Article Cite This: Acc. Chem. Res. 2018, 51, 3006−3014
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Intelligent Micro/nanomotors with Taxis Published as part of the Accounts of Chemical Research special issue “Fundamental Aspects of Self-Powered Nano- and Micromotors”. Ming You,† Chuanrui Chen,† Leilei Xu,† Fangzhi Mou,*,† and Jianguo Guan*,†,‡ †
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State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, Wuhan University of Technology, Wuhan 430070, P. R. China ‡ International School of Materials Science and Engineering, Wuhan University of Technology, Wuhan 430070, P. R. China CONSPECTUS: Micro/nanomotors (MNMs) are micro/nanoscale devices that can convert energy from their surroundings into autonomous motion. With this unique ability, they may revolutionize application fields ranging from active drug delivery to biological surgeries, environmental remediation, and micro/nanoengineering. To complete these applications, MNMs are required to have a vital capability to reach their destinations. Employing external fields to guide MNMs to the targets is common and effective way. However, in application scenarios where targets are generally unknown or dynamically change, MNMs must possess the capability of selfnavigation or self-targeting. Taking advantage of tactic movements toward or away from signal sources, numerous intelligent MNMs with self-navigation or self-targeting have been demonstrated and attracted much attention during the past few years. In this Account, we elucidate the intelligent response mechanisms of such tactic MNMs, which are summarized as two main models. One is that local vector fields, including those of chemical concentration gradients, gravity, flows, and magnetic fields existing in systems, achieve the overall alignment of asymmetric MNMs via aligning torques, directing the MNMs to swim toward or away from the signal sources. Another is that isotropic MNMs may produce propulsion forces with direction solely determined by the local vector field regardless of their Brownian rotations. Then we discuss and highlight the recent progress in tactic MNMs, including chemotactic, phototactic, rheotactic, gravitactic, and magnetotactic motors. Artificial chemotactic MNMs can be designed with different morphologies and compositions if asymmetric reactions are associated with chemical concentration gradients. In these systems, asymmetric phoretic slip flows are induced, leading to torques that enable the anisotropic particles to align and exhibit chemotaxis. For phototactic MNMs, light irradiation establishes asymmetric fields surrounding the motors via light-induced chemical reactions or physical effects to generate phototactic motion. Shapeasymmetric MNMs reorient in natural fluid flows because of torques applied by the flows, inducing rheotactic movements. MNMs with either the centroid or magnetic components distributed asymmetrically maintain orientation under the torque triggered by gravity or magnetic forces, generating tactic motions. In the end, we envision the future development of synthetic tactic MNMs, including enhancement of the sensitivity of motors to target signals, increasing the diversity of chemical motor systems, and combining multiple mechanisms to endow the tactic motors with multiple functionality. By highlighting the current achievements and offering our perspective on tactic MNMs, we look forward to inspiring the emergence of the next generation of intelligent MNMs with taxis. light,9−12 magnetic fields,6,13,14 ultrasound,15,16 electric fields,17−19 and temperature,20 under the condition that the motors are always effectively monitored and the targets are determinate. However, for uncertain or dynamically changing environments, motors must self-adaptively move to the target locations and fulfill the tasks. This requires MNMs to be intelligent rather than manipulated by alteration of external signals. In nature, many living organisms perform tactic behaviors after millions of years of evolution. They are able to sense
1. INTRODUCTION Micro/nanomotors (MNMs) are artificial micro/nanoscale devices that can harvest energy from their surroundings and convert it into mechanical energy to generate autonomous motion.1−3 With the small size and autonomous propulsion, they are considered to have potential revolutionary applications in environmental remediation,4−7 biomedicine,8 etc. To complete these tasks, MNMs are indispensably required to exhibit controllable or purposeful motion to reach target locations while they are vulnerable to the constant perturbation of Brownian random motion or local fluid flow. This has led to the development of various motion manipulation strategies based on external fields, including © 2018 American Chemical Society
Received: June 20, 2018 Published: November 16, 2018 3006
DOI: 10.1021/acs.accounts.8b00291 Acc. Chem. Res. 2018, 51, 3006−3014
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Accounts of Chemical Research surrounding environmental changes (which are generally the vector fields given by signal sources) and accordingly move toward or away from specific locations. These phenomena are known as taxis. For example, in dark environments many insects fly toward light sources. Bacteria like Escherichia coli meander toward or away from sources of nutrients or threats by temporally sensing the chemical gradient and accordingly regulating flagellar rotations through complex signal processing.21−23 Inspired by the tactic behaviors of organisms, growing efforts have been devoted to the development of intelligent MNMs that are capable of achieving self-navigation and self-targeting. Early in 2007, Hong et al.24 observed that Pt/Au bimetallic rods accumulate near H2O2-secreting gel. After this, a large number of artificial tactic motors emerged, such as chemotactic Janus spheres and microtubes,25 magnetotactic motors with magnetic anisotropy,26,27 phototactic isotropic semiconductor microspheres28 and nanotrees,29 and rheotactic motors with shape asymmetry.30,31 With vector fields, such as chemical concentration gradient, light, fluid flow, gravity, and magnetic fields, tactic motors can regulate their motions to move toward or away from target locations, achieving intelligent selfnavigation and self-targeting. This Account first expounds the basic principle for generating artificial tactic movements and then discusses artificial tactic motors developed to date. It ends with a summary of the remaining obstacles, possible solutions, and an outlook on the future development of tactic MNMs. With continuous and bursting innovation in this field, artificial MNMs with taxis are expected to become the next generation of intelligent MNMs, offering revolutionary techniques for practical applications such as biomedicines, environmental remediation, and micro/nanoengineering.
Figure 1. Schematic illustration of the tactic mechanisms of MNMs. (A, B) The tactic motion of asymmetric MNMs based on their reorientation under a vector field due to the indirect and direct aligning torque (M). (A) In the presence of a chemical gradient (∇C), the asymmetric MNM is subjected to an indirect phoretic aligning torque (MP) and thus is reoriented along the direction of the chemical gradient. The curved trajectory (red dashed line) occurs because MP is not strong enough to suppress the rotational Brownian diffusion of the MNM. (B) In a vector field of gravity, flow, magnetic field, etc., the asymmetric MNM receives a direct torque (MF) that aligns it along the vector field and usually exhibits a straight-line trajectory (red dashed line), as MF dominates over the rotational Brownian forces. (C) Tactic motion of an isotropic MNM exerted by photoinduced propulsion forces regardless of its Brownian rotations.
temporally or continuously along the vector field to move toward or away from the source. However, MNMs generally rotate randomly because of their small size and the rotational Brownian diffusion, governed by rotational Brownian diffusion coefficient (DR), as described by eq 3:35
2. MECHANISMS OF TACTIC MOVEMENTS In a system with a signal source, a vector field is established by the signal source. Once a tactic MNM wanders into the system, it interacts with the local vector field, resulting in movement toward or away from the signal source. This is equivalent to sensing of the signal source by the MNM. A tactic MNM in the vector field possesses an effective potential energy Utaxis (color map in Figure 1), and it moves toward or away from the source to lower the total potential energy.32−34 Utaxis is determined by the property of the vector field and that of the MNM itself, as described in eq 1: Utaxis = sm ·μ(x)
DR = kBT /8πηR 03
where kBT is the thermal energy, η is the viscosity of the liquid, and R0 is the radius of the particle. Random rotations caused by Brownian motion mostly make the symmetry axis of MNMs misaligned with the local vector field. Hence, synthetic tactic MNMs need to respond to the local vector field usually in the following two models to realize taxis. In the first model, MNMs with asymmetric structures (Figure 1A,B) usually experience an aligning torque M resulting from the indirect or direct interaction with a local vector field, such as that of a chemical concentration gradient, gravity, flow, or magnetic field. M orients the MNMs temporally or continuously, and thereby, the MNMs acquire the directional propulsion forces to seek or escape from the source. Another model is that isotropic MNMs may produce propulsion forces whose direction is solely determined by the local vector field regardless of their Brownian rotations (Figure 1C). In regard to the response of asymmetric MNMs to concentration gradients of chemicals, such as fuels and motor−fuel reaction regulators, various chemotactic MNMs have been developed. As shown in Figure 1A, when a chemotactic MNM is misaligned with the direction of the chemical gradient, the chemical products will be asymmetrically distributed on two sides of the symmetry axis of the MNM. This makes its propulsion force deviate from its
(1)
where μ(x) is the effective potential of the vector field, which depends on the position x relative to the signal source, and sm is a parameter denoting the response of the MNM to the vector field. The effective potential energy of tactic MNMs at the signal source is set to be zero. The direction of tactic movements is determined by the sign of sm: for sm > 0, the MNM exhibits positive taxis by moving toward the signal source; in the case of sm < 0, the MNM moves away from the signal source and exhibits negative taxis. The gradient of Utaxis (∇Utaxis) can be physically regarded as a force (Ftaxis) (eq 2), Ftaxis = −∇Utaxis
(3)
(2)
suggesting that the taxis of the MNM is based on the effective attraction/repulsion between the tactic MNM and the source. To achieve effective attraction/repulsion between tactic MNMs and a signal source and thus realize tactic motions, MNMs have to acquire directional propulsion forces 3007
DOI: 10.1021/acs.accounts.8b00291 Acc. Chem. Res. 2018, 51, 3006−3014
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Accounts of Chemical Research
Figure 2. Synthetic chemotactic MNMs. (A) Aggregation of Pt/Au bimetallic rods near the H2O2-secreting agarose gel. Reproduced with permission from ref 24. Copyright 2007 American Physical Society. (B) SiO2/Pt Janus and Ti/Pt microtubular MNMs: (a) rotational diffusion scheme; (b) Janus MNMs and (c) microtubes deviating toward the region of higher H2O2 concentration. Reproduced with permission from ref 25. Copyright 2013 Wiley-VCH. (C) Doxorubicin (Dox)- and Pt NP-loaded stomatocyte MNMs: (a) average velocities of the MNMs and the Doxloaded MNMs upon addition of solutions with different concentrations of H2O2 and (b) time-lapse images of the movement of a single MNM (green circle). Reproduced with permission from ref 41. Copyright 2015 Wiley-VCH. (D) Self-propelled oil droplet driven by a surfactant concentration gradient. The inset shows the propulsion mechanism of the chemotactic oil droplet. Reproduced from ref 37. Copyright 2009 American Chemical Society. (E) A CaCO3/Cobalt Janus MNM migrates toward HeLa cells following a pH gradient. Reproduced with permission from ref 38. Copyright 2016 Nature Publishing Group. (F) Schematic description of the chemotaxis of catalytic Pd NP-coated polymer beads in a pH gradient. Reproduced with permission from ref 39. Copyright 2013 Wiley-VCH.
rotations. In a uniform environment, isotropic MNMs cannot move because of the force symmetry, while in a vector field, the isotropic MNMs with corresponding responses will generate field-induced chemical products or energies asymmetrically distributed across the particles along the vector field. Because of its isotropic structure, the distribution of chemical products or energies does not change with the Brownian rotation of MNMs but is determined only by the vector field. Hence, the isotropic MNMs will acquire a directional propulsion force along the vector field and show tactic behavior (Figure 1C). For example, because of the limited penetration depth of light in semiconductor particles, isotropic semiconductor MNMs perform asymmetric photocatalytic reactions across them along the light direction, thereby realizing directional diffusiophoretic propulsion forces and phototactic motions regardless of their Brownian rotations.28 The design strategies and motion behaviors of various kinds of tactic MNMs are introduced and analyzed in the next section.
symmetry axis and geometric center. The deviated propulsion force will produce a phoretic aligning torque MP to rotate the MNM until its symmetry axis is aligned with the direction of the chemical gradient. MP is an indirect aligning torque because the torque is not directly from the chemical gradient but rather arises from the deviation of the propulsion force from the geometric center of the particle in response to the chemical gradient. By a similar mechanism, phototactic MNMs based on asymmetric structures have also been developed. In this case, the photocatalytic products or photothermal energy are asymmetrically distributed across the symmetry axis to generate MP, aligning the MNMs along the direction of the light or light intensity gradient.36 When exposed to a vector field of flow, gravity, or magnetic field, asymmetric MNMs with customized responses will be subjected to a force F directly from the local vector field. If the symmetry axes of the MNMs are misaligned with the local vector field at this moment, an aligning torque (MF) resulting from F enables the MNMs to self-reorient along the local vector field. Consequently, rheotaxis, gravitaxis, and magnetotaxis are achieved, as summarized in Figure 1B. The overall tactic motions of asymmetric MNMs can be mainly considered as combinations of the directional motions along the vector field and the random motions resulting from Brownian rotation. The tactic MNMs will move in an approximate straight line if MP or MF is strong enough to suppress their rotational Brownian diffusion. Otherwise, they will meander toward or away from the signal source. For instance, chemotactic MNMs move with their symmetry axis constantly deviating from the direction of the chemical gradient and usually perform intelligent “deviating−rectifying” behaviors. Other than the asymmetric tactic MNMs, isotropic MNMs can achieve tactic motions regardless of their Brownian
3. MICRO/NANOMOTORS WITH TAXIS 3.1. Chemotactic Micro/nanomotors
Chemical gradients are ubiquitous in biological and environmental scenarios. Cell metabolites and natural/artificial chemical sources establish in vivo and in vitro chemical gradients, which attract or repel chemotactic MNMs. With delicate functionalization, chemotactic MNMs are promising for active environmental remediation and biomedical applications like targeted drug delivery and tumor therapy. As asymmetric MNMs are able to reorient in the chemical gradient of fuels or motor−fuel reaction regulators under MP (Figure 1A), synthetic chemotactic MNMs sensitive to 3008
DOI: 10.1021/acs.accounts.8b00291 Acc. Chem. Res. 2018, 51, 3006−3014
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Figure 3. Biohybrid chemotactic MNMs. (A) Functionalized sperm micromotors: (a) schematic diagram of cargo loading and chemotactic movement mechanism and (b) motion trajectories in the presence of a chemoattractant. Reproduced with permission from ref 44. Copyright 2017 Wiley-VCH. (B) Cargo-loaded neutrophil motors: (a) schematic illustration of the preparation process and (b) time-lapse images of the motion with and without E. coli. Reproduced with permission from ref 45. Copyright 2017 Wiley-VCH. (C) Bacteria-based microrobots: (a) laser confocal scanning microscopy image and (b, c) distributions of the microrobots in the presence of (b) a chemoattractant and (c) a chemorepellent. Reproduced with permission from ref 46. Copyright 2013 Wiley.
chemical signals of H2 O2 ,24−26 surfactants,37 and pH values38,39 have been demonstrated. As Figure 2A shows, an agarose hydrogel filled with 30% H2O2 slowly releases molecules to establish a H2O2 gradient, and Pt−Au bimetallic rods with a length of 2.0 μm could sense the H2O2 gradient and move toward and accumulate around the gel.24 Besides bimetallic rods, Janus micromotors,40 microtubes,25 (Figure 2B), and stomatocyte motors41 (Figure 2C) also exhibit chemotactic behaviors in response to H2O2 concentration gradients. Apart from an environmental chemical gradient, a self-generated gradient could also lead to chemotactic motion of artificial nanomotors. As shown in Figure 2D, an oil droplet asymmetrically consumes surfactant (dissolved in water) at one end of the droplet, leading to a concentration gradient, and the droplet exhibits tactic motion toward regions of higher surfactant concentration.37 In addition, a CaCO3/Co Janus micromotor can track a pH gradient and exhibits directed motion in the extremely weak acidic environment generated by HeLa cells in situ (Figure 2E), providing a new solution for tumor targeting and drug delivery systems.38 In another case where OH− acts as a motor−fuel reaction regulator to adjust the decomposition rate of H2O2 (Figure 2F), polymer microspheres with randomly distributed Pd nanoparticles (NPs) respond to the OH− concentration gradient and exhibit tactic movements toward the OH− source.39 Apart from the synthetic chemotactic MNMs, varieties of artificial biohybrid motors have been developed utilizing the intrinsic chemotactic characteristics of living organisms.42,43 They are promising for targeted cargo delivery and detection of toxins, as they need no additional fuels and the living organism can be selected according to specific application scenarios. Chen et al. functionalized natural sperm cells by loading them with artificial Fe2O3@Dox NPs and demonstrated their motion along the chemical gradient created by egg cells (Figure 3A),44 offering a promising method for targeted cargo delivery and
tumor therapy. Hybrid motors consisting of living neutrophils and bacteria-membrane-modified mesoporous silica nanoparticles exhibit chemotactic motion toward Escherichia coli, which generates a neutrophil chemoattractant concentration gradient (Figure 3B).45 Park et al.46 obtained bacteria-based microrobots by selectively attaching Salmonella typhimurium bacteria to one hemisphere of modified PS microbeads, which show different chemotactic behaviors in gradients of a chemoattractant and a chemorepellent for S. typhimurium (Figure 3C). Synthetic and hybrid chemotactic MNMs with various morphologies, compositions, and propulsion mechanisms can be developed when fuels or chemicals that can regulate the motor−fuel reactions or the swimming direction of living organisms exist as concentration gradients. They are able to implement intelligent self-navigation and self-targeting, which allow them to achieve active tasks like environmental remediation (e.g., tracking and cleaning of pollutants in water)37 and in vivo/in vitro active cargo delivery.47 3.2. Phototactic Micro/nanomotors
Light sources, both natural and artificial, can establish vector fields due to the directionality of light. Since Sen’s group first reported the directional exclusion of chemical motors with light in 2009,12 many efforts have been devoted to lightresponsive MNMs, bringing about the bursting emergence of both single MNMs10,48−50 and swarms of MNMs51,52 that can actively regulate their motion behaviors in response to light sources. Phototactic MNMs can be built through two different mechanisms. One is to establish a directional propulsion force regardless of the Brownian motion of isotropic particles. As a demonstration, Chen et al.28 developed isotropic phototactic micromotors utilizing the limited penetration depth of light in semiconductor particles, which induces asymmetric decomposition of H2O2 and a directional net O2 concentration 3009
DOI: 10.1021/acs.accounts.8b00291 Acc. Chem. Res. 2018, 51, 3006−3014
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Figure 4. Artificial phototactic MNMs. (A) Isotropic TiO2 MNMs: (a) schematic diagram of the negative phototactic mechanism and (b) simulated distribution of the O2 concentration under UV irradiation for different times. Reproduced with permission from ref 28. Copyright 2016 Wiley-VCH. (B) Nanotree motors: (a) schematic demonstration of the propulsion mechanism and (b) programmable phototactic behaviors of the nanotree achieved by chemical modifications. Reproduced with permission from ref 29. Copyright 2016 Macmillan Publishers Limited, part of Springer Nature. (C) SiO2/C Janus MNMs: (a) propulsion mechanism and (b) phototactic behavior of the MNM. Reproduced with permission from ref 36. Copyright 2016 Nature Publishing Group.
Figure 5. Rheotactic MNMs. (A) Asymmetric hematite/polymer MNMs: (a) alignment model and (b) upstream migration of the motors with a catalytic protrusion under different flows. Reproduced with permission from ref 30. Copyright 2015 AAAS. (B) Rh/Au bimetallic MNMs: (a) orientation mechanism and (b) collective rheotactic motion of Rh−Au bimetallic rods in H2O2 solution and an acoustic field under imposed flow. Reproduced from ref 31. Copyright 2017 American Chemical Society.
the negatively charged nanotree rotates and aligns its long axis along the direction of the incident light to generate directed phototactic motion. Figure 4C demonstrates the movement of a SiO2/C Janus micromotor toward lower light intensities in an inhomogeneous laser field.36 Local demixing of a binary critical mixture resulting from heating of the carbon cap by a photothermal effect induces thermophoretic slip flows, which allow the MNMs to align under MP and escape from regions of high light intensity. Thanks to the photothermal conversion of the liquid medium, the micromotors can also move phototactically and gather into a swarm along the convection flows.52
gradient across the particle independent of its Brownian rotations (Figure 4A). This leads to local fluid flows that allow the particles to escape from the light source, exhibiting negative phototaxis. The other mechanism to generate phototactic motion is to align asymmetric particles through light-induced MP generated from light-induced diffusiophoresis or thermophoresis. Dai et al.29 developed a phototactic Si/ TiO2 nanotree motor with a silicon trunk and TiO2 branches (Figure 4B). When suspended in H2O2 solution and illuminated with UV light, the motor generates H+ and OH− at the branches and trunk, respectively, creating a local electric field near the nanotree surface. Upon sensing the electric field, 3010
DOI: 10.1021/acs.accounts.8b00291 Acc. Chem. Res. 2018, 51, 3006−3014
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Figure 6. Negative-gravitactic MNMs. (A) Polystyrene/Pt Janus MNMs: (a) propulsion mechanism and (b) swimming trajectories of motors with diameters of 0.95 μm (black), 1.55 μm (red), and 2.4 μm (blue) in H2O2 solution. Reproduced from ref 53. Copyright 2013 American Chemical Society. (B) L-shaped photothermal swimmer: (a) experimental setup, (b) geometrical sketch, and (c) motion trajectories of the swimmer under different illumination intensities. Reproduced with permission from ref 54. Copyright 2014 Nature Publishing Group. (C) TiO2/SiO2 Janus MNMs: (a) concentration field (color-coded) and fluid flow (black streamlines) around a motor and (b) its lift-off trajectory. Reproduced with permission from ref 55. Copyright 2018 Wiley-VCH.
aligned along the flow direction. As a result, the micromotors turn their Rh ends against the flow direction and move upstream. MNMs with asymmetric morphology could sense fluid flows and spontaneously align themselves along the flow direction to migrate against/along a shear flow. Rheotaxis systems may take artificial biomimetic systems to another level and aid in understanding the behaviors of active particles in an imposed flow. In addition, the rheotaxis of MNMs is of particular interest for their future operation and applications in blood vessels, such as active drug delivery and microsurgery.
Considering the advantages of light and advancements in optical techniques, phototactic MNMs are expected to be promising for cargo delivery and micro/nanoengineering. Phototactic MNMs responsive to near-IR (NIR) light are envisioned to operate in vivo because of the high penetration depth of the NIR light in tissues. 3.3. Rheotactic Micro/nanomotors
For biological or microfluidic systems, fluid flows, such as blood flow in blood vessels and flow in microfluidic channels, always exist. When MNMs with an asymmetric morphology work in such environments, they are subjected to MF directly resulting from shear force. When MF is strong enough to suppress the Brownian motion, the orientation of the asymmetric MNMs remains unchanged, thus making it possible to generate directed positive/negative rheotactic motion, allowing the MNMs to work as in vivo and in vitro cargo carriers. Palacci et al.30 reported that a microparticle with a photocatalytic hematite protrusion migrated upstream in imposed flows under light, known as positive rheotaxis (Figure 5A). During the upstream migration, the hematite protrusion always faced the imposed flow because of the integration of the alignment with the polarity of the self-propulsion. Ren and coworkers later proposed Rh/Au bimetallic micromotors that can achieve both positive and negative rheotaxis using a combination of chemical fuel and an acoustic field (Figure 5B).31 Fluid flow makes the micromotors experience a larger drag force on their tails in shear flow, causing them to be
3.4. Gravitactic Micro/nanomotors
Most solid particles are likely to settle to substrates if their density is larger than that of the dispersed medium. The reported investigations on MNMs mainly focus on in-plane motion near a substrate. However, enabling MNMs to swim freely in three dimensions is of significance for their practical applications. To achieve this goal, the MNMs must have the ability to take off from the substrate after sedimentation, which is known as negative gravitaxis. Anisotropic particles are aligned if the mass or chemical reaction is distributed asymmetrically along the direction of gravity. This may be used to manufacture negative-gravitactic MNMs with threedimensional motion performance when a strong enough upward driving force is generated. The first example of a synthetic gravitaxis system was reported by Campbell and Ebbens.53 They took advantage of the asymmetric mass distribution of spherical polystyrene/Pt 3011
DOI: 10.1021/acs.accounts.8b00291 Acc. Chem. Res. 2018, 51, 3006−3014
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Figure 7. Magnetotactic MNMs. (A) Doxorubicin/Pt−Ni-loaded stomatocytes: (a) scheme and (b−e) motion trajectories of the motor. Reproduced with permission from ref 26. Copyright 2016 Wiley-VCH. (B) Double-fueled magnetic micromotor: (a) schematic representation of the motor structure and (b) magnetotactic trajectories. Reproduced from ref 27. Copyright 2017 American Chemical Society.
along H are frequently observed (Figure 7B).27 These doublefueled enzyme-based motors with self-navigation toward a magnetic source may contribute to the biomedical applications of MNMs in the future. Magnetotactic MNMs can utilize environmental H, including the geomagnetic field, to navigate themselves, exhibiting self-awareness compared with magnetic particles passively towed by a strong gradient H. In view of the advantages of H and intelligent self-navigation, magnetotactic MNMs are possible for biomedical applications, including active drug delivery and tumor therapy.
Janus MNMs to maintain a configuration in a liquid medium. In this case, the MNMs generate upward driving forces through either a self-phoretic or nanobubble recoil mechanism due to the photocatalytic decomposition of H2O2 by the “capdown” Pt layer, exhibiting gravitactic motion. Besides Janus spheres, other particles with an asymmetric mass distribution caused by their shape, such as L-shaped photothermal swimmers (Figure 6B), can also show negative gravitaxis.54 They are subjected to an upward driving force resulting from local demixing of the binary mixture at a critical composition and perform enhanced negative gravitaxis and various trajectories with increasing light intensity. Apart from an asymmetric distribution of mass, asymmetric physical or chemical fields surrounding MNMs along the gravity direction may also make them reorient, producing negative-gravitactic MNMs. For example, Singh and colleagues developed light-induced negative-gravitactic swimmers of TiO2/SiO2 Janus MNMs by illumination from underneath the substrate (Figure 6C).55 In their demonstration, photocatalytic decomposition of H2O2 by TiO2 induces a local fluid flow near the motor, enabling it to move and reorient to a capdown configuration, under which circumstance the motor exhibits negative gravitaxis. The development of negative gravitactic movements is essential for the design of “micro/nanoelevators” and various potential applications such as vertical cargo transport and dynamic separation of active and passive particles.
4. SUMMARY AND OUTLOOK Tactic movement enables MNMs to be intelligent. In this Account, we first elucidated the intelligent responses of tactic MNMs using two models. One is that local vector fields, including chemical gradients, gravity, flows, and magnetic fields existing in systems make the overall alignment of asymmetric MNMs via an aligning torque M, directing the MNMs to swim toward or away from the sources. The other is that isotropic MNMs may produce directional propulsion forces independent of Brownian rotations. Then a variety of tactic MNMs based on them were introduced. In chemical gradients of fuels and chemicals that can regulate motor−fuel reactions, asymmetrically built MNMs achieve directed motion and chemotaxis by aligning themselves under M resulting from asymmetric distributions of products. Phototactic MNMs can be built through both light-induced self-alignment of anisotropic MNMs and directed propulsion of isotropic MNMs. MNMs with asymmetric morphology when exposed to fluid flows may suppress Brownian motion and exhibit rheotactic motion. For eccentric particle MNMs, the asymmetric distribution of mass or catalytic component results in M that allows the MNMs to align and exhibit negative gravitactic motions. Magnetotactic MNMs that are built by asymmetrically introducing magnetic components into MNMs will migrate toward the magnetic source. These tactic MNMs have been demonstrated to self-navigate to target locations and are useful for active drug delivery, microsurgeries, environmental remediation, and dynamic separation of active and passive particles. Despite the remarkable achievements, tactic MNMs are still in their infancy. In the near future, great attention should be paid to some challenges before they achieve revolutionary practical applications. First, all tactic MNMs are required to
3.5. Magnetotactic Micro/nanomotors
Magnetic fields (H) are noninvasive and biocompatible with most living organisms, and they possess high penetration depth.13 They have been widely used for motion manipulation of magnetic MNMs since the first report by Mallouk in 2007.14 To achieve the guidance and manipulation of MNMs by H, magnetic components are usually incorporated in anisotropy.14,56,57 Here we mainly summarize the intelligent response of magnetic MNMs to H, which is known as magnetotaxis.58,59 Peng and colleagues fabricated a magnetic nanomotor by incorporating nickel−platinum particles inside the asymmetric stomatocyte polymer matrix, which can regulate its motion direction in response to changes in the direction of H (Figure 7A).26 In a gradient H, double-fueled Janus swimmers with MnFe2O4 nanoparticles incorporated onto one hemisphere are immobile without fuel entities but perform directional magnetotactic movement upon the addition of fuels. When H is insufficient to maintain the orientation, curved trajectories 3012
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ACKNOWLEDGMENTS The authors are grateful for financial support from the National Natural Science Foundation of China (21474078, 21875175, 21705123, and 51521001), the Fundamental Research Funds for the Central Universities (WUT: 2017III028 and 2018III012), the Top Talents Lead Cultivation Project, and the Natural Science Foundation of Hubei Province (2015CFA003)
further enhance the sensitivity to signal sources in order to improve the motion behaviors as well as to expand the effective operation range of the signal sources and thus the application range of tactic motors. For chemotactic MNMs, the surroundings are usually too complicated because of the coexistence of different chemical gradients, which may have an undesirable impact on the chemotactic movement of MNMs. There are two possible approaches to advance synthetic chemotactic motors. One is to enhance the sensitivity of the motors to chemical concentration gradients by tailoring the surface properties of the motors. The other is to introduce signal amplification/conversion systems that can sense environmental clues and transduce them into secondary signals to regulate the motion behaviors of motors. Actually, these two approaches can also apply to the other types of motors for the improvement of tactic motion behaviors. Second, only a few artificial chemotactic motors have been developed to date. Thus, new systems should be developed to enable tactic movements toward different chemical sources. Furthermore, tactic MNMs based on new mechanisms should also be explored, such as MNMs with thermotaxis or aerotaxis and phototactic motors based on light of different wavelengths. Finally, MNMs that combine multiple tactic movements may bring unexpected motion behaviors and promising applications. With the intriguing properties of tactic MNMs, we anticipate that they will bring about quantities of fascinating applications, such as active chemical detectors and sensors, intelligent drug delivery, automatic microsurgeries, and customized chemical motor systems.
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REFERENCES
(1) Ozin, G. A.; Manners, I.; Fournier-Bidoz, S.; Arsenault, A. Dream Nanomachines. Adv. Mater. 2005, 17, 3011−3018. (2) Wang, J. Nanomachines: Fundamentals and Applications; WileyVCH: Weinheim, Germany, 2013. (3) Wang, W.; Duan, W. T.; Ahmed, S.; Mallouk, T. E.; Sen, A. Small power: Autonomous nano- and micromotors propelled by selfgenerated gradients. Nano Today 2013, 8, 531−554. (4) Moo, J. G. S.; Pumera, M. Chemical Energy Powered Nano/ Micro/Macromotors and the Environment. Chem. - Eur. J. 2015, 21, 58−72. (5) Gao, W.; Wang, J. The Environmental Impact of Micro/ Nanomachines: A Review. ACS Nano 2014, 8, 3170−3180. (6) Mou, F. Z.; Pan, D.; Chen, C. R.; Gao, Y. R.; Xu, L. L.; Guan, J. G. Magnetically Modulated Pot-Like MnFe2O4 Micromotors: Nanoparticle Assembly Fabrication and their Capability for Direct Oil Removal. Adv. Funct. Mater. 2015, 25, 6173−6181. (7) Moo, J. G. S.; Wang, H.; Zhao, G. J.; Pumera, M. Biomimetic Artificial Inorganic Enzyme-Free Self-Propelled Microfish Robot for Selective Detection of Pb2+ in Water. Chem. - Eur. J. 2014, 20, 4292− 4296. (8) Li, J.; Esteban-Fernández de Á vila, B.; Gao, W.; Zhang, L.; Wang, J. Micro/Nanorobots for Biomedicine: Delivery, Surgery, Sensing, and Detoxification. Sci. Rob. 2017, 2, No. eaam6431. (9) Xu, L.; Mou, F.; Gong, H.; Luo, M.; Guan, J. Light-Driven Micro/Nanomotors: from Fundamentals to Applications. Chem. Soc. Rev. 2017, 46, 6905−6926. (10) Mou, F.; Li, Y.; Chen, C.; Li, W.; Yin, Y.; Ma, H.; Guan, J. Single-Component TiO2 Tubular Microengines with Motion Controlled by Light-Induced Bubbles. Small 2015, 11, 2564−2570. (11) Zheng, J.; Dai, B.; Wang, J.; Xiong, Z.; Yang, Y.; Liu, J.; Zhan, X.; Wan, Z.; Tang, J. Orthogonal Navigation of Multiple VisibleLight-Driven Artificial Microswimmers. Nat. Commun. 2017, 8, 1438. (12) Ibele, M.; Mallouk, T. E.; Sen, A. Schooling Behavior of LightPowered Autonomous Micromotors in Water. Angew. Chem., Int. Ed. 2009, 48, 3308−3312. (13) Gao, W.; Sattayasamitsathit, S.; Manesh, K. M.; Weihs, D.; Wang, J. Magnetically Powered Flexible Metal Nanowire Motors. J. Am. Chem. Soc. 2010, 132, 14403−14405. (14) Dhar, P.; Cao, Y.; Kline, T.; Pal, P.; Swayne, C.; Fischer, T. M.; Miller, B.; Mallouk, T. E.; Sen, A.; Johansen, T. H. Autonomously Moving Local Nanoprobes in Heterogeneous Magnetic Fields. J. Phys. Chem. C 2007, 111, 3607−3613. (15) Xu, T.; Soto, F.; Gao, W.; Garcia-Gradilla, V.; Li, J.; Zhang, X.; Wang, J. Ultrasound-Modulated Bubble Propulsion of Chemically Powered Microengines. J. Am. Chem. Soc. 2014, 136, 8552−8555. (16) Wang, W.; Castro, L. A.; Hoyos, M.; Mallouk, T. E. Autonomous Motion of Metallic Microrods Propelled by Ultrasound. ACS Nano 2012, 6, 6122−6132. (17) Yoshizumi, Y.; Honegger, T.; Berton, K.; Suzuki, H.; Peyrade, D. Trajectory Control of Self-Propelled Micromotors Using AC Electrokinetics. Small 2015, 11, 5630−5635. (18) Fan, D.; Yin, Z.; Cheong, R.; Zhu, F.; Cammarata, R.; Chien, C.; Levchenko, A. Subcellular-Resolution Delivery of a Cytokine through Precisely Manipulated Nanowires. Nat. Nanotechnol. 2010, 5, 545−551. (19) Gangwal, S.; Cayre, O. J.; Bazant, M. Z.; Velev, O. D. Inducedcharge Electrophoresis of Metallodielectric Particles. Phys. Rev. Lett. 2008, 100, 058302.
AUTHOR INFORMATION
Corresponding Authors
*E-mail:
[email protected] (J.G.). *E-mail:
[email protected] (F.M.). ORCID
Fangzhi Mou: 0000-0002-9644-8277 Jianguo Guan: 0000-0002-2223-4524 Notes
The authors declare no competing financial interest. Biographies Ming You is currently a Ph.D. candidate under Prof. Jianguo Guan’s supervision at Wuhan University of Technology (WUT). His research is focused on the development of magnetically actuated micro/ nanomotors. Chuanrui Chen is currently a Ph.D. student under Prof. Jianguo Guan’s supervision at WUT. He works on biocompatible and bioinspired micro/nanomotors. LeiLei Xu earned a Ph.D. from WUT and became an associate professor there in 2012. Her current research is focused on micro/ nanofunctional materials for solar energy conversion involving photocatalysis and light-driven micro/nanomotors. Fangzhi Mou earned a Ph.D. from WUT and became an associate professor there in 2013. His research interests include micro/ nanomotors, responsive photonic crystals, and their applications. Jianguo Guan is a Changjiang Scholar Distinguished Professor of MOE, China, and Chief Professor of WUT. He has coauthored over 200 papers in peer-reviewed journals. His current research interests mainly include conducting/magnetic composite materials, micro/ nanomotors, photonic crystals, and metamaterials. 3013
DOI: 10.1021/acs.accounts.8b00291 Acc. Chem. Res. 2018, 51, 3006−3014
Article
Accounts of Chemical Research
with Targeting Bacteria (Salmonella Typhimurium). Sens. Actuators, B 2016, 224, 217−224. (43) Stanton, M. M.; Simmchen, J.; Ma, X.; Miguel-López, A.; Sánchez, S. Biohybrid Janus Motors Driven by Escherichia coli. Adv. Mater. Interfaces 2016, 3, 1500505. (44) Chen, C.; Chang, X.; Angsantikul, P.; Li, J.; Esteban-Fernández de Á vila, B.; Karshalev, E.; Liu, W.; Mou, F.; He, S.; Castillo, R.; Liang, Y.; Guan, J.; Zhang, L.; Wang, J. Chemotactic Guidance of Synthetic Organic/Inorganic Payloads Functionalized Sperm Micromotors. Adv. Biosyst. 2018, 2, 1700160. (45) Shao, J.; Xuan, M.; Zhang, H.; Lin, X.; Wu, Z.; He, Q. Chemotaxis-Guided Hybrid Neutrophil Micromotors for Targeted Drug Transport. Angew. Chem., Int. Ed. 2017, 56, 12935−12939. (46) Park, D.; Park, S. J.; Cho, S.; Lee, Y.; Lee, Y. K.; Min, J. J.; Park, B. J.; Ko, S. Y.; Park, J. O.; Park, S. Motility Analysis of Bacteria-Based Microrobot (Bacteriobot) Using Chemical Gradient Microchamber. Biotechnol. Bioeng. 2014, 111, 134−143. (47) Luo, M.; Feng, Y.; Wang, T.; Guan, J. Micro-/Nanorobots at Work in Active Drug Delivery. Adv. Funct. Mater. 2018, 28, 1706100. (48) Gao, Y.; Mou, F.; Feng, Y.; Che, S.; Li, W.; Xu, L.; Guan, J. Dynamic Colloidal Molecules Maneuvered by Light-Controlled Janus Micromotors. ACS Appl. Mater. Interfaces 2017, 9, 22704−22712. (49) Mou, F.; Kong, L.; Chen, C.; Chen, Z.; Xu, L.; Guan, J. LightControlled Propulsion, Aggregation and Separation of Water-Fuelled TiO2/Pt Janus Submicromotors and Their “on-the-fly” Photocatalytic Activities. Nanoscale 2016, 8, 4976−4983. (50) Wang, Y.; Zhou, C.; Wang, W.; Xu, D.; Zeng, F.; Zhan, C.; Gu, J.; Li, M.; Zhao, W.; Zhang, J.; Guo, J.; Feng, H.; Ma, X. Photocatalytically Powered “Match-like” Nano-Motor for LightGuided Active SERS Sensing. Angew. Chem., Int. Ed. 2018, 57, 13110−13113. (51) Zhang, J.; Guo, J.; Mou, F.; Guan, J. Light-Controlled Swarming and Assembly of Colloidal Particles. Micromachines 2018, 9, 88. (52) Deng, Z.; Mou, F.; Tang, S.; Xu, L.; Luo, M.; Guan, J. Swarming and Collective Migration of Micromotors under Near Infrared Light. Appl. Mater. Today 2018, 13, 45−53. (53) Campbell, A. I.; Ebbens, S. J. Gravitaxis in Spherical Janus Swimming Devices. Langmuir 2013, 29, 14066−14073. (54) ten Hagen, B.; Kummel, F.; Wittkowski, R.; Takagi, D.; Lowen, H.; Bechinger, C. Gravitaxis of Asymmetric Self-Propelled Colloidal Particles. Nat. Commun. 2014, 5, 4829. (55) Singh, D. P.; Uspal, W. E.; Popescu, M. N.; Wilson, L. G.; Fischer, P. Photogravitactic Microswimmers. Adv. Funct. Mater. 2018, 28, 1706660. (56) Chen, X.; Jang, B.; Ahmed, D.; Hu, C.; De Marco, C.; Hoop, M.; Mushtaq, F.; Nelson, B. J.; Pane, S. Small-Scale Machines Driven by External Power Sources. Adv. Mater. 2018, 30, No. 1705061. (57) Zhao, G.; Sanchez, S.; Schmidt, O. G.; Pumera, M. Micromotors with Built-in Compasses. Chem. Commun. 2012, 48, 10090−10092. (58) Santomauro, G.; Singh, A. V.; Park, B. W.; Mohammadrahimi, M.; Erkoc, P.; Goering, E.; Schütz, G.; Sitti, M.; Bill, J. Incorporation of Terbium into a Microalga Leads to Magnetotactic Swimmers. Adv. Biosyst. 2018, 1800039. (59) Huang, H.; Huang, T.; Charilaou, M.; Lyttle, S.; Zhang, Q.; Pané, S.; Nelson, B. J. Investigation of Magnetotaxis of Reconfigurable Micro-Origami Swimmers with Competitive and Cooperative Anisotropy. Adv. Funct. Mater. 2018, 28, 1802110.
(20) Tu, Y.; Peng, F.; Sui, X.; Men, Y.; White, P. B.; van Hest, J. C. M.; Wilson, D. A. Self-Propelled Supramolecular Nanomotors with Temperature-Responsive Speed Regulation. Nat. Chem. 2017, 9, 480−486. (21) Bren, A.; Eisenbach, M. How Signals Are Heard During Bacterial Chemotaxis: Protein-Protein Interactions in Sensory Signal Propagation. J. Bacteriol. 2000, 182, 6865−6873. (22) Sourjik, V. Receptor Clustering and Signal Processing in E. coli Chemotaxis. Trends Microbiol. 2004, 12, 569−576. (23) Rosen, G. Fundamental Theoretical Aspects of Bacterial Chemotaxis. J. Theor. Biol. 1973, 41, 201−208. (24) Hong, Y.; Blackman, N. M.; Kopp, N. D.; Sen, A.; Velegol, D. Chemotaxis of Nonbiological Colloidal Rods. Phys. Rev. Lett. 2007, 99, 178103. (25) Baraban, L.; Harazim, S. M.; Sanchez, S.; Schmidt, O. G. Chemotactic Behavior of Catalytic Motors in Microfluidic Channels. Angew. Chem., Int. Ed. 2013, 52, 5552−5556. (26) Peng, F.; Tu, Y.; Men, Y.; van Hest, J. C.; Wilson, D. A. Supramolecular Adaptive Nanomotors with Magnetotaxis Behavior. Adv. Mater. 2017, 29, 1604996. (27) Schattling, P. S.; Ramos-Docampo, M. A.; Salgueirino, V.; Stadler, B. Double-Fueled Janus Swimmers with Magnetotactic Behavior. ACS Nano 2017, 11, 3973−3983. (28) Chen, C.; Mou, F.; Xu, L.; Wang, S.; Guan, J.; Feng, Z.; Wang, Q.; Kong, L.; Li, W.; Wang, J.; Zhang, Q. Light-Steered Isotropic Semiconductor Micromotors. Adv. Mater. 2017, 29, 1603374. (29) Dai, B.; Wang, J.; Xiong, Z.; Zhan, X.; Dai, W.; Li, C.-C.; Feng, S.-P.; Tang, J. Programmable Artificial Phototactic Microswimmer. Nat. Nanotechnol. 2016, 11, 1087−1092. (30) Palacci, J.; Sacanna, S.; Abramian, A.; Barral, J.; Hanson, K.; Grosberg, A. Y.; Pine, D. J.; Chaikin, P. M. Artificial Rheotaxis. Sci. Adv. 2015, 1, No. e1400214. (31) Ren, L.; Zhou, D.; Mao, Z.; Xu, P.; Huang, T.; Mallouk, T. E. Rheotaxis of Bimetallic Micromotors Driven by Chemical-Acoustic Hybrid Power. ACS Nano 2017, 11, 10591−10598. (32) Bauer, A. L.; Jackson, T. L.; Jiang, Y. A Cell-Based Model Exhibiting Branching and Anastomosis during Tumor-Induced Angiogenesis. Biophys. J. 2007, 92, 3105−3121. (33) Jiang, Y.; Levine, H.; Glazier, J. Possible Cooperation of Differential Adhesion and Chemotaxis in Mound Formation of Dictyostelium. Biophys. J. 1998, 75, 2615−2625. (34) Montiel, O.; Sepúlveda, R.; Orozco-Rosas, U. Optimal Path Planning Generation for Mobile Robots Using Parallel Evolutionary Artificial Potential Field. J. Intell. Rob. Syst. 2015, 79, 237−257. (35) Dhont, J. K. G. An Introduction to Dynamics of Colloids; Elsevier: Amsterdam, 1996; pp 183−186. (36) Lozano, C.; Ten Hagen, B.; Lowen, H.; Bechinger, C. Phototaxis of Synthetic Microswimmers in Optical Landscapes. Nat. Commun. 2016, 7, 12828. (37) Toyota, T.; Maru, N.; Hanczyc, M. M.; Ikegami, T.; Sugawara, T. Self-Propelled Oil Droplets Consuming “Fuel” Surfactant. J. Am. Chem. Soc. 2009, 131, 5012−5013. (38) Guix, M.; Meyer, A. K.; Koch, B.; Schmidt, O. G. CarbonateBased Janus Micromotors Moving in Ultra-Light Acidic Environment Generated by HeLa Cells in situ. Sci. Rep. 2016, 6, 21701. (39) Dey, K. K.; Bhandari, S.; Bandyopadhyay, D.; Basu, S.; Chattopadhyay, A. The pH Taxis of an Intelligent Catalytic Microbot. Small 2013, 9, 1916−1920. (40) Popescu, M. N.; Uspal, W. E.; Bechinger, C.; Fischer, P. Chemotaxis of Active Janus Nanoparticles. Nano Lett. 2018, 18, 5345−5349. (41) Peng, F.; Tu, Y.; van Hest, J. C.; Wilson, D. A. Self-Guided Supramolecular Cargo-Loaded Nanomotors with Chemotactic Behavior towards Cells. Angew. Chem., Int. Ed. 2015, 54, 11662− 11665. (42) Nguyen, V. D.; Han, J.-W.; Choi, Y. J.; Cho, S.; Zheng, S.; Ko, S. Y.; Park, J.-O.; Park, S. Active Tumor-Therapeutic Liposomal Bacteriobot Combining a Drug (paclitaxel)-Encapsulated Liposome 3014
DOI: 10.1021/acs.accounts.8b00291 Acc. Chem. Res. 2018, 51, 3006−3014
