Magnetic Helical Micro-and Nanorobots:Toward Their Biomedical Applications

Magnetic helical micro- and nanorobots can perform 3D navigation in various liquids with a sub- micrometer precision under low-strength rotating magnetic fields （〈 10 rer）. Since magnetic fields with low strengths are harmless to cells and tissues, magnetic helical micro/ nanorobots are promising tools for biomedical applications, such as minimally invasive surgery, cell manipulation and analysis, and targeted therapy. This review provides general information on magnetic helical micro/nanorobots, including their fabrication, motion control, and further functionalization for biomedical applications.

Untethered Micro/Nanorobots for Remote Sensing:Toward Intelligent Platform

Untethered micro/nanorobots that can wirelessly control their motion and deformation state have gained enormous interest in remote sensing applications due to their unique motion characteristics in various media and diverse functionalities.Researchers are developing micro/nanorobots as innovative tools to improve sensing performance and miniaturize sensing systems,enabling in situ detection of substances that traditional sensing methods struggle to achieve.Over the past decade of development,significant research progress has been made in designing sensing strategies based on micro/nanorobots,employing various coordinated control and sensing approaches.This review summarizes the latest developments on micro/nanorobots for remote sensing applications by utilizing the self-generated signals of the robots,robot behavior,microrobotic manipulation,and robot-environment interactions.Providing recent studies and relevant applications in remote sensing,we also discuss the challenges and future perspectives facing micro/nanorobots-based intelligent sensing platforms to achieve sensing in complex environments,translating lab research achievements into widespread real applications.

Swarming Responsive Photonic Nanorobots for Motile-Targeting Microenvironmental Mapping and Mapping-Guided Photothermal Treatment

Micro/nanorobots can propel and navigate in many hard-to-reach biological environments,and thus may bring revolutionary changes to biomedical research and applications.However,current MNRs lack the capability to collectively perceive and report physicochemical changes in unknown microenvironments.Here we propose to develop swarming responsive photonic nanorobots that can map local physicochemical conditions on the fly and further guide localized photothermal treatment.The RPNRs consist of a photonic nanochain of periodically-assembled magnetic Fe_(3)O_(4)nanoparticles encapsulated in a responsive hydrogel shell,and show multiple integrated functions,including energetic magnetically-driven swarming motions,bright stimuli-responsive structural colors,and photothermal conversion.Thus,they can actively navigate in complex environments utilizing their controllable swarming motions,then visualize unknown targets(e.g.,tumor lesion)by collectively mapping out local abnormal physicochemical conditions(e.g.,pH,temperature,or glucose concentra-tion)via their responsive structural colors,and further guide external light irradiation to initiate localized photothermal treatment.This work facilitates the development of intelligent motile nanosensors and versatile multifunctional nanotheranostics for cancer and inflam-matory diseases.

Injectable Nanorobot-Hydrogel Superstructure for Hemostasis and Anticancer Therapy of Spinal Metastasis

Surgery remains the standard treatment for spinal metastasis.However,uncontrolled intraoperative bleeding poses a significant challenge for adequate surgical resection and compromises surgical outcomes.In this study,we develop a thrombin(Thr)-loaded nanorobothydrogel hybrid superstructure by incorporating nanorobots into regenerated silk fibroin nanofibril hydrogels.This superstructure with superior thixotropic properties is injected percutaneously and dispersed into the spinal metastasis of hepatocellular carcinoma(HCC)with easy bleeding characteristics,before spinal surgery in a mouse model.Under near-infrared irradiation,the self-motile nanorobots penetrate into the deep spinal tumor,releasing Thr in a controlled manner.Thr-induced thrombosis effectively blocks the tumor vasculature and reduces bleeding,inhibiting tumor growth and postoperative recurrence with Au nanorod-mediated photothermal therapy.Our minimally invasive treatment platform provides a novel preoperative therapeutic strategy for HCC spinal metastasis effectively controlling intraoperative bleeding and tumor growth,with potentially reduced surgical complications and enhanced operative outcomes.

Enzyme-driven Nanorobots Walking Along Predesigned Tracks on the DNA Origami for Cargo Transport and Catalysis

In molecular engineering,designing and synthesizing molecular machines with capable of performing complex tasks,remains a formidable challenge.DNA is an excellent candidate for building molecular robots because it is highly programmable.Here,we present an artificial nanorobot,in which a DNA cube serves as the inert‘body’,and nucleic acid catalysts based on an enzymatic nicking reaction act as the‘legs’for walking.The nanorobot can execute a series of actions,such as‘start’,‘turn’,and‘stop’when it walks along a predefined track.Its performance could be confirmed and monitored by using an atomic force microscope(AFM)and fluorescence spectroscopy.Inspired by biological machines,we artificially designed a series of specialized tasks that combined walking with control of cargo transport and catalysis.Real-time fluorescence kinetics curves provide monitoring signals for cargo transport and catalytic processes.Our work can enrich the toolbox of DNA machinery and has great potential for engineering molecular nanofactories.

Blade-Coated Porous 3D Carbon Composite Electrodes Coupled with Multiscale Interfaces for Highly Sensitive All-Paper Pressure Sensors

Flexible and wearable pressure sensors hold immense promise for health monitoring,covering disease detection and postoperative rehabilitation.Developing pressure sensors with high sensitivity,wide detection range,and cost-effectiveness is paramount.By leveraging paper for its sustainability,biocompatibility,and inherent porous structure,herein,a solution-processed all-paper resistive pressure sensor is designed with outstanding performance.A ternary composite paste,comprising a compressible 3D carbon skeleton,conductive polymer poly(3,4-ethylene dioxythiophene):poly(styrenesulfonate),and cohesive carbon nanotubes,is blade-coated on paper and naturally dried to form the porous composite electrode with hierachical micro-and nano-structured surface.Combined with screen-printed Cu electrodes in submillimeter finger widths on rough paper,this creates a multiscale hierarchical contact interface between electrodes,significantly enhancing sensitivity(1014 kPa-1)and expanding the detection range(up to 300 kPa)of as-resulted all-paper pressure sensor with low detection limit and power consumption.Its versatility ranges from subtle wrist pulses,robust finger taps,to large-area spatial force detection,highlighting its intricate submillimetermicrometer-nanometer hierarchical interface and nanometer porosity in the composite electrode.Ultimately,this all-paper resistive pressure sensor,with its superior sensing capabilities,large-scale fabrication potential,and cost-effectiveness,paves the way for next-generation wearable electronics,ushering in an era of advanced,sustainable technological solutions.

缉“毒”除污的微纳米机器人

现代社会中,化学和相关工业的快速发展导致水环境污染问题日益严重,这对水质检测以及水资源的处理技术提出了更高的要求,然而目前尚难以快速、高效地实现对低浓度、痕量的污染物的检测和处理。为此,科学家们设计出一类新型的智能材料——微纳米机器人。基于微纳米机器人的可控运动性能、精准识别能力、高效吸附效果和原位降解能力,可以对痕量污染物建立高灵敏度的响应,从而实现水中污染物的有效检测与处理。为了能够让广大读者深入理解微纳米机器人在水污染检测和处理领域的发展前沿和未来研究趋势,本文以微纳米机器人组织“污染刺客联盟”为背景,简单有趣地介绍了微纳米机器人在水环境检测、监测和处理方面的应用及其科学机理。

Nanorobotic Agents Communication Using Bee-Inspired Swarm Intelligence

The main goal of this paper is to design nanorobotic agent communication mechanisms which would yield coordinated swarm behavior. Precisely we propose a bee-inspired swarm control algorithm that allows nanorobotic agents communication in order to converge at a specific target. In this paper, we present experiment to test convergence speed and quality in a simulated multi-agent deployment in an environment with a single target. This is done to measure whether the use of our algorithm or random guess improves efficiency in terms of convergence and quality. The results attained from the experiments indicated that the use of our algorithm enhance the coordinated movement of agents towards the target compared to random guess.

Nanorobot Drug Delivery System for Curcumin for Enhanced Bioavailability during Treatment of Alzheimer’s Disease

Robotics has emerged as a collegiate course about 20 years ago at Stanford University, Stanford, CA. From the first IRB6, the electrically powered robot in 1974, the industry has grown over a 30-year period. A leading supplier of robots has put out over 100,000 robots by year 2001. Robot capable of handling 500 kg load was introduced in 2001, IRB 7000. A number of advances have been made in nanostructuring. About 40 different nanostructuring methods were reviewed recently [1]. Nanobots can be developed that effect cures of disorders that are difficult to treat. Principles from photodynamic therapy, fullerene chemistry, nanostructuring, X-rays, computers, pharmacokinetics and robotics are applied in a design of nanorobot for treatment of Alzheimer’s disease. The curcuma longa that has shown curative effects in rats’ brain with Alzheimer’s is complexed with fullerenes. The drug is inactive when caged. It is infused intrathecally into the cerebrospinal system. Irradiation of the hypothalamous and other areas of the brain where Alzheimer’s disease is prevalent lead to breakage of fullerenes and availability of the drug with the diseased cells. Due to better mass transfer, better cure is affected. The other plausible reactions such as addition polymerization of fullerene, polycurcumin formation and other hydrolysis reactions are modeled along with the drug action under the Denbigh scheme of reactions. The fractional yield of drug-curcumin interaction is a function of intensity of radiation, frequency of radiation, patient demographics, age, gender, and other disorders etc. Chromophore in curcumin is used as a sensor and computer imaging and feedback control design can result in more bioavailability for curcumin therapeutic action to cure Alzheimer’s disease. This study examines the principles used in the design, the strategy of the design of the nanorobot drug delivery system with a specific target and pharamacokinetic formulation of the associated competing parallel reactions. The burrow and link capabilities at a nanoscopic level are also available if needed.

基于专利引文网络的医用纳米机器人技术前沿识别研究

目的 通过对医用纳米机器人的专利分析识别技术前沿。方法 本研究以德温特专利数据库收录的专利为研究对象,采用主题检索的方式对医用纳米机器人的专利进行检索分析。采用Ucinet软件对2016—2021年的专利绘制专利共被引网络,对引文网络中的专利进行聚类分析并采用VOSViewer可视化,通过对聚类结果解读以识别技术前沿。结果 医用纳米机器人领域共有专利213项,2016—2021年专利数量152项,该领域专利数量占比接近70%。2016—2021年申请的专利共引用专利1071项,其中被引频次>2次的专利用于构建共被引网络,形成2个专利引文网络,第1个引文网络包含5项专利,识别出2个技术前沿,分别为三维电磁驱动技术、磁感应式药物递送系统;第2个引文网络包含11项专利,识别出3个技术前沿,分别为纳米药物载体、磁性纳米粒子、纳米机器人制备技术。结论 本研究通过对医用纳米机器人领域的专利引文网络分析,识别该领域的技术前沿,可以从情报学角度为医用纳米机器人研发提供信息支撑。

CURRENT TRENDS OF MICRO-AND NANOMECHANICS

Introduction Scaling down to the micro- and nanoscale is a strong current trend in the development of science and technology. ＇Small is energy efficient and cost effective＇ has long been for the motto of the semiconductor industry, including micro- and nanoelectronics, micro-electro-mechanical systems （MEMS） and nanoelectro-mechanical systems （NEMS）.

磁场驱动用螺旋碳纳米线截断筛选及磁性修饰

为实现螺旋碳纳米线新型微纳米机器人磁场驱动运动,开展了螺旋碳纳米线截断、磁性修饰及磁场驱动运动研究。提出硝酸氧化-超声振动-滤纸过滤的长度截断筛选方法,实现了螺旋碳纳米线分散且可控截取长度2~8μm。实验对比研究了磁控溅射镍、化学镀镍、水热法生长Fe_(3)O_(4)纳米颗粒的磁性修饰方法。通过扫描电子显微镜、能量色散X射线谱分析等方法对修饰效果进行了评价,获得了具有较强磁性的螺旋碳纳米线。微流道液体中磁场驱动特性实验表明:磁控溅射修饰的螺旋碳纳米线可实现较为快速(3.35μm/s)的微纳米机器人运动特性,轨迹运动精度可控小于5μm。

Ultrasound-driven BaTiO_(3) nanorobots patching immunologic barrier to cure chronic rheumatoid arthritis

The disruption and reconstruction of the TREM2^(+) tissue resident macrophage(TRM)barrier on the surface of synovial lining play a key role in the activation and"remission"of rheumatoid arthritis(RA),which engender the prediction of this immunologic barrier as a potential driver for the achievement of"cure"in RA.However,strategies to promote the reconstruction of this barrier have not been reported,and the effect of patching this barrier remains unidentified.On the other hand,appropriate piezoelectric stimulation can reprogram macrophages,which has never been exerted on this barrier TRM yet.Herein,we design piezoelectric tetragonal BaTiO_(3)(BTO)ultrasound-driven nanorobots(USNRs)by the solvothermal synthesis method,which demonstrates satisfactory electro-mechanical conversion effects,paving the way to generate controllable electrical stimulation under ultrasound to reprogram the barrier TRM by minimally invasive injection into joint cavity.It is demonstrated that the immunologic barrier could be patched by this USNR effectively,thereby eliminating the hyperplasia of vessels and nerves(HVN)and synovitis.Additionally,TREM2 deficiency serum-transfected arthritis(STA)mice models are applied and proved the indispensable role of TREM2 in RA curing mediated by USNR.In all,our work is an interesting and important exploration to expand the classical tetragonal BTO nanoparticles in the treatment of autoimmune diseases,providing a new idea and direction for the biomedical application of piezoelectric ceramics.

Intelligent micro/nanorobots for improved tumor therapy

A major bottleneck underlying nanomaterial-based tumor therapy lies in complex biological environment and physiological barriers.Micro/nanorobots with the features of self-propulsion and controllable navigation have gradually become a research hotspot in the tumor therapeutic community,exhibiting their advantages in efficient cargo loading,controllable cargo delivery,stimulitriggered cargo release,deeper tumor tissue penetration,and enhanced cargo accumulation in tumor tissue.In this review,the self-propulsion and controllable navigation are introduced as two major properties of micro/nanorobots,in which micro/nanorobots are propelled by chemical reactions,physical fields,and biological systems and could be navigated by chemotaxis,remote magnetic guidance,and light.Then,the recent advances of micro/nanorobots for chemotherapy,immunotherapy,photothermal therapy,photodynamic therapy,chemodynamic therapy,and multimodal tumor therapy would be discussed.Finally,the perspective and challenges are also mentioned.It is expected that this review gives an insight into intelligent micro/nanorobots for improved tumor therapy,aiming for more extensive and in-depth investigations,and final applications in the clinic.

微纳米机器人在肿瘤治疗领域的研究进展

综述了近年来国内外关于微纳米机器人在肿瘤治疗领域的研究进展。首先介绍微纳米机器人及其驱动方式,归纳每种驱动方式的优势、局限及适用场景,从细胞/亚细胞的尺寸和优异的运动性能两方面论述微纳米机器人在肿瘤药物精准递送中具备的独特优势,并从逆血流主动运动、增强高渗透长滞留(EPR)效应和突破生物屏障的角度展开分析。重点阐述了微纳米机器人在化学治疗、光学治疗、免疫治疗、栓塞治疗等肿瘤传统疗法和新兴疗法中的治疗原理、作用机制及应用前景,在此基础上提出微纳米机器人在肿瘤治疗领域当前面临的挑战及应对策略,并对未来的发展方向进行了展望。

治疗癌症的“奇兵”——微纳米马达

目前癌症的发病率正在逐渐上升,为实现精准且低毒害的治疗目标,科学家们设计了智能的微纳米马达材料。这类微小的智能装置可在外界条件控制下靶向于甚至进入癌细胞,从而靶向运输药物,最终实现癌症的治疗。为了使这项技术得到更广泛的认识,本文采用拟人化手法,以微纳米马达与免疫细胞共同消灭癌细胞的故事为主体,简单介绍微纳米马达的制备、驱动方式以及治疗原理。

以纳米机器人为载体在癌症靶向治疗方面的优势和展望

随着纳米技术的飞速发展,纳米级别的机器人也更多的应用到外科手术领域。纳米机器人由于其微纳级的体积、可智能化操作和对人体内的创伤小等优点,常常作为纳米载体,携带抗肿瘤药物深入病灶部位进行治疗。本文结合靶向治疗的各种方法,对使用纳米机器人携带药物治疗恶性肿瘤展开深入的研究与探讨,介绍了纳米机器人靶向治疗的基本原理,分析了靶向治疗相比于传统疗法的优势与缺陷,并做出了总结和对未来提出了可行的展望。

Pushing the frontiers: Chip-based detection based on micro-and nano-structures

Changes in trace substances in human metabolites, which are related to disease processes and health status, can serve as chemical markers for disease diagnosis and symptom monitoring. Real-time online detection is an inevitable trend for the future of health monitoring, and the construction of chips for detection faces major challenges. The response of sensors often fails to meet the requirements for chipbased detection of trace substances due to the low efficiency of interfacial heterogeneous reactions, necessitating a rational design approach for micro-and nano-structures to improve sensor performance with respect to sensitivity and detection limits. This review focuses on the influence of micro-and nanostructures that used in chip on sensing. Firstly, this review categorizes sensors into chemiresistors, electrochemical sensors, fluorescence sensors, and surface enhanced Raman scattering(SERS) sensors based on their sensing principle, which have significant applications in disease diagnosis. Subsequently, commencing from the application requirements in the field of sensing, this review focuses on the different structures of nanoparticle(NP) assemblies, including wire, layered, core-shell, hollow, concave and deformable structures. These structures change in the size, shape, and morphology of conventional structures to achieve characteristics such as ordered alignment, high specific surface area, space limitation,vertical diffusion, and swaying behavior with fluid, thereby addressing issues such as poor signal transmission efficiency, inadequate adsorption and capture capacity, and slow mass transfer speed during sensing. Finally, the design direction of micro-and nano-structures, and possible obstacles and solutions to promote chip-based detection have been discussed. It is hope that this article will inspire the exploration of interface micro-and nano-structures modulated sensing methods.

未来采油工程新技术——纳米机器人

纳米机器人是根据分子水平生物学设计制造的在纳米空间进行操作的"功能分子器件",已广泛应用于医疗和军事领域。近年来提出的采油纳米机器人在驱替过程中,能够了解井间基质、裂缝和流体性质,以及与油气生产相关变化;测量油藏的储层参数、液体参数、流体和地层界面的空间分布等;纳米机器人的作用已被沙特阿美公司2010年6月在Arab-D地层中注入的纳米机器人取得里程碑式的研究进展所证实。但油藏中如何布署纳米机器人、如何对纳米机器人在油藏中进行遥测和定位、纳米机器人如何探测注入(渗流)通道以外的油气资源等问题有待解决和面临着很多挑战。尽管在储层改造、清蜡降黏、油层解堵、原油驱替、污水处理等采油工程技术领域真正应用的纳米机器人还有一段距离,但正是纳米机器人在采油工程领域近乎无限的可能性,有助于延长油井开采时间和减缓油田自然递减,从而展望纳米机器人将会有较好的应用前景。