Lab on a Chip最新文献

Organ-on-a-chip systems provide invaluable preclinical insights into disease simulation, mechanism investigation and drug screening. By closely simulating the physiological conditions of human organs, these platforms enhance our understanding of complex biological processes. Here, we applied a leaf vein microfluidic chip as a controllable, endothelialized in vitro platform to investigate how hierarchical flow distribution and uniform shear influence tumor cell migration and behavior within a bone-mimetic microenvironment as a model demonstration. The hierarchical leaf vein architecture, resembling mammalian blood vessels, enables mechanistic studies of spatial distribution and migration under physiologically relevant conditions. Additionally, the system incorporates specialized chambers embedded with 3D hydrogel containing human umbilical vein endothelial cells (HUVECs) and bone stromal cells (HS-5) as the dormancy niche, and HUVECs and osteoclast precursor cells (THP-1) as the "vicious cycle" niche. These chambers serve as a demonstration of bone-mimetic units for examining specific microenvironmental responses. These bone microenvironments were modified by conditioned medium (CM) from primary tumor cells, facilitating their roles as the bone pre-metastatic niche. Cell morphology of lung cancer cells (A549) was observed throughout the dynamic culture process. Perfused medium and hydrogels were harvested to investigate the potential mechanisms. For the dormancy niche, the upregulation of angiogenin, MIP-3α, Wnt-5a, and TGF-β2 and the downregulation of CCL7 indicated that tumor-secreted factors may reactivate dormant tumor cells by activating angiogenesis, pro-inflammatory, and epithelial-mesenchymal transition related pathways. These changes in OPN and BMP-1 expression suggested potential involvement in bone microenvironment remodeling which were inferred from cytokine and gene expression profiles. For the "vicious cycle" niche, the upregulation of CCL5, CXCL5 and VCAM-1 may be associated with the recruitment of leukocytes and promotion of tumor invasion, based on cytokine profiling. These cytokines can serve as potential biomarkers for assessing disease progression or providing a basis for developing new targeted therapies. Taken together, the successful construction and application of this leaf vein chip establish a versatile, mechanistically tractable platform for future drug screening, pathological analysis, and microenvironment-targeted strategies relevant to bone metastasis.

Superhydrophobic surfaces are widely investigated in microfluidics for drag reduction; however, their role in transporting viscoplastic biological fluids such as blood, mucus, and hydrogels remains poorly understood. Here, high-resolution two-phase simulations are performed to investigate pressure-driven viscoplastic flow in superhydrophobic grooved microchannels, focusing on three critical design indices: liquid/air interface pinning, central unyielded-plug breakage, and pressure-drop reduction. Groove geometry and flow inertia, represented by the Reynolds number, jointly determine whether the liquid/air interface remains pinned in the Cassie state or undergoes depinning, and a correlation is derived to predict this transition. For identical groove aspect ratios, the critical Reynolds number for depinning is markedly lower in thinner microchannels. Groove depth and width strongly influence plug deformation and breakage. Additional correlations quantify pressure drop and plug breakage, and the resulting predictive design map enables the optimization of superhydrophobic microchannels for lab-on-a-chip devices handling viscoplastic fluids.

Culturing neuronal networks in vitro is a tedious and time-consuming endeavor. In addition, how the composition of the culture medium and environmental variables such as temperature, osmolarity, and pH affect the spiking behavior of neuronal cultures is difficult to study using electrophysiology. In this work, we present "inkube", an incubation system that has been combined with an electrophysiology setup and a fully automatic perfusion system. This setup allows for the precise measurement and control of the temperature of up to 4 microelectrode arrays (MEAs) in parallel. In addition, neuronal activity can be electrically induced and recorded from the MEAs. Inkube can continuously monitor the medium level to automatically readjust osmolarity. Using inkube's unique capability to precisely control the environmental variables of a neural culture, we found that medium evaporation influences the spiking response. Moreover, decreasing medium temperature by only 1.5 °C significantly affected spike latency, a measure commonly used to show plasticity in in vitro experiments. We finally provide a proof-of-concept experiment for drug screening applications, where inkube automatically and precisely varies the concentration of magnesium ions in the medium. Given its high level of autonomy, the system can record, stimulate, and control the medium continuously without user intervention. Both the hardware and the software of inkube are completely open-source.