Microsystems & Nanoengineering最新文献

Recent innovations in skin microphysiological systems (MPSs) have gained momentum following regulatory advances such as the FDA Modernization Act 2.0 and the global shift toward alternatives to animal testing. This review highlights the development of three major technologies-3D bioprinting, skin organoids, and skin-on-a-chip-and their roles in replicating human skin physiology for research and preclinical applications. We examine how these platforms model complex skin functions, including epidermal barrier formation, vascular and immune interactions, and disease phenotypes such as psoriasis, atopic dermatitis, melanoma, and viral infections. In addition to summarizing their utility in toxicological screening and therapeutic evaluation, we explore how current OECD test guidelines may guide future validation efforts. Finally, we discuss emerging strategies for integrating automation and machine learning-based image analysis to enable scalable, high-content screening of skin MPS models across diverse applications.

State-of-the-art high-density multielectrode arrays enable the recording of simultaneous spiking activity from hundreds of neurons. Although significant efforts have been dedicated to enhancing neural recording devices and developing more efficient sorting algorithms, there has been relatively less focus on the allocation of microelectrodes-a factor that undeniably affects spike sorting effectiveness and ultimately the total number of detected neurons. Here, we systematically examined the relationship between optimal electrode spacing and spike sorting efficiency by creating virtual sparser layouts from high-density recordings through spatial downsampling. We assessed spike sorting performance by comparing the quantity of well-isolated single units per electrode in sparse configurations across various brain regions (neocortex and thalamus), species (rat, mouse, and human) and various spike-sorting algorithms. Enabling the theoretical estimation of optimal electrode arrangements, we complement experimental results with a geometrical modeling framework. Contrary to the general assumption that higher electrode density inherently leads to more efficient sorting, both our theoretical and experimental results reveal a clear optimum for electrode spacing specific to species and regions. We demonstrate that carefully choosing optimal electrode distances could yield a total of 1.7-3.75 times increase in spike sorting efficiency. These findings emphasize the necessity of species- and region-specific microelectrode design optimization.

Capsule endoscopy has revolutionized gastrointestinal (GI) diagnosis but is limited to imaging, often requiring invasive procedures for subsequent therapy. This work presents a magnetically actuated robotic capsule endoscope (MARCE) that integrates controllable magnetic navigation, real-time visualization, and targeted drug delivery via microneedle patches to bridge the gap between diagnosis and therapy. The MARCE features a retractable micro-camera for continuous monitoring of the GI tract, dual-layer hyaluronic acid microneedle patches enabling multi-point drug administration, and an electrothermally triggered protective cover to prevent premature dissolution in GI fluids. Sized similarly to conventional clinical capsules (11.8 mm in diameter and 21.5 mm in length), the MARCE demonstrates controlled epinephrine release from its microneedle patches (up to 0.4 mg) and provides sufficient magnetic actuation force (~0.58 N) and torque (~18.4 N mm) for intestine locomotion and penetration. Driven by a custom-developed electromagnetic actuation system, the MARCE achieves precise 3D locomotion with an average positional error <1.5 mm controlled microneedles penetration (with a peak force of 0.15 N), and successful drug delivery across multiple lesions in ex-vivo porcine intestinal tissue. This integrated platform streamlines diagnostic-therapeutic workflows, offering a minimally invasive solution for GI disorders such as bleeding, with potential to enhance patient comfort and treatment precision.

Cell therapy products are rapidly transforming clinical practice, but their short shelf-lives and inability to undergo terminal sterilization create major challenges for sterility testing. Conventional rapid microbiological methods (RMMs) are hindered by the dense cellular background of therapeutic samples, which masks rare microbial contaminants and necessitates pre-analytical processing. Efficient separation of microorganisms from high-density cell suspensions is therefore a critical prerequisite for enabling real-time, in-process sterility assurance. Here, we systematically elucidate the Dean flow-dominated migration mechanism and determine its effective range for continuous, label-free separation of non-typical contaminants ≤ 5 μm in microchannels exceeding 40 μm in height. We demonstrate that particles with ap/h < 0.05 undergo exclusive Dean-induced lateral migration, while those near the inertial focusing threshold (ap/h ≈ 0.07) exhibit a Reynolds number-dependent transition between unfocused and centerline-focused streams. Leveraging these principles, we designed optimized channel geometries that achieved > 95% separation efficiency and > 96% purity of T cells versus three morphologically distinct bacteria at 10⁵ bacteria/mL. At ultra-low loads (< 10 CFU/mL), culture-based assays confirmed 100% detection for inocula > 1 CFU/mL. Our findings validate Dean migration as a governing mechanism for submicron particle separation and provide a path toward integrating microfluidic modules into closed CAR-T manufacturing platforms, advancing real-time microbial quality control in cell therapy production.

Continuous glucose monitoring (CGM) is vital for diabetes care, but current invasive electrochemical sensors of blood glucose often cause potential infection and skin irritation. Non-invasive sensors in sweat glucose are promising alternatives but limited by low sensitivity and poor compatibility with complex sweat environments, because the sweat glucose has concentrations of 20 - 600 μmol/L and are 100-fold more dilute than the blood glucose. Here, we report a portable optical sensing system that integrates an optical watch prototype with functionalized plasmonic silver-coated silicon nanopillars substrate for non-invasive and label-free glucose detection in sweat. The nanopillar sensor with wide-range plasmonic hot spots is functionalized with 4-mercaptophenylboronic acid for selective glucose capture and optical signal transduction through both Raman scattering and plasmonic detection. The optical watch system has a compact LED illumination at 623-660 nm and wireless transmission of data to a smartphone application. Significantly, the whole system demonstrated excellent sensitivity down to 22 μmol/L and high selectivity in detecting glucose in artificial sweat, which were validated by human sweat samples to confirm its applicability in real-life scenarios. Our study offers a promising portable and non-invasive alternative to traditional CGM and highlights the potential of integrating nanophotonic sensors with wearable platforms for continuous health monitoring and personalized medicine.

Human exhaled gas is rich in biomarker information that could be used for early diagnosis of disease. With the development of nanotechnology and the Internet of Medical Things (IoMT), AI-assisted nano gas sensor arrays as a non-invasive exhaled gas detection platform brings fascinating technological solutions to the field of breath detection. Herein, we designed a new heterojunction sensing array by anchoring n-GaN nanoparticles on MOF-derived p-MO_x porous nanosheets. The gas sensor arrays demonstrated remarkable response speed (10 s), excellent repeatability, and extreme anti-humidity with a lower detection limit of 1 ppb at room temperature. Energy band structure combined with density functional theory (DFT) calculations were used to analyze the entire gas sensing process. Furthermore, we developed a new breath detection device and successfully performed clinical patient exhaled gas detection. With the assistance of ensemble learning, the recognition accuracy of lung cancer patients and healthy volunteers can reach 95.8%. This work provides an innovative technology for the construction of heterojunction sensor arrays and exhaled gas detection device, which has a promising application prospect in the field of early disease diagnosis and IoMT.

Controllable droplet manipulation is essential for applications from biochemical analysis to soft robotics. Despite significant advances, existing methods struggle to achieve broadly tunable, asynchronous control of multiple droplets, limiting their efficiency in three-dimensional and dynamic environments. Here, we introduce a droplet ultrasonic tweezer (DUT), which leverages broadly tunable acoustic control to enable three-dimensional multi-droplet manipulation and enhance condensing surface renewal. The DUT generates a twin-trap acoustic field from a single phased-array focal point, allowing droplet coalescence and confinement at five specific trapping positions. Leveraging this capability, we demonstrate synchronous directional transport of three droplets and asynchronous control of their relative positions. Moreover, the DUT's vertically extensible twin trap enables synchronous manipulation of droplets across double-layer surfaces. Beyond transport, programmable spatial modulation of the acoustic field enhances microdroplet coalescence and suppresses merged-droplet detachment, increasing the droplet detachment size and expanding the swept area for more effective surface renewal. Our results establish a robust paradigm for applications in optical surface self-cleaning, condensation heat transfer, and atmospheric water harvesting, offering a scalable solution for precise droplet control.

Despite its huge potential, such as in biomedical research for bioparticle sorting and sensing, near-field optical trapping suffers from limited trapping efficiency due to the weak evanescent field accompanied by shallow penetration depth (~100 nm). Moreover, such optical trapping approaches are susceptible to perturbations from trapped particles, making them less robust and impractical. Here, we demonstrate, for the first time, a thin-walled hollow microbottle resonator with gradient-wall thickness to realize large-scale and robust optical trapping based on mode field strength antinodes, instead of the evanescent field. The microbottle resonator combined with off-equatorial fiber taper coupling collaboratively enables the excitation of axial high-order Whispering Gallery Modes (WGMs). In addition, the unique feature of the gradient-wall thickness design mitigates the adverse impact of the perturbation from trapped particles on mode field distributions, making the gradient-thickness protected (GTP) microbottle resonator more robust and stable. This enables large-scale optical trapping over an axial span exceeding 195 μm, with a threshold power of 0.198 mW for 500-nm-radius polystyrene particles. The GTP WGM microbottle resonator also achieves tunable localized optical trapping. This work demonstrates a scalable optical manipulation framework for applications in single-particle analysis, bioparticle manipulation, and label-free sensing.

Xuan paper (also known as Chinese rice paper), traditionally used for calligraphy and painting, has rarely been explored as a functional material. In this study, Xuan paper is repurposed for the first time as a humidity-sensitive material, exhibiting state-of-the-art sensitivity over a wide humidity range. A humidity sensor with a thickness below 0.09 mm and a mass below 0.012 g was fabricated using only Xuan paper, sodium chloride (NaCl) aqueous solution, and conductive carbon ink through a simple three-step process. Characterization of the sensor shows that NaCl crystals are combined with sparse cellulose fibers, facilitating moisture absorption and forming an electrochemical sensing system. To investigate the electrochemical properties of the sensor, electrochemical impedance spectroscopy was measured. The results reveal a transition in the conduction mechanism across a wide relative humidity range (11-97%), with an output variation as high as 2.65 × 10⁴ times. The large output variation enables easy readout without sophisticated circuits, paving the way for versatile applications. To enable humidity readout and wireless transmission, a flexible eight-channel readout circuit was developed based on a microcontroller (Arduino). The readout circuit and supporting smartphone application facilitated the practical tests of the humidity sensor, demonstrating its capabilities in environmental humidity monitoring, humidity-based touch sensing, urination monitoring, and motion state detection. This study attempts to address the longstanding trade-off between high performance and complex fabrication processes in humidity sensors and reveals the potential of Xuan paper as a functional material.

This narrative review evaluates the suitability of conventional biopolymer-based microencapsulation strategies, originally developed for facultative and aerotolerant probiotics, for the protection and delivery of extremely oxygen-sensitive (EOS) next-generation probiotics (NGPs). With increasing interest in NGPs, there is a pressing need to establish whether conventional formulation approaches can be effectively translated for these highly oxygen-sensitive bioactives. We reviewed commonly used microencapsulation materials and techniques, assessing their suitability and potential to preserve EOS bacterial viability. Hydrated pectin- and gellan-based microcomposite systems, particularly when combined with xanthan gum or other polymers, exhibited the strongest oxygen-protection performance. In contrast, alginate alone demonstrated inconsistent barrier properties, though its performance improved when blended or coated with chitosan. Dehydrated microcomposite systems did not yield additional viability benefits compared to their hydrated counterparts. Importantly, none of the studies explicitly quantified oxygen exposure parameters or established threshold levels required for effective protection of EOS strains. Despite some microcomposite systems demonstrating potential for EOS colonic delivery, our findings highlight a critical gap in formulation science for these sensitive bioactives and underscore the need for the development of bespoke, tailored delivery systems that advance beyond conventional approaches designed for facultative or aerotolerant strains. Addressing these gaps will support the advancement of microencapsulation technologies, improve biotherapeutic NGP formulation, and ultimately facilitate the translation of exploratory clinical findings into rationally designed, accessible, and effective microbiome-based interventions.