Lab on a Chip最新文献

Rare cell heterogeneity significantly impacts diagnosis, prognosis, therapeutic options and responses, particularly in diverse diseases like cancer. While single-cell analysis is the most effective route, isolating cells individually with high selectivity, purity, efficiency and throughput remains a major challenge. Thus, we present a unified platform coined “SC-DEPOT” to perform all analytical steps from selective isolation from a mixture of cells to parallel single-cell analysis. The platform integrates three sequential modules – one hydrodynamic and two DEP-based – to independently execute distinct and complementary functions. First, the hydrodynamic module focuses all cells towards the channel centerline. Then by DEP, slanted interdigitated electrodes selectively redirect target cells to the channel walls, where they are finally captured in cell-sized micropockets by insulator-based DEP (iDEP). This final stage builds on our previously reported iDEP device, which isolates cells in nanoliter-scale chambers – which are addressed by “wireless” bipolar electrodes (BPEs) – to facilitate individual analysis. The added two preceding steps enhance sample purity to 96% and enable an eightfold increase in channel width compared to a previous limitation of 100 μm. This result is important because it yields an eight-fold to sixteen-fold enhancement in volumetric throughput for samples comprising a mixture of cell types or only one cell type, respectively. The final iDEP module isolates single cells at 94% efficiency and transfers them into the sealable chambers at 92% efficiency. This combination of high throughput and gentle, extended capture from highly concentrated backgrounds expands the utility of the SC-DEPOT device in clinical workflows.

Lipid nanocarriers utilise the self-assembly of amphiphilic molecules to generate particle formulations capable of drug encapsulation and dynamic interactions with user-defined cell types, enabling applications within targeted therapeutic delivery. This offers increased bioavailability, stability, and reduced off-target effects, with the promise of application to numerous cell types and consequently, diseases. Here, we have developed a highly accessible, cleanroom-free method for the fabrication of poly(methyl methacrylate) millifluidic vertical flow focusing (VFF) devices via laser cutting, multilayered solvent and heat-assisted bonding. We demonstrate that these can be used for one-step production of targeted lipid nanocarriers via the production of cardiomyocyte-targeting vesicle nanoparticles loaded with the hydrophobic drug menadione. We characterise vesicle size using dynamic light scattering (DLS) and cryogenic transmission electron microscopy (cryo-TEM), whilst also probing the membrane viscosity of vesicles produced via flow-focusing for the first time using molecular rotors. Finally, we apply cardiomyocyte-targeting, menadione-loaded vesicles to H9C2 tissue culture demonstrating significant inhibition of cell viability via targeted delivery, showcasing the potential of our device to produce formulations for therapeutic delivery. As a flow-based method, VFF can facilitate rapid formulation investigation and produce large sample volumes for cell-based validation studies, whilst avoiding inter-batch sample variation. Furthermore, the accessible nature of this VFF approach will help to democratise millifluidics, facilitating the wider adoption of flow-based production methods to develop nanomedical formulations.

During their 120-day circulatory lifespan, red blood cells (RBCs) undergo repeated mechanical deformation as they traverse microcapillaries and splenic inter-endothelial slits (IES). This cyclic mechanical loading gradually impairs RBC deformability, ultimately leading to their clearance by the spleen. However, current platforms for investigating RBC fatigue often couple mechanical loading with real-time observation, which obscures the cumulative impact of cyclic strain. To address this limitation, we developed an integrated microfluidic chip equipped with a dedicated “S”-shaped fatigue zone–each RBC experiences hundreds of extrusion events during a single continuous pass through this zone–followed by a physically decoupled observation zone. This design enables clear separation of fatigue induction from biomechanical evaluation. Our findings show that cyclic extrusion drives a progressive morphological transition in the RBC population from discocytes to echinocytes and spherocytes, along with reduced cell volume and surface area, increased membrane shear modulus, and elevated sphericity. Combined experiments and simulations reveal that the passage of spherocytes depends not only on their deformability but also critically on the relative size of the cells versus the channel dimensions. Furthermore, simulations of splenic filtration identify the sphericity index–not membrane stiffness–as the primary geometric factor governing RBC retention in IES. This work presents a high-throughput, label-free platform that disentangles RBC fatigue induction from post-fatigue analysis. It provides mechanistic insights into how repetitive mechanical stress regulates RBC aging and clearance, offering a valuable tool for advancing our understanding of RBC physiology in health and disease.

The human sweating rate reflects body hydration status and holds intrinsic significance for monitoring physiological health. This work presents a fully printed sweat rate sensor architecture, where the internal sensing layer is fabricated via aerosol jet printing at micrometer resolution to detect nanoliter-scale sweat volume changes in microfluidic channels. The sensor transduces internal microstructural variations into radiofrequency (RF) signals through energy coupling, enabling wireless transmission to external terminals. Leveraging the RF sensor's wireless compatibility, a pulse wave sensor for monitoring physiological changes is integrated into the system. This allows simultaneous operation with the sweat rate sensor without wired connections, ultimately forming a wireless and battery-free wearable patch suitable for detecting the skin sweating rate and heart rate during human activities. By analyzing the patch's wireless signals and extracting parameters including resonant frequency and amplitude, we develop a dual-mode sensing patch. The system evaluates the effects of daily activities like resting, walking, exercising and environmental factors like temperature on skin perspiration and heart rate. In addition, the fully printed technology adopted in this work provides ideas for the lightweight and low-cost development of wearable sweat sensing systems.

The reduced effectiveness of chemotherapy in many patients undergoing treatment highlights the need for novel drug combinations that target drug resistance mechanisms contributing to tumor survival. Dynamic conditions within the tumor microenvironment influence the response to anti-cancer drugs. Accordingly, identifying effective drug concentrations and interactions (additive, synergistic, or antagonistic) in relevant tumor tissue models will inform new treatment combinations. To address this need for combinatorial chemotherapeutic (CTx) screening assays, we have developed a new assay called CombiCTx, which uses a device with three reservoirs containing gels loaded with anti-cancer drugs. The drug-loaded device is inverted and placed in a standard culture dish above cancer cells, and both are then enclosed in gel. Drugs diffuse from the reservoirs and expose cancer cells to overlapping dynamic drug gradients. We imaged diffusion of the anti-cancer drug doxorubicin in the assay using time-lapse microscopy, and established an imaging protocol for quantifying MDA-MB-231 breast cancer cell survival responses along drug gradients. Finally, evaluating combination effects of navitoclax and gemcitabine with CombiCTx revealed localized effects of navitoclax, attributed to limited diffusion, while gemcitabine seemed to diffuse readily throughout the assay and revealed a mild synergy in navitoclax affected regions. These data demonstrate the capacity of CombiCTx to evaluate the cytotoxic effects of anti-cancer drug combinations while accounting for drug diffusion differences, which is relevant in the context of the 3D tumor environment and may thereby help inform clinical treatment strategies.

Small-scale fires in confined spaces represent critical precursors to catastrophic disasters, making their early suppression essential for safeguarding lives and property. However, at present, fire extinguishing systems used in confined space still suffer from several limitations, such as large physical scale, the absence of real-time temperature monitoring, delayed release of the extinguishing agent and early efficient fire extinguishing ability. These shortcomings seriously hinder the timely prevention of early fire and restrict the choice of appropriate post-fire management strategies. To overcome these challenges, we have developed an integrated fire extinguishing system based on high-performance composite microcapsules. This miniaturized system integrates real-time wireless monitoring, early warning, rapid fire extinguishing and cooling capacity at the initial stage of fire. The system consists of three core components: a mounting assembly supporting flexible installation, a fire suppression module composed of two-dimensional microcapsule patches, and a temperature-sensing unit for continuous environmental monitoring. The microcapsule patches, thermally triggered to release fire-extinguishing agents, exhibit high extinguishing efficiency and rapid cooling, thereby enabling proactive fire containment in confined spaces. The sensing module provides real-time thermal surveillance with wireless data transmission to remote terminals. Importantly, the temperature monitoring and early-warning system operates independently of the extinguishing agent release to ensure there is no delay in suppression. Experimental validation confirms the system's efficacy in rapid fire suppression, ambient cooling, and intelligent early warning, offering an innovative solution for confined space fire risk mitigation.

Digital microfluidic devices enable parallel, quantitative and flexible handling of discrete droplets via electrowetting on dielectric (EWOD) force. However, droplet splitting behavior in conventional digital microfluidic devices is limited by the geometry of actuating electrodes. In this study, we proposed a gravity-induced size-tuning splitting (GITS) method, which has no requirements for specialized electrodes or complicated chip configurations. Both experimental and simulation results demonstrated that gravity facilitates the droplet generation by directionally enhancing the EWOD force in a vertical digital microfluidic chip. Further observation revealed that the size tunability was affected by the droplet volume, voltage amplitude, and especially contact line ratios between droplet and electrodes. Moreover, to achieve reliable on-chip operations, the critical size of the droplet for passive dropping was investigated, which exhibited a functional relationship with the gap height. Then GITS was implemented by integrating an artificial intelligence (AI)-driven feedback control of the contact line and the gravity induced droplet dropping. As a result, it achieved wide splitting ratios from 1 to 7.33, with the coefficient of variation below 3%. Finally, GITS was applied to manage reagents of various sizes for on-chip cell viability assays, demonstrating its potential for flexible reagent configuration in future biomedical applications.