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.

Development of micro-and nanorobotics: A review

Micro-and nanorobotic is an emerging field of research arising from the cross-fusion of micro/nano technology and robotics and has become an important part of robotics. Micro-and nanorobots have the advantages of small size, low weight, large thrust-toweight ratio, high flexibility, and high sensitivity. Due to the characteristics distinguishing from macroscopic robots, micro-and nanorobots have stimulated the research interest of the scientific community and opened up numerous application fields such as drug delivery and disease diagnosis. In the past 30 years, research on micro-and nanorobots has made considerable progress.This article provides a comprehensive overview of the development of these robots. First, the application of the robots is reviewed. Then, the key components of the robots are discussed separately, covering their actuation, design, fabrication and control. In addition, from the perspectives of intelligence and sensing, clinical applications, materials and performance, the challenges that may be encountered in the development of such robots in the future are discussed. Finally, the entire article is summarized, and concepts for future micro-and nanorobots are described.

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.

Recent progress on the design and fabrication of micromotors and their biomedical applications

The advancement in the micro-/nanofabrication techniques has greatly facilitated the development of micromotors.A variety of micromotors have been invented with powerful functions,which have attracted a broad range of interests from chemistry, physics,mechanics,biology and medicine.In this paper,we reviewed recent progress in micromotors and highlighted representative works.The mechanisms of micromotors by internal and external energy sources were described.We described general fabrication strategies of the popular micromotors (wire,tubular,helical and Janus)including bottom-up and top-down approaches.In the application section,we primarily focused on the biological applications,such as biological cargo delivery, biosensing and surgery.At last,we discussed the current challenges and provided future prospects.

Bird’s Eye View on the Recent Advances in Drug Delivery Systems

Successful treatment of most of the diseases is limited by a lack of safe and effective methods of drug delivery. Drug delivery methods have significant effects on the pharmacological efficacy of a drug. Every drug has an optimum concentration range within which maximum benefit is derived;and concentrations above or below the range can be toxic or provide no therapeutic benefits at all. Therefore, development of an efficient drug delivery system remains an important challenge in medicine, and this can be achieved only through multidisciplinary approaches to the mechanisms of delivery of drugs to targets in tissues. Thus, several drug delivery and drug targeting systems are currently being developed. Targeting is an ability to direct the drug(s) to the desired site. There are two major mechanisms, viz., active and passive for drug targeting. Controlled drug release and subsequent biodegradation are also indispensable for developing successful formulations. Colloidal drug vehicles such as micelles, vesicles, liquid crystal dispersions, and nanomaterials consisting of miniscule nanoparticles of 5 - 200 nm diameter have shown great promise as drug delivery systems. In this context, past decades have witnessed certain major advancements. This review article emphasizes on these advances in the field of drug delivery systems.

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.

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.

基于集群纳米机器技术和合成生命化学的动态人工细胞

人工细胞构筑在基础和应用生物技术研究中具有重要意义.然而,现有的人工细胞区室化的构建往往是静态的,与动态的自然细胞存在差距.基于此,我们通过前沿磁控纳米机器技术和无细胞转录-翻译溶液化学系统来构筑一个可编程控制的动态人工细胞.通过物理控制二维或三维磁场的方向、强度和频率,基于不同形态的DNA和磁性颗粒产生不同形貌的簇、链和片等区室化排列.这些不同形貌的动态人工细胞结构呈现出特殊的转录-翻译性能.集群机器人技术和合成生命化学的融合利用可为构筑富有想象力的人工细胞提供新的研究范式,并为生命过程的理解和颠覆性的生物应用提供重要支撑.

Swarming magnetic photonic-crystal microrobots withon-the-fly visual pH detection and self-regulated drug delivery

Swarming magnetic micro/nanorobots hold great promise for biomedical applications,but at present suffer from inferior capabilities to perceive and respond to chemical signals in local microenvironments.Here we demonstrate swarming magnetic photonic crystal microrobots(PC-bots)capable of sponta-neously performing on-the-fly visual pH detection and self regulated drug delivery by perceiving local pH changes.The magnetic PC-bots consist of pH-responsive hydrogel microspheres with encapsulated one-dimensional periodic assemblies of Fe3O4 nanoparticles.By programming extemnal rotating magnetic fields,they can self-organize into large swarms with much-enhanced collective velocity to actively find targets while shining bright“blinking”structural colors.When approaching the target with abnormal pH conditions(e.g.an ulcerated superficial tumor lesion),the PC-bots can visualize local pH changes on the fly via pH-responsive structural colors,and realize self-regulated release of the loaded drugs by recognizing local pH.This work facilita tes the develop-ment of intelligent micro/nanorobots for active“motile-targeting”tumor diag-nosis and treatment.

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.

Light hybrid micro/nano-robots:From propulsion to functional signals

Untethered motile micro/nanorobots(MNRs)that can operate in hard-to-reach small space and perform noninvasive tasks in cellular level hold bright future in healthcare,nanomanufacturing,biosensing,and environmental remediation.Light,as a flexible encoding method with tunable freedom of intensity,wavelength,polarization,and propagation direction,endows unique spatialtemporal precision and dexterity to the manipulation of MNRs.Meanwhile,light has been extensively investigated as functional signals in bioimaging,phototherapy,as well as photoelectrochemical reactions.The hybridization of light and other actuation method ushers in novel MNRs with broadened design space,improved controllability,and advanced functionality.In this review,the fundamental mechanisms of light-driven MNRs will be revisited.On top of it,light hybrid systems,coupling with magnetic,electric,chemical,or ultrasound field,will be reviewed,with light for propulsion or as functional signal.The rational hybridization of multiple stimulus in MNRs not only promises simple combination of two driving forces,but more importantly,motivates rethinking of light-driven MNRs for unprecedented applications.

Design and analysis of an untethered micro flapping robot which can glide on the water

Flapping-wing flying insects possess various advantages,such as high agility and efficiency.The design and manufacture of insect-scale flapping-wing micro aerial vehicle(FWMAV)have attracted increasing attention in recent decades.Due to the limitations of size and weight,the FWMAV with an onboard battery which can fully mimic insect flight has not been achieved.In this work,we design and fabricate a highly integrated flapping-wing microrobot named Robomoth.The Robomoth consists of a carbon chassis,customized power and control devices,and two piezoelectric ceramic actuators symmetrically distributed in the thorax and controlled individually.It weighs 2.487 g,spans 5.9 cm in length,possesses 9 cm of wingspan,and carries a 0.355 g rechargeable lithium battery.We demonstrate the mobility of the Robomoth through untethered gliding and making turns on the water surface.A simplified dynamic model of the flapping system is proposed to explain the relationship between the driving frequency and the flapping amplitude.The Robomoth is one new untethered bioinspired flapping-wing robot that can perform stable water surface motion,which holds potential applications such as search and rescue on the water.The robot can also provide insight for designing insect-scale flying vehicles.

Extracellular Milieu and Membrane Receptor Dual-Driven DNA Nanorobot for Accurate in Vivo Tumor Imaging

Precise diagnostic approaches have great potential in cancer intervention and prognosis.Although diverse DNA nanoprobes have been reported for tumor diagnosis,precise tumor imaging in vivo still encounters a great challenge due to the scarcity of exquisite design methodology.Herein,by assembling three programmable modules on a DNA triangular prism,we engineered a DNA nanorobot for simultaneous recognition of extracellular pH and cancer cell membrane receptor in an intelligent manner.Since the design uses two heterogeneous types of biomarkers as inputs,pH-RE not only could discriminate target tumor cells from similar cell mixtures with a recognition accuracy as high as 98.8%,but also could perform precise tumor imaging in living mice by intravenous injection.We expect that this extracellular pH and membrane receptor dual-driven DNA nanorobot will facilitate the establishment of a novel design paradigm for precise cancer diagnosis and therapy.

A mathematical model for preventing HIV virus from proliferating inside CD4 T brownian cell using Gaussian jump nanorobot

We present a statistical distribution of a nanorobot motion inside the blood.This distribution is like the distribution of A and B particles in continuous time random walk scheme inside the fAuid reactive anomalous transport with stochastic waiting time depending on the Gaussian distribution and a Gaussian jump length which is detailed in Zhang and Li[J.Stat.Phys,Published Online with doi:10.1007/s10955-018-2185-8,2018].Rather than estimating the length parameter of the jumping distance of the nanorobot,we normalize the Probability Density Function(PDF)and present some reliability properties for this distribution.In addition,we discuss the truncated version of this distribution and its statistical properties,and estimate its length parameter.We use the estimated distance to study the conditions that give a finite expected value of the first meeting time between this nanorobot in the case of nonlinear flow with independent d-dimensional Gaussian jumps and an independent d-dimensional CD4 T Brownian cell in the blood(d-space)to prevent the HIV virus from proliferating within this cell.