Coupling of nanostraws with diverse physicochemical perforation strategies for intracellular DNA delivery.

Effective intracellular DNA transfection is imperative for cell-based therapy and gene therapy. Conventional gene transfection methods, including biochemical carriers, physical electroporation and microinjection, face challenges such as cell type dependency, low efficiency, safety concerns, and technical complexity. Nanoneedle arrays have emerged as a promising avenue for improving cellular nucleic acid delivery through direct penetration of the cell membrane, bypassing endocytosis and endosome escape processes. Nanostraws (NS), characterized by their hollow tubular structure, offer the advantage of flexible solution delivery compared to solid nanoneedles. However, NS struggle to stably self-penetrate the cell membrane, resulting in limited delivery efficiency. Coupling with extra physiochemical perforation strategies is a viable approach to improve their performance. This study systematically compared the efficiency of NS coupled with polyethylenimine (PEI) chemical modification, mechanical force, photothermal effect, and electric field on cell membrane perforation and DNA transfection. The results indicate that coupling NS with PEI modification, mechanical force, photothermal effects provide limited enhancement effects. In contrast, NS-electric field coupling significantly improves intracellular DNA transfection efficiency. This work demonstrates that NS serve as a versatile platform capable of integrating various physicochemical strategies, while electric field coupling stands out as a form worthy of primary consideration for efficient DNA transfection.

Nanochannel Electro-Injection as a Versatile Platform for Efficient RNA/DNA Programming on Dendritic Cells.

The utilization of dendritic cell (DC) vaccines is a promising approach in cancer immunotherapy, and the modification of DCs for the expression of tumor-associated antigens is critical for successful cancer immunotherapy. A safe and efficient method for delivering DNA/RNA into DCs without inducing maturation is beneficial to achieve successful DC transformation for cell vaccine applications, yet remains challenging. This work presents a nanochannel electro-injection (NEI) system for the safe and efficient delivery of a variety of nucleic acid molecules into DCs. The device is based on track-etched nanochannel membrane as key components, where the nano-sized channels localize the electric field on the cell membrane, enabling lower voltage (<30 V) for cell electroporation. The pulse conditions of NEI are examined so that the transfection efficiency (>70%) and biosafety (viability >85%) on delivering fluorescent dyes, plasmid DNA, messenger RNA, and circular RNA (circRNA) into DC2.4 are optimized. Primary mouse bone marrow DC can also be transfected with circRNA with 68.3% efficiency, but without remarkably affecting cellular viability or inducing DC maturation. These results suggest that NEI can be a safe and efficient transfection platform for in vitro transformation of DCs and possesses a promising potential for developing DC vaccines against cancer.

Nanoporous Gold Ring-Integrated Photothermal Intraocular Lens for Active Prevention of Posterior Capsular Opacification.

Posterior capsular opacification (PCO) is the leading complication after cataract surgery, and is mainly induced by the proliferation and migration of residual lens epithelial cells (LECs). Although numerous attempts have been made to reduce the incidence of PCO, this complication remains a critical challenge in postoperative visual recovery. This study aims to report a functionalized intraocular lens (R-IOL) with a region-confined photothermal effect for the active prevention of PCO after implantation. The outer rim of R-IOL (non-optical area) is decorated with a nanoporous gold (NPG) ring, which can effectively eliminate the LECs around R-IOL, ultimately inhibiting the migration of LECs from the periphery to the visual axis center in the initial stage, and preventing the subsequent PCO. Furthermore, the mechanism of LECs elimination can be attributed to apoptosis induced by mild photothermal therapy. After in vivo implantation for 30 days, PCO is rarely observed in the R-IOL group, whereas the considerably higher incidence of PCO (75%) is found in the pristine IOL (P-IOL) group. The region-confined photothermal effect based on NPG not only provides an active strategy to effectively prevent PCO, but also introduces new opportunities for the treatment of undesirable hyperplasia.

Anomalous dispersion of bioinspired flower-like microparticles for oil/water separation.

Hydrophobic particles have been suffering from aggregation in aqueous media, which limits their applications in oil/water separation. Surfactants have been used to increase the dispersity of the hydrophobic particles in water, but this approach compromises particles' hydrophobicity and oil absorption capabilities. Recently, hierarchical microparticles decorated with nanospikes were found to exhibit long-term anomalous dispersion in liquid medium without adding any surfactants. However, whether this anomalous dispersion phenomenon was applicable to 2D nano-petals decorated microparticles still remains unknown. Here, we developed a ZnO-based flower-like microparticles (FLMPs) whose surfaces were attached with 2D nano-petals, and we examined their anomalous dispersity. Our results showed that both hydrophilic and hydrophobic FLMPs could achieve anomalous dispersity either in water or organic solvents, likely due to reduced interparticle collision by the 2D nano-petals. In addition, the functional hydrophobic FLMPs also possessed a large surface area and superhydrophobic surfaces to efficiently absorb oil spills on water and oil emulsion suspended in water. In contrast, the hydrophobic microbeads (MBs) without nano-petals structure seriously aggregated in water and exhibited reduced oil absorption abilities. Our work demonstrated the new finding of 2D nano-pedal structure-mediated anomalous dispersity, and provided a new method for effective oil/water separation using superhydrophobic particles without surfactants.

Reduced Graphene Oxide Nanohybrid-Assembled Microneedles as Mini-Invasive Electrodes for Real-Time Transdermal Biosensing.

A variety of nanomaterial-based biosensors have been developed to sensitively detect biomolecules in vitro, yet limited success has been achieved in real-time sensing in vivo. The application of microneedles (MN) may offer a solution for painless and minimally-invasive transdermal biosensing. However, integration of nanostructural materials on microneedle surface as transdermal electrodes remains challenging in applications. Here, a transdermal H2 O2 electrochemical biosensor based on MNs integrated with nanohybrid consisting of reduced graphene oxide and Pt nanoparticles (Pt/rGO) is developed. The Pt/rGO significantly improves the detection sensitivity of the MN electrode, while the MNs are utilized as a painless transdermal tool to access the in vivo environment. The Pt/rGO nanostructures are protected by a water-soluble polymer layer to avoid mechanical destruction during the MN skin insertion process. The polymer layer can readily be dissolved by the interstitial fluid and exposes the Pt/rGO on MNs for biosensing in vivo. The applications of the Pt/rGO-integrated MNs for in situ and real-time sensing of H2 O2 in vivo are demonstrated both on pigskin and living mice. This work offers a unique real-time transdermal biosensing system, which is a promising tool for sensing in vivo with high sensitivity but in a minimally-invasive manner.

Nanospikes functionalization as a universal strategy to disperse hydrophilic particles in non-polar media.

Dispersion of hydrophilic particles in non-polar media has many important applications yet remains difficult. Surfactant or amphiphilic functionalization was conventionally applied to disperse particles but is highly dependent on the particle/solvent system and may induce unfavorable effects and impact particle hydrophilic nature. Recently 2 µm size polystyrene microbeads coated with ZnO nanospikes have been reported to display anomalous dispersity in phobic media without using surfactant or amphiphilic functionalization. However, due to the lack of understanding whether this phenomenon was applicable to a wider range of conditions, little application has been derived from it. Here the anomalous dispersity phenomenons of hydrophilic microparticles covered with nanospikes were systematically assessed at various conditions including different particle sizes, material compositions, particle morphologies, solvent hydrophobicities, and surface polar groups. Microparticles were functionalized with nanospikes through hydrothermal route, followed by dispersity test in hydrophobic media. The results suggest nanospikes consistently prevent particle aggregation in various particle or solvent conditions, indicating the universal applicability of the anomalous dispersion phenomenons. This work provides insight on the anomalous dispersity of hydrophilic particles in various systems and offers potential application to use this method for surfactant-free dispersions.

Machine learning-coupled tactile recognition with high spatiotemporal resolution based on cross-striped nanocarbon piezoresistive sensor array.

Flexible pressure sensor arrays have been playing important roles in various applications of human-machine interface, including robotic tactile sensing, electronic skin, prosthetics, and human-machine interaction. However, it remains challenging to simultaneously achieve high spatial and temporal resolution in developing pressure sensor arrays for tactile sensing with robust function to achieve precise signal recognition. This work presents the development of a flexible high spatiotemporal piezoresistive sensor array (PRSA) by coupling with machine learning algorithms to enhance tactile recognition. The sensor employs cross-striped nanocarbon-polymer composite as an active layer, though screen printing manufacture processes. A miniaturized signal readout circuit and transmission board is developed to achieve high-speed acquisition of distributed pressure signals from the PRSA. Test results indicate that the developed PRSA platform simultaneously possesses the characteristics of high spatial resolution up to 1.5 mm, fast temporal resolution of about 5 ms, and long-term durability with a variation of less than 2%. The PRSA platform also exhibits excellent performance in real-time visualization of multi-point touch, mapping embossed shapes, and tracking motion trajectory. To test the performance of PRSA in recognizing different shapes, we acquired pressure images by pressing the finger-type device coated with PRSA film on different embossed shapes and implementing the T-distributed Stochastic Neighbor Embedding model to visualize the distinction between images of different shapes. Then we adopted a one-layer neural network to quantify the discernibility between images of different shapes. The analysis results show that the PRSA could capture the embossed shapes clearly by one contact with high discernibility up to 98.9%. Collectively, the PRSA as a promising platform demonstrates its promising potential for robotic tactile sensing.

Multichannel microneedle dry electrode patches for minimally invasive transdermal recording of electrophysiological signals.

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.

Technological Advances of Wearable Device for Continuous Monitoring of In Vivo Glucose.

Managing diabetes is a chronic challenge today, requiring monitoring and timely insulin injections to maintain stable blood glucose levels. Traditional clinical testing relies on fingertip or venous blood collection, which has facilitated the emergence of continuous glucose monitoring (CGM) technology to address data limitations. Continuous glucose monitoring technology is recognized for tracking long-term blood glucose fluctuations, and its development, particularly in wearable devices, has given rise to compact and portable continuous glucose monitoring devices, which facilitates the measurement of blood glucose and adjustment of medication. This review introduces the development of wearable CGM-based technologies, including noninvasive methods using body fluids and invasive methods using implantable electrodes. The advantages and disadvantages of these approaches are discussed as well as the use of microneedle arrays in minimally invasive CGM. Microneedle arrays allow for painless transdermal puncture and are expected to facilitate the development of wearable CGM devices. Finally, we discuss the challenges and opportunities and look forward to the biomedical applications and future directions of wearable CGM-based technologies in biological research.

Fabrication of Multiple-Channel Electrochemical Microneedle Electrode Array via Separated Functionalization and Assembly Method.

Real-time monitoring of physiological indicators inside the body is pivotal for contemporary diagnostics and treatments. Implantable electrodes can not only track specific biomarkers but also facilitate therapeutic interventions. By modifying biometric components, implantable electrodes enable in situ metabolite detection in living tissues, notably beneficial in invasive glucose monitoring, which effectively alleviates the self-blood-glucose-managing burden for patients. However, the development of implantable electrochemical electrodes, especially multi-channel sensing devices, still faces challenges: (1) The complexity of direct preparation hinders functionalized or multi-parameter sensing on a small scale. (2) The fine structure of individual electrodes results in low spatial resolution for sensor functionalization. (3) There is limited conductivity due to simple device structures and weakly conductive electrode materials (such as silicon or polymers). To address these challenges, we developed multiple-channel electrochemical microneedle electrode arrays (MCEMEAs) via a separated functionalization and assembly process. Two-dimensional microneedle (2dMN)-based and one-dimensional microneedle (1dMN)-based electrodes were prepared by laser patterning, which were then modified as sensing electrodes by electrochemical deposition and glucose oxidase decoration to achieve separated functionalization and reduce mutual interference. The electrodes were then assembled into 2dMN- and 1dMN-based multi-channel electrochemical arrays (MCEAs), respectively, to avoid damaging functionalized coatings. In vitro and in vivo results demonstrated that the as-prepared MCEAs exhibit excellent transdermal capability, detection sensitivity, selectivity, and reproducibility, which was capable of real-time, in situ glucose concentration monitoring.

Advances in Multifunctional Electronic Catheters for Precise and Intelligent Diagnosis and Therapy in Minimally Invasive Surgery.

The advent of catheter-based minimally invasive surgical instruments has provided an effective means of diagnosing and treating human disease. However, conventional medical catheter devices are limited in functionalities, hindering their ability to gather tissue information or perform precise treatment during surgery. Recently, electronic catheters have integrated various sensing and therapeutic technologies through micro/nanoelectronics, expanding their capabilities. As micro/nanoelectronic devices become more miniaturized, flexible, and stable, electronic surgical catheters are evolving from simple tools to multiplexed sensing and theranostics for surgical applications. The review on multifunctional electronic surgical catheters is lacking and thus is not conducive to the reader's comprehensive understanding of the development trend in this field. This review covers the advances in multifunctional electronic catheters for precise and intelligent diagnosis and therapy in minimally invasive surgery. It starts with the summary of clinical minimally invasive surgical instruments, followed by the background of current clinical catheter devices for sensing and therapeutic applications. Next, intelligent electronic catheters with integrated electronic components are reviewed in terms of electronic catheters for diagnosis, therapy, and multifunctional applications. It highlights the present status and development potential of catheter-based minimally invasive surgical devices, while also illustrating several significant challenges that remain to be overcome.

Au24Cd Nanoenzyme Coating for Enhancing Electrochemical Sensing Performance of Metal Wire Microelectrodes.

Dopamine (DA), ascorbic acid (AA), and uric acid (UA) are crucial neurochemicals, and their abnormal levels are involved in various neurological disorders. While electrodes for their detection have been developed, achieving the sensitivity required for in vivo applications remains a challenge. In this study, we proposed a synthetic Au24Cd nanoenzyme (ACNE) that significantly enhanced the electrochemical performance of metal electrodes. ACNE-modified electrodes demonstrated a remarkable 10-fold reduction in impedance compared to silver microelectrodes. Furthermore, we validated their excellent electrocatalytic activity and sensitivity using five electrochemical detection methods, including cyclic voltammetry, differential pulse voltammetry, square-wave pulse voltammetry, normal pulse voltammetry, and linear scanning voltammetry. Importantly, the stability of gold microelectrodes (Au MEs) modified with ACNEs was significantly improved, exhibiting a 30-fold enhancement compared to Au MEs. This improved performance suggests that ACNE functionalization holds great promise for developing micro-biosensors with enhanced sensitivity and stability for detecting small molecules.

Integrated Multiplex Sensing Clear Aligner for In Situ Monitoring of Dental Enamel Demineralization.

Clear aligners have become one of the most important tools in orthodontic treatment. However, over a lengthy period of orthodontic treatment, enamel demineralization or even dental caries could be susceptible for occurrence. Therefore, early diagnosis of enamel demineralization has been widely investigated. Nevertheless, for reasons including bulky monitoring equipment and complexity of operation, few techniques reported to date possessed clinical utility. The combination of flexible electronics and electrochemical sensing technology presented a promising strategy. Herein, an integrated multiplex sensing clear aligner (IMSCA) system, including a clear aligner with a multiplex sensor array patch, was developed for in situ monitoring of Ca2+, pH, and PO43- in the oral environment to provide a foundation for early diagnosis of enamel demineralization. The IMSCA exhibited a broad linear response range, great selectivity, temporal stability, reproducibility, and biological safety. Results of enamel demineralization simulating experiments and human permanent tooth demineralization experiments validate the capability of the IMSCA to indicate the occurrence of enamel demineralization. All results ultimately point to the promising clinical utility of the IMSCA, which facilitates the quantitative characterization of enamel demineralization in complex oral environments. This study provides a novel strategy in the early diagnosis of enamel demineralization.

Lubricant-entrenched slippery surface-based nanocarriers to avoid macrophage uptake and improve drug utilization.

INTRODUCTION: Reducing the protein adsorption of nanoparticles (NPs) as drug carriers to slow their rapid clearance by macrophages uptake is a critical challenge for NPs clinical translational applications. Despite extensive research efforts to inhibit cellular uptake, including covering biological agents or surface chemical coatings to impart "stealth" properties to NPs, their stability remains insufficient. OBJECTIVES: Developed a novel surface modification technology based on a physical infusion engineering approach to achieve persistent inhibition of protein adhesion and cellular uptake by nanocarriers. METHODS: The nanoparticles were prepared based on conventional drug carrier mesoporous silica NPs through a two-step process. A functional nanoscale slippery surface was formed by grafting "liquid-like" brushes on the particles surface, and then a lubricant-entrenched slippery surfaces (LESS) was formed by infusing silicone oil lubricant into the entire surface. Co-incubation with macrophages (in vitro and in vivo) was used to examine the anti-uptake properties of modified NPs. The anti-adhesion properties of LESS coating surfaces to various liquids, proteins and cells were used to analyze the anti-uptake mechanism. Loaded with drugs, combined with tumor models, to evaluate the drug utilization of modified NPs. RESULTS: Relying on the stable and slippery LESS coating, the modified surface could prevent the adhesion of various liquids and effectively shield against the adhesion of proteins and cells, as well as remarkably reduce macrophage cellular uptake in vitro and in vivo. In addition, the LESS coating does not affect cell activity and allows NPs to be loaded with drugs, significantly improving the utilization of drugs in vitro and in vivo. This allows the NPs to reach to the target tumor site for drug delivery without active clearance by macrophages. CONCLUSION: Our research introduces a new nanocarrier technology to improve anti-biofouling performance and stealth efficiency that will facilitate the development of nanomedicines for clinical transformation applications.

3D-assembled microneedle ion sensor-based wearable system for the transdermal monitoring of physiological ion fluctuations.

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.

A 3D-printed microneedle extraction system integrated with patterned electrodes for minimally invasive transdermal detection.

Point-of-Care-Testing (POCT) is a convenient and timely clinical analysis method, leading the development trend of advanced biosensors. The development of POCT equipment that can achieve minimally invasive percutaneous monitoring can avoid the pain felt by the subjects and achieve in vivo and efficient measurement. Here, we reported the development of a microneedle (MN) extraction system based on patterned electrodes, which could provide convenient and minimally invasive detection of bio-analytes (including glucose, pH, and H2O2). The 3D-printed hollow MN array was used as a painless transdermal tool, while the interstitial fluid was extracted under negative-pressure conditions. The patterned electrodes could improve the electrochemical performance of the sensor, with the synergistic effect of the micropillar structure to increase the enzyme coating surface area and the nanomaterial electron layer. The patterned electrodes were placed on the back of the MN arrays for electrochemical detection. In vitro and in vivo studies showed that the MN-extraction system could detect the corresponding bio-analytes in a minimally invasive manner and it did not cause significant tissue damage. The system developed in this work will provide promising technology to expand the application of POCT for minimal tests on interstitial fluids.

Nanopore Electroporation Device for DNA Transfection into Various Spreading and Nonadherent Cell Types.

Cell transfection plays a crucial role in the study of gene function and regulation of gene expression. The existing gene transfection methods, such as chemical carriers, viruses, electroporation, and microinjection, suffer from limitations, including cell type dependence, reliance on cellular endocytosis, low efficiency, safety concerns, and technical complexity. Nanopore-coupled electroporation offers a promising approach to localizing electric fields for efficient cell membrane perforation and nucleic acid transfection. However, the applicability of nanopore electroporation technology across different cell types lacks a systematic investigation. In this study, we explore the potential of nanopore electroporation for transfecting DNA plasmids into various cell types. Our nanopore electroporation device employs track-etched membranes as the core component. We find that nanopore electroporation efficiently transfects adherent cells, including well-spreading epithelial-like HeLa cells, cardiomyocyte-like HL-1 cells, and dendritic-cell-like DC2.4 cells. However, it shows a limited transfection efficiency in weakly spreading macrophages (RAW264.7) and suspension cells (Jurkat). To gain insights into these observations, we develop a COMSOL model, revealing that nanopore electroporation better localizes the electric field on adherent and well-spreading cells, promoting favorable membrane poration conditions. Our findings provide valuable references for advancing nanopore electroporation as a high-throughput, safe, and efficient gene transfection platform.

Capacitive-piezoresistive hybrid flexible pressure sensor based on conductive micropillar arrays with high sensitivity over a wide dynamic range.

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.

Personalized Machine Learning-Coupled Nanopillar Triboelectric Pulse Sensor for Cuffless Blood Pressure Continuous Monitoring.

A wearable system that can continuously track the fluctuation of blood pressure (BP) based on pulse signals is highly desirable for the treatments of cardiovascular diseases, yet the sensitivity, reliability, and accuracy remain challenging. Since the correlations of pulse waveforms to BP are highly individualized due to the diversity of the patients' physiological characteristics, wearable sensors based on universal designs and algorithms often fail to derive BP accurately when applied on individual patients. Herein, a wearable triboelectric pulse sensor based on a biomimetic nanopillar layer was developed and coupled with Personalized Machine Learning (ML) to provide accurate and continuous monitoring of BP. Flexible conductive nanopillars as the triboelectric layer were fabricated through soft lithography replication of a cicada wing, which could effectively enhance the sensor's output performance to detect weak signal characteristics of pulse waveform for BP derivation. The sensors were coupled with a personalized Partial Least-Squares Regression (PLSR) ML to derive unknown BP based on individual pulse characteristics with reasonable accuracy, avoiding the issue of individual variability that was encountered by General PLSR ML or formula algorithms. The cuffless and intelligent design endow this ML-sensor as a highly promising platform for the care and treatments of hypertensive patients.

Interrogation on the Cellular Nano-Interface and Biosafety of Repeated Nano-Electroporation by Nanostraw System.

Cell perforation is a critical step for intracellular drug delivery and real-time biosensing of intracellular signals. In recent years, the nanostraws system has been developed to achieve intracellular drug delivery with minimal invasiveness to the cells. Repeated cell perforation via nano-system could allow delivery of multiple drugs into cells for cell editing, but the biosafety is rarely explored. In this work, a nanostraw-mediated nano-electroporation system was developed, which allowed repeated perforation of the same set of cells in a minimally invasive manner, while the biosafety aspect of this system was investigated. Highly controllable fabrication of Al2O3 nanostraw arrays based on a porous polyethylene terephthalate (PET) membrane was integrated with a microfluidic device to construct the nanostraw-electroporation system. The pulse conditions and intervals of nano-electroporation were systematically optimized to achieve efficient cells perforation and maintain the viability of the cells. The cells proliferation, the early apoptosis activities after nanostraw-electroporation and the changes of gene functions and gene pathways of cells after repeated nano-electroporation were comprehensively analyzed. These results revealed that the repeated nanostraw-electroporation did not induce obvious negative effects on the cells. This work demonstrates the feasibility of repeated nano-electroporation on cells and provides a promising strategy for future biomedical applications.