Lab on a Chip最新文献

Ensuring caprock integrity is essential for maintaining long-term containment security in geological carbon dioxide (CO₂) storage. Fracture networks of caprocks act as leakage pathways for stored CO₂. Interactions between brine and CO₂ trigger salt precipitation within fractures, potentially sealing fractures to restrict further leakage. The mechanisms governing salt precipitation in structurally diverse fractures remain poorly understood at the pore-scale. We employed microfluidics to examine the effects of the fracture geometry, CO₂ phase, and brine composition on salt precipitation, aggregation, and migration. The fracture geometry influences salt dynamics, with salt coverage 1.6- and 3.3-fold that of the unfractured model in discrete and interconnected models, respectively. The brine composition alters salt aggregation behavior: CaCl₂ brine yields larger, more stable precipitated salt, resulting in up to ∼51% greater salt coverage than NaCl. The CO₂ phase exerts dominant control—supercritical carbon dioxide (scCO₂) displacement enhances NaCl precipitation by ∼683% compared with gas-phase CO₂, due to improved brine film retention and evaporation. The brine film reaccumulation mechanism under scCO₂ displacement further suppresses salt migration, sustaining salt aggregation in interconnected fractures. Our findings offer fundamental insights into salt sealing and migration in multiscale porous media, with vital influence on leakage risk assessment and injectivity control in geological CO₂ storage.

Emerging non-viral gene delivery platforms provide alternatives to viral methods. However, they remain limited in scalability and efficiency for clinical translation. We present a fractal-shaped droplet microfluidic system that achieves approximately 98% efficiency and 80% viability at throughputs exceeding 10⁷ cells per min, enabling efficient, large-scale, and clinically relevant cell engineering.

Salivary glucose monitoring provides a non-invasive alternative to blood-based diabetes tests; however, low analyte levels and unstable microfluidic wetting have hindered its translation. Here, we introduce a retainer-based microfluidic system that integrates a capillary-driven, superhydrophilic microchannel with a miniaturized three-electrode enzymatic sensor for continuous salivary glucose monitoring. This device maintains sustained hydrophilicity for at least 120 days without compromising flexibility or biocompatibility. The gold working electrode, functionalized with glucose oxidase immobilized in a carbon nanotube–chitosan matrix and a thin glutaraldehyde overlayer, offers sensitive and stable detection. The integrated sensor shows a chronoamperometric sensitivity of 15.48 μA mM⁻¹ cm⁻² and a limit of detection of <42 μM. The in vitro measurements using glucose-spiked artificial saliva show the reproduced postprandial profiles with rapid signal stabilization and high run-to-run repeatability over three cycles. Overall, this work captures the potential of the retainer-based microfluidic system as a practical pathway toward continuous, non-invasive salivary glucose monitoring.

Correction for ‘Sequential trench well based microfluidic platform to isolate bacteria from whole blood with large volume processing’ by Cheonggyu Lee et al., Lab Chip, 2025, 25, 6650–6661, https://doi.org/10.1039/d5lc00931f.

We fabricated a double-cylinder micro-chamber (DCMiC) platform using stereolithography-printed master molds, followed by PDMS replica molding and integration into a 96-well plate format for scalable and reproducible generation of Ewing sarcoma spheroids. The simple yet novel DCMiC design stabilizes spheroids during media exchange, enabling reliable long-term culture and high-throughput drug screening. Using this platform, we screened 11 small-molecule compounds previously shown to target vulnerabilities relevant to Ewing sarcoma, including epigenetic regulators, DNA damage response, growth signaling and metabolic pathways. As a result, we identified Torin 2, talazoparib, and trabectedin as top 3 candidates with potent anti-Ewing sarcoma activity. To more accurately model the metastatic tumor microenvironment, we incorporated human lung fibroblasts to generate heterotypic spheroids, which consistently conferred resistance to all 3 compounds. Transcriptomic profiling revealed that fibroblasts reprogram Ewing sarcoma cells by activating pro-survival NFκB and TGF-β1/SMAD signaling while repressing tumor-suppressive programs, highlighting how stromal cues promote therapy resistance. Mechanistically, exogenous TGF-β1 was sufficient to induce resistance in tumor-only spheroids, whereas pharmacological inhibition of TGF-β1 signaling restored drug sensitivity in heterotypic spheroids. These findings establish the DCMiC platform as a low-cost, physiologically relevant system for modeling tumor–stroma interactions and enabling scalable drug discovery in clinically relevant contexts for Ewing sarcoma and other solid tumors.

An online, micro free-flow electrophoresis (μFFE) assay was developed for the real-time measurement of insulin in a continuous, competitive immunoassay. Fluorescently labeled insulin and anti-insulin monoclonal antibody were mixed with the sample stream online and flowed through an incubation capillary into the μFFE device. Under an electric field, the bound antibody : insulin-FITC complex was separated from free insulin-FITC. When unlabeled insulin was introduced, labeled and unlabeled insulin competed for binding sites on the antibody, and the separated peaks of the bound complex and free insulin-FITC responded in real-time. Temporal resolution of 30 seconds was achieved following injections of unlabeled insulin, with a limit of detection of 63 nM and a linear response over the tested range of 50 nM to 1 μM insulin. The development of this assay supports the eventual integration of an organ-on-a-chip system capable of measuring direct cellular efflux in tandem with the affinity μFFE detection system. To approximate such an online cellular response, glucose-stimulated insulin secretion was collected offline from human islets and injected into the affinity μFFE instrument. A measurable change in insulin secretion was observed between samples exposed to low and high glucose, demonstrating sufficient limit of detection, linearity, the compatibility of the instrument with a complex biological matrix.

In the field of nano-fluidics, the generation and manipulation of minuscule droplets with volumes ranging from attoliters (aL) to femtoliters (fL) represents a crucial frontier. Such ultrasmall droplets exhibit immense potential in single-molecule detection, targeted drug delivery, and fundamental research into nanoscale biochemical processes, owing to their unique physicochemical properties, such as low Reynolds number flow and interface-dominated mass transport. Furthermore, ordered liquid-patterned arrays hold promise for applications in optically tunable nano-lenses. However, generation and manipulation of attoliter-scale droplets have long posed significant challenges, particularly for open-interface operations like dispensing, merging, splitting, and patterning into arrays. This study introduces acoustic nano-scissors generated by lateral modes of high-frequency bulk acoustic waves. The induced acoustofluidic effect in thin liquid films forms shear forces between the adjacent wave peaks and wave valleys, thereby successfully cutting the liquid into attoliter-scale droplets at an open interface. This approach could produce droplets with volumes more than three orders of magnitude smaller than those from existing acoustic solutions. Furthermore, the acoustic nano-scissors could generate ordered attoliter droplet arrays with specific patterns, with fast droplet splitting and merging controlled by switching on and off the device. This work provides a novel and flexible solution for various applications requiring attoliter droplet arrays on open interfaces.

Three-dimensional (3D) cell cultures offer superior potential in replicating native tissue microenvironments by better supporting cell–cell and cell–extracellular matrix (ECM) interactions that are critical for guiding cellular behavior and functionality in engineered tissues. Among 3D approaches, scaffold-free techniques have gained attention for their ability to produce high-cellular density, and well-organized tissue-like constructs. In particular, cell sheets are uniquely suited for regenerative applications due to their contiguous architecture, large-area coverage, and integration potential with host tissues. However, current biofabrication methods for cell sheet production often require altering culture conditions (e.g., temperature, pH) or applying external stimuli (e.g., magnetic or electrical fields), which can damage cells, compromise sheet integrity, or demand costly, non-adaptable equipment. Here, we present a rapid, self-assembly-based technique using unmodified polydimethylsiloxane (PDMS) molds as culture vessels. When seeded at a critical cell density, adherent cells spontaneously self-assemble into planar 3D cell sheets within 6 hours, without substrate modification or specialized equipment. Our qRT-PCR analysis revealed significant upregulation of E-cadherin in cell sheets, confirming that cell–cell adhesion, rather than cell-substrate anchorage, drives sheet formation. We showed that our technique is versatile, supporting the creation of large-area and patterned sheets, stacked multi-layer constructs, and co-culture configurations. Notably, fibroblast cell sheets, demonstrated progressive ECM production, with histological analysis confirming collagen deposition over time. Overall, our approach preserves cell viability and function while offering a simple, rapid, and cost-effective alternative to conventional methods for fabricating cell sheets. This platform holds broad potential for applications in tissue engineering, regenerative medicine, disease modeling, and cultivated meat production.

This study introduces a human-relevant in vitro model using iPSC-derived sensory neurons and keratinocytes in MEA-integrated microfluidic chips. Neurons expressed nociceptor markers, showed TRPV activity, and formed contacts with keratinocytes. Stimuli evoked electrophysiological responses, highlighting neuron–keratinocyte interactions relevant to pruritus, pain, and skin disorders, supporting therapeutic development.

Microfluidic immunoassays are crucial for early detection and capture of circulating tumor cells (CTCs). The method of immobilizing functional receptors, such as antibodies (Abs), plays a critical role in determining the effectiveness of these systems. In this study, we present a microfluidic channel functionalized with boronic acids to facilitate the directed immobilization of native Abs, thereby improving their interaction with target antigens and cells. We evaluated the selectivity and efficiency of CTC capture using the anti-epithelial cell adhesion molecule (EpCAM) as the capture Ab. Using EpCAM-positive PC-9 human pulmonary adenocarcinoma cells and EpCAM-negative HeLa cervical cancer cells as models, our comparisons revealed that oriented Ab immobilization through covalent boronate formation resulted in approximately 5.2 times more PC-9 cell capture compared to random covalent Ab immobilization. Additionally, directional Ab immobilization demonstrated a roughly 30.8-fold increase in selectivity for EpCAM-expressing CTCs. This versatile Ab immobilization platform offers a promising approach for selective cell capture under dynamic flow conditions.