This paper reports an implantable nanoscale neural probe (INNP) developed through a layer-by-layer deposition process based on MEMS manufacturing technology and a precision machining technique based on atmospheric microplasma jet, marking the first successful application of solid-state sensing methods for in vivo intracellular electrophysiological analysis. The exposed tip lengths of INNPs are precisely controlled to as low as $\sim 40$ nm, with diameters of $\sim 100 \text{nm}$. Electrochemical stability, biocompatibility and minimal invasiveness of INNP during acute implantation were validated. Significant recordings of in vivo intracellular action potentials and ion currents were acquired: The amplitude and half-width of action potential spikes were $\sim 8.31 \text{mV}$ and $\sim 1.11 \text{ms}$ respectively, with the amplitude of superimposed action potential spikes reaching up to $\sim 70 \text{mV}$, while the amplitudes for fast electrical synaptic currents and postsynaptic currents (PSCs) ranged from tens of pA to several nA, with halfwidths of $\sim 0.10 \text{ms}$ and $\sim 2.24 \text{ms}$ respectively. Notably, pain stimuli resulted in a significant increase in amplitudes of negative spikes of PSCs along with a significant decrease in half-widths, and triggered an evident generation of positive spikes. This work represents a significant breakthrough in the development of next-generation nanoscale implantable brain-computer interface (BCI) devices aimed at single-neuron intracellular analysis.

Cardiovascular disease is a common illness that seriously threatens human health, especially among middle-aged and elderly individuals. It is characterized by high morbidity and mortality, with millions of deaths occurring worldwide each year. Using electrodes for detecting the electrophysiological signals of myocardial tissue is an effective approach for studying heart diseases. However, most existing electrodes are rigid and have a much higher elastic modulus than myocardial tissue, resulting in poor mechanical compatibility. To address this issue, this study employed thermoplastic polyurethane (TPU) as the flexible substrates and liquid metal-polymer as the conductive material to fabricate flexible electrodes. These electrodes exhibit excellent conductivity, deformability, and biocompatibility. The performance of the electrodes was verified, and myocardial tissue was successfully cultured on the flexible electrodes, with stable electrophysiological signals successfully recorded.

To address the difficulty of balancing sensitivity and nonlinearity in MEMS piezoresistive pressure sensors, this study proposes an MEMS piezoresistive pressure sensor with a narrow cross-beam membrane–short beam structure. The structure introduces a tapered design at the ends of a conventional cross beam and incorporates short beams to enhance stress concentration in the sensitive regions, thereby improving output sensitivity while maintaining low nonlinearity. Finite-element analysis was performed to evaluate the stress distribution and deflection characteristics and to compare the proposed structure with conventional cross-beam and other diaphragm structures. Under identical overall dimensions, the proposed structure improves sensitivity by 61% relative to the conventional cross beam. Based on the finite-element results, multivariate fitting models for surface stress and deflection were established, and nonlinear optimization was used to determine the constrained optimal geometrical parameters within the validated design domain. Simulation results indicate that, over a pressure range of 0–1 kPa, the proposed sensor achieves a sensitivity of 12.23 mV/V/kPa and a maximum nonlinearity of 0.196% FSS, demonstrating favorable performance for micropressure detection.

Neural probes targeting single neurons are instrumental in overcoming the ambiguity associated with population-averaged signals and the attenuation of extracellular signals to reveal the fundamental units of neural coding. However, current neural probes are limited by resolution, structural design, and micro/nanotechnology, making it challenging to penetrate single neurons in vivo to directly record various neural signals. Here, we report a multilayer carbon-structured nanoprobe (MLCNP) for intracellular electrophysiological and chemical recordings in vivo. The sensing layers, composed of graphene and feather-shaped carbon nanowires (FCNW), and the protective layer of nanodiamond are prepared via microwave plasma chemical vapor deposition. The controlled exposure of nanotips, roughening of FCNW sensing layers, and adsorption of Pt nanoparticles on their surface are achieved through microplasma jet branch etching (MPJBE). The multilayer carbon structures and the MPJBE treatment significantly enhance the cathodic charge, peak cathodic current and sensitivity to dissolved O2 of nanoprobes. The MLCNP with a tip diameter of approximately 70 nm and an exposed sensing area length of about 900 nm, demonstrates good cytocompatibility, minimal invasive damage, and selective O2-sensing capabilities. Finally, intracellular electrophysiological signals and variations in O2 concentration, along with other potential biochemical signals, are successfully recorded in vivo, and the effects of pain stimulation on electrophysiological spikes were analyzed. The developed nanoprobe based on the new materials and processes and its successful acquisition of electrical and biochemical signals at the single-neuron level in vivo, hold profound significance for a deeper understanding of the intrinsic mechanisms of the nervous system.

Existing microfabrication processes are generally characterized by unavoidable residues and thermal damage, lack of material selectivity, and limited controllability, which significantly impact the texturing quality of high-performance coatings such as diamond-like carbon (DLC). Hence, this paper reports a maskless modulation strategy for curved surface based on cold atmospheric plasma jet (CAPJ) for gentle and controllable sinusoidal texturing of functional coatings. Through the development of multi-freedom motion and monitoring systems along with the regulation of key process parameters, the consistency and uniformity of graphical modulation on DLC surfaces are greatly enhanced. The surface morphology and composition changes of etched dots, lines, and sinusoidal textures were comprehensively characterized and analyzed at atomic and molecular scales by SEM, SDM, EDS, XPS, XRD, FTIR, profilometer, and Raman spectrometer, demonstrating the exceptional properties of our strategy in terms of selectivity, residue-free, and absence of thermal damage, further achieving high-quality on-demand modulation of standard multi-period sinusoidal profiles with amplitudes as low as 60 nm on curved DLC. The developed novel micro/nanofabrication process holds significant potential for gentle and selective surface treatment in interdisciplinary MEMS devices.

Reliable unidirectional fluid transport in microscale conduits remains a long-standing challenge for minimally invasive medicine, where transient pressure fluctuations often induce backflow, clogging, and cross-contamination. In biological microcirculation, such instabilities are efficiently suppressed by flexible venous valves. However, translating these mechanically active structures into artificial microcatheters is impractical at extreme aspect ratios because of fabrication, alignment, and reliability concerns. Herein, we introduce a geometry-encoded flow-regulation strategy enabled by an on-tip femtosecond laser fabrication method, demonstrating a 3D Tesla microvalve to be directly inscribed along the curved tip of microscale catheters (inner diameter less than 100 μm). By implementing in situ optical alignment during writing, conformal fabrication of complex microarchitectures is achieved. The microvalve produces functional “liquid-diode” behavior through asymmetric viscous and inertial dissipation. The integrated Tesla valve restores flow rectification under low-Reynolds-number conditions, strongly suppressing reverse flow while maintaining low forward resistance. Experiments and simulations reveal vortex-mediated energy dissipation in the reverse direction (reduced by 73.5% during flow initiation and 82.0% during termination), converting unstable infusion into robust, unidirectional transport. This work demonstrates that microfluidic flow stability can emerge from geometry alone when coupled with precise laser-enabled on-tip integration. The proposed approach establishes a general framework for function-oriented biomimicry in extreme-aspect-ratio medical devices, with implications for precision drug delivery, implantable microfluidics, and long-term minimally invasive therapies.

The limited physiological relevance of current organ-on-a-chip models often stems from an inability to integrate organ-specific tissue architectures with functional vascularization. Here, we introduce an open-top microfluidic platform that integrates phase-guide flow control with high-resolution 3D stamps to enable programmable fabrication of complex vascularized microtissues via sequential cell seeding and high-fidelity hydrogel patterning. Our approach enables the creation of three distinct vascularized models: a vascularized tumor model demonstrating enhanced doxorubicin spatial accumulation and pharmacological effects mediated by the functional vascular network; a vascularized colonic model featuring biomimetic crypt architectures that exhibited barrier dysfunction and specific inflammatory cytokine release profiles upon lipopolysaccharide challenge; and a vascularized myocardial model with aligned myocardial bundles showing anisotropic contractility and pharmacological responses. For colonic and myocardial model, a bilayered gel strategy is utilized to ensure the stability of the predefined tissue topology while simultaneously supporting the formation of self-assembly and a perfusable vascular network. Each model successfully established functional vascular-tissue interfaces, enabling the study of complex physiological interactions. This work provides a robust and versatile platform for constructing high-fidelity organotypic models that recapitulate critical structural, vascular, and functional features of human tissues, with significant implications for precision medicine and drug screening applications.

Industrialization and clinical translation applications based on organoids are often limited by low automation, high matrix consumption, and poor reproducibility. Here we present the VitroOrganoSphere (VOS) system, an automated droplet-engineered organoid sorting platform, which integrates droplet generation, photoelectric detection, fluorescence-based content evaluation, sorting, and automated dispensing into 96-well plates. Monodisperse droplets (CV <3%) are deposited as single droplets per well with Matrigel consumption as low as ∼0.3 μL. Real-time quality control enables rejection of empty or overloaded droplets and selective collection of droplets with appropriate encapsulation of viable organoids. Under the rigorous screening of two droplet selection criteria (size and sample content), the VOS system ultimately achieved a recovery rate of over 90% and accuracy of over 95%. Encapsulated organoids maintain viability and exhibit enhanced growth compared with manual methods. Drug sensitivity testing using patient-derived tumor organoids reliably distinguishes drug-sensitive and drug-resistant samples and reveals interpatient heterogeneity across multiple therapeutic agents. The VOS system establishes a standardized workflow for automated organoid-based drug screening and supports applications in precision medicine.

The viability assessment of patient-derived tumor organoids is essential for preclinical drug screening, with microscopic imaging serving as a key method for evaluating drug effects. Traditional image analysis methods, such as manual evaluation and fluorescence staining, suffer from low efficiency, dye toxicity, and fluorescence degradation, making them unsuitable for high-throughput drug screening. Additionally, current artificial intelligence (AI)-based tools face challenges in precise segmentation for the accurate quantitative analysis of viable and nonviable organoids. To address these challenges, we introduce OrganoidViT, a novel deep learning model utilizing vision transformer technology for the precise segmentation of viable and nonviable colorectal cancer organoids in bright-field microscopy images, ensuring an accurate efficacy assay of different drugs. Trained on custom datasets of colorectal cancer organoids prepared using microdroplet technology, OrganoidViT facilitates high-throughput segmentation without fluorescence imaging, with experimental results indicating superior performance of OrganoidViT (accuracy of 99.7

The geometric mismatch between rigid planar microelectrode arrays (MEAs) and soft three-dimensional (3D) organoids, alongside high electrode-tissue interface impedance, limits the fidelity of in vitro bioelectronic interrogations. We present a self-folding 3D bioelectronic micro-cage featuring dealloyed nanoporous electrodes to omnidirectionally encapsulate hiPSC-derived cardiac organoids for multimodal electrophysiological and thermal monitoring. Fabricated via a wafer-scale MEMS process, the planar SiO2/PI bilayer utilizes an intrinsic residual stress gradient to spontaneously self-assemble into a 3D conformal cage upon release. Crucially, a magnetron co-sputtered Au-Cu alloy was employed for the electrode layer. During the selective etching of the Cu sacrificial layer, simultaneous dealloying occurs, generating a high-surface-area nanoporous gold electrode structure. The scaffold achieved a predictable folding radius optimized for ~500 μm organoids. The optimized nanoporous gold electrodes exhibited significantly reduced electrochemical impedance (8.3kΩ at 1 kHz) and a massively enhanced charge storage capacity (53 mC/cm²) compared to standard bare gold. Integrated serpentine resistive sensors exhibited highly linear temperature-dependent resistance changes (R² = 0.9993), enabling on-device temperature monitoring during organoid assays. Functionally, the micro-cage recorded synchronized 3D extracellular field potentials from cardiac organoids and monitored electrophysiological responses to externally applied thermal perturbations and pharmacological agents, including Verapamil and Norepinephrine. These results demonstrate a promising MEMS-compatible platform for organoid-based electrophysiological recording, temperature monitoring, and proof-of-concept drug-response assessment.

This paper reports on a pH -nanosensor fabricated through layer-by-layer sputtering, atomic layer deposition (ALD) and microplasma jet branch etching (MPJBE) techniques, which achieved unprecedented recordings of abnormal intracellular pH levels in fresh brain tissue from inflammatory pain mice. The pH -nanosensor features a complete coverage of a thin $\text{Al}_{2} \mathrm{O}_{3}$ layer on large-surface-area $\text{IrO}_{\mathrm{x}}$ nanowires outside its tip collection site, with a tip resolution of the pH -nanosensor below 300 nm and an exposed length at the submicron scale, ensuring that the detection area is entirely intracellular. Electrochemical testing indicates that the introduction of $\text{Al}_{2} \mathrm{O}_{3}$ layer enhances the stability of the pH -nanosensor after multiple insertions into physiological environments while minimally affecting superior electrochemical properties, pH sensing sensitivity and reversibility of $\text{IrO}_{\mathrm{x}}$. Moreover, the pH -nanosensor exhibits good pH -selectivity, cytocompatibility, and minimal penetration damage. Finally, by inserting the pH -nanosensor into pyramidal neurons within the anterior cingulate cortex (ACC), a region associated with pain perception, intracellular pH values from complete Freund's adjuvant (CFA)-induced inflammation brain slices were recorded. The proposed pH -nanosensor holds significant research value for detecting biochemical markers at single-neuron scales to facilitate early diagnosis and monitoring of diseases.

Precise and long-term electroanalysis at the single-cell level is crucial for the accurate diagnosis and monitoring of brain diseases. The reliable protection in areas outside the signal acquisition points at sharp ultramicroelectrode (UME) tips has a significant impact on the sensitivity, fidelity, and stability of intracellular neural signal recording. However, it is difficult for existing UMEs to achieve controllable exposure of the tip functional structure, which affects their ability to resist environmental interference and shield noise, resulting in unsatisfactory signal-to-noise ratio and signal fidelity of intracellular recordings. To address this issue, we chose a dense and electrochemically stable diamond-like carbon (DLC) film as the UME protection coating and developed a method to precisely control the exposed degree of the functional structure by directly fixed-point processing of the UME tip by the strong site-selectivity and good controllability of the atmospheric microplasma jet. By analyzing the interaction between the microplasma jet and the UME tip, as well as the changes in the removal length and microstructure of UME tips with processing time, the exposed tip length was precisely controlled down to the submicron scale. Biocompatibility experiments, electrochemical aging tests and real-time intracellular pH recording experiments have demonstrated that the DLC-UME with effective tip protection processed by microplasma jet has the potential to enable long-term detection of intracellular high-fidelity signals.

Cellular spheroids, closely resembling native tissue microenvironments, have emerged as pivotal constructs in biomedicine as they can facilitate complex cell-cell and cell-matrix interactions. However, current methods for constructing spheroid assembloids with spatial arrangement or heterogeneous structures are limited, which has become a barrier for studying tissue engineering and in vitro disease modeling. Here, we demonstrate an acoustofluidic pick-and-place operation system capable of spatially assembling of spheroids into desired patterns in both two dimensional (2D) and three dimensional (3D) spaces. The underlying physical mechanism of the device is systematically studied to explain the interrelationship between trapping cell spheroids, acoustic streaming, and the acoustic radiation force (ARF) induced by the acoustically activated microneedle. We exploit these mechanisms to successfully transfer cellular spheroids into hydrogel solutions, enabling them to be precisely patterned and fused into assembloids of predefined shapes. Besides, we demonstrate arranging MC3T3-E1 cellular spheroids into a ring shape to fabricate the osteogenic tissues. Besides, a co-culture model involving tumor cells (MCF-7) and normal human dermal fibroblasts (NHDFs) is constructed to validate our method’s ability to reconstruct heterogeneous tumor model, revealing that the fibroblast spheroids promote tumor spheroid invasion. Our method holds significant potential prospects in regenerative medicine, disease model construction and drug screening.

Mural cells are essential for maintaining the proper functions of microvasculatures. However, a key challenge of microvascular tissue engineering is identifying a cellular source for mural cells. We showed that in vitro , circulating fibrocytes (CFs) can (1) shear and stabilize the microvasculatures formed by vascular endothelial cells (VECs) in a collagen gel, (2) form gap junctions with VECs and (3) induce basement membrane formation. CFs transplanted into nude mice along with VECs in either collagen gel or Matrigel exhibited activities similar to those mentioned above, that is, sheathing microvasculatures formed by VECs, inducing basement membrane formation and facilitating the connection of the engineered microvasculatures with the host circulation. Interestingly, the behaviour of CFs also differs from that of human brain vascular pericytes (HBVPs) in vitro , which often infiltrate the lumen of capillary-like structures in a mosaic pattern, actively proliferate and exhibit lower endocytosis and migration capacities. We concluded that CFs are a suitable cellular source for mural cells in the construction of tissue-engineered microvasculatures.

Elastic modulus is a valuable pathological biomarker to make diagnoses. As normal tissue becomes afflicted with diseases, the local modulus changes. Here, we present a modulus characterization probe based on a shape-memory alloy (SMA) microwire integrating both sensing and actuation to quantify modulus variations. Under controlled current input, SMA microwire contracts to generate active sensing force. The extent of contraction dynamically changes in response to the tissue modulus, which is quantified through real-time resistance changes. The maximum modulus measurement range was in the GPa range, improved by three orders of magnitude compared to conventional methods. It provided a spatial resolution of 2 mm with a data resolution of 1.53 mN in the kPa range and a spatial resolution of 1 mm with a data resolution of 1.50 mN in the MPa range. The device was proved to be able to be used to target tumors and distinguish tissues in in vivo and ex vivo tests.

This paper reports a novel integrated self-referencing electrode all-in-one implantable flexible probe (SAIFP), realizing neural recording, electric stimulation, and in-situ pH sensing. SAIFP has 128 recording electrodes (REs) and 4 runway-shaped electrodes (RsEs), both of which have been modified with iridium oxide (IrOx). Meanwhile, a self-referencing electrode (Sref) is integrated into SAIFP by electroplating with Ag/AgCl. RsEs are utilized in conjunction with Sref to facilitate in-situ pH detection, and concurrently, RsEs fulfill the dual purpose of stimulating electrodes (STs), enabling targeted electric stimulation. In short, the SAIFP, capable of actualizing more functions within a limited implantation area, further advances the study of the operational mechanisms of the brain.

This paper reports a novel multifunctional implantable nanoelectrode (MINE) based on a theta-tube, featuring one channel with Ag/AgCl for self-referencing, another channel for injection, and a precisely exposed collection point on the tip for fixed-point recording of electromotive force (EMF) and pH values. The protective coating on the tip is selectively etched by the atmospheric microplasma jet, exposing the functional coating and theta-tube channels Comparative analysis of curves of cyclic voltammetry (CV) and impedance-frequency, and stability of current and EMF of nanoelectrodes (NEs) with five different protective coatings for the first time confirms that the NE coated with Parylene-C offers superior detection reliability. Real-time recordings of intracellular EMF and pH values during in situ self-referencing and injection demonstrate that the MINE provides stable and reliable intracellular fixed-point recording capability, along with the potential for in-situ drug delivery and in-vivo intracellular monitoring, which holds significant promise for accurate diagnosis, real-time monitoring, and in-situ treatment of neurological diseases.

Wearable biosensors capable of long-term operation facilitate future precision medicine and personalized health monitoring by in-situ acquisition, real-time processing, and continuous transmission of biological signals. Self-powered technologies provide effective strategies to achieve the above goals, but make the entire bioelectronic system more complex. Ultimately, challenges of material engineering, miniaturization, and performance enhancement converge into the all-in-one engineering of self-powered wearable biosensor systems. Matching the power output of the energy module with the power consumption requirements of the signal module is the basic prerequisite for achieving all-in-one design. This review takes power as the entry point to comprehensively analyze and summarize the mechanisms, performance ranges, enhancement strategies, application examples, and future prospects of self-powered wearable biosensors. We review the principles, engineering strategies, and capabilities in energy collection, management, and storage of current self-powered technologies to determine the output power range and methods for performance enhancement. Next, we discuss and compare the strategies and mechanisms for signal acquisition, processing, and transmission, focusing on the performance, size, wearability and enhancement strategies of each module. Most importantly, we summarize the four representative all-in-one engineering strategies in the system, covering design principles, basic materials, targeted parts, integration levels, advantages and disadvantages. Finally, we outline key challenges and potential solutions for six modules in preparation for intelligent and networked sensing.

The advancement of neural interface technologies enables high-density, large-scale recordings of neural activity at single-neuron resolution, essential for elucidating complex brain circuits and computations. However, the structural complexity and tough meninges of non-human primate (NHP) brains present significant challenges for conventional silicon-based neural probes, often resulting in insufficient mechanical strength and unstable signal acquisition. In this study, single-shank silicon neural probes are systematically optimized for NHP applications through probe handle layer reinforcement, precision tip sharpening, and microstructuring with iridium oxide (IrOx) electrode modification. These combined strategies markedly improve mechanical robustness, membrane penetration, and electrochemical performance without increasing probe dimensions. Acute in vivo experiments in rhesus macaques demonstrate stable implantation, minimal cortical indentation, and reliable, high-fidelity neural recordings at the single-neuron level. This work provides a robust and practical solution for high-quality, large-scale neural recordings in NHPs, establishing a solid foundation for future advances in brain-machine interfaces and systems neuroscience.

This paper reports a multimodal MEMS electronic device (MMED) with microwrinkle structures for pulsed field ablation (PFA), pH sensing, ECG recording and electrical pacing in cardiac surgery. Taking advantage of stress unconcentration during the curing of PDMS, microwrinkles with a characteristic size of 10 mu m on electrodes are obtained, which facilitates improved electrical stimulation and recording capabilities. Further, 40, coating on microwrinkle electrodes by lift-off process improves the electrochemical performance. The pH sensitivity of IrOx, electrodes is up to 51.03 mV/pH. By using living rats, we show that the device with stretchable designs can establish conformal contact with curved heart surfaces, support high-quantity ECG recording and programmable electrical pacing. Meanwhile, the effectiveness of PFA is successfully performed on living swine hearts by thoracotomy. Integrating MEMS multimodal technologies into medical instruments may improve surgical performance and patient well-being.