaging and advanced image analysis algorithms.

A continuum model for magnetic particle flows in microfluidics applicable from dilute to packed suspensions.

The manipulation of magnetic microparticles has always been pivotal in the development of microfluidic devices, as it encompasses a broad range of applications, such as drug delivery, bioanalysis, on-chip diagnostics, and more recently organ-on-chip development. However, predicting the behavior and trajectory of these particles remains a recurring and partly unresolved question. Magnetic particle-laden flows can display intricate collective behaviors, such as packed plugs, column-shaped aggregates, or fluidization, which are difficult to predict.

Multiomic Droplet-Based Assay for Ultralow Input Samples.

The extraction and separation of cellular compounds are crucial steps in numerous biological protocols, particularly in multiomics studies, where several cellular modalities are examined simultaneously. While magnetic particle extraction is commonly used, it may not be applicable for ultralow input samples. Microfluidics has made possible the analysis of rare or low-materiality samples such as circulating tumor cells or single cells through miniaturization of numerous protocols.

Tunnelling nanotube formation is driven by Eps8/IRSp53-dependent linear actin polymerization.

Tunnelling nanotubes (TNTs) connect distant cells and mediate cargo transfer for intercellular communication in physiological and pathological contexts. How cells generate these actin-mediated protrusions to span lengths beyond those attainable by canonical filopodia remains unknown. Through a combination of micropatterning, microscopy, and optical tweezer-based approaches, we demonstrate that TNTs formed through the outward extension of actin achieve distances greater than the mean length of filopodia and that branched Arp2/3-dependent pathways attenuate the extent to which actin polymerizes in nanotubes, thus limiting their occurrence.

Cancer-associated fibroblasts actively compress cancer cells and modulate mechanotransduction.

During tumor progression, cancer-associated fibroblasts (CAFs) accumulate in tumors and produce an excessive extracellular matrix (ECM), forming a capsule that enwraps cancer cells. This capsule acts as a barrier that restricts tumor growth leading to the buildup of intratumoral pressure. Combining genetic and physical manipulations in vivo with microfabrication and force measurements in vitro, we found that the CAFs capsule is not a passive barrier but instead actively compresses cancer cells using actomyosin contractility.

High-throughput extraction on a dynamic solid phase for low-abundance biomarker isolation from biological samples.

Liquid biopsy, in particular circulating tumor DNA (ctDNA) analysis, has paved the way for a new noninvasive approach to cancer diagnosis, treatment selection and follow-up. As a crucial step in the analysis, the extraction of the genetic material from a complex matrix needs to meet specific requirements such as high specificity and low loss of target. Here, we developed a new generation of microfluidic fluidized beds (FBs) that enable the efficient extraction and preconcentration of specific ctDNA sequences from human serum with flow rates up to 15 µL/min.

Construction of a Multitubular Perfusable Kidney-on-Chip for the Study of Renal Diseases.

The organ-on-chip model offers versatility and modularity of in vitro models while approaching the biological fidelity of in vivo models. We propose a method to build a perfusable kidney-on-chip aiming at reproducing key features of the densely packed segments of nephrons in vitro; such as their geometry, their extracellular matrix, and their mechanical properties. The core of the chip is made of parallel tubular channels molded into collagen I that are as small as 80 μm in diameter and as close as 100 μm apart.

On-line dual-stage enrichment via magneto-extraction and electrokinetic preconcentration: A new concept and instrumentation for capillary electrophoresis.

This study reports on the development of a new concept of on-line dual preconcentration stages for capillary electrophoresis (CE), in which two completely different preconcentration approaches can be realized in the same capillary. In the first stage, a dynamic magneto-extraction of target analytes on circulating magnetic beads is implemented within the capillary. In the second one, electrokinetic preconcentration of eluted analytes via large volume sample stacking is carried out to focus them into a nano band, prior to CE separation of enriched analytes.

Correction: Developing an advanced gut on chip model enabling the study of epithelial cell/fibroblast interactions.

Correction for 'Developing an advanced gut on chip model enabling the study of epithelial cell/fibroblast interactions' by Marine Verhulsel , , 2021, , 365-377, https://doi.org/10.1039/d0lc00672f.

Correction to 'Mathematical modelling of oxygen transport in a muscle-on-chip device' (2022) by Hardman .

[This corrects the article DOI: 10.1098/rsfs.2022.

Precise and fast control of the dissolved oxygen level for tumor-on-chip.

cell cultures are most often performed in unphysiological hyperoxia since the oxygen partial pressure of conventional incubators is set at 141 mmHg (18.6%, close to ambient air oxygen 20.1%).

Mathematical modelling of oxygen transport in a muscle-on-chip device.

Muscle-on-chip devices aim to recapitulate the physiological characteristics of muscle tissue and so maintaining levels of oxygen transported to cells is essential for cell survival and for providing the normoxic conditions experienced . We use finite-element method numerical modelling to describe oxygen transport and reaction in a proposed three-dimensional muscle-on-chip bioreactor with embedded channels for muscle cells and growth medium. We determine the feasibility of ensuring adequate oxygen for muscle cell survival in a device sealed from external oxygen sources and perfused via medium channels.

Direct imaging and automatic analysis in tumor-on-chip reveal cooperative antitumoral activity of immune cells and oncolytic vaccinia virus.

Organ-on-chip and tumor-on-chip microfluidic cell cultures represent a fast-growing research field for modelling organ functions and diseases, for drug development, and for promising applications in personalized medicine. Still, one of the bottlenecks of this technology is the analysis of the huge amount of bio-images acquired in these dynamic 3D microenvironments, a task that we propose to achieve by exploiting the interdisciplinary contributions of computer science and electronic engineering. In this work, we apply this strategy to the study of oncolytic vaccinia virus (OVV), an emerging agent in cancer immunotherapy.

Modular microfluidic system for on-chip extraction, preconcentration and detection of the cytokine biomarker IL-6 in biofluid.

The cytokine interleukin 6 (IL-6) is involved in the pathogenesis of different inflammatory diseases, including cancer, and its monitoring could help diagnosis, prognosis of relapse-free survival and recurrence. Here, we report an innovative microfluidic approach that uses the fluidization of magnetic beads to specifically extract, preconcentrate and fluorescently detect IL-6 directly on-chip. We assess how the physical properties of the beads can be tuned to improve assay performance by enhancing mass transport, reduce non-specific binding and multiply the detection signal threefold by transitioning between packed and fluidization states.

Deciphering HER2-HER3 Dimerization at the Single CTC Level: A Microfluidic Approach.

Microfluidics has provided clinicians with new technologies to detect and analyze circulating tumor biomarkers in order to further improve their understanding of disease mechanism, as well as to improve patient management. Among these different biomarkers, circulating tumor cells have proven to be of high interest for different types of cancer and in particular for breast cancer. Here we focus our attention on a breast cancer subtype referred as HER2-positive breast cancer, this cancer being associated with an amplification of HER2 protein at the plasma membrane of cancer cells.

A Multitubular Kidney-on-Chip to Decipher Pathophysiological Mechanisms in Renal Cystic Diseases.

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a major renal pathology provoked by the deletion of or genes leading to local renal tubule dilation followed by the formation of numerous cysts, ending up with renal failure in adulthood. , renal tubules are tightly packed, so that dilating tubules and expanding cysts may have mechanical influence on adjacent tubules. To decipher the role of this coupling between adjacent tubules, we developed a kidney-on-chip reproducing parallel networks of tightly packed tubes.