Flexible pressure sensors are the foundation of wearable/implantable biosensing and human–machine interfaces, and mainly comprise piezoresistive-, capacitive-, piezoelectric-, and triboelectric-type sensors. As each type of sensor exhibits different electro-mechanical behaviors, it is challenging to detect various physiological mechanical signals that cover a large pressure range using a given sensor configuration, or even a single type of sensor. Here, we report a capacitive–piezoresistive hybrid flexible pressure sensor based on face-to-face-mounted conductive micropillar arrays as a solution to this challenge. The sensor exhibited high sensitivity over a wide dynamic range of five orders of magnitude, which covers almost the full range of physiological mechanical signals. A process for fabricating large-scale and morphologically homogeneous conductive micropillar arrays was first developed and refined. This track-etched-membrane-based process provides a facile, cost-effective, and highly flexible way to precisely adjust the morphology, modulus, and conductivity of the micropillars according to the application requirements. Subsequently, conductive-micropillar-array-based pressure sensors (MAPS) were developed and optimized to attain all-round sensing performance. The pillar contact behaviors generated significant variations in both the capacitance and resistance of the MAPS in the low-pressure regime (10⁻⁴–0.2 kPa), providing high sensitivity in both the capacitive and piezoresistive working modes. The vertical contact, bending and thickening of the pillars under medium pressure (0.2–16 kPa) led to a continuous linear response in both modes. Configuration and optimization enabled the MAPS to detect acoustic pressure (<1 Pa), milligram weights, soft touch (<1 kPa), arterial pulses (1–16 kPa preload), joint motions and plantar pressure (∼100 kPa), and the hybrid sensing mode allowed the MAPS to work in a desirable way. In this work, the piezoresistive mode was mainly employed for a higher accuracy and sampling rate, and can apparently simplify IC design for wearable applications. The circuit converts the resistive variations into electrical signals via the voltage division method and directly reads out the signals after further amplification, filtering and transmission. The improved facile and highly adjustable fabrication process, as well as the flexible hybrid sensing strategy, will benefit the unified design, batch production, quantifiable optimization, and functional diversity of wearable/implantable bioelectronics.

Programmed cell death protein-1 (PD-1) on T-cells combined with programmed cell death ligand-1 (PD-L1) critically accounts for tumor immune evasion. Anti-PD-1 (aPD-1) blocks the binding of PD-1 to PD-L1, thus allowing T-cell activation for tumor cell eradication. Currently, the major challenges for cancer immunotherapy are how to improve the response rate and overcome drug resistance. Dermal administration turns out to be a promising route for immunotherapy since skin is a highly active immune organ containing a large population of resident antigen-presenting cells. Microneedle arrays can pierce the immune-cell-rich epidermis, leading to a robust T-cell response in the microenvironment of tumor cells. Herein, we successfully developed a microneedle patch loaded with pH-responsive tumor-targeted lipid nanoparticles (NPs), which allows local delivery of aPD-1 and cisplatin (CDDP) precisely to cancer tissues for cancer therapy. For in vivo studies, aPD-1/CDDP@NPs delivered through microneedles effectively boosted the immune response, thereby a remarkable effect on tumor regression was realized. Synergistic anticancer mechanisms were therefore activated through robust microneedle-induced T-cell response, blockage of PD-1 in T-cells by aPD-1, and an increase in direct cytotoxicity of CDDP in tumor cells. Strikingly, transdermal delivery using MNs increased the response rate in the animal model unresponsive to aPD-1 systemic therapy. This exhibited promise in the treatment of immunotherapy-unresponsive cancers. Taken together, microneedle-mediated local delivery of nano-encapsulated chemotherapeutic and immunotherapeutic agents at tumor skin sites provides a novel treatment strategy and insights into cancer therapy.

Monitoring human health is of considerable significance in biomedicine. In particular, the ion concentrations in blood are important reference indicators related to many diseases. Microneedle array-based sensors have enabled promising breakthroughs in continuous health monitoring due to their minimally invasive nature. In this study, we developed a microneedle sensing-array integrated system to continuously detect subcutaneous ions to monitor human health status in real time based on a fabrication strategy for assembling planar microneedle sheets to form 3D microneedle arrays. The limitations of preparing 3D microneedle structures with multiple electrode channels were addressed by assembling planar microneedle sheets fabricated via laser micromachining; the challenges of modifying closely spaced microneedle tips into different functionalized types of electrodes were avoided. The microneedle sensing system was sufficiently sensitive for detecting real-time changes in Ca²⁺, K⁺, and Na⁺ concentrations, and it exhibited good detection performance. The in vivo results showed that the ion-sensing microneedle array successfully monitored the fluctuations in Ca²⁺, K⁺, and Na⁺ in the interstitial fluids of rats in real time. By using an integrated circuit design, we constructed the proposed microneedle sensor into a wearable integrated monitoring system. The integrated system could potentially provide information feedback for diseases related to physiological ion changes.

The collection of multiple-channel electrophysiological signals enables a comprehensive understanding of the spatial distribution and temporal features of electrophysiological activities. This approach can help to distinguish the traits and patterns of different ailments to enhance diagnostic accuracy. Microneedle array electrodes, which can penetrate skin without pain, can lessen the impedance between the electrodes and skin; however, current microneedle methods are limited to single channels and cannot achieve multichannel collection in small areas. Here, a multichannel (32 channels) microneedle dry electrode patch device was developed via a dimensionality reduction fabrication and integration approach and supported by a self-developed circuit system to record weak electrophysiological signals, including electroencephalography (EEG), electrocardiogram (ECG), and electromyography (EMG) signals. The microneedles reduced the electrode–skin contact impedance by penetrating the nonconducting stratum corneum in a painless way. The multichannel microneedle array (MMA) enabled painless transdermal recording of multichannel electrophysiological signals from the subcutaneous space, with high temporal and spatial resolution, reaching the level of a single microneedle in terms of signal precision. The MMA demonstrated the detection of the spatial distribution of ECG, EMG and EEG signals in live rabbit models, and the microneedle electrode (MNE) achieved better signal quality in the transcutaneous detection of EEG signals than did the conventional flat dry electrode array. This work offers a promising opportunity to develop advanced tools for neural interface technology and electrophysiological recording.

The emergence of wearable devices capable of continuous biomarker monitoring has significantly transformed the traditional landscape of healthcare, offering real-time insights into physiological changes, enabling early detection of disease, and facilitating individualized therapeutic. Nucleic acid aptamers, as a highly sensitive biorecognition elements with programmable properties, provide an innovative solution for building a new generation of continuous monitoring system. This review presents recent developments in aptamers-based wearable electrochemical sensors for continuous monitoring of biomarkers. Firstly, the core advantages of aptamers in continuous monitoring are summarized, including unique reversible binding properties, excellent biostability and engineerable modification ability, which make them ideal recognition elements for building real-time biosensing interfaces. Secondly, this review provides insights into the design principles of aptamers-based electrochemical sensors, including the characterization of aptamers, the immobilization methods on the electrode surface and the sensing strategies of sensors. Besides, this review highlights recent research advances in the field, focusing on the design of different types of sensors as well as their applications. Specifically, according to the difference target acquisition methods, the type of sensors is classified into non-invasive sensors, which involve monitoring biomarkers present in accessible biofluids such as sweat, saliva and wound exudate, and low-invasive sensors utilizing microneedle patch technology to sample biomarkers within interstitial fluids. Finally, this review introduces the challenges and discuss potential solutions for future development of aptamers-based wearable biosensors, including how to achieve effective biomarkers detection, ensure reversible binding response and ensure long-term stability, etc. This review provides useful reference for the development of aptamers-based electrochemical continuous monitoring technology in healthcare applications.