搜索结果：Biomedical microdevices

Electrical stimuli play a crucial role in activating cell signaling pathways and promoting essential functions such as migration, proliferation, and differentiation, while also enabling communication between specific cell types. Bioelectronics aims to modulate the biological activity of living tissues and organs through minimally invasive electrical stimulation. This work aims to develop and validate cytocompatible, subcellular-sized wireless microdevices fabricated through a scalable silicon microtechnology process. These microdevices consist of a micrometer-scale silicon dioxide platform integrating ZnO nanosheets (NSs) as the active piezoelectric material. They establish electromechanical interactions with cells, driven by intrinsic cellular forces or by external ultrasound actuation in the biomedical range. This study demonstrates the underpinning mechanism of this electromechanical interaction. Mechanical forces, whether generated intrinsically by cells or applied through ultrasound, deform the nanostructures and generate localized piezopotentials that depolarize the membrane and trigger calcium transients. Pharmacological studies revealed that calcium entry occurs mainly through voltage-gated calcium channels (VGCCs) and stretch-activated cation channels (SACCs), with a minor contribution from intracellular stores. Membrane potential imaging confirmed dynamic depolarization events, validating direct cell-nanogenerator coupling. Ultrasound actuation further enhanced the effect, with 58% of cells activated, underscoring the promise of piezoelectric nanogenerators for minimally invasive cellular-level bioelectronic interfaces and biomedical applications.

3D ice lithography (3DIL) is an emerging direct-write technique that fabricates intricate 3D structures using frozen precursors. Here, we report the use of ethanol as a renewable and low-toxicity precursor for 3DIL, intended for the first time for the fabrication of intricate porous microstructures for in vitro and in vivo biomedical applications. The first nanoindentation analysis of 3DIL materials reveals mechanical properties (Young's modulus 2-4 GPa) comparable to biocompatible polymers. TEM shows that the material is an amorphous carbon that undergoes controlled graphitization under annealing at very high temperatures (1300°C). Due to its chemical composition, mechanical properties, and stability in water, cross-linked ethanol scaffolds support in vitro endothelial cell adhesion and proliferation with high confluency. Patterned neurostimulation electrodes implanted in mouse brains elicit no significant increase in astrocytic or microglial activation, indicating excellent in vivo biocompatibility. Additionally, we present for the first time the use of optically transparent substrates and the first patterning of neurostimulation electrodes using 3DIL. This study positions 3DIL using ethanol as a versatile, direct-write technique using renewable precursors to produce novel microdevices in biomedical engineering.

The increasing development of ingestible medical devices for gastrointestinal diagnostics, drug delivery, and physiological monitoring has created a growing demand for reliable and long-lasting power sources. Conventional batteries limit device lifetime, increase capsule size, and raise safety concerns, making biomechanical energy harvesting from gastrointestinal motility a promising alternative for self-powered ingestible systems. This review aims to provide a comprehensive overview of biomechanical energy harvesting from gastrointestinal mechanical activity for powering ingestible biomedical devices, with emphasis on energy sources, transduction mechanisms, materials, system integration, limitations, and future research directions. Recent literature on gastrointestinal biomechanics and energy harvesting technologies was analyzed, focusing on major transduction mechanisms such as piezoelectric, triboelectric, and electromagnetic generators. The review also evaluates material selection, device architectures, encapsulation strategies, and power management circuits from a system-level integration perspective. Piezoelectric, triboelectric, and electromagnetic energy harvesters demonstrate the ability to convert low-frequency gastrointestinal mechanical energy into electrical energy suitable for ultra-low-power biomedical devices. Hybrid energy harvesting systems improve energy reliability and output performance. However, several challenges remain, including low energy density, variability in gastrointestinal mechanical forces, miniaturization constraints, material durability, electrical conversion losses, and lack of standardized testing protocols. Biomechanical energy harvesting has significant potential to enable battery-free ingestible biomedical devices. Future developments in hybrid energy systems, ultra-low-power electronics, biodegradable materials, and adaptive power management are expected to support the development of fully autonomous self-powered ingestible medical devices.

Droplet-based microfluidics has witnessed tremendous progress in the past two decades, and this technique has been demonstrated as one of the most promising technologies to synthesize high-end and versatile materials with advanced functions, which provide great possibilities for numerous applications. Herein, the recent progress in preparing high-value natural microspheres by droplet-based microfluidic techniques is summarized comprehensively. We start with an in-depth articulation of the working principles of droplet-based microfluidics and surface modification for microdevices. Subsequently, droplet-based microspheres' fabrication methods have been discussed and summarized. Furthermore, the emerging representative biomedical applications of the different types of natural microspheres are outlined systematically. After that, we consider the challenges that hinder droplet-based microfluidic improvement in academic and industrial applications. Eventually, we will point out the perspectives of droplet-based microfluidics and aim to advance droplet-based microfluidics and sophisticated applications. The scope of this review is not only to offer an in-depth understanding of droplet-based microfluidics but also to open new pathways for versatile applications.

Current endovascular aneurysm treatments rely on catheter-based delivery systems, which inherently restrict access to tortuous anatomies and small-caliber vessels. To address this limitation, we introduce a tetherless microdevice platform that combines magnetic guidance with near-infrared (NIR) triggered shape-memory polymer (SMP) deployment for wireless aneurysm therapy. In this system, an external actuator magnet steers a microdevice-integrated effector magnet through anatomically realistic silicone vascular phantoms, while melanin-doped PLA structures enable precise NIR-induced shape recovery. Because NIR light penetrates biological tissue, deployment can be activated non-invasively from outside the body. The platform supports two device architectures tailored to different clinical needs: a spiral flow disruptor with a retrievable magnet for partial inflow modulation and a petalloid occluder designed for permanent sealing of narrow-neck aneurysms. Their navigation behavior was modelled using a flow-responsive, magnetically modulated stick-slip (F-MMSS) framework that captures the influence of pulsatile flow and wall interactions. Experimentally, magnetic steering was demonstrated under physiologically relevant flow rates and NIR activation achieved reliable deployment through ex vivo tissue. Particle image velocimetry and computational fluid dynamics confirmed substantial reductions in intra-aneurysmal velocity across multiple geometries. Material characterization further verified that PLA-melanin composites exhibit suitable bio and hemocompatibility for preliminary use. Together, these results establish a proof-of-concept platform for wireless navigation and remote deployment of endovascular microdevices, motivating future in vivo evaluation.

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Precise, contactless manipulation of micro- and nanoscale biological entities is pivotal for biomedical research, diagnostics, and therapeutic applications. However, most existing approaches suffer from limited programmability, low selectivity, or require physical contact and labeling, which restrict their applicability in complex biomedical environments. Here, we present a bipolar electrode-associated micromotor propulsion (BAMP) platform based on a rotating alternating current-flow field effect transistor (ROT-FFET), enabling the programmable control of cell enrichment, trajectory steering, and separation via electric field modulation. In a specific range of frequencies and voltages, particles or cells behave as active, interacting micromotors, mimicking the dynamics of living systems. By dynamically reconfiguring induced-charge electroosmotic (ICEO) flow and dielectrophoretic (DEP) forces, this system achieves real-time manipulation of synthetic particles and live cells (e.g., yeast, 293T, and red blood cells) with velocities up to 3.5 μm s-1. Notably, contactless and label-free sorting of cells is finally demonstrated by exploiting their dielectric properties. In the future, the precise controllability of this approach can be combined with directed motion to develop modular building blocks for bottom-up fabrication with broad applicability in additive manufacturing, hybrid microrobotics, and biomedical microdevices.

Magnetic microrobots are emerging as powerful tools for biomedical applications. However, widespread reliance on composite materials to achieve programmed magnetic responsiveness, biomimetic elasticity, and biocompatibility of the microdevices results in complex fabrication protocols involving delicate material and processing optimization. An intrinsically magnetic, programmable, soft, biocompatible, and easily-processable alternative material for development of magnetic microrobots may be liquid crystal polymers (LCPs). To establish LCPs as magnetic systems, this work studies for the first time in detail the manipulation of pristine LCP microobjects with magnetic torques acting on their intrinsic anisotropic diamagnetism. Rotation of planar LCP microdisks in a rotating magnetic field is characterized to identify the step-out frequency, the key characteristic of magnetic microrobots defining the regime in which their motion is synchronized with the field. Frequencies up to 0.6 Hz, comparable to rotational frequencies of biological microswimmers, are achieved using readily available fields below 0.3 T. Furthermore, the magnetic properties of LCP microobjects are programmed via photoalignment to adjust microobject orientation relative to the applied field and step-out frequencies. These findings establish a promising foundation for a new class of advanced microrobots that in the future may combine the magnetic responsiveness of LCPs with their shape-morphing capabilities.

Motor proteins drive motion in living systems. Myosin motors adsorbed on a surface propel actin filaments by hydrolyzing ATP. This makes them interesting systems for applications in nanotechnology, e.g. as sensors, for transporting molecular cargo or driving other forms of molecular motion. However, their effective functioning requires the proper combination of materials with adequate surface chemistry and hydrophobic properties. Here, we investigate a set of materials systems used as substrates and analyze their compatibility with the actomyosin system. As a reference, we used glass slides coated with trimethylchlorosilane (TMCS) where coating is performed in liquid phase, since this is a commonly used approach. We then explored an alternative vapor phase deposition method to coat glass slides with various silane compounds: in addition to TMCS, we also used perfluoro-octyltrichlorosilane (FOTCS) and perfluoro-dodecyltrichlorosilane (FDDTCS). In vitro motility assays (IVMAs), where surface-adsorbed myosin motor fragments propel actin filaments, were then used to measure the sliding velocity on the different surfaces. Filaments propelled on FOTCS-functionalized surfaces by chemical vapor deposition exhibited the highest average sliding velocity (3.9 ± 1.2 μm/s; mean ± SD) and retained a high fraction of motile actin filaments (87%), comparable to TMCS-functionalized surfaces (3.3 ± 0.4 μm/s, 90% motile). In addition, we also used a UV-curable polymer as active substrate material, which we have successfully treated to either promote or inhibit motor adsorption and therefore motility. We have evaluated the hydrophobic characteristics and the roughness of the different functionalized surfaces. In addition, we patterned microchannels with physical and chemical contrast, to confine the motor adsorption and consequently motion of the myosin- driven actin filaments to the patterned microchannel bottoms. This gas-phase deposition technique uses just a low cost commercial oven and offers a promising method for tailoring the surface properties of various materials, paving the way for standardizing and advancing the application of myosin-propelled actin filaments in nanotechnology and microdevices.

Brain vasculature is a complex and heterogeneous structure that serves specialized roles in maintaining brain health and homeostasis. There is substantial interest in developing representative human models of the brain vasculature for drug screening and disease modeling applications. Many contemporary strategies have focused on culturing neurovascular cell types in hydrogels and microdevices, but it remains challenging to achieve anatomically relevant vascular structures that have similar function to their in vivo counterparts. Here, we present a strategy for isolating microvessels from cryopreserved human cortical tissue and culturing these vessels in a biomimetic gelatin-based hydrogel contained in a microfluidic device. We provide histological evidence of arteriole and capillary architectures within hydrogels, as well as anastomosis to the hydrogel edges allowing lumen perfusion. In capillaries, we demonstrate restricted diffusion of a 10 kDa dextran, indicating intact passive blood-brain barrier function. We anticipate this bona fide human brain vasculature-on-a-chip will be useful for various biotechnology applications.

Optimizing drug administration remains a central challenge in the development of modern therapies, especially in the context of conditions that require spatiotemporal control of active substance release. In this context, hydrogels have been intensively investigated as polymeric platforms for drug delivery, through their three-dimensional hydrophilic structure, tunable properties, and compatibility with biological environments. This analysis presents an integrated approach to hydrogels used in drug administration, addressing the physicochemical fundamentals, the constitutive polymeric materials, and the mechanisms of response to relevant physiological stimuli. Recent experimental studies have been discussed, which highlight the use of hydrogels based on natural, synthetic, and hybrid polymers for controlled and targeted release, in correlation with various administration routes, including oral, injectable, transmucosal, and topical ones. Advanced functionalization strategies that allow adaptive responses to pH, temperature, glucose, enzymes, and reactive oxygen species are also analyzed. Furthermore, emerging directions integrating hydrogels with biosensors, microdevices, and wireless communication systems for real-time monitoring and on-demand release are highlighted. Overall, the analysis emphasizes the role of smart hydrogels as multifunctional platforms for complex therapeutic strategies while also underlining the current challenges associated with clinical translation and long-term performance.

Three-dimensional (3D) microfabrication/nanofabrication technologies have revolutionized various fields by enabling the precise construction of complex microstructures/nanostructures1-6. However, existing methods face challenges in fabricating intricate 3D architectures from a diverse range of materials beyond conventional polymers. Here we introduce a universal 3D microfabrication/nanofabrication strategy compatible with a broad range of materials by precisely manipulating optofluidic interactions within a confined 3D space, enabling the creation of volumetric, free-form 3D microstructures/nanostructures. A femtosecond-laser-induced heating spot generates a localized thermal gradient, providing precise spatiotemporal control over optofluidic interactions of the nanoparticle-laden dispersions. This enables the rapid and highly localized assembly of nanoparticles with diverse shapes and compositions-including metals, metal oxides, carbon nanomaterials and quantum dots-into complex 3D microstructures. To demonstrate its versatility, we fabricate multifunctional microdevices, such as 3D microfluidic valves with size-selective sieving functionality, achieving fast separation of microparticles/nanoparticles with distinct dimensions, as well as microrobots integrated with four distinct functional materials, achieving multimodal locomotion powered by different external stimuli. This optofluidic 3D microfabrication/nanofabrication method unlocks new opportunities for advanced material innovation and miniaturized device development, paving the way for broad applications in colloidal robotics7, microphotonics/nanophotonics, catalysis and microfluidics.

Impedimetric biosensors are useful for pathogen detection as they combine electrical impedance spectroscopy with the specificity of immunological reactions. These devices can be engineered to detect minute changes in electrical impedance caused by interactions between immobilized recognition elements and target antigens in a sample. They are advantageous in allowing for label-free and real-time detection, with the ability to operate without electroactive materials. Herein, we report an impedimetric biosensor containing nanoyeast expressing SARS-CoV-2 antibody fragments as the active layer. Using nanoyeast offers key advantages such as biocompatibility and stability. The single-chain antigen-binding fragment (scFab) against receptor binding domain of SARS-CoV-2 was mutated according to in silico predictions. It was expressed in Saccharomyces cerevisiae fused to the agglutinin 2 (Aga2), where the binding to Aga1 on the yeast cell wall displays the scFab on the surface of nanofragmented yeast (NY). Electrical impedance monitoring confirmed the successful immobilization of NY onto an adsorbed chitosan layer. This biosensor architecture detected SARS-CoV-2 spike protein with a limit of detection (LoD) of 5 × 10⁻¹⁸ g/mL. It distinguished viral concentrations ranging from 0.3 to 80 plaque-forming units per milliliter (PFU/mL) and demonstrated selectivity for SARS-CoV-2 over H1N1 influenza and Dengue virus. These findings suggest that this biosensing technology could be further adapted for other biomedical and clinical analyses, being promising to improve current pathogen detection methods. [Image: see text] The online version contains supplementary material available at 10.1007/s10544-026-00799-w.

Differentiation and detection of live and dead cells are critical for assessing cell viability in biomedical research, evaluating drug efficacy, and monitoring cytotoxicity in therapeutic applications. We present a microfluidic sensor that consists of two successive resistive pulse sensing channels. An excitation signal composed of a low-frequency AC (75 kHz) component and a DC bias was used to measure four key parameters. Through the AC measurement, differences in cell impedance causes variations in phase angle and voltage peak. From the DC measurement, cell size can be inferred from the resistive pulse magnitude, and the cell's zeta potential is represented by the transit time difference. Human umbilical vein endothelial cells (HUVECs) and human mesenchymal stem cells (hMSCs) were used to demonstrate the device's utility. A soft margin support vector machine (SVM) was applied to define the decision boundary based on analysis of the four parameters. For both cell types, live and dead cells formed distinct clusters, achieving maximum classification accuracies of up to 100%. Additionally, HUVECs treated with either ethanol or staurosporine (STS) were classified with accuracies up to 100%. Compared to previous microfluidic resistive pulse sensor (RPS), this approach can determine cell viability without the need for complex labeling or modifications. Unlike impedance cytometry, it does not require high-frequency measurements, significantly reducing hardware requirements and data processing complexity, while still providing multiparametric measurements of cells. These measurements allow the use of soft SVM to classify cell groups with higher accuracy than single-parameter differentiation.

Accurate malaria diagnosis is essential for effective case management and transmission control; however, the sensitivity, operational requirements, and field applicability of current conventional methods are limited. Hemozoin, an optically and magnetically active crystalline biomarker produced by Plasmodium species, offers a reagent-free target for next-generation diagnostics. This scoping review, following PRISMA-ScR and Joanna Briggs Institute guidance, synthesizes recent advances in hemozoin-based detection technologies and maps the current landscape. Twenty-four studies were reviewed, spanning eight major technology classes: magneto-optical platforms, magnetophoretic microdevices, photoacoustic detection, Raman/SERS spectroscopy, optical and hyperspectral imaging, NMR relaxometry, smartphone-based microscopy, and flow cytometry. Magneto-optical systems-including Hz-MOD, Gazelle™, and RMOD-demonstrated the highest operational readiness, with robust specificity but reduced sensitivity at low parasitemia. Photoacoustic Cytophone studies demonstrated promising sensitivity and noninvasive in vivo detection. Raman/SERS platforms achieved sub-100 infected cell/mL analytical sensitivity but remain laboratory-bound. Microfluidic and smartphone-based tools offer emerging, potentially low-cost alternatives. Across modalities, performance varied by parasite stage, with reduced detection of early ring forms. In conclusion, hemozoin-targeted diagnostics represent a rapidly evolving field with multiple viable translational pathways. While magneto-optical devices are closest to field deployment, further clinical validation, improved low-density detection, and standardized comparison across platforms are needed to support future adoption in malaria-endemic settings.

Traditional toxicology, with its reliance on animal models and oversimplified cell cultures, often fails to predict human responses due to interspecies differences and limited physiological relevance. Organ-on-a-chip (OoC) technology, as a microengineering breakthrough, enables reconstruction of human-relevant organ functions, providing a powerful tool for toxicity testing. However, OoC remains largely regarded as a technological platform rather than a distinct research discipline. In this review, we propose organ-on-a-chip toxicology (OCT) as a groundbreaking interdisciplinary paradigm that integrates advanced engineering, toxicological science, and biomedical research to redefine toxicological assessment. OCT transcends conventional OoC technology by providing a unified framework for elucidating toxicity effects and mechanisms at molecular, cellular, and organ levels. It uniquely enables comprehensive systemic toxicity modeling, incorporating full absorption-distribution-metabolism-excretion pathways and inter-organ signaling. Leveraging cutting-edge bioengineering, organoid-driven cellular fidelity, and AI-enhanced data analytics, OCT delivers unparalleled precision in drug safety evaluation, personalized toxicology, environmental hazard assessment, and food health. Despite current challenges in standardization, scalability, and regulatory acceptance, OCT holds the potential to revolutionize toxicological science by offering predictive, ethical, and human-centric insights, minimizing animal testing while advancing global health risk assessments.

The clinical translation of mesenchymal stem cell (MSC) therapies remains limited due to rapid cell clearance and stress-induced viability loss during injection. These limitations emphasize the need to develop delivery systems allowing MSCs to persist in the tissue and exert their biological effect. Cell microencapsulation within alginate (Alg) biomaterials is a promising strategy, where arginine-glycine-aspartic acid (RGD)-coupled alginate (RAlg) hydrogels have recently demonstrated improved bioactivity. However, achieving precise encapsulation and injectability while preserving cell viability remains an ongoing challenge. This study presents an injectable delivery platform using electrosprayed RAlg microcapsules that enhance viability and sustain the release of MSCs. Electrospray parameters were optimized to yield a microcapsule size of 175.4 ± 21.1 μm with high uniformity and consistent spherical morphology. Electron microscopy images of the microcapsules revealed a highly ordered microporous architecture. Physicochemical characterization confirmed that the presence of RGD peptides did not significantly alter the swelling, viscoelasticity, and encapsulation efficiency of Alg. Successful encapsulation of MSCs were observed, with cells assuming a round morphology within the microcapsule. After 14 days, RAlg maintained significantly higher cell viability at 91.3% than Alg alone (84.9%). Furthermore, a time-dependent release of cells was observed, with intact microcapsules at day 1, partial degradation with 59-61% cell release at day 7, and extensive degradation with 78-81% release by day 14. Both RAlg and Alg had comparable release performance. Overall, this study demonstrates the potential of electrosprayed RAlg microcapsules as a biocompatible and injectable platform for the sustained delivery of viable MSCs in regenerative medicine applications.

This study explores the use of near-infrared (NIR) spectroscopy in the 1.3–2.6 μm wavelength range, employing a handheld miniaturized microelectromechanical systems (MEMS)-based spectrometer for the rapid, non-invasive detection of COVID-19 from various biofluids. A total of 238 samples—including nasopharyngeal (NSP) swabs, nasal swabs, and saliva—from both COVID-19 positive and negative individuals are analysed. Machine learning algorithms process the spectral data to develop predictive models for the disease classification. Models based on a single biofluid achieve detection accuracies between 75% and 80%, while combining scans from multiple biofluids of the same individual improves accuracy to 88%. The study highlights trade-offs between sample accessibility and diagnostic performance. Overall, the findings demonstrate that NIR spectroscopy serves as a viable low-cost, portable, and rapid point-of-care (POC) solution, with strong potential for scalable mass screening—particularly in resource-limited settings.

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