Lab on a Chip最新文献

3D printing is reshaping droplet microfluidics by converting digital designs into sealed, volumetric devices that integrate non-planar droplet generators and junctions, as well as embedded distributors. This Critical Review distills design rules that link geometry, key dimensionless groups (Ca, φ, λ), and wetting control to the robust production of single and multiple emulsions. We compare 3D printing modalities using criteria specific to droplet microfluidics, attainable feature size, optical clarity, chemical resistance, surface roughness, native wettability, and cleanability, and provide practical guidance on material–fluid compatibility, extractables, and long-run stability. We formalize scale-up via hydraulic balancing and unit-resistor strategies that preserve monodispersity across arrays, and outline selective surface treatments and multi-material printing approaches for achieving durable wettability patterns. Finally, we highlight AI/digital-twin workflows for predictive design and adaptive control, and map pathways toward standardized, manufacturable devices. These principles offer a conservative, application-oriented blueprint for 3D-printed droplet microfluidic devices.

Wearable technologies have emerged as powerful tools for non-invasive healthcare monitoring, enabling continuous detection of biomarkers to support personalized medicine and disease management. However, most biological biomarkers stay inside tissue and cannot be accessed on the skin surface through simple contact. Microneedle (MN) technology provides a solution for the wearable technologies to sample biofluid, detect biomarkers, and monitor electrophysiological signals. This article provides a comprehensive overview of the latest development in this field, highlighting MN design principles, functional integration with microfluidics, microelectronics, and artificial intelligence as well as the practical applications. We conclude by discussing the challenges in technical development, clinical validation, industrialization and regulatory compliance, as well as future prospects for MN-integrated wearable devices.

Currently, the CRISPR/Cas12a based sensor has become a powerful tool for gene editing and molecular diagnostics. However, most CRISPR/Cas12a sensors are primarily limited to the detection of a single target type, due to their strict dependence on the specific recognition of the PAM sequence within a precisely designed double-stranded DNA (dsDNA) and crRNA for cleavage activity regulation. Herein, we designed an allosteric key strand (KS) controlled CRISPR/Cas12a biosensor via toehold-based strand displacement reaction (TSDR). By simply reconfiguring KS into different conformations with functional nucleic acid structures, this sensor could selectively respond to various target molecules from nucleic acids to non-nucleic acid molecules without changing the sequence of crRNA and targeted PAM-dsDNA. The trans-cleavage activity of CRISPR/Cas12a could be triggered through leveraging proximity-based TSDR in response to target binding. The proposed sensor achieved sensitive and specific detection of various targets, including nucleic acids (HPV-16), small molecules (kanamycin), and enzymes (uracil-DNA glycosylase). Furthermore, by integrating lateral flow assay technology, this CRISPR/Cas12a-based system enabled point-of-care testing (POCT) for the detection of multiple target types. This approach can overcome the sequence-specific limitations, thereby improving the versatility of CRISPR/Cas12a sensors for extending more target types detection. We anticipate this innovative technology will serve as a flexible and accessible sensing platform, facilitating rapid diagnosis in the field of POCT and enabling its broader application across diverse biotechnological domains.

The on-chip storage of dried reagents is an important technological challenge that must be addressed to improve the capabilities of microfluidic point-of-care (POC) chips. In this work, we investigate the use of poly (lactic-co-glycolic acid) (PLGA) as an encapsulant for the storage and controlled release of dried reagents integrated into disposable thermoplastic microfluidic chips. The PLGA layer allows multiple solid reagent deposits to remain isolated during sample introduction at room temperature and controllably released into the sample volume after heating the chip above a critical threshold temperature. Simple manual pipetting of a PLGA/ethyl acetate solution serves to form a protective PLGA shell encapsulating deposited reagents, with robust sealing between the PLGA and thermoplastic cyclic olefin polymer (COP) substrate preventing reagent leakage during sample introduction. When using a shell thickness below 20 μm to encapsulate nucleic acids as model reagents, over 90% of the deposits are retained following extended aqueous flow, while heating the chip above 40 °C leads to dramatic shrinkage of the PLGA, resulting in delamination of the encapsulating film and rapid reagent release. Using this approach, an on-chip loop-mediated isothermal amplification (LAMP) assay for the detection of methicillin-resistant Staphylococcus aureus (MRSA) is implemented using multiple encapsulated LAMP primer sets integrated directly into an array of on-chip wells. The PLGA encapsulation technique is shown to be a simple and effective method for reagent-integrated microfluidic device manufacturing, offering a new path towards true sample-in, answer-out point-of-care assays.

Hydrodynamic dispersion of solutes is a pivotal phenomenon in microfluidic systems, wherein the axial spreading of various dissolved species—including ions, chemical compounds, biomolecules, dyes, pharmaceuticals, and nanoparticles—occurs due to the coupled effects of molecular diffusion and the non-uniform velocity profiles inherent to confined laminar flows. Given its profound impact on a broad range of applications—spanning analytical, diagnostic, bioengineering, pharmaceutical, environmental, and chemical processing systems—mastering the mechanisms of dispersion is crucial for enhancing separation efficiency, reproducibility, reaction performance, and analytical throughput, while minimizing sample volume, energy consumption, and undesired side effects. This comprehensive review provides a structured synthesis of the fundamental concepts, historical development, and governing mechanisms underlying Taylor–Aris dispersion in micro- and nanofluidic systems. Special emphasis is placed on the role of flow profile design, channel cross-sectional geometry, and surface physicochemical properties in modulating dispersion intensity. Through a systematic analysis of analytical, numerical, and experimental studies conducted from 2000 to 2025, we identify prevailing challenges, unresolved questions, and methodological gaps in the literature. Notably, this work addresses a key void by offering the first coherent classification that concurrently explores the mechanistic origins and engineering control strategies of hydrodynamic dispersion across diverse operating regimes. By bridging classical theories with emerging microfluidic architectures, this article not only deepens the understanding of dispersion phenomena but also lays the foundation for future innovations in colloid and interface science. As such, it provides an essential resource for researchers aiming to optimize transport, separation, and energy conversion processes in advanced fluidic systems.

Although microfluidic-based nanoprecipitation represents a powerful approach for the reproducible fabrication of various nanosized drug carrier systems, industrial translation remains limited. While versatile chip designs implementing advanced mixing elements exist, analytical tools for elucidating the precipitation mechanism, identifying critical process parameters, and monitoring carrier formation within the chip are sparse. Conventional characterization methods used for micromixers, such as tracing fluorescent dyes and/or computational fluid dynamics simulations, provide mostly indirect, often only two-dimensional insight, limiting their predictive value for scale-up and regulatory translation. In this study, a novel toolset combining confocal Raman and confocal fluorescence microscopy, as well as Foerster resonance energy transfer microscopy, was established to monitor solvent fluid dynamics and the in situ self-assembly of liposomes under varying flow conditions within a serpentine micromixer. This integrative approach enabled real-time spatial resolution of nanocarrier formation within the microfluidic device, confirming that vesicle formation predominantly occurs at the interface between the aqueous and ethanolic phases, underscoring the robustness of the setup. Beyond advancing mechanistic insight, the complementary use of two confocal microscopy techniques and a Foerster resonance energy transfer-based method offers a powerful toolset for process optimization and in-process quality control. Coupled with advances in additive manufacturing, this approach paves the way for rational micromixer design and the scalable production of microfluidic nanocarrier-based therapeutics, overcoming limitations and accelerating the industrial large-scale production of nanosized therapeutics.

The diagnosis of heart failure in emergency settings requires rapid and sensitive detection of brain natriuretic peptide (BNP), a low-abundance biomarker of heart failure with a clinical rule-out threshold of 100 pg mL⁻¹ (0.03 nM). The current gold standards for BNP testing in clinical practice all rely on immunoassays that necessitate cold-chain storage for antibodies, limiting their utility at the point-of-care. We now propose an enzyme-free, isothermal amplification strategy employing a dual-aptamer system to measure BNP at clinically relevant levels. Upon simultaneous binding to the target BNP, both of the aptamers release their complementary DNAs, consequently triggering a cyclic amplification reaction. The resulting secondary DNA structures can be detected via a lateral flow test (LFT) format, providing visual readouts close to the patient in 30 min at room temperature. This work advances the field by combining the specificity of aptamers with the simplicity of LFTs, offering the sensitivity of conventional immunoassays while eliminating any enzymatic steps. This work bridges the gap between lab-based immunoassays and POC needs, offering a reliable, equipment-free alternative for heart failure diagnosis in resource-limited settings. Future studies will validate its performance with blood samples for clinical deployment.

Flexible electronics with the features of soft, ultrathin, and shape adaptable properties, are believed as next-generation devices for physiological monitoring, digital diagnostics, and human–computer interaction. With the development of devices towards miniaturization and integration, thermal management has emerged as an essential challenge, which not only influences device performance and long-term stability but also affects user comfort. Various thermal management strategies, including passive and active approaches, have been employed to regulate the operating temperature. Nevertheless, it is still challenging to develop thermal regulation systems with a large temperature regulation range, good temperature uniformity, and high mechanical flexibility. Recently, the microfluidics-based thermal regulation method has emerged as a promising method that integrates active and passive thermoregulation methods. This review explores the thermal management mechanisms enabled by microfluidic devices, emphasizing an integrated strategy that combines material selection, structural geometry, and system optimization to enhance thermal performance. We analyze heat transfer principles in microchannels and highlight applications in device-level thermal management, personal thermal regulation, and thermal regulation interface for human–machine interaction and healthcare, addressing their specific demands. Finally, we outline the challenges and future perspectives for advancing microfluidics-based thermal management systems, focusing on capability, integration, and applications.

Wearable biosensors have revolutionized healthcare by enabling continuous, minimally invasive monitoring of health parameters. While traditional wearables primarily measure physiological signals, recent advancements now allow biochemical sensing of microbial biomarkers across diverse human biofluids, including sweat, saliva, wound exudate, interstitial fluid, tears, breath, and urine. These biomarkers, including microbial nucleic acids, metabolites, and host immune mediators, provide valuable information for diagnosing and managing infections. Wearable microfluidic devices are designed to sample these biofluids directly from the body and allow for rapid identification of microbial signatures and associated host responses. Moreover, some wearables' use of living microorganisms as functional components has opened new opportunities for biosensing and therapeutic delivery. The integration of artificial intelligence improves the interpretation of complex and dynamic data streams, and facilitates precise and adaptive decision-making. Additionally, by addressing biomechanical interactions between microorganisms, host tissues, and wearable interfaces, mechanomedicine principles provide insights into these systems. In the near future, these interdisciplinary innovations have the potential to transform infection control, personalized healthcare, and global health surveillance.