Engineered Microneedles for Interstitial Fluid Cell‐Free DNA Capture and Sensing Using Iontophoretic Dual‐Extraction Wearable Patch

Interstitial fluid (ISF), as an emerging source of biomarkers, is unmistakably significant for disease diagnosis. Microneedles (MNs) provide a minimally invasive approach for extracting the desired molecules from ISF. However, existing MNs are limited by their capture efficiency and sensitivity, which impedes early disease diagnosis. Herein, an engineered wearable epidermal system is presented with a combination of reverse iontophoresis and MNs for rapid capture and sensing of Epstein‐Barr virus cell‐free DNA (an important biomarker of nasopharyngeal carcinoma). Owing to a dual‐extraction effect demonstrated by reverse iontophoresis and MNs, the engineered wearable platform successfully isolates the cell‐free DNA target from ISF within 10 min, with a threshold of 5 copies per µL and a maximum capture efficiency of 95.4%. The captured cell‐free DNA is also directly used in a recombinase polymerase amplification electrochemical microfluidic biosensor with a detection limit of 1.1 copies per µL (or a single copy). The experimental data from immunodeficient mouse models rationalizes the feasibility and practicality of the wearable system. Collectively, the developed method opens an innovative route for minimally invasive sampling of ISF for cell‐free DNA‐related cancer screening and prognosis.     

4D Printing of a Bioinspired Microneedle Array with Backward‐Facing Barbs for Enhanced Tissue Adhesion

Microneedle (MN), a miniaturized needle with a length‐scale of hundreds of micrometers, has received a great deal of attention because of its minimally invasive, pain‐free, and easy‐to‐use nature. However, a major challenge for controlled long‐term drug delivery or biosensing using MN is its low tissue adhesion. Although microscopic structures with high tissue adhesion are found from living creatures in nature (e.g., microhooks of parasites, barbed stingers of honeybees, quills of porcupines), creating MNs with such complex microscopic features is still challenging with traditional fabrication methods. Here, a MN with bioinspired backward‐facing curved barbs for enhanced tissue adhesion, manufactured by a digital light processing 3D printing technique, is presented. Backward‐facing barbs on a MN are created by desolvation‐induced deformation utilizing cross‐linking density gradient in a photocurable polymer. Barb thickness and bending curvature are controlled by printing parameters and material composition. It is demonstrated that tissue adhesion of a backward‐facing barbed MN is 18 times stronger than that of barbless MN. Also demonstrated is sustained drug release with barbed MNs in tissue. Improved tissue adhesion of the bioinspired MN allows for more stable and robust performance for drug delivery, biofluid collection, and biosensing.     

Cancer Stem Cell‐Platelet Hybrid Membrane‐Coated Magnetic Nanoparticles for Enhanced Photothermal Therapy of Head and Neck Squamous Cell Carcinoma

Cell membrane–based nanosystems with desirable characteristics have been studied extensively for many therapeutic applications. However, current research has focused on single cell membrane, and multifunctional fused membrane materials from different membrane types are still rare. Herein, a platelet–cancer stem cell (CSC) hybrid membrane‐coated iron oxide magnetic nanoparticle (MN) {[CSC‐P]MN} is presented for the first time for the enhanced photothermal therapy of head and neck squamous cell carcinoma (HNSCC). Inherited from the original source cells, the platelet membrane shows immune evading ability due to the surface marker comprising a number of “don't eat me” signals, and the CSC membrane has homotypic targeting capabilities due to the specific surface adhesion molecules. The [CSC‐P]MNs possess superior characteristics for immune evasion, active cancer targeting, magnetic resonance imaging, and photothermal therapy. Compared with single cell membrane–coated MNs, [CSC‐P]MNs exhibit prolonged circulation times and enhanced targeting abilities. Moreover, the [CSC‐P]MNs exhibit a superior photothermal ability that provides excellent HNSCC tumor growth inhibition, particularly in an immunocompetent Tgfbr1/Pten conditional double knockout HNSCC mouse model that contains a more complex tumor microenvironment that is similar to the human HNSCC microenvironment. Collectively, this biomimetic multimembrane‐coated nanoplatform may provide enhanced antitumor efficacy in the complex tumor microenvironment.     

Targeted Delivery of Anesthetic Agents to Bone Tissues using Conductive Microneedles Enhanced Iontophoresis for Painless Dental Anesthesia

Pain management during dental procedures is a cornerstone for successful daily practice. In current practice, the traditional needle and syringe injection is used to administer local anesthesia. However, the appearance of long needles and the pain associated with it often leads to dental anxiety deterring timely interventions. Microneedles (MNs) have emerged as a minimally invasive alternative to hypodermic needles and shown to be effective in transdermal drug delivery applications. In this article, the potential use of MNs for local anesthesia delivery in dentistry is explored. The development of a novel conductive MN array that can be used in combination with iontophoresis technique to achieve drug penetration through the oral mucosa and the underlying bone tissue is presented. The conductive MN array plays a dual-role, creating micro-conduits and lowering the resistance of the oral mucosa. The reduced tissue resistance further enhances the application of a low-voltage current that is able to direct and accelerate the drug molecules to target the sensory nerves supplying teeth. The successful delivery of lidocaine using this new strategy in a clinically relevant rabbit incisor model is shown to be as effective as the current gold standard.     

A mobility-based load control scheme in Hierarchical Mobile IPv6 networks

By introducing a mobility anchor point (MAP), Hierarchical Mobile IPv6 (HMIPv6) reduces the signaling overhead and handoff latency associated with Mobile IPv6. In this paper, we propose a mobility-based load control (MLC) scheme, which mitigates the burden of the MAP in fully distributed and adaptive manners. The MLC scheme combines two algorithms: a threshold-based admission control algorithm and a session-to-mobility ratio (SMR)-based replacement algorithm. The threshold-based admission control algorithm gives higher priority to ongoing mobile nodes (MNs) than new MNs, by blocking new MNs when the number of MNs being serviced by the MAP is greater than a predetermined threshold. On the other hand, the SMR-based replacement algorithm achieves efficient MAP load distribution by considering MNs’ traffic and mobility patterns. We analyze the MLC scheme using the continuous time Markov chain in terms of the new MN blocking probability, ongoing MN dropping probability, and binding update cost. Also, the MAP processing latency is evaluated based on the M/G/1 queueing model. Analytical and simulation results demonstrate that the MLC scheme outperforms other schemes and thus it is a viable solution for scalable HMIPv6 networks.     

Energy optimal channel attempt rate and packet size for ALOHA based underwater acoustic sensor networks

The fast mobile internet protocol version 6 (FMIPv6) was suggested as a fast handover mechanism over the mobile wireless Internets in order to reduce the handover latency of a mobile node (MN). However, FMIPv6 was originally designed to deal with single MN’s. In mobile wireless Internet, a multiple MNs may do a handover at the same time as a consequence of its movement from one network to another new one. This will therefore lead to the bandwidth waste and low handover performance. This paper intends to propose a multiple handover-based mobile node (MHB-MN) control method and an enhanced FMIPv6 mechanism in order to resolve the abovementioned problem. The proposal of such an MHB-MN method aims at having one mobile node work as a guide for a group of neighboring MNs. This means that the guide of MN prepares itself for a handover before actually taking the initial steps of the actual handover operation. Based on obtained results, it is plainly observable that by MHB-MN method, the handover initiation time, handover latency and handover control messages can be reduced compared to those of FMIPv6. Furthermore, the contention of the wireless channel for multiple MNs can be improved by the use of fewer control messages. Finally, the paper introduces an analytical model to show that by enabling the MHB-MN method and enhancing the FMIPv6 method, a multiple of nodes can perform rapid handover processes with low handover latency compared to that of the FMIPv6 technique.     

DMAP: integrated mobility and service management in mobile IPv6 systems

Mobile IPv6 (MIPv6) is a work in progress IETF standard for enabling mobility in IPv6 networks and is expected to have wide deployment. We investigate an integrated mobility and service management scheme based on MIPv6 with the goal to minimize the overall network signaling cost in MIPv6 systems for serving mobility and service management related operations. Our design extends IETF work-in-progress Hierarchical Mobile IPv6 (HMIPv6) with the notion of dynamic mobility anchor points (DMAPs) for each mobile node (MN) instead of static ones for all MNs. These DMAPs are access routers chosen by individual MNs to act as a regional router to reduce the signaling overhead for intra-regional movements. The DMAP domain size, i.e., the number of subnets covered by a DMAP, is based on the MN’s mobility and service characteristics. Under our DMAP protocol, a MN interacts with its home agent and application servers as in the MIPv6 protocol, but optimally determines when and where to launch a DMAP to minimize the network cost in serving the user’s mobility and service management operations. We demonstrate that our DMAP protocol for integrated mobility and service management yields significantly improved performance over basic MIPv6 and HMIPv6.     

Scheme for improving transmission performance of realtime traffic using priority queues in HMIPv6

Hierarchical Mobile IPv6 (HMIPv6) has been proposed by the Internet Engineering Task Force (IETF) to reduce handoff latency and signaling overhead. In the new protocol, Mobility Anchor Point (MAP) receives all packets in place of Mobile Node (MN) and MAP services are transferred to Care of Address (CoA) of MN. However, a MAP may be a single point of performance bottleneck because the MAP should not only handle signaling traffic but also process data tunneling traffic for all MNs registered in a MAP domain. So, MAPs need MAP management scheme for the multimedia services or real time services. We propose a MAP selection scheme that can select different MAPs according to the traffic characteristics of MNs and a multilevel queue processing method that can process binding updates based on the priorities of queues in a MAP when MNs send BU. Quantitative results of the performance analysis show that our proposal can reduce the location update cost by 31% and the total cost by 14%. With the multilevel queues, we could reduce the total cost by 12% and 17% for D=4 and D=8 respectively.     

Antitumor Platelet‐Mimicking Magnetic Nanoparticles

Nanoparticles possess the potential to revolutionize cancer diagnosis and therapy. The ideal theranostic nanoplatform should own long system circulation and active cancer targeting. Additionally, it should be nontoxic and invisible to the immune system. Here, the authors fabricate an all‐in‐one nanoplatform possessed with these properties for personalized cancer theranostics. Platelet‐derived vesicles (PLT‐vesicles) along with their membrane proteins are collected from mice blood and then coated onto Fe₃O₄ magnetic nanoparticles (MNs). The resulting core–shell PLT‐MNs, which inherit the long circulation and cancer targeting capabilities from the PLT membrane shell and the magnetic and optical absorption properties from the MN core, are finally injected back into the donor mice for enhanced tumor magnetic resonance imaging (MRI) and photothermal therapy (PTT). Meanwhile, it is found that the PTT treatment impels PLT‐MNs targeting to the PTT sites (i.e., tumor sites), and exactly, in turn, the enhanced targeting of PLT‐MNs to tumor sites can improve the PTT effects. In addition, since the PLT membrane coating is obtained from the mice and finally injected into the same mice, PLT‐MNs exhibit stellar immune compatibility. The work presented here provides a new angle on the design of biomimetic nanoparticles for personalized diagnosis and therapy of various diseases.     

A network-layer soft handoff approach for mobile wireless IP-based systems

Handoff is the process during which a mobile node (MN) needs to change its connectivity point to the wireless internetwork from one access node (AN) to another during an ongoing communication. If MNs are allowed to have two or more simultaneous connections to the internetwork through different ANs, then the handoff is said to be soft; otherwise, it is said to be hard. Traditionally, during forward-link soft handoff, multiple identical copies of each packet are simultaneously transmitted to the MN through the associated ANs. At the MN's physical-layer, the received signals are combined on a bit-by-bit basis resulting in improving the bit-error rate. However, this approach requires tight synchronization of the ANs involved in the soft handoff. In addition, as shown in the literature, the capacity often decreases due to the increase of the number of channels used by MNs during soft handoff. In this paper, we propose, analyze, simulate, and implement a soft handoff scheme called soft handoff over IP (SHIP) for forward-link that 1) overcomes the need for synchronization and 2) increases the capacity of the network. Through both analytic and simulation studies, we show that SHIP achieves significant performance improvements. We derive analytic expressions of the power-capacity relationship for two-dimensional (2-D) and one-dimensional (1-D) cell models. By comparing our scheme with the hard handoff, we empirically show that the capacity increases by about 30% and 20%, respectively, for the 2-D and 1-D cell models. Further, the simulation results show that SHIP saves up to 30% of the total power consumed by the ANs.     

Efficient Drug Delivery into Skin Using a Biphasic Dissolvable Microneedle Patch with Water-Insoluble Backing

Dissolvable microneedle patches (MNPs) enable simplified delivery of therapeutics via the skin. However, most dissolvable MNPs do not deliver their full drug loading to the skin because only some of the drug is localized in the microneedles (MNs), and the rest remains adhered to the patch backing after removal from the skin. In this work, biphasic dissolvable MNPs are developed by mounting water-soluble MNs on a water-insoluble backing layer. These MNPs enable the drug to be contained in the MNs without migrating into the patch backing due to the inability of the drugs to partition into the hydrophobic backing materials during MNP fabrication. In addition, the insoluble backing is poorly wetted upon MN dissolution in the skin, which significantly reduces drug residue on the MNP backing surface after application. These effects enable a drug delivery efficiency of >90% from the MNPs into the skin 5 min after application. This study shows that the biphasic dissolvable MNPs can facilitate efficient drug delivery to the skin, which can improve the accuracy of drug dosing and reduce drug wastage.     

DMAP-FR: Dynamic Mobility Anchor Points for Mobility,Service and Failure Recovery Management in Mobile IPv6 Systems

In this paper, we propose and analyze DMAP-FR, a mobility and service management scheme with failure recovery (FR) control in Mobile IPv6 systems. The basic idea behind DMAP-FR is to leverage access routers (ARs) running as regional mobility anchor points (MAPs) as in Hierarchical Mobile IPv6 (HMIPv6) for mobility and service management for mobile nodes (MNs). However, unlike HMIPv6, DMAP-FR allows the MAP of each MN to be determined dynamically based on the mobility and service characteristics of the MN and the failure behavior of ARs with the goal to minimize the network traffic. DMAP-FR incorporates fault tolerance mechanisms to allow the system to quickly recover from AR and MAP failures. We identify the best dynamic regional area size for the selection of MAP for each MN such that the overall network traffic due to servicing mobility, service and fault tolerance related operations is minimized. We demonstrate that DMAP-FR outperforms HMIPv6 for the same AR failure rate.     

Dynamic multi-step paging scheme in PMIPv6-based wireless networks

In Proxy Mobile IP (PMIPv6) networks, proxy-registrations are performed even for idle MNs, resulting in unnecessary signaling traffic. Although there have been many IP paging techniques aimed at reducing the unnecessary location update, they focus only on Mobile IP (MIP) since they had been developed before PMIPv6 was proposed. Thus, adopting existing IP paging support is not sufficient to support mobility in PMIPv6 networks. For more efficient support, we propose a dynamic multi-step paging scheme that pages an MN in multiple incremental steps instead of flooding paging messages to a whole paging area to significantly reduce the signaling traffic caused by the proxy location updates in the PMIPv6 networks. In addition, to improve the paging delay performance that may be deteriorated by the multi-step paging, the proposed scheme configures paging area dynamically to raise the efficiency of locating MNs. The size of a paging area is designed to be determined based on the speed of an MN. We also develop a thorough analytical model for evaluating the performance of the proposed scheme compared with a static paging scheme in terms of the signaling cost and the paging delay. Thorough analysis and simulation demonstrate that in the PMIPv6 network, our paging scheme can significantly reduce the signaling cost for IP paging, achieving a shorter paging delay, compared to that of a paging scheme with a fixed paging area.     

一种基于协作分集技术的切换机制

现有切换管理机制主要采用基于提前切换准备的方法来降低切换过程中的服务中断时间,但是这类切换机制对移动预测算法具有很高的依赖性,因而实际部署的效果不佳。为解决该问题,该文提出了基于协作分集技术的切换机制,通过在切换过程中引入异构协作分集,延长了切换过程中源基站能够为移动终端提供服务的时间,降低对移动预测算法的依赖,从而很好地解决了现有移动管理机制的不足。     

Load balancing and its performance evaluation for layer 3 and IEEE 802.21 frameworks in PMIPv6‐based wireless networks

Mobile IP (MIP) requires mobile nodes (MNs) to register with the home agents (HAs) whenever the MNs change their point of attachment (PoA: access point (AP) or base station (BS)) in different subnets. Thus, such registrations cause excessive signaling overhead and long service delay. To solve this problem, proxy mobile IPv6 (PMIPv6) has been proposed by the IETF NETLMM working group. In PMIPv6, a new entity called mobile access gateway (MAG) performs the mobility‐related signaling with the local mobility anchor (LMA) on behalf of the MN and establishes a tunnel with the LMA. However, a number of MNs must be associated with an MAG, which means that the MAG can be easily overloaded. Therefore, in this paper, we propose a load balancing mechanism among the MAGs in the PMIPv6 network. The PMIPv6 handover signaling procedure is extended to support the proposed load balancing mechanism. We also discuss using IEEE 802.21 Media Independent Handover (MIH) protocol for load balancing to determine the load status at the candidate PoAs, in addition to the load status at the candidate MAGs. To evaluate the performance, we analyze the average waiting time in the queue at the MAG. Through simulations and numerical analysis, we show that the proposed load balancing mechanism can produce less queueing delay at the MAG and a higher data transmission rate at the PoA than when a load balancing operation is not performed in the PMIPv6 network. Copyright © 2009 John Wiley & Sons, Ltd.     

Human gait recognition based on Haralick features

This paper proposes a supervised feature extraction approach that is capable of selecting distinctive features for the recognition of human gait under clothing and carrying conditions, thus improving the recognition performances. The principle of the suggested approach is based on the Haralick features extracted from gait energy image (GEI). These features are extracted locally by dividing vertically or horizontally the GEI locally into two or three equal regions of interest, respectively. RELIEF feature selection algorithm is then employed on the extracted features in order to select only the most relevant features with a minimum redundancy. The proposed method is evaluated on CASIA gait database (Dataset B) under variations of clothing and carrying conditions for different viewing angles, and the experimental results using k-NN classifier have yielded attractive results of up to 80% in terms of highest identification rate at rank-1 when compared to existing and similar state-of-the-art methods.     

Selecting sampling interval of transient response for the improved Prony method

A sampling interval selection scheme for use with the improved Prony method is proposed. Since natural frequency extraction is a numerically ill-conditioned problem, a small change in the sampling interval results in a large change in the extracted natural frequencies. From the perturbation of the eigenvectors of the matrix, the accuracy criterion of the extracted natural frequencies is derived. The proposed scheme is validated using natural frequency extraction from the synthetic response, the method of moments (MM) response, and the measured response.     

Microneedle Patch Integrated with Porous Silicon Confined Dual Nanozymes for Synergistic and Hyperthermia-Enhanced Nanocatalytic Ferroptosis Treatment of Melanoma

Superficial melanoma is the deadliest form of skin cancer without desirable clinically therapeutic options. Nanozymes, artificial nanomaterials with physicochemical performance and enzyme catalytic properties, have attracted considerable attention for antitumor therapy. However, the therapeutic efficiency of nanozymes is vulnerable to the tumor microenvironment (TME) and delivery process. Herein, a microneedle (MN) patch that integrates porous silicon (PSi) loaded with dual nanozymes is devised to bidirectionally regulate TME and accurately deliver nanocomplex to initiate ferroptosis for melanoma treatment. Benefitting from the channel confinement effect of PSi, the copper-doped graphene quantum dots and palladium nanoparticles coloaded PSi (CuGQD/PdNPs@PSi) exhibit synergistic effect with enhanced mimicking peroxidase and glutathione oxidase activities, which are ≈2–3-fold higher than those of monoconfined nanozyme or nonconfined nanozyme complexes. Additionally, the synergistic catalytic performance of CuGQD/PdNPs@PSi can be improved via photostimuli hyperthermia. The CuGQD/PdNPs@PSi can induce ferroptosis manifested by upregulation of lipid peroxides and inactivation of glutathione peroxidase 4. Furthermore, loading of nanocomplexes into MNs for administration resulted in a satisfactory melanoma growth inhibition of 98.8% within 14 days. Therefore, MNs encapsulated with CuGQD/PdNPs@PSi can provide a potentially nanocatalytic strategy for ferroptosis-inducing tumor treatment while also meeting the medical needs of eradicating superficial tumors.     

Efficient routing for wireless mesh networks using a backup path

Wireless mesh networks (WMNs) have a proven record in providing viable solutions for some of the fundamental issues in wireless networks such as capacity and range limitations. WMN infrastructure includes clusters of mobile ad‐hoc networks connected through a fixed backbone of mesh routers. The mesh network can be constrained severely because of various reasons, which could result in performance degradation such as a drop in throughput or long delays. Solutions to this problem often focus on multipath or multichannel extensions to the existing ad‐hoc routing protocols. In this paper, we propose a novel solution by introducing an alternative path to the mesh backbone that traverses the mobile ad‐hoc networks part of the WMN. The new routing solution allows the mobile nodes (MNs) to establish direct communication among peers without going through the backbone. The proposed alternative ad‐hoc path is used only when the mesh backbone is severely constrained. We also propose, for the first time in WMNs, using MNs with two interfaces, one used in the mesh backbone communication and the other engaged in the ad‐hoc network. A scheme is presented for making the MN aware of link quality measures by providing throughput values to the ad‐hoc on‐demand distance vector protocol. We use piggybacking on route reply messages in ad‐hoc on‐demand distance vector to avoid incurring additional costs. We implemented our solution in an OPNET simulator and evaluated its performance under a variety of conditions. Simulation results show that the alternative ad‐hoc path provides higher throughput and lower delays. Delay analysis show that the throughput improvement does not impose additional costs. Copyright © 2012 John Wiley & Sons, Ltd.     

雷达遥感农业应用综述

雷达遥感具有全天时、全天候监测的能力,对植被具有一定的穿透能力,对植被散射体形状、结构、介电常数敏感;这些特性使得其在农业应用中极具潜力。该文首先介绍了雷达遥感在农业中的应用领域,概略总结了目前在农作物识别与分类、农田土壤水分反演、农作物长势监测等多个领域研究的综述文献;然后分别阐述了雷达散射计和各类SAR特征(包括:SAR后向散射特征、极化特征、干涉特征、层析特征)在农业各领域中应用的现状和取得的研究成果,最后结合农业应用需求和SAR技术发展总结了目前研究中存在的问题和原因,并对未来的发展进行了展望。